SURG.00011 Products for Wound Healing and Soft Tissue Grafting: Investigational

This document addresses soft tissue (e.g., skin, ligament, cartilage, etc.) substitutes that are considered investigational.

Note: For information on products used to treat osteochondral defects, please refer to the applicable guidelines used by the plan.

Note: See definition section for information on The Women’s Health and Cancer Rights Act of 1998 (WHCRA).

The following products are considered investigational and not medically necessary for all uses:

This document describes clinical studies and expert recommendations, and explains whether soft tissue grafting and wound care products are appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

This document discusses many soft tissue grafting and wound care products. These products are made from different materials, including human, animal, or plant sources. Some are synthetic and some combine more than one type of material. They are used in various forms like sheets, powders, gels, or sprays, and they differ in how they are stored or prepared. These products are intended to help repair skin, tendons, or other soft tissue, often after surgery or injury. While some products are widely used in medical care, many others have not been studied enough to know if they work or are safe. Some products may not help people heal, or could lead to problems like infections, new health problems, or unnecessary treatments. This summary explains which products may be useful and which are not based on current studies.

Some soft tissue products have been studied more than others. Some products, for example, Regeneten, has had multiple studies published describing the clinical performance of the product. On the other hand, many other products have no studies published at all. However, despite some product having multiple studies published, they have been determined to be insufficient to demonstrate clinical utility. These decisions are based on a wide array of reasons, but predominantly poor study methodology, including small study populations, lack of control or comparison groups, selection and other bias, high dropout rates, short follow-up times and others. Additionally, while some studies have been adequate, the results have been mixed or demonstrate better results as a result of the comparison group. Better studies are needed to know if these treatments improve health.

While some soft tissue grafting products may be appropriate, they are not addressed in this document. Readers should see CG-SURG-127 for products that have been determined to have enough scientific evidence to support their use.

The products listed in this document have not been proven to improve health and are not considered clinically appropriate. Using unproven or unnecessary treatments can lead to treatment that does not help, and possible new health problems.

A wide variety of products are available for soft tissue grafting and wound treatment. These products differ in species source (e.g., human cadaveric, synthetic, bovine, porcine, equine, a combination of several types, etc.), tissue source (e.g., dermis, pericardium, intestinal mucosa, etc.), bioburden reduction (e.g., nonsterile, sterile), additives (e.g., antibiotics, surfactants), delivery formats (e.g., wet packaged, freeze-dried), and preparation requirements (e.g., multiple rinses, rehydration). Additionally, they are procured, produced, manufactured, or processed in sufficiently different manners that they cannot be addressed and evaluated as equivalent products. This is made evident not only in the wide range of shelf-life recommendations for these types of products, but also in the descriptions of their physical properties. Additionally, there are a limited number of comparative studies available addressing the clinical outcomes for allographic, xenographic, and composite products, and the results are heterogeneous (Diffley, 2025; Kollmez, 2025).

Below, findings of recent or notable studies published in peer-reviewed medical literature are summarized for each product where such information is available. The literature discussed and included in this document should not be construed to represent all of the scientific evidence available on a topic or reviewed in document development. Products where no published evidence has been identified are listed in the investigational and not medically necessary section of this document, but discussion of such products will not be found below.

AC5 Advanced Wound System (Arch Therapeutics, Inc., Framingham, MA) is a synthetic, self-assembling peptide-based wound matrix cleared through the FDA’s 510(k) process (K182681). Under the supervision of a health care professional, AC5 Topical Gel is a topical dressing used for the management of partial and full-thickness wounds, such as pressure sores, leg ulcers, diabetic ulcers, and surgical wounds.

In a prospective, single-arm study by Treadwell (2024), 15 individuals (6 men, 9 women; ages 25 to 80) with challenging acute or chronic wounds were recruited. Their wounds had a mean duration of 21 months (the oldest at 7 years) and a mean surface area of 9.5 cm² (the largest at 32 cm²). Eleven individuals received weekly AC5 applications, and four received AC5 treatment every other week, for up to 8 weeks. Among the weekly group, 64% achieved more than 50% wound area reduction at 4 weeks, and 73% had more than 60% reduction at 8 weeks. In the every-other-week group, 25% reached 50% reduction by 4 weeks, and 50% by 8 weeks. No adverse events were reported. The authors reported that AC5 easily conformed to uneven wound geometry, including tunneled or undermined wounds. They concluded that the weekly application of AC5 appeared more effective compared to biweekly application.

Affinity is a cryopreserved human amnion-derived tissue allograft and is treated as human tissue for transplantation under the FDA’s HCT/P process.

Serena (2020) reported on the results of an unblinded prospective RCT involving 76 participants with diabetic foot ulcers (DFUs) treated with either Affinity plus standard care (n=38) or standard care alone (n=38). Wound closure for the Affinity group was significantly greater than that of the control group at both 12 weeks (55% vs. 29%, p=0.02) and 16 weeks (58% vs. 29%, p=0.01). At 16 weeks, wound closure was reported in 60% of Affinity participants compared to 48% of control participants (p=0.04). The authors reported that the probability of wound closure with Affinity compared to standard care increased by 75% (hazard ratio [HR], 1.75). The authors concluded that the use of Affinity increased the frequency and probability of DFU wound closure. Additional data from well-designed trials are warranted to support these conclusions.

AlloMax is an acellular, non-cross-linked allograft dermis product and is treated as human tissue for transplantation under the FDA’s HCT/P process.

A case series study involving 65 participants undergoing tissue expander breast reconstruction was described by Venturi (2013). The results of this study are limited but include a complication rate of 4.6% (3 participants). These included one case of cellulitis and two cases of partial mastectomy flap necrosis requiring debridement. No seromas or explantations were reported. Histological verification of full graft incorporation was demonstrated in the first 20 biopsies.

A second retrospective case series involving 203 participants (348 breasts) undergoing mastectomy with immediate breast reconstruction was reported by Rundell in 2014. The authors reported that infection occurred in 6.6% of participants, with 3.7% being major infections requiring intravenous antibiotics and 2.9% being minor infections requiring oral antibiotics only. Seromas occurred in 3.4% of cases and reconstruction failure occurred in 0.6% of cases. The authors stated that the analysis suggested that the complication prevalence was significantly higher in individuals with a BMI > 30 (p=0.03).

AlloPatch is a product composed of acellular human dermis treated as human tissue for transplantation under the FDA’s HCT/P process.

At this time, there is limited evidence published in the peer-reviewed literature addressing the use of this product. The most rigorous study to date involved 45 participants with chronic refractory DFUs (Zelen, 2016b). A total of 40 participants in this investigator blinded randomized controlled trial (RCT) were assigned in a 1:1 fashion to either standard care alone (n=20) or AlloPatch plus standard care (n=20). AlloPatch grafts were applied weekly for up to 12 weeks. Initial ulcer size at baseline was greater in the AlloPatch group compared to controls (4.7 cm² vs. 2.7 cm²). At 6 weeks, the authors reported that 65% of the AlloPatch group participants were completely healed (13/20) compared to 5% in the control group (1/20). At 12 weeks, the proportions of DFUs healed were 80% and 20%, respectively. The mean time to heal within 12 weeks was 40 days in the AlloPatch group compared to 77 days for controls. No differences between groups were reported with regard to adverse or serious adverse events. The authors reported that, “Weekly application of HR-ADM [human reticular acellular dermis matrix] is an effective intervention for promoting closure of non-healing DFUs.”

This group published a continuation study with an additional 40 participants (n=20 per group) and results of the total 80 participant population were reported by Zelen in 2018. In the continuation population, the AlloPatch group had more smokers (7 vs. 1, p=0.044) and the control group was older (67 years vs. 55 years, p=0.008). At 6 weeks, 85% of the AlloPatch group compared to15% of the controls were completely healed (p=2.7 x 10^-6). The mean PAR in wounds was greater in the AlloPatch group (62% vs. 50%, p=2.7 x 10^-6). Mean time to healing at the 6-week time point was 27 days for the AlloPatch group compared to 41 days for controls (p=9.9 x 10^-7). At 6 weeks, 2 AlloPatch participants (5%) and 19 control participants (48%) were withdrawn from the study due to failure to have a 50% reduction in wound area. At 12 weeks, 80% of AlloPatch participants and 30% of the control participants had complete wound healing (p=8.4 X 10^-6). At 12 weeks, mean time to heal was 38 days in the AlloPatch group compared to 72 days in the control group (p=3.9 x 10^-7). After adjusting for age and baseline wound area, the HR for the AlloPatch compared to the control group was 8 (p=3.7 x 10^-7). No adverse events related to the study treatment were reported.

AMNIOEXCEL is a dehydrated human amnion-derived tissue allograft and is treated as human tissue for transplantation under the FDA’s HCT/P process.

Snyder (2016) reported on the results of a prospective, open label, randomized, parallel group trial involving 29 adults with type 1 or type 2 diabetes mellitus who have one or more ulcers presenting for more than 1 month with no signs of infection/osteomyelitis. Participants were randomized in a 1:1 fashion to receive treatment with either standard care (n=14) or AMNIOEXCEL plus standard of care (n=15) until wound closure or 6 weeks. The authors reported that 35% of participants in the experimental group achieved complete wound closure at or before week 6 compared to 0% in the standard of care group (p=0.017). They observed that there was a more robust response noted in the per protocol population, with 45.5% of participants in the experimental group achieving complete wound closure, while 0% of standard of care alone participants achieved complete closure (p=0.0083).

Amniofix is a product that consists of an injectable form of processed allogeneic amniotic tissue and is treated as human tissue for transplantation under the FDA’s HCT/P process.

Zelen (2013b) report on 45 participants with plantar fasciitis randomized in a single-blind fashion to receive one of three treatments: (1) standard care plus injection with 1.25 cc of sterile 0.9% saline (control group); (2) standard care plus injection with 0.5 cc Amniofix (0.5 cc group), and (3) standard care plus injection with 1.25 cc Amniofix (1.25 cc group). All participants also received injection with 2 cc of 0.5% Marcaine plain, and the use of tramadol for pain was allowed as needed throughout the study. There were 15 participants in each group. A total of 41 participants (91.1%) completed the 8-week follow-up period. All 4 participants who failed to complete the study were in the control group. The authors report that significant benefits were seen in all groups throughout the study compared to baseline on the American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot Scale (p<0.01). Additionally, the AOFAS scale outcomes were significantly higher for both Amniofix groups compared to controls (p<0.001). No differences were noted between the two Amniofix groups. At the end of week 1, the median reduction in pain was 3 points for controls and 6 points and 5 points for those receiving 0.5 cc and 1.25 cc of Amniofix, respectively (p<0.001; p=0.004). Using the Wong-Baker FACES Pain Rating Scale, a visual analog pain scale (VAS), controls reported moderate to severe pain throughout the 8-week study period. Both Amniofix groups reported a significant reduction of pain from very severe at baseline to within the mild to moderate range at 1 week and reported continuing reduction in pain over the study period (p<0.001), with no statistically significant difference between groups. Based upon the physical and mental scales on the SF-36v2 quality of life tool, it was reported that both Amniofix groups had significant improvements from baseline compared to controls. No difference between Amniofix groups was reported. At the end of the first follow-up week, significantly more participants in both Amniofix groups compared to controls needed additional treatment with tramadol (57.1% of controls, 73.3% of the 0.5 cc group, and 100% of the 1.25 cc group). This was not significant for the 0.5 cc group compared to controls but was for the 1.25 cc group compared to controls (p=0.004) as well as the 1.25 cc group compared to the 0.5 cc group (p=0.032). At the second follow-up visit, rates of tramadol use were significantly lower in all groups (p>0.05 for all groups). No adverse events related to treatment were observed in any study participants. This study indicates some benefit from the use of Amniofix for individuals with plantar fasciitis. However, due to the small study population and lack of investigator blinding, further research is warranted to fully understand the efficacy of this treatment method.

Artacent is a product composed of dehydrated acellular human amniotic membrane and is treated as human tissue for transplantation under the FDA’s HCT/P process.

Sledge (2020) reported on a study involving 26 participants who were participants in an RCT that was discontinued due to logistical issues. All participants had non-infected DFUs that had failed previous standard care and were treated weekly or biweekly with Artacent Wound. The primary endpoint of 100% healing at 12 weeks was reported in 17 participants (65%). The incidence of adverse events potentially related to the grafting product was 12% (4/34) and serious adverse events were reported in 6% (2/34).

In a large retrospective, claims-based cohort study, Tettlebach and colleagues (2025) used U.S. Medicare data (2020-2023) to compare outcomes of Artacent Wound plus standard wound care versus sharp debridement alone for lower-extremity diabetic ulcers. After 1:1 matching on 6 key baseline covariates, 1244 wound episodes (622 per group) were analyzed. Artacent Wound treatment was associated with significantly lower rates of major amputation (2.6% vs. 5.6%;p<0.0066), corresponding to 1 major amputation prevented for every 32 individuals treated, and substantially reduced healthcare utilization, including fewer inpatient admissions, emergency department visits, and skilled nursing facility admissions. Minor amputation rates trended lower with Artacent Wound but did not reach statistical significance. Limitations included the retrospective, observational design, reliance on claims-based proxies for wound size, depth, and care quality, and potential residual confounding despite matching. The cohort was restricted to Medicare fee-for-service beneficiaries, limiting generalizability to younger or commercially insured individuals, and healing rates could not be directly assessed.

Artelon Tissue Reinforcement (Artelon, Inc., Marietta, GA) is a synthetic grafting material made from degradable polyurethaneurea which provides a scaffold that is incorporated into the individual’s native tissue. It is intended for use in general surgical procedures for the reinforcement of soft tissue where weakness exists, as well as for reinforcement of soft tissues that are repaired by suture or suture anchors, during tendon repair surgery including reinforcement of rotator cuff, patellar, Achilles, biceps, or quadriceps tendons. Artelon is not intended to replace normal body structure or provide the full mechanical strength to support the rotator cuff, patellar, Achilles, biceps, or quadriceps tendons. Sutures, used to repair the tear, and sutures or bone anchors, used to attach the tissue to the bone, provide mechanical strength for the tendon repair. Artelon is cleared through the FDA’s 510(k) process (K071887).

Nilsson, (2010) published the results of an RCT consisting of 109 participants with osteoarthritis of the carpometacarpal joint of the thumb. In this study, 72 participants were treated with Artelon and 37 were treated with standard tendon interposition arthroplasty. There was a significant loss to follow-up, with less than 50% of participants having available data at the 1-year follow-up time point. The authors report that swelling and pain were more common in the Artelon group, and 6 implants were removed because of such symptoms. Interestingly, 5 of these participants did not receive antibiotics preoperatively according to the study protocol. In the intention-to-treat analysis but not in the per-protocol analysis, significantly better pain relief (VAS) was obtained in the control group. Self-perceived disability evaluated by the DASH (disability of arm-shoulder-hand) questionnaire improved in both groups. However, these findings are not particularly useful, given the significant loss to follow-up reported.

At this time, the available peer-reviewed published articles addressing Artelon TMC are case series studies involving 13 and 15 participants each (Jörheim, 2009; Nilsson, 2005; respectively). This level of evidence is inadequate to fully evaluate the safety and efficacy of this product. Further investigation is warranted.

Cuttica (2023) reported the results of a retrospective case series study involving 18 participants undergoing surgical treatment for insertional Achilles tendinosis with tendon repair augmentation using Artelon. The study reported on pain score, strength, and ankle motion. The Wilcoxon signed-rank test was used to compare baseline and final follow-up VAS scores. One participant had 2 suture anchor pull-out from the calcaneus. Final strength was obtained for 17 participants, with 15 (83.24%) reported as being 5/5 and 2 (11.76%) being 4/5. Final active dorsiflexion was measured in all participants, with 17 (94.44%) reaching at least 10°. No participants had evidence of foreign body reaction or neritic complications, required return to the operating room, developed deep vein thromboses, or developed other major complications. The authors concluded that Achilles tendon augmentation with Artelon is a viable option in the treatment and that its use has minimal morbidity and can be an alternative to other forms of augmentation.

ARTIA reconstructive tissue mesh (Allergan Inc. Dublin, Ireland) is a product derived from porcine acellular dermal matrix (ADM). ARTIA is intended for use as a soft tissue patch to reinforce soft tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue membranes which require the use of reinforcing or bridging material to obtain the desired surgical outcome. The implant is intended for reinforcement in plastic and reconstructive surgery. It is intended for single patient; one time use only. ARTIA is cleared through the FDA’s 510(k) process (K162752).

King (2023) reported a retrospective non-randomized comparative trial involving the use of ARTIA for implant-based breast reconstruction in 63 participants compared to 181 participants who received treatment with AlloDerm ADM. Bilateral procedures were done in 95 participants for a total of 276 breasts (n=98 ARTIA and n=178 AlloDerm). Significantly more participants in the ARTIA group received prepectoral reconstruction (69.4% vs. 46.6%, p<0.01). Eleven underwent delayed reconstruction, while 265 underwent immediate reconstruction, with no significant difference between groups (p=0.34). Two stage reconstruction with tissue expanders was utilized in the majority of cases (243 breasts), with no difference in reconstruction technique between groups (p=0.2). The authors reported no significant differences between groups with regards to major complications (28.6% vs. 31.2%, p=0.69) or minor complications (9.1% vs. 14.0%, p=0.24), including hematoma, infection, seroma, dehiscence, necrosis, capsular contracture, and explantation. The results of this study appear to indicate equivalent outcomes between ARTIA and the standard of care product. However, the small sample size and other methodological issues impair the generalizability if these findings. Further investigation with more robust trials is warranted to establish the clinical utility of this product.

Avaulta (C.R. Bard, Inc., Murray Hill, New Jersey) is a composite product composed of polypropylene mesh with acellular cross-linked collagen of bovine origin. Avaulta Plus and Avaulta Biosynthetic Support System are indicated for tissue reinforcement and long-lasting stabilization of fascial structures of the pelvic floor in vaginal wall prolapse where surgical treatment is intended either as mechanical support or bridging material for the fascial defect. Avaulta is cleared through the FDA’s 510(k) process (K063712).

The use of Avaulta Plus and Avaulta Biosynthetic Support System for the treatment of vaginal prolapse has been described in one prospective case series study involving 40 participants (Bondili, 2012). Participants were followed for up to 3 years (median 27 months (range 20-36). The primary outcome was quality of life (QoL) and satisfaction as measured by the International Consultation on Incontinence Modular Questionnaire-Vaginal Symptoms (ICIQ-VS) tool. Twelve participants (30%) were undergoing a second procedure to address prolapse. Of the 40 participants, 19 (47%) underwent anterior repair, 20 (5%) posterior repair, and 1 (2.5%) underwent both anterior and posterior procedures. Vaginal laxness improved significantly, with 67.25% of participants reporting preoperative laxness which improved to 5% of participants with laxness at follow-up (p<0.0001). Decreased vaginal sensation also improved, from 30% to 7.5% (p<0.01). Sexual activity was reported to improve from only 32% to 100% postoperatively. The authors report that 1 participant continued to have prolapse symptoms (2.5%), resulting in a 97.5% success rate (p<0.0025). Only 2 participants (5%) needed to digitate the vagina to vacate their bowels, a significant decrease from 12 (57%) preoperatively (p<0.001). Vaginal pain decreased from 55% preoperatively to 2.5% postoperatively (p<0.0001). No surgical complications were mentioned.

A retrospective case series study by Oliveira (2020) involved 97 participants with ≥ stage II genital wall prolapse repair with Avaulta. Mean follow-up was 2.9 years with 12 participants lost. Postoperative complications were experienced by 29.1% (n=23) of participants, with one removal due to hematoma. Other complications included voiding dysfunction (n=10), urinary infection (n=7), vesicovaginal fistula (n=1), pelvic abscess linked to hysterectomy (n=2), and mesh exposure (n=6). For participants with voiding dysfunction and bladder injury, a prolonged bladder drainage by a Foley catheter was required for a mean duration of 11.2 days. Four of the participants with vaginal mesh exposure required additional surgery to partially remove the mesh in 3 cases and a colpoplasty procedure to cover the mesh in the remaining case. Self-reported improvements were reported with regard to vaginal discomfort (n=79 at baseline vs. 4 at last follow-up, p>0.01), pelvic heaviness (n=46 at baseline vs. 3 at last follow-up, p>0.01), and voiding dysfunction (n=16 at baseline vs. 2 at last follow-up, p>0.01). No anterior wall prolapse was present in 79.1% of participants at last follow-up and stage I and II prolapse was reported in 19% and 3%, respectively. No apical and posterior prolapse was reported in 98.5% and 83.6%, respectively. Eight participants (12 %) had a recurrence at 3 years.

Avive Soft Tissue Membrane is a product derived from allograft amnion and umbilical cord membrane, which is regulated through the U.S. FDA’s HCT/P process as human tissue for transplantation.

Cox (2023) reported the first use of Avive in a prospective propensity-matched cohort study involving 77 participants (97 nerves) who underwent revision nerve decompression. Mean follow-up was 9.0 months. Avive was applied to the median nerve in 47.4% of cases, ulnar nerve in 39.2% of cases, and radial nerve in 13.4% of cases. In the Avive cohort, S4 sensory recovery was achieved in 58% of participants, S3+ in 33%, S3 in 7%, S0 in 2%, and improvement from baseline in 87%, strength was improved in 92%. Mean total active motion was 94.8%. Mean Quick Disability of Arm, Shoulder & Hand (QuickDASH) score was 36.1, and 96% reported improved or resolved symptoms. For between-group comparisons, postoperative pain was significantly lower in Avive group participants (p=0.001). Improved or resolved symptoms were more frequently reported in the Avive group (p<0.0001). Finally, clinically important improvement in pain was reported in 64.9% in the Avive group compared to 40.8% the control group (p=0.002). This initial pilot study indicates some benefit to the use of Avive in revisions nerve surgery. Further investigation is needed to fully understand the benefits and harms of such use.

In December 2020, the FDA granted De Novo (DEN200035) approval of the BEAR Implant (Miach Orthopaedics Inc. Westborough, MA). BEAR is a decellularized xenograft derived from bovine collagen and is indicated for repair of anterior cruciate ligament tear (ACL). The graft implant is combined with autologous whole blood to form a clot that replaces the ACL and functions as a bridge between the torn ends of the ligament.

Murray (2020) and Barnett (2021) both reported the results of the BEAR II trial, a double-blind RCT involving 100 participants aged 13-35 years with a complete midsubstance ACL injury treated with BEAR (n=65) or autograft ACL (n=35). Participants underwent surgery within 45 days of the index injury. Participant outcomes were assessed at 2 years by an independent examiner blinded to the procedure. Murray reported that the results on the International Knee Documentation Committee (IKDC) Subjective Score were 88.9 points for the BEAR group and 84.8 points for the control group (no p-value reported). The side-to-side difference in AP knee laxity in the BEAR group was 1.61 mm compared to 1.77 mm in the control group (no p-values reported). The BEAR group had a significantly higher mean hamstring muscle strength index than the control group at 2 years (98.2% vs. 63.2%; p<0.001). The report by Barnett stated that repeated-measures testing revealed a significant effect of group on the IKDC Subjective Score (p=0.015), most pronounced at 6 months after surgery (86 points in the BEAR group vs. 78 points in the control group; p=0.001). Results on the Knee Injury and Osteoarthritis Outcome Score-Symptoms subscale scores were significantly in favor of the BEAR group (p=0.010) attributable to higher BEAR scores at 1 year (88 vs. 82; p=0.009). Hamstring strength was significantly better in the BEAR group compared to controls (p<0.001). Clearance for return to sports at 1 year after surgery was granted to approximately 88% of BEAR group participants and 76% of control group participants (p=0.261). The authors concluded that participants undergoing the BEAR procedure had earlier resolution of symptoms as well as increased satisfaction with knee function and hamstring muscle strength.

Barnett (2020) also compared sex-specific outcomes following ACL reconstruction within 45 days of injury in 65 participants with complete ACL tear treated with BEAR. The results demonstrated no significant sex difference on the postoperative IKDC Subjective Score or any of the five Knee Injury and Osteoarthritis Outcome (KOOS) scores at 12 and 24 months. Additionally, AP laxity testing demonstrated differences that were similar in the two sexes at 2 years (1.7 mm and 1.5 mm in females and males, respectively; p=0.72). At 6 months postoperatively, males had a larger deficit in hamstring strength on the operated leg (14.0% vs. 1.7%; p=0.03) and a larger deficit in quadriceps strength on the operated leg (11.3% vs. 2.0%; p=0.004); however, no differences were noted at 12 or 24 months. Interestingly, females demonstrated superior single leg hop testing at both 6 and 12 months (91.3% vs. 78.1%, p=0.001 and 96.9% vs. 87.0%, p=0.01, respectively). No significant differences were reported with regard to ipsilateral ACL reinjury rates.

Menghini and others (2022) completed a cohort study using data from the above-mentioned BEAR II trial, examining the cross-sectional area (CSA) of the treated compared to contralateral native ACLs (n=65 in the BEAR group, n=35 in the autograft group, n=100 in the native group). CSA is a known predictor of strength and knee function. The authors reported that at 24 months, CSA in the autologous group peaked at 69%, 61% in the BEAR group, and 42% in the native group, with significant between-group differences (p<0.001). They concluded that while the BEAR ACLs remained significantly larger, the autograft ACL had a CSA profile comparable with that of the contralateral native ACL.

Flannery (2023) reported the results of a retrospective analysis of 65 individuals from the BEAR II RCT, that compared BEAR graft to traditional ACL reconstruction using non-contemporaneous quantitative MRI to predict positive functional outcomes from 6-24 months post-ACL surgery. The study images were obtained at 6 months post-surgery, additionally single-leg hop test ratios, arthrometric knee laxity values, and IKDC subjective scores were measured at 6 and 24 months. The results demonstrated that CSA (r=0.44, p=0.01), volume (r=0.44, p=0.01), and estimated failure load (r=0.48, p= 0.01) measures at 6 months were predictive of the change in single-leg hop ratio from 6 to 24 months in bivariate analysis. The authors concluded that using qualitative MRI at 6 months post-surgery may be a predictor of longer term functional outcomes. This information may be useful in rehabilitation planning, return to sport decisions, and injury risk reduction.

Current evidence does not yet support that use of BEAR Implant for the treatment of ACL injury is a durable equivalent to standard of care ACL reconstruction.

BellaDerm is a product composed of acellular human dermis and is treated as human tissue for transplantation under the FDA’s HCT/P process.

Solomon and others (2013) published the results of a retrospective case series study involving 47 participants who underwent penis girth enhancement utilizing circumferential grafting with allograft material. The participants received either aseptic AlloDerm (n=9), Belladerm (n=20), and Repriza (n=21). Mean follow-up was 11.25 months (range 1 to 120 months). The rate of infection, which the authors defined as an open wound with graft exposure, occurred in 20 (42%) of 47 participants. Of these, 17 (36%) participants had graft exposure only and 3 (6%) participants sustained graft exposure and total graft loss. Graft exposure or loss occurred in 3 AlloDerm participants, 9 Belladerm participants, and 8 Repriza participants. No AlloDerm participants sustained graft loss, whereas 2 with Belladerm and 1 with Repriza did. No statistical differences between groups with regard to infection or graft loss was reported.

BioBraceImplant (CONMED Corp., Largo, FL) is a bioresorbable scaffold made from bovine tendon collagen and reinforced with polyL-lactic-acid (PLLA) yarn. The device is designed for surgical reinforcement of weakened soft tissues it supports tissue healing in surgeries such as tendon repairs, including rotator cuff, patellar, Achilles, biceps, and quadriceps tendons. BioBrace is not intended to replace normal body structures or provide the full mechanical strength to support the rotator cuff, patellar, Achilles, biceps, or quadriceps tendons. Sutures, used to repair the tear, and sutures or bone anchors, used to attach the tissue to the bone, provide mechanical strength for the tendon repair. BioBrace is cleared through the FDA’s 510(k) process (K203627).

CardioCel (Admedus Inc, Brisbane, Australia) is a product produced from bovine pericardial tissue, it is indicated for use as a patch in pericardial closure and the repair of cardiac and vascular defects including intracardiac defects; septal defects, valve and annulus repair; great vessel reconstruction, peripheral vascular reconstruction and suture line buttressing. CardioCel is cleared through the FDA’s 510(k) process (K130872).

Pavy (2017) published the results of a retrospective series of 102 participants who underwent procedures addressing a variety of congenital heart diseases, including septal defects to pulmonary outflow disorders. No infections, intraoperative implantation difficulties or postoperative mortality were reported to be associated with CardioCel. Graft failure reoperations occurred in 5 participants (5%), 4 of whom had the patch implanted for aortic angioplasty (2 in the ascending aorta and 2 in the aortic arch), and 1 participant had a monocusp replacement. The median time between the first and the second operation for graft failure was 245 (range 5-480) days. The authors concluded that, “Our experience shows that the patch is well tolerated in the septal, valvar and pulmonary artery positions. However, we experienced graft failures in infants in the aortic position.”

Bell (2019) reported on the results of another series study involving 377 participants with congenital heart defects who received surgical treatment with 501 CardioCel patches. Median follow-up was 31 months (1-60 months), and 11 deaths (2.9%) were reported, with 1 reportedly related to Cardiocel. The authors reported no echocardiographic or radiological evidence of patch calcification in any participant. The overall freedom from reintervention at 3- and 5-years post-implantation was 96%. A total of 14 (2.8%) implants required 18 reinterventions (3.6%) at the site of implantation. No differences in performance of CardioCel in neonates (0-28 days), infants (29-365 days) or children older than 1 year (p=0.22) were reported. Patukale (2023) reported on the mid-term performance of CardioCel for the repair of congenital heart defects. The retrospective study included a total of 1184 CardioCel patches implanted in 752 pediatric participants. Median age at implant was 12 months with median follow-up of 2.1 years. The authors reported the probability of freedom from CardioCel-related reintervention as 93% at 1 year, 91% at 3 years, and 88% at 5 years, respectively. A multivariable regression analysis indicated that participants undergoing aortic valve repair had a higher incidence of reintervention compared to other sites (HR, 7.15, p=0.008). They also stated that the probability of reintervention was higher in neonates (HR, 6.71, p=0.0007), especially when used for augmentation of the pulmonary arteries (HR, 14.38, p=0.029).

Irimie (2025) reported the midterm outcomes of a single-center retrospective cohort study that evaluated aortic valve reconstruction using cusp patch-plasty with CardioCel in 167 individuals with moderate-to-severe aortic insufficiency. Over a mean follow-up of approximately 4.2 years, early mortality was low (0.6%), and overall survival remained high at 95.7% at 6 years. During follow-up, 10 individuals (approximately 6%) developed relevant aortic insufficiency (at least 3+), all of whom underwent successful aortic valve replacement, resulting in a 7.8% cumulative risk of valve reoperation and/or significant insufficiency at 6 years. Importantly, no degeneration or calcification of the explanted CardioCel patches was observed, and most failures were attributed to progression of underlying cusp pathology or suture-line tears, particularly in individuals with bicuspid aortic valves, rather than patch-related deterioration. Limitations included the retrospective, non-randomized design, single-center experience, and heterogeneity of valve phenotypes and repair techniques, which introduce selection bias and limit generalizability. Follow-up imaging was not uniformly scheduled, and the absence of a comparator group (for example, other patch materials or valve replacement) precludes definitive conclusions regarding relative superiority. Longer-term follow-up and comparative studies are needed.

carePATCH (ExtremityCare, Conshohocken, PA) is a dehydrated, dual-layer amniotic membrane allograft intended for use as a barrier to protect wounds from the environment. It is treated as human tissue for transplantation under the FDA’s HCT/P process.

Hodge (2025) reported the results of a retrospective case series that evaluated carePATCH, as an adjunct to standard care in the management of hard-to-heal wounds that had failed to achieve adequate size reduction with standard care alone. Included in the study were 13 elderly individuals (mean age 75 years) with 13 chronic wounds including VLUs, pressure ulcers, post-surgical wounds, VSUs, and arterial wounds who were treated at a single wound care provider group. Across all wound types, the median percentage area reduction was 77.4% at the final application, increasing to 100% 1 week after the final application, with statistically significant improvements in percentage area reduction at both time points (p=0.017 and p=0.003, respectively). Analyses demonstrated consistent wound surface area regression that remained stable after treatment completion, and no allograft-related adverse events were reported. These findings suggest that carePATCH may provide meaningful wound regression when used as an adjunct in complex, real-world individuals with chronic wounds refractory to standard care. However, interpretation is limited by the retrospective, non-comparative design, small sample size, single-site experience, and heterogeneity of wound types, which preclude causal inference and generalizability. Additional limitations include potential selection and survivorship bias, short post-treatment follow-up, and reliance on surrogate outcomes (surface area reduction rather than long-term closure or individual-reported outcomes). Larger, prospective controlled studies across multiple centers are needed to confirm effectiveness, durability of healing, and comparative value versus other advanced wound therapies.

CellerateRX Surgical Hydrolyzed Collagen Powder (Sanara Med Tech, Fort Worth, TX) is a wound dressing that is derived from bovine collagen. CellerateRX is purported to absorb wound fluid and maintain a moist wound environment, it may be used in the management of partial and full thickness wounds, pressure ulcers (Stage I-IV) and venous ulcers, ulcers caused by mixed vascular etiologies, venous stasis and diabetic ulcers, 1^st and 2^nd degree burns, cuts, abrasions and surgical wounds. CellerateRX is cleared through the FDA’s 510(k) process (K171645).

A retrospective nonrandomized, controlled study by Sultan (2024) involving 76 individuals undergoing spinal fusion with paraspinal flap reconstruction evaluated the use of CellerateRX (n=47) compared to standard care (n=29) . Compared to the standard care group, the CellerateRX group had a higher rate of seroma formation (approximately 28% vs. 7%, p=0.03), but no significant differences in wound dehiscence (p=0.17), hematoma (p=1.0), infection (p=0.58) or reoperation (p=0.58). Additional well-designed research with larger, more diverse populations and longer follow-up is warranted.

Clarix is a product composed of cryopreserved acellular human amniotic membrane and umbilical cord and is treated as human tissue for transplantation under the FDA’s HCT/P process.

Bemenderfer (2019) provided the only currently available published peer-reviewed study on this product. The unblinded non-randomized study involved 104 participants undergoing total ankle arthroplasty who received skin closure with either Clarix (n=54) or standard care (n=50). The authors reported that the use of Clarix significantly decreased the overall time to skin healing (28.5 days vs. 40 days; p=0.03). No differences between groups were reported with regard to reoperations, skin dehiscence, local wound care, or antibiotic prescriptions.

Ross (2022) reported a single center, retrospective study of pain outcomes in 52 individuals with musculoskeletal spinal disorders who were treated with ClarixFLO via epidural and facet injections. Conditions treated included; spondylosis (n=44), intervertebral disc (n=31), radiculopathy (n=18), stenosis (n=2), and other conditions. Pain was rated by participants on a scale of 0-10 where 0 indicated no pain and 10 indicated the worst imaginable pain. The average baseline pain score was 4.9, the mean duration of symptoms was 54.2 months. After ClarixFLO treatment, pain ratings decreased to 3.4 at 2 weeks (p<0.0001) and 3.5 at 3-4 weeks (p=0.0023). During the follow-up period (average 10.6 weeks), pain was reduced to 2.8 (p<0.0001) compared to baseline. There were no adverse events reported, and the authors concluded that additional larger studies are needed to confirm the safety and efficacy of ClarixFLO in epidural and facet injections.

Madan (2023) published a study that analyzed the use of ClarixFLO in the treatment of cystitis and bladder pain. In the first study, 5 natal females average age 64.4 (± 20.1 years) who had a median chronic radiation cystitis (CRC) duration of 10 years that was refractory to previous treatment modalities, received amniotic bladder therapy with ClarixFLO. The therapy was comprised of intra-detrusor injections of 100 mg micronized ClarixFLO diluted in 0.9% preservative-free sodium chloride. Outcomes measured were the Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, and SF-12 Health Survey prior to surgery and 2, 4, 8 and 12 weeks post-injection. After treatment with ClarixFLO the BPIC-SS scores improved from baseline to 12 weeks (36.6 compared to 12.6); this was also associated with an improvement in ICSI, ICPI, OAB, and SF-12 scores. Additionally, uroflow assessments showed increases in voided volumes for all individuals. One individual was diagnosed with an acute urinary tract infection at 2 weeks which was treated successfully with oral antibiotics. No other adverse events were observed. The authors concluded that the results provide proof of the potential benefits of ClarixFLO in treating CRC.

A study by Radoiu (2023) involved 10 natal females aged 47.4 (± 14.4 years) with interstitial cystitis/bladder pain syndrome (IC/BPS) that had been refractory to previous treatment modalities for an average 7.8 years who received intra-detrusor injections of 100 mg ClarixFLO diluted in 0.9% preservative-free sodium chloride. Again, the outcomes measured were the ICSI, ICPI, BPIC-SS, Overactive Bladder Assessment Tool, and the SF-12 Health Survey prior to surgery and 2, 4, 8 and 12 weeks post-operatively. After treatment with ClarixFLO, voiding symptoms and bladder pain improved from pre-injection to 3 months. BPIC-SS decreased from 37.4 at baseline to 12.2 at 3 months (p<0.001). There were no adverse events reported. The authors concluded that ClarixFLO may be a treatment option for individuals with IC/BPS symptoms based on the preliminary results.

In a single-center, retrospective case series study by Krystofiak (2024) Clarix Flo was used to treat acute muscle or ligament tears in 10 collegiate athletes. The authors reported an average return to play of nearly 30 days, with no complications observed. These preliminary results suggest potential to expedite recovery with Clarix Flo, but additional high-quality investigations with larger, more diverse populations and longer follow-up are warranted.

A controlled retrospective study involving 113 individuals undergoing meniscectomy was reported by Duru (2024). Treatment with platelet rich plasma was done in 40 participants, treatment with Clarifix Flo in 24 participants, and no adjunctive therapy was done in 49 participants. The authors reported significant differences at baseline between the groups with regard to sex, age, and International Cartilage Repair Society (ICRS) classification grade (p<0.05). The average VAS pain severity was significantly decreased only in the Clarifix Flo group at 6 months, compared to baseline (p=0.0143), but not at 12 months (p=0.12). No significant differences in pain severity of frequency were noted in the platelet rich plasma or no adjunctive therapy groups through 12 months. At 12 months. No differences between groups were reported with regard to Lysholm Knee Scoring Scale, IKDC Subjective Knee Evaluation Form Scores or overall, Knee Injury and Osteoarthritis Outcome Score results. The Clarifix Flo group did demonstrate a reduced reoperation rate (8.3%) compared to the platelet-rich plasma (30%) and no adjunctive therapy groups (40.8%, no p-values provided). However, the single-center design, retrospective methodology, and relatively short follow-up limit the conclusiveness of these findings. While these results indicate some potential benefit, additional high-quality trials with larger, more diverse cohorts and longer follow-up are necessary.

CorMatrix (CorMatrix Cardiovascular Inc., Roswell, Georgia) is an extracellular matrix scaffold produced from acellular porcine small intestinal submucosa. The CorMatrix suite of products are cleared through the FDA’s 510(k) process; including CorMatrix Patch for Cardiac Tissue Repair which is intended for use as an intracardiac patch or pledget for tissue repair (i.e., atrial septal defect (ASD), ventricular septal defect (VSD), etc.) and suture-line buttressing (K063349) and CorMatrix ECM for Vascular Repair which is intended for use as a patch material for repair and reconstruction of peripheral vasculature including the carotid, renal, iliac, femoral, and tibial blood vessels which may be used for patch closure of vessels, as a pledget, or for suture line buttressing when repairing peripheral vessels (K140789).

At this time, there is very limited peer-reviewed published evidence addressing the use of CorMatrix. The data that is available addresses its use in cardiovascular surgical procedures. The largest of these studies is a retrospective, nonrandomized control study involving 111 participants undergoing coronary artery bypass surgery (CABG) who had pericardial reconstruction with CorMatrix, compared to 111 control participants who underwent a standard CABG procedure without pericardial reconstruction (Boyd, 2010). The authors reported that postoperative atrial fibrillation occurred in 39% of controls compared to 18% of CorMatrix participants. No other results were significantly different. The safety and value of CorMatrix is difficult to interpret in this study, as it is the pericardial reconstruction procedure that seems to be the significant variable. Another publication by Quarti (2011) describes the use of CorMatrix in a wide variety of cardiovascular surgeries, with no comparison groups provided. While the authors report no significant complications due to the use of CorMatrix, this study provides little in the way of helpful data to determine the safety and efficacy of this product. Similarly, Kelley and others (2017) reported the results of a retrospective case series study of 25 participants who underwent anterior leaflet augmentation. They reported a 32% recurrence rate of mitral regurgitation and concluded that further research is needed. Finally, Ashfaq (2017) reported good results from the use of CorMatrix in a case series of 15 pediatric participants undergoing atrioventricular (AV) septal defect repair. They reported 12 (80%) participants either improved or had stable left AV valve performance remaining at "mild" or less insufficiency, two (13%) declined from "none" to mild, and one (7%) from declined from mild to "severe," No residual shunting or left ventricular outflow tract (LVOT) obstruction was noted at follow-up. Only one (7%) reoperation was performed after 3 years due to left AV valve zone of apposition dehiscence. No permanent pacemakers were needed, and no deaths were reported.

Hu and others (2021) reported the results of a retrospective cohort study of 38 pediatric participants undergoing aortic valve repair with the aortic cusp extension procedures with either autologous pericardium (n=30) or CorMatrix (n=8). The authors reported that for the entire cohort the peak trans‐valvular gradient significantly decreased immediately postoperatively (p=0.0017). No significant changes were observed at the 5-year follow‐up timepoint (p=0.36). In the autologous group participants with aortic stenosis at baseline the peak trans‐valvular gradient did not significantly change at follow‐up (p=0.12). The CorMatrix group had only 4 participants with aortic stenosis at baseline, which did not allow for sufficient data for between‐group tests. Moderate-to-severe aortic regurgitation was reported in 28 (93%) of autologous group participants at baseline, which improved to 11 (37%) postoperatively, but increased to 21 (70%) at follow‐up. Eight (100%) CorMatrix group participants had moderate-to-severe aortic regurgitation, which improved to 3 (38%) postoperatively and increased to 7 (88%) at time of follow‐up. Between‐group data indicated a significant difference in favor of the autologous group (p=0.017). Freedom from reoperation at 5 years was significantly poorer in the CorMatrix group (12.5%) compared to the autologous group (62.5%, p=0.01). The most common reason for reoperation in the autologous group was for repair of moderate to severe aortic regurgitation and severe aortic regurgitation in the CorMatrix participants. While no CorMatrix participants had severe aortic regurgitation postoperatively, 88% developed it at 5 years follow‐up. The authors concluded that autologous pericardium may outperform CorMatrix for aortic valve repair using the cusp extension method. However, several methodological weaknesses of this study limit the generalizability of these findings and further study is warranted.

Cymetra, an injectable micronized particulate form of aseptic AlloDerm (decellularized human dermis), has been proposed as a minimally invasive tissue graft product. It is treated as human tissue for transplantation under the FDA’s HCT/P process.

Morgan (2007) published a retrospective, nonrandomized controlled trial involving 19 participants undergoing injection laryngoplasty with Cymetra or medialization laryngoplasty. The authors reported no significant difference between groups at 3 months follow-up. No long-term comparison data was provided. Another report of a retrospective case series study involving 10 participants who all received injection laryngoplasty was reported by Milstein et al (2005). The authors of this study reported significant improvement in voice quality, glottal closure, and vocal fold bowing. Of the study population, only 8 participants (40%) were found to have lasting benefit. Finally, Karpenko and others (2003) reported the results of a case series study (n=10). The results indicated that there were no significant quantitative or subjective voice quality improvements. They also stated that significant improvements were identified in maximum phonation time, relative glottal area, and subjective judgment of glottal competency. However, these results were not maintained at the 3-month study interval.

Cytal Wound Matrix (ACell Inc., Columbia, MD) is composed of porcine-derived extracellular matrix scaffolds, specifically known as urinary bladder matrix. Cytal Wound Matrix is intended for the management of wounds including: partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunnel/undermined wounds, surgical wounds (donor sites/ grafts, post-Mohs surgery, post-laser surgery, podiatric, wound dehiscence), trauma wounds (abrasions, lacerations, second-degree burns, and skin tears), and draining wounds. The device is intended for one-time use. Cytal is cleared through the FDA’s 510(k) process (K152721).

Huen (2022) published a retrospective case series study involving 10 pediatric participants undergoing corporal graft and correction of ventral curvature in proximal hypospadias repair. Median follow up was 14.1 months. Mean ventral curvature after degloving was 80 ± 50 degrees. All participants had straight erections at baseline and 9 had straight erections verified at a subsequent artificial erection test at least 6 months from the corporoplasty (90%). The remaining participant underwent a further procedure and had straight erections per parental history. No participants developed corporal diverticulum or demonstrated induration at site of corporoplasty on physical exam. There were no parental reports of atypical adverse systemic effects. This unique use of a graft product may provide some clinical benefit. However, the clinical utility should be established in larger, more robust trials.

DermaBind (HealthTech Wound Care, Inc., Rolling Meadows, IL) is a dehydrated intact placental membrane allograft that preserves all native layers of the placental membrane (amnion, spongy layer, and chorion), including cytokines and growth factors. It is intended for use on trauma wounds, pressure injuries, dehisced wounds, DFUs and VSUs. DermaBind is regulated by the FDA under HCT/P process as human tissue for transplantation.

Mendivil (2025) reported on a retrospective, observational, uncontrolled, multicenter real-world case series that described clinical use of DermaBind as a protective wound covering for hard-to-heal wounds of mixed etiology that had failed at least 4 weeks of standard care. The study included 27 individuals with 36 wounds, most commonly pressure ulcers (63.9%), followed by DFUs (19.4%) and VLUs (8.3%), in an elderly, highly comorbid population (mean age 72.4 years). Over an average treatment duration of 6.7 weeks, wounds demonstrated a mean percentage surface area reduction of 69.1%, with 25% achieving complete closure and 77.8% achieving at least 50% area reduction, a commonly used prognostic marker of healing trajectory. Grafts were applied weekly, wastage was minimal due to close graft-to-wound size matching, and no adverse events were reported, suggesting good tolerability when used as a wound covering in real-world practice. The author emphasized that DermaBind was used in a manner consistent with its homologous protective role, often alongside aggressive wound bed preparation, offloading, compression, nutrition optimization, and management of comorbidities. Limitations include the non-randomized, retrospective, uncontrolled design, small sample size, heterogeneity of wound types and concomitant therapies, and non-standardized outcome assessments and follow-up intervals, which preclude causal inference or efficacy claims. Additional limitations include missing baseline data, provider-reported outcomes, lack of recurrence assessment, absence of formal statistical analysis, and manufacturer funding and involvement in data collection and manuscript development. The authors noted that the study was descriptive and not meant to demonstrate efficacy. Larger, prospective, controlled studies to evaluate comparative effectiveness and durability of healing are needed.

Dermacyte (Merakris Therapeutics, Triangle Park, NC) is an amniotic membrane allograft regulated by the FDA under HCT/P process as human tissue for transplantation.

Ditmars (2024) described the results of a multicenter retrospective trial involving 11 individuals with a total of 18 refractory diabetic or venous leg ulcers with Dermacyte. Ulcer volumes decreased by about 34% after the first application (p<0.005; 95% confidence interval [CI], -0.5319 to -0.1790), and most ulcers reached a 50% reduction in size after about three applications (p<0.0001). Both ulcer types showed rapid improvement, although healing trajectories varied, especially among “rapid responders.” While these findings appear promising, the small study population, short follow-up period, further high-quality research with larger, more diverse cohorts is warranted.

Geistlich Derma-Gide (Geistlich Pharma, Princeton, NJ) is an acellular porcine collagen xenograft sheet. The product is designed to manage wounds, including partial and full thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, surgical wounds (donor sites/grafts, post Moh’s surgery, post laser surgery, podiatric, wound dehiscence), and traumatic skin wounds (abrasions, laceration, second degree burns, skin tears). Geistlich Derma-Gide is cleared through the FDA’s 510(k) process (K182838).

Derma-Gide was the subject of a 2024 multicenter prospective, parallel-group RCT comparing its efficacy to standard of care for treating full-thickness, non-infected, non-ischemic diabetic foot ulcers (DFUs)(Armstrong, 2024). Standard of care consisted of a moisture-retentive, conformable collagen alginate dressing. The study included 105 participants who were randomized to either treatment groups (n=54 Derma-Gide); n=51 standard of care) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n=47 Derma-Gide; n=33 standard of care). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing and quality of life. The proportion of wounds healed at 12 weeks in the Derma-Gide was 83% compared to 45% for standard of care, p=0.00004. The time to heal within 12 weeks was shorter in the Derma-Gide group, 42 days compared to 62 in standard of care, p=0.005. The PAR values at 12 weeks was a mean of 93.6 for the PR Derma-Gide BM participants compared to 50.5 for standard of care. The DFUs treated with Derma-Gide healed at a higher rate than those treated with standard of care (ITT: 83% vs. 45%, , PP: 92% vs. 67%, p=0.005). Wounds treated with Derma-Gide also healed faster than those treated with standard of care; mean of 42 versus 62 days for standard of care (p=0.00074) and mean wound area reduction within 12 weeks of 94% compared to 51% for standard of care standard of care (p=0.0023). In the standard of care group, 17 participants were withdrawn or lost to follow-up. A total of 14 were withdrawn due to the index ulcer presenting a PAR <50% at week 6, while one participants ulcer was reopened at the healing confirmation visit. Additionally, two participants were removed due to adverse events, but there was reportedly no causal relationship between the adverse events and the treatment.

DermaPure is an acellularized human skin-derived product regulated through the FDA’s HCT/P process as human tissue for transplantation.

In a retrospective case series by Corlee (2024) of 42 participants diagnosed with insertional Achilles tendinopathy, individuals underwent partial detachment of the Achilles tendon, excision of the retrocalcaneal exostosis, thorough debridement, and repair augmented with DermaPure without suture anchor reattachment. Over a mean follow-up of 20.8 months, the average visual analog scale score improved from 5.1 to 1.9, and participants achieved weight-bearing at an average of 4.4 weeks. Of the 42 participants, 11 (26.2%) experienced complications, including a single rupture (2.4%) in the early postoperative period. No infections were reported, and 4 participants (9.5%) required reoperation. The authors suggest that these findings indicate ADM augmentation without anchor fixation can offer satisfactory outcomes and may justify further investigation under controlled, comparative designs.

DuraGen Dural Graft Matrix and DuraGen PLUS are (Integra Lifesciences Corp. Plainsboro, N.J.) absorbable implants intended for the repair of dura mater. These products are a sutureless onlay graft comprised of a porous, highly purified bovine collagen matrix treated with a proprietary process to remove antigenic components plus a thin layer of hydroxypropyl methyl cellulose (HfPMC). DuraGen is indicated as a dura substitute for the repair of dura mater. The graft area porous scaffold that is purported to promote rapid fibrin clot formation while promoting natural dural growth, it contours to surfaces of the brain and spinal cord forming a biological seal to protect against CSF leakage. DuraGen is cleared through the FDA’s 510(k) process (K120600).

Hamrick (2023) performed a retrospective, single-center study of 106 individuals who had Chiari decompression surgery by a single surgeon. The study compared the incidence of graft-related complications after posterior fossa surgery using AlloDerm alone compared to AlloDerm with a DuraGen underlay. The inclusion criteria were ≥ 18 years of age, radiographic and clinical findings of Chiari 1 malformation. The exclusion criteria were individuals younger than 18 years, had a previous Chiari decompression, or had Chiari type 2 with associated spina bifida. The AlloDerm-only group had a percutaneous cerebrospinal fluid (CSF) leak rate of 8.6% versus a 0% rate in the dual graft group (p=0.037). At initial follow-up, there was a 15.5% combined rate of pseudomeningocele formation plus CSF leak in the AlloDerm-only group, and 18.8% in the AlloDerm plus DuraGen group (p=0.659). However, the pseudomeningoceles were larger in the AlloDerm-only group (p=0.004) and 5 individuals in the group required surgical repair (56%). All pseudomeningoceles resolved without the need for surgery in the AlloDerm plus DuraGen group (p=0.003). The authors concluded that DuraGen underlay with a sutured AlloDerm dural patch resulted in fewer CSF-related complications and eliminated the need for reoperation compared with AlloDerm alone. This single-center study provides promising evidence that dural grafts with a DuraGen may decrease the risk of complications, however larger RCT’s are needed to analyze the efficacy of DuraGen in reducing rates of postoperative pseudomeningoceles and cerebrospinal fluid leak following Chiari decompression surgery.

Xu (2023) completed a retrospective case series review of 1011 individuals who had an open surgical procedure for microvascular decompression using a retrosigmoid approach. The study objective was to identify factors that may lead to CSF leak after a microvascular decompression procedure. Of the individuals who had the procedure, 37 (3.7%) presented with postoperative CSF leaks. Individuals with and without CSF leaks were not statistically different in age, sex, BMI, diagnoses, prior treatment, or comorbidities. In both groups most individuals presented with Type I trigeminal neuralgia. The results demonstrated that CSF leak after a craniotomy occurred more frequently compared with a craniectomy (13.5% compared to 3.0%), p=0.001. Individuals were more likely to develop a CSF leak with closure of air cells with bone wax, (p=0.002) and compared to the use of Cranios/Norian bone cement, (p=0.01), CSF leak rates were higher with the use of both Durepair (dural substitute) or DuraGen (dural onlay), p=0.04. The authors concluded that the results showed an increased risk for postoperative CSF leak when primary dural closure was not established. Creating a water-tight closure of the dura, regardless of dural substitutes and other dural overlays may be critical to decrease the risk of CSF leaks and postoperative outcomes. Due to the small sample size additional studies are needed to confirm the findings.

DuraMatrix-Onlay/ DuraMatrix-OnlayPlus, DuraMatrix Onlay and DuraMatrix Suturable

DuraMatrix(Collagen Matrix Inc, Oakland, NJ) is a suite of products derived from acellular bovine Achilles tendon. DuraMatrix Collagen Dura Substitute Membranes are indicated as dural substitutes for the repair of dura mater. DuraMatrix and has been cleared through the FDA’s 510(k) process (K061487).

Mekonnen (2023) described a retrospective case series study involving 33 participants who underwent a duraplasty procedures using DuraMatrix-Onlay Plus collagen dura membrane. The majority of procedures were elective operations for the resection of a lesion (n=19, 58%). Average graft size was 17.69 ± 4.73 cm². At a mean follow-up of 3 months, no postoperative CSF leaks were reported. The rates of infection, dural substitute complication, and removal were 6%, 6%, and 3%, respectively. The clinical utility of this product warrants further investigation in more robust trials.

Akiyama (2025) reported on a retrospective single-center study that evaluated a multilayer collagen matrix (DuraGen^®) repair technique for reconstruction of the posterior internal auditory canal (IAC) wall during retrosigmoid vestibular schwannoma surgery, aiming to reduce postoperative cerebrospinal fluid (CSF) rhinorrhea. There were 51 individuals who underwent IAC drilling with mastoid air cell exposure and received bone wax sealing followed by multilayer DuraGen placement reinforced with fibrin glue. Individuals were stratified by the extent of mastoid air cell violation (type A: craniotomy site + IAC; type B: IAC only). The overall CSF leak rate was low (3.9%), with leaks occurring only in type A cases (5.6%) and none observed in type B individuals, and no major complications attributable to DuraGen were reported. These findings suggest that multilayer DuraGen repair is a feasible and safe adjunct for IAC closure and that the extent of mastoid air cell exposure is a key determinant of leak risk, with particularly favorable outcomes when exposure is limited to the IAC. However, the study is limited by its retrospective design, single-center experience, small cohort, and the absence of a non-DuraGen control group, which precludes definitive conclusions regarding efficacy relative to other closure methods. In addition, surgeon-dependent technique may influence generalizability. Larger prospective multicenter studies are needed to confirm effectiveness.

DuraMatrix Suturable (Collagen Matrix Inc, Oakland, NJ) is a product derived from bovine dermis collagen and is indicated for surgical dural repair and prevention of CSF leak. DuraMatrix Suturable is cleared through the FDA’s 510(k) process (K061487).

DuraSorb(Polydioxanone Surgical Scaffold) (Integra Lifesciences Corp., Princeton, NJ) is a fully-resorbable knitted mesh. It is indicated for use in reinforcement of soft tissue where weakness exists. DuraSorb is cleared through the FDAs 510(k) approval process (K181094).

ENDURagen is a product composed of porcine ADM and is cleared through the FDA’s 510(k) process (K013625).

McCord and others (2008) have published the only available study addressing the use of Enduragen. Their retrospective case series involved 69 participants who underwent 192 reconstructive or cosmetic eyelid procedures with Enduragen grafts. Eight procedures were for spacers in the upper lid, 104 were for spacers in the lower lid, and 17 were for lateral canthal reinforcement. There were 13 eyelid complications, for a complication rate of 10%. Nine cases required surgical revision, and there were four cases of infection, all of which were successfully treated with oral and topical antibiotics. The results of this study are insufficient to adequately evaluate the safety and efficacy of Enduragen. Further research is needed.

Barmettler (2018) published the results of a prospective, randomized clinical trial involving 39 participants (42 eyelids) undergoing lower eyelid retraction repair with spacer graft. Participants were assigned to undergo their procedure with autologous auricular cartilage (n=19 eyelids), SurgiMend (n=11 eyelids), or Enduragen (n=12 eyelids). The authors reported no significant differences between groups with regard to 6-month measures including MRD2, conjunctival injection, tearing, discomfort, itching, corneal abrasions, or repeat procedures.

Epiflex (German Institute for Cell and Tissue Replacement (DIZG), Berlin, Germany) is a human acellular dermal matrix derived from decellularized human skin. It is intended for temporary skin replacement following thermal injuries, replacement for lost or insufficient dermis and soft tissue. It has not been approved for cleared for use in the U.S.

Halm-Pozniak (2025) reported on a prospective observational case series that evaluated superior capsule reconstruction (SCR) using Epiflex in individuals with massive, irreparable rotator cuff tears, focusing on early graft integrity and short- to mid-term clinical outcomes. Among 29 analyzed individuals, early postoperative MRI (mean of approximately 10 weeks) demonstrated a high rate of structural graft failure (59% complete failure), most commonly at the greater tuberosity attachment. Despite this, individuals experienced significant improvements in pain, activity, range of motion, and overall Constant Score at early follow-up (approximately 9 weeks), with gains maintained at approximately 1 year. Functional outcomes did not differ between individuals with intact versus failed grafts during the observation period. No revisions were required within follow-up. These findings suggest that, while early structural failure of Epiflex grafts after SCR is common, clinical improvement can occur independent of graft integrity in the short to mid-term. However, interpretation is limited by the observational design, modest sample size, single graft type and technique, and short MRI follow-up window that may overemphasize early failures without capturing longer-term remodeling. Additionally, the study lacks a comparator group (e.g., fascia lata autograft or alternative treatments), and relies on the Constant Score. Larger, controlled studies with longer radiographic and clinical follow-up are needed to clarify the relationship between graft integrity and durable outcomes and to optimize graft selection and fixation strategies.

Fortiva (RTI Biologics, Alachua, FL) is an implantable surgical mesh comprised of porcine dermis that has been processed, terminally sterilized and is stored hydrated and ready to use. The device is designed to perform as a scaffold that allows for neovascularization and permits replacement of the device with host tissue. Fortiva is intended for use as a soft tissue patch to reinforce soft tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue membranes. Indications for use include the repair of hernias and /or body wall defects which require the use of reinforcing or bridging material to obtain the desired surgical outcome. The device is intended for single patient use only. Fortiva is cleared through the FDA’s 510(k) process (K123356).

Maxwell (2019) published the results of a retrospective non-randomized controlled study investigating the use of Fortiva (n=72) compared to Strattice (n=98) and AlloDerm (n=59) in 229 participants undergoing abdominal wall reconstruction. The incidence of recurrence of abdominal wall defect was significantly higher in the AlloDerm group (20.3%) compared with the Fortiva (10.2%) and Strattice groups (6.9%) (p=0.040). The 1-, 3-, and 5-year survival rates for the repair with Fortiva were 1.4% and 6.9%, and 0%. For Strattice, the results were 5.1%, 9.2%, and 10.2%, and for AlloDerm, 6.8%, 18.5%, and 20.3%. Although participants in the AlloDerm group had the longest median hernia-free interval, 26.8 months (2-60 months), this was not found to be significantly different from Fortiva and Strattice (data not provided). The most common complication was surgical site infection (26.2%), followed by delayed healing (24.0%). Seroma formation was reported to have been significantly lower in the Fortiva group compared to the Strattice and AlloDerm groups (1.4% vs. 13.3% vs. 11.9%; p=0.021).

GalaFLEX mesh (TEPHA, Inc. Lexington, MA) is a sterile, knitted, synthetic, resorbable mesh product composed of poly-4-hydroxybutyrate. GalaFLEX mesh is indicated for use as a transitory scaffold for soft tissue support, and to repair, elevate, and reinforce deficiencies where weakness or voids exist, that require the addition of material to obtain the desired surgical outcome in plastic and reconstructive surgery, and general soft tissue reconstruction. GalaFLEX is cleared through the FDA’s 510(k) process (K140533).

Adams (2018) published a case series report involving 62 participants undergoing mastopexy procedures. The authors reported that 89.7% of participants had successful ptosis correction and maintenance at 1 year. Both participant and surgeon satisfaction for breast shape, droop/sag of the breast, and maintenance of results at 1 year was reported as high. Adverse events deemed to be related to the device occurred in 5 participants (8.0%), including nerve pain, breast swelling, ptosis, and 2 instances of asymmetry. It is not clear how the safety and efficacy of this product compares to other products, including those considered the standard of care for breast procedures. Additional comparative trials are warranted.

Sigalove (2023) reported a retrospective case series of 263 individuals (499 breasts) who had immediate, two-stage expander-implant, prepectoral breast reconstruction that compared GalaFLEX plus AlloDerm combination (n=135/250 breasts) to AlloDerm only (n=128/249 breasts). In the GalaFLEX plus AlloDerm group the lower third of the expander was covered by the AlloDerm and the rest of the expander was covered by GalaFLEX Complications after reconstruction were compared between the groups. Mean BMI, preoperative chemotherapy use, skin reducing mastectomy, and bilateral reconstructions were higher in the AlloDerm only group, whereas nipple-sparing mastectomy and unilateral reconstructions were higher in the GalaFLEX plus AlloDerm group. Individuals in the AlloDerm-only group were followed up for an average of 41.9 months, whereas those in the GalaFLEX plus AlloDerm group were followed for an average of 15 months from the date of initial surgery (p<0.0001). Complications occurred in 19 breasts that received AlloDerm-only and 16 breasts that received GalaFLEX plus AlloDerm; overall complication rates were 7.6% and 6.4%, respectively. All complications occurred within the first year after initial surgery; 61% of individuals in the GalaFLEX plus AlloDerm group had at least 1 year of follow-up, and 17% had at least 2 years of follow-up. The rate of complication was 7.6% in the AlloDerm-only group and 6.4% in the GalaFLEX plus AlloDerm group. The rate of infection, major skin necrosis, seroma, capsular contracture, prosthesis exposure/extrusion, and prosthesis loss were less than or equal to 3.0% in the GalaFLEX plus AlloDerm group and did not differ significantly from those in the AlloDerm-only group. There were no significant differences in complications between the two groups with the exception of skin necrosis (5.2% for the AlloDerm-only group compared to 1.2% for the GalaFLEX plus AlloDerm group), which the authors noted was driven by a higher rate of intermediate skin necrosis. However, the rate of major skin necrosis did not differ significantly between the groups. The study is limited by its retrospective nature and the relatively short follow-up duration. The authors concluded that the GalaFLEX has a comparable safety profile, however additional long-term data and clinical experience are needed to comprehensively understand the safety profile of GalaFLEX bioabsorbable matrix for use in breast reconstruction.

Buccheri and colleagues (2025) reported on a prospective observational study that evaluated the long-term efficacy and safety of GalaFLEX used as an internal support in primary mastopexy for grade III breast ptosis, comparing outcomes with standard mastopexy alone over a 12-month follow-up. There were 60 individuals divided into two groups: mastopexy with GalaFLEX placement at the lower pole versus mastopexy without scaffold. Objective morphologic measurements showed that while early postoperative results were similar between groups, individuals treated with GalaFLEX demonstrated significantly better maintenance of lower pole support at 12 months, as evidenced by a smaller increase in nipple-to-inframammary fold distance, indicating delayed recurrence of ptosis. No significant differences were observed in sternal notch-to-nipple distance, operative time, or overall complication rates, and only minor wound-healing issues occurred in both groups, supporting the scaffold’s short-term safety. Overall, the findings suggest that GalaFLEX provides effective temporary internal reinforcement that enhances long-term breast shape stability without increasing morbidity. However, the study is limited by its small sample size, lack of randomization, single-surgeon design, and relatively short follow-up period given the long natural history of breast ptosis. In addition, individual self-selection into treatment groups (including willingness to pay for the scaffold) introduces potential selection bias, and the absence of validated individual-reported outcome measures (for example, BREAST-Q) limits assessment of individual satisfaction. Larger randomized studies with longer follow-up are needed to confirm durability and generalizability of these results.

A retrospective single-surgeon case series evaluated the long-term safety, durability, and satisfaction associated with GalaFLEX used for soft-tissue support across a wide range of aesthetic breast procedures, including mastopexy, augmentation-mastopexy, implant exchange, capsulorrhaphy, and breast reduction (Sinclair, 2024). Individuals with breast ptosis 68% (n=167) made up the larger portion of the study. Among the overall 248 individuals with a mean follow-up of 2.9 years (up to 9.3 years), the overall complication rate was low (8.0%), with an unplanned reoperation rate of 2.8%; the most common complication was delayed wound healing (2.8%), typically managed conservatively, and only one complication was directly attributable to GalaFLEX (palpable scaffold requiring removal). Reported satisfaction was high (mean 3.42/4), and remained stable over time with no significant differences across follow-up intervals up to 9 years. Limitations included the retrospective design of the study, absence of a control or comparator group, single-surgeon experience, and reliance on a non-validated satisfaction scale. Additionally, outcomes were not assessed with objective aesthetic measurements or standardized photography, and selection bias cannot be excluded. Prospective comparative studies are needed to confirm superiority, define individual selection, and quantify long-term benefits relative to alternative support materials.

The Gentrix devices (ACell, Inc., Columbia, MD) are products composed of porcine-derived extracellular matrix scaffolds, specifically known as urinary bladder matrix. Gentrix Surgical Matrix Thick and Gentrix Surgical Matrix Extend are intended for implantation to reinforce soft tissue where weakness exists in individuals requiring gastroenterological or plastic & reconstructive surgery. Reinforcement of soft tissue within gastroenterological and plastic & reconstructive surgery includes, but is not limited to, the following procedures: hernia and body wall repair, colon and rectal prolapse repair, tissue repair, and esophageal repair. The devices have been cleared through the FDA’s 510(k) process (K170763).

Wang (2018) published a non-randomized controlled trial involving 65 participants who underwent paraesophageal hernia (PEH) repair with (n=32) or without (n=33) reinforcement with Gentrix. There was no difference reported between groups with regard to recurrence rates, size of recurrence, postoperative symptomatic or quality of life improvement. The authors noted that participants in the unreinforced group who suffered recurrence had more severe symptoms and a higher rate of dissatisfaction. Of the 3 participants with recurrences after Gentrix placement, reoperation demonstrated anterior failure where no reinforcement had occurred because of the posteriorly placed U-shaped graft. It is not clear how the safety and efficacy of this product compares to other products, including those considered the standard of care.

The Gore Bio-A Fistula Plug (W.L. Gore & Associates, Inc., Elkton, MD) is a surgical mesh comprised of porous synthetic copolymer fiber material that is bioabsorbable and has been demonstrated to be both biocompatible and non-antigenic. The device is intended for use in the reinforcement of soft tissue for the repair of anorectal fistulas. Gore Bio-A is cleared through the FDA’s 510(k) process (K083266).

Ommer and others published the results of a case series study involving 50 participants with trans-sphincteric (n=28) or supra-sphincteric (n=12) anal fistula who were treated with Gore Bio-A (2012). Postoperatively, 1 participant developed an abscess which had to be managed surgically. In 2 participants, the plug had fallen out within 2 weeks after surgery. Six months after surgery, the fistula had been healed in 20 participants (50.0%). Three additional fistulas healed after an additional 7 to 12 months. The authors reported that the overall healing rate was 57.5% (23/40). However, they noted that healing rates differ significantly between the surgeons (from 0 to 75%), and also varied depending on the number of previous interventions. In individuals having had only drainage of the abscess, success occurred in 63.6% (14/22) whereas, in those having had one or more flap fistula reconstructions, the healing rate decreased slightly to 50% (9/18). Further study is warranted to better understand the impact of surgeon experience as well as optimal selection criteria for individuals requiring treatment for anal fistulas. Heydari (2013) described the results of a retrospective case series study involving 48 participants with 49 anal fistulas treated with the Gore Bio-A. The overall healing rate was reported to be 69.3% (34/49 fistulas, 33/48 participants). Eight participants (24.2%) had complete healing by 3 months after surgery, 21 participants (63.6%) had healed by 6 months, and 4 participants (12.1%) had healed by 12 months. At 3 months, there were no reports of perineal pain or fecal incontinence. The authors reported no incidents of dislodged devices, anal stenosis, bleeding, or local infection.

In 2018, Jordan and others published the results of a retrospective comparative study involving 87 participants undergoing breast reconstruction with mesh underlay reinforcement at 123 sites with either polypropylene mesh (n=58) or Gore Bio-A (n=65). The overall incidence of bulge or hernia was 11.4%. The Gore Bio-A group experienced significantly more bulges/hernias than the polypropylene mesh group (20% vs. 1.7%). They concluded that the use of Gore Bio-A was associated with a 13.3-fold risk of bulge/hernia (p=0.016) and was not appropriate for anterior rectus fascia reinforcement following abdominal tissue transfer.

In 2017, the American Society of Colon and Rectal Surgeons (ASCRS) published a new pactice guideline for the management of anal fissures (Stewart, 2017). Their recommendations do not mention the use of grafts or plugs of any kind.

Gore Acuseal Vascular Graft Patch (W.L. Gore & Associates, Inc., Elkton, MD) is an expanded polytetrafluoroethylene (ePTFE) separated by an elastomeric layer and may be available both with and without covalently bound bioactive heparin. The GORE ACUSEAL Vascular Graft is intended for use as a vascular prosthesis in individuals requiring vascular access. It has been cleared through the FDA’s 510(k) process (K130215).

Stone (2014) published the results of a prospective randomized study comparing clinical outcomes of Acuseal compared to bovine pericardium patching (Vascu-Guard) when used for primary closure for carotid endarterectomy. This study involved 200 participants assigned in a 1:1 fashion and the mean follow-up period was 15 months. They reported that mean hemostasis time was 4.90 min for Acuseal compared to3.09 min for Vascu-Guard (p=0.027). The mean operative times were similar for both groups (2.09 hr vs. 2.16 hr, p=0.669). The incidence of reexploration for neck hematoma was higher in the Vascu-Guard group; 6.12% compared to 1.03% (p=0.1183). The incidence of perioperative ipsilateral neurologic events was 3.09% for Acuseal patching compared to 1.02% for Vascu-Guard patching (p=0.368). The respective freedom from ≥ 70% carotid restenosis at 1, 2, and 3 years were 100%, 100%, and 100% for ACUSEAL patching compared to 100%, 98%, and 98% for Vascu-Guard patching (p=0.2478).

AbuRahma (2023) reported on the 10-year results of the study previously published by Stone et al. (2016). Mean follow-up time was 81 months (range 0-149 months). No significant differences were reported between groups for rates of long-term death, 47% in the Acuseal group compared to 48% in the Vascu-Guard group p=0.9402). Similarly, the incidence of late strokes was reported to be 5% in both groups (p=1.0). One patch complication was noted in the Acuseal group (infection) compared to the Vascu-Guard group (aneurysmal dilatation and rupture, no p-values provided). No significant differences in the rate of reintervention was reported (5% in the Acuseal group compared to 4% in the Vascu-Guard group, no p-values provided). The rate of ≥50% restenosis was 9% for the Acuseal group compared to 22% for Vascu-Guard group (p=0.0186). The rates of ≥80% restenosis, freedom from stroke, freedom from stroke/death, freedom from ≥80% restenosis, and overall survival rates were all not significantly different between groups for any time point (p=0.564, p=0.1112, p=0.8591, p=0.9407, p=0.9123, respectively). The authors concluded that both product are durable and have similar clinical outcomes at 10 years, except that ACUSEAL patching has significantly better rates of freedom from ≥ 50% restenosis.

Grafix CORE is a grafting product derived from allogeneic chorion membrane. It is treated as human tissue for transplantation under the FDA’s HCT/P process.

Frykberg (2016) reported the results of a prospective case series study involving participants with complex DFUs ≤ 15 cm in their longest dimension and extending through the dermis with exposed muscle, tendon, fascia, bone, or joint capsule. All were treated with weekly applications of Grafix CORE. The intent-to-treat (ITT) population included 31 participants and the per-protocol population included 27 participants. The ITT participant population had significant co-morbidities, with 80% having hypertension, 60% current or former smokers, 55% having heart disease, and 45% having a previous partial foot amputation. Prior advanced treatment (for example, negative pressure wound therapy) for the index wound had occurred in 67.7% of participants. At 16 weeks, 96.3% of the per-protocol group had 100% granulation of the index wound and complete closure occurred in 59.3%. The mean area reduction of the index wound at day 28 was 54.3% and 72.8% at 8 weeks. At the end of the 16-week study period the mean wound area reduction was 92.3%. No Grafix-related adverse events were reported. This study demonstrated the use of Grafix CORE in the healing of complex DFUs. However, the small study population and lack of controls hampers the generalizability of these results.

Raspovic (2018) reported a retrospective case series analysis of 360 participants with 441 DFUs treated with Grafix PRIME or Grafix CORE using data from Net Health’s Wound Expert electronic health records database. The mean size of the index wound was 5.1 cm² with 3.9 mm depth. Mean wound duration prior to study treatment was 102 days. The mean duration of treatment with a Grafix product was 89.3 days (median 56.0). Complete wound closure at the end of treatment occurred in 59.4% of participants. Median time to closure was 42.0 days with a median of 4 graft applications. The proportion of closure decreased as wound size increased, with 72.3% of wounds between 0.25 cm² to 2 cm² having complete healing at a median of 21 days and 4 applications. For wounds larger than 25 cm², only 27.8% achieved complete healing at a median of 105 days and 11 applications. The authors did not provide any data regarding the percentage of participants receiving treatment with Grafix PRIME compared to those receiving Grafix CORE.

Helicoll (Encoll Corp., Freemont, CA) is a bioengineered reconstituted collagen sheet that maintains a physiologically moist microenvironment at the wound surface. Helicoll is intended for the topical wound management that includes: partial and full-thickness wounds, pressure ulcers, venous ulcers, chronic vascular ulcers, diabetic ulcers, trauma wounds (abrasions, lacerations, second-degree bums, skin tears), and surgical wounds (donor sites/grafts, post-Mohs' surgery, post-laser surgery, podiatric, wound dehiscence. The device is intended for one time use only. It is cleared under the FDA 510(k) process (K040314).

A randomized controlled clinical trial by Narayan (2024) enrolled 28 individuals with DFUs and compared Helicoll to an unspecified dehydrated human amnion and chorion membrane product over 4 weeks. The study showed that 85.71% (12/14) of participants in the Helicoll group achieved at least a 50% reduction in DFU size, compared to 50% (7/14) in the dehydrated membrane group (p=0.245). Complete closure was observed in 10 and 7 participants, respectively. The Helicoll group demonstrated a mean DFU size reduction of 86.48%, while the dehydrated membrane group recorded 77.70%. The authors noted that their statistical analysis indicated a significant difference in mean wound reduction rates (93.62 ± 0.12% vs. 77.71 ± 0.28%, p=0.05), suggesting enhanced wound-healing capabilities for Helicoll in managing DFU.

HYALOMATRIX is a synthetic wound covering product composed of a benzyl ester of hyaluronic acid. HYALOMATRIX is indicated for the management of wounds including partial and full-thickness wounds, second-degree burns, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds, trauma wounds, and draining wounds. The device is intended for one-time use. HYLAOMATRIX is approved through the FDA’s 510(k) process (K073251).

The currently available evidence addressing the use of HYALOMATRIX is limited mostly to uncontrolled, unblinded case series studies. Only one RCT has been published to date involving 16 participants with VSUs, 9 of which were treated with HYLAOMATRIX and 7 treated with standard wound care (Alvarez, 2017). The authors reported that the incidence of wound healing at 12 weeks was 66.6% for the HYALOMATRIX group compared to 14.2% for controls (p=0.066). At 16 weeks, the incidence of wound healing was 87.5% of participants in the HYALOMATRIX group compared to 42.8% in the control group (p=0.059). The mean time to healing in the Hyalomatrix group was 41 days compared with 104 days in the control (p=0.029). The largest studies available involve 300, 262, 79, and 57 participants (Gravante, 2007; Caravaggi, 2003 and 2011; Gravante 2010, respectively). The Carravaggi study addresses chronic wounds while the Gravante studies address burns. The rest of the studies published involve significantly fewer than 30 participants and encompass a variety of indications including various surgically created wounds (Faga, 2013; Landi, 2014; Onesti, 2014), traumatic wounds (Kozusko, 2023; Onesti, 2014; Vaienti, 2013), and chronic ulcers (Motolese, 2013).

Integra Bilayer Matrix Wound Dressing (Integra Lifesciences Corp., Plainsboro, N.J.) is comprised of granulated cross-linked bovine tendon collagen, glycosaminoglycan, and a semipermeable silicone layer. The product is indicated for the management of wounds including partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds (donor sites/grafts, post-Moh's surgery, post-laser surgery, podiatric, wound dehiscence), trauma wounds (abrasions, lacerations, second-degree burns, skin tears) and draining wounds. The device is intended for one-time use. It was cleared through the FDAs 510(k) process (K021792).

Integra Flowable Wound Matrix (Integra Lifesciences Corp., Plainsboro, N.J.) was also cleared through the FDAs 510(k) process (K072113). It is comprised of granulated cross-linked bovine tendon collagen and glycosaminoglycan. The product is indicated for the management of wounds including partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds (donor sites/grafts, post-Moh's surgery, post-laser surgery, podiatric, wound dehiscence), trauma wounds (abrasions, lacerations, second-degree burns, skin tears) and draining wounds. The device is intended for one-time use.

In 2017, Campitiello published an RCT comparing Integra Flowable Wound Matrix compared to standard care for the treatment of 46 participants with DFUs with irregular geometries. There were 23 participants in each group who were evaluated once a week for 6 weeks. The authors reported that the overall complete healing rate was 69.56%, with the rate in the Integra group being 86.95% compared to 52.17% in the control group (odds ratio [OR], 1.67, p=0.001). Mean time to healing was 29.73 days in the Integra group compared to 42.78 in the control group (p<0.000). The amputation and rehospitalization rates in the Integra group were 4.34% compared to 30.43% in controls (relative risk [RR], 0.16, p=0.028). The authors concluded that Integra Flowable Wound Matrix was significantly superior to the wet dressing, but that additional research will shed more light on the promising advantages of this material in healing diabetic foot ulcers.

KeraMatrix (Keraplast Technologies, LLC., San Antonio, TX) is comprised of freeze-dried acellular animal-derived keratin and has been approved through the FDA’s 510(k) process (K080949).

At this time, the most rigorous evidence is a nonrandomized controlled study involving 40 participants with superficial or partial thickness burn injuries treated with Keramatrix, compared to 40 historical controls who received standard of care treatment (Loan, 2016). The results indicated a significantly faster mean healing time in the Keramatrix group compared to controls (8.7 days vs. 14.4 days, p<0.05), hospital inpatient days (0 days vs. 2.6 days, p<0.05), and number of outpatient appointments following initial therapy (1.2 vs. 3.3, p<0.05). No differences in complications were reported.

MatrACELL is a decellularized allograft product composed of human cardiovascular tissue treated as human tissue for transplantation under the FDA’s HCT/P process.

Hopkins (2014) published a nonrandomized controlled study involving 108 consecutive participants undergoing cardiovascular reconstructive procedures using MatrACELL pulmonary artery patches during pulmonary arterioplasty. A second retrospective cohort of 100 participants who received arterioplasty patches using classical cryopreserved pulmonary artery allografts (n=59 participants) or synthetic materials (n=41 participants) was used for comparison. The reported results included that 106 participants with 118 decellularized patches had no device-related serious adverse events, no device failures, and no evidence of calcifications on chest roentgenograms. In contrast, the control participants experienced an overall 14.0% patch failure rate requiring device-related reoperations (p<0.0001) at mean duration of 194 ± 104 days (range, 25 to 477 days). The authors concluded that the intermediate-term data obtained in this study suggest favorable performance by decellularized pulmonary artery patches, with no material failures or reoperations provoked by device failure.

MatriDerm is a decellularized dermis allograft product treated as human tissue for transplantation under the FDA’s HCT/P process.

Riml (2011) reported a study of 30 participants undergoing nasal tip skin grafts non-randomly assigned to receive either conventional FTSG, retroauricular perichondrodermal composite grafts, or skin transplantation supplemented with MatriDerm. Ten participants were assigned to each group. This retrospective study was conducted in a randomized and blinded manner by assigned reviewers using the Manchester scale. The authors report that 2 (20%) of the MatriDerm participants developed fistulae and concluded that MatriDerm was not suitable for nasal tip reconstruction.

Another study by Haslik evaluated the use of MatriDerm for the management of full-thickness skin defects (2010). This case series study involved 17 participants with upper extremity skin wounds, all of whom received MatriDerm in conjunction with unmeshed skin grafts. The reported take rate was 96%. A 12-month follow-up Vancouver scale score of 1.7 and DASH (disability of arm-shoulder-hand) score showed excellent hand function in participants with burn injury and participants with a defect due to the harvest of a radial forearm flap achieved satisfying hand function.

Wallner (2023) published a retrospective study that compared the use of single autologous split-thickness skin graft (STSG) alone or in combination with MatriDermADMin 147 cases of severe traumatic soft tissue defects of the leg with exposed structures, such as tendons, ligaments, vessels, bone of the lower extremities. Severe soft tissue defects consisted of 18 open fractures with extensive decollement, 43 thermic and chemical burns, 78 severe soft tissue lesions, and 8 ulcers. Overall, soft tissue defects were more severe in the MatriDerm plus STSG group. The healing rate, defined as the number of individuals with take rate ≥ 75%, was 88/147 (60%) and no significant differences between the groups was reported (p=0.15). Despite variable wound complexity between the groups there were no differences in scar tissue quality 12 months postoperatively. The overall complication rate was approximately 25%. In 15% of the cases, a surgical revision was required. The number of cases with at least one necessary surgical revision was 4 in the STSG-only group compared to 18 in the MatriDerm plus STSG group (p=0.02). The number of individuals with documented adverse events (33%) or necessary revision surgery (21%) was higher in the STSG plus MatriDerm group. The complications reported after more than 100 days included scar instability, fistula formation, and swelling. Additionally, the use of negative pressure wound therapy may have impacted the STSG take rate. The authors concluded that surgical treatment with STSG and additional MatriDerm application is a satisfactory alternative for dermis replacement in individuals with severe skin defects, independent of age. Due to the higher rate of adverse events, complications, and surgical revision, further studies with larger, well-designed trials are needed to fully evaluate the safety and efficacy of MatriDerm..

In a retrospective single-center original article, Do (2024) evaluated 12 individuals who underwent maxillectomy for oral cancer treated with a combination of MatriDerm and Neoveil. Over a follow-up ranging from 2 to 20 months, 41.7% of participants experienced fistula formation, but no surgical revisions were required. The incidence of fistulas depended on tumor stage, bone invasion, defect dimensions, and sinus mucosa preservation (p<0.05), rather than product-specific performance. None of the participants developed mouth-opening limitations, indicating potential benefits of the combined technique. However, since this study combined Matriderm and Neoveil in all participants, the relative benefits of each product alone cannot be determined and further research is needed.

Matrion is a products made from donated human placental membrane, including the amniotic layer, chorionic layer, and the trophoblast layer. It is intended for the replacement of damaged skin, including DFUs, VLUs, pressure ulcers, dehisced surgical wounds and traumatic burns. It is regulated through the FDA’s HCT/P process as human tissue for transplantation.

Reyzelman (2025) reported on a multicenter, prospective randomized controlled trial that evaluated Matrion as an adjunct to standard of care for persistent, treatment-resistant diabetic foot ulcers (DFUs). After a 4 week run-in phase to exclude wounds likely to heal with standard of care alone, 108 individuals were included in the modified intention-to-treat analysis (n=57 Matrion, n=51 standard of care). At 12 weeks, wound closure rates were higher with Matrion, reaching statistical significance in the per-protocol population (48% vs. 27%, p=0.0499), with Matrion-treated wounds showing greater and faster percentage area reduction, earlier achievement of at least 50% area reduction, and shorter median time to healing (6-8 weeks vs. 9 weeks). Recurrence rates during 6 month follow-up were low and comparable between groups. Safety outcomes were favorable: serious adverse events were less frequent in the Matrion group than in standard of care, and no serious events were directly attributed to the graft. Limitations included a moderate sample size, potential underpowering due to protocol changes and exclusions during the run-in phase, and heterogeneity in standard of care practices across sites, including variable offloading and dressing strategies. The open-label design and reliance on per-protocol significance for the primary endpoint also introduce potential bias. Larger, fully standardized trials with longer follow-up are needed to confirm durability, generalizability, and comparative effectiveness across broader DFU populations.

The use of honey has been proposed for the treatment of various skin conditions including burns, chronic ulcers, and superficial abrasions. It is hypothesized that honey, with its antibacterial properties, can significantly improve skin healing when applied topically to skin wounds. Several randomized controlled trials have been published involving MediHoney (Derma Sciences, Princeton, N.J.). Medihoney iscleared through the FDA’s 510(k) process (K072956).

Jull (2008) published the largest of these trials, which included 368 participants randomized to receive treatment with either calcium alginate dressing impregnated with manuka honey or standard care with whatever dressings were appropriate for the individual at that time. After following the participants for a total of 12 weeks of follow-up, the authors concluded that there was no significant difference in outcomes between the two groups. It was noted that the honey-treated group experienced significantly greater numbers of adverse events (p=0.013). Contradicting these findings is a study by Gethin and Cowman (2008). In this study, 108 participants with venous ulcers were randomized to receive treatment with either honey dressing or standard hydrogel therapy. The findings were that the honey-treated group had significantly better results in terms of median reduction in wound size at 12 weeks (44% vs. 33%, p=0.037), but no significant differences between groups in other primary endpoints were reported.

The other most studied condition addressed in the literature is the treatment of burns. The largest study currently available addressing burns involved 150 participants randomized to receive treatment with either silver sulphadiazine (SSD) or honey (Malik, 2010). Each participant functioned as his or her own control, with one burn site randomly treated with SSD and the other with honey. The authors report that the honey-treated sites had significantly faster re-epithelialization and healing of superficial and partial thickness burns than the SSD sites (13.47 days vs. 15.62 days, p<0.0001). Additionally, the honey-treated sites achieved complete healing significantly faster than SSD sites (21 days vs. 24 days, p<0.0001).

Lund compared the use of honey-coated dressing for breast malignant wounds. In this study, 67 participants, 79% of whom had breast cancer, were randomized to receive treatment with either honey-coated dressing (n=34) or silver dressing (n=33). The authors report no significant differences between groups, and they concluded that the possible antibacterial effect of either treatment “could not be confirmed in these malignant wounds.”

MegaDerm Plus (L & C Bio, Seoul, Korea) is a suite of products (MegaDerm Plus, MegaDerm HD, MegaFill, MegaSheet) made from acellularized human skin-derived ADM allograft, and is regulated through the FDA’s HCT/P process as human tissue for transplantation.

In 2012 Kim reported on a prospective non-randomized study investigating the use of MegaDerm in parotidectomy procedures involving 109 participants who underwent treatment with Megaderm (n=58) or no implant (n=51). Decision on what group the participants were allotted was made by the participant in consultation with the surgeon. The study initially enrolled 134 participants but 25 were lost to follow-up. The authors reported a significantly higher rate of seroma at postoperative week 1 in the Megaderm group compared to the control group (14 vs. 6, respectively, p=0.22). However, no significant differences between groups were reported with regard to other complications, including infection (p=1.0), Hematoma (p=0.182), skin necrosis (p=1.0), and pain (p=0.28). Additionally, no difference between groups were reported with regard to patient-reported Frey’s syndrome quality scores at 3, 6, and 12 months. However, the incidence of Frey’s syndrome was significantly higher in the MegaDerm group at 3, 6 but not 12 months (p=0.32, 0.037 and 0.28, respectively). The authors stated that the use of MegaDerm for parotidectomy procedures, however, the higher rate of seroma is of concern and should be further evaluated in studies with less potential for selection bias.

In 2017, Kim retrospectively assessed 73 individuals to determine whether Megaderm (n=29) could replace absorbable mesh (n=22) or porous polyethylene (n=22) in orbital wall reconstruction. Enophthalmos, range of eyeball movement, diplopia, and infraorbital nerve numbness were evaluated at 1 and 3 weeks, and 3 and 6 months. At 6 months, complete resolution of all of these measures was reported in all groups (p=1.0). The most common complication was transient and self-limited diplopia, which developed in the early postoperative stage, one in the mesh group and 2 in the polyethylene group. No MegaDerm group participants developed diplopia. Infraorbital numbness was observed in 1 mesh group participant and 1 polyethylene group participant. Transient and self-limited lagophthalmos was reported in 1 mesh group participant. No p-value was provided for these intergroup comparisons. The authors concluded that MegaDerm, based on the results of this study, would be an excellent alternative material for orbital wall reconstruction. However, additional research is needed to verify these findings in a more robust trial.

Park (2023) retrospectively compared freeze-dried Megaderm to pre-hydrated Megaderm in 78 individuals undergoing immediate implant-based breast reconstruction with latissimus dorsi muscle coverage. The freeze-dried form was used in 26 individuals, while 52 individuals received the pre-hydrated product. The overall complication rate did not differ significantly, 30.8% in the freeze-dried group compared to 55.8% in the pre-hydrated group (no p-value provided). Seroma was more frequent in the pre-hydrated ADM group (n=20 vs. 4) but the difference between the two groups was not statistically significant (p=0.120). The pre-hydrated version showed a higher mean shape score of 3.46 plus or minus 0.5 compared to 3.08 plus or minus 0.7 in the freeze-dried cohort (p=0.019). The authors concluded that while complication rates were similar between pre-hydrated ADM and freeze-dried ADM, aesthetic outcome was better in pre-hydrated ADM in terms of symmetry. Further investigation into the use of MegaDerm and its variants are needed to better understand the clinical utility of this product.

In a single-blind, randomized, controlled trial published in 2024, Han evaluated 56 individuals undergoing immediate prepectoral direct-to-implant breast reconstruction using Megaderm with and without a basement membrane. Specifically, 30 participants received Megaderm HD (with basement membrane) and 26 participants received Megaderm Flex HD (without basement membrane). The total drainage volume was 893 milliliters plus or minus 399 in the Megaderm HD group compared to 859 milliliters plus or minus 341 in the Megaderm Flex HD group (p=0.74). Drains were removed at approximately 17 to 18 days. No significant differences between groups were observed in terms of overall complication rates between the 2 groups (26.7 vs. 23.1, respectively, p=0.76), the rate of seromas (3 vs. 0, respectively, p=0.09),infection (1 vs. 0, respectively, p=0.35), wound dehiscence (2 vs. 3, respectively, p=0.52), mastectomy flap necrosis (0 vs. 1, respectively, p=0.28), or capsular contracture (3 vs. 2, respectively, p=0.76). The authors concluded that Megaderm Flex HD in implant-based breast reconstruction was safe.

Collagen meniscus implants (e.g., Menaflex) have been proposed as a treatment method for individuals with a damaged knee meniscus. Menaflex is a human-derived acellular collagen product treated as human tissue for transplantation under the FDA’s HCT/P process.

Rodkey (2008) published a study with 311 participants with irreparable injury of the medial meniscus or a previous partial medial meniscectomy. The study population was divided into two groups, those with prior meniscal surgery (chronic group) and those with no prior surgery (acute group). These populations were further randomized to receive either treatment with a collagen meniscus implant or a partial meniscectomy only. The mean duration of follow-up was 59 months (range, 16 to 92 months). Repeat arthroscopies done in the experimental group at 1 year showed significantly (p=0.001) increased meniscal tissue compared with that seen after the original index surgery. In the chronic group, participants who had received the collagen implant regained a significantly higher degree of pre-surgery activity than did the controls (p=0.02). This group also underwent significantly fewer non-protocol reoperations (p=0.04). The authors reported no significant differences between the two treatment groups in the acute arm of the study.

Zaffahnini conducted a long-term trial of the performance of the Menaflex implant in 33 participants. This nonrandomized controlled trial allowed participants to choose treatment with either Menaflex (n=17) or partial medial meniscectomy (n=16). Participants were evaluated at baseline, 5 years and then 10 years after surgery. At 10 years, the authors report that the Menaflex group showed significant improvement compared to meniscectomy with regard to visual analog scale for pain (p=0.004), International Knee Documentation Committee knee form (p=0.0001), Teger index (p=0.026), SF-36 Physical Health Index (p=0.026), and SF-36 Mental Health Index (p=0.004). Radiographic evaluation showed significantly less medial joint space narrowing in the Menaflex group than in controls (p=0.0003). There were no significant differences reported between groups regarding Lysholm score (p=0.062) and Yulish score (p=0.122). Genovese score remained constant between 5 and 10 years after surgery (p=0.5).

Another case series study of 22 participants followed for 10 years was reported by Monllau (2011). The results of this study demonstrated that several measures improved, including the visual analog pain scale and radiographic joint line narrowing. The Lysholm score was significantly improved, from 59.9 at baseline, 89.6 at 1 year (p<0.001), and 87.5 at 10 years (p<0.001). Failure rate was only reported to be 8% in the 25 participants initially implanted.

Van Der Straeten published the results of a cohort study of 313 participants who received treatment with the collagen meniscal implant and were followed for a mean follow-up of 6.8 years (2016). A total of 56.5% of the implants were still intact and in place; 27.4% had been removed. This included 63 implants converted to a knee arthroplasty (19.2%). The overall cumulative allograft survivorship was 15.1% at 24.0 years. Simultaneous osteotomy significantly deteriorated survival (0% at 24.0 years) (p=0.010). The authors stated that 61% of participants underwent at least one additional surgery (range 1-11) for clinical symptoms after implantation. They concluded that the collagen meniscal implant did not delay or prevent tibiofemoral OA progression.

Another large cohort study was reported by Waterman (2016). This study involved 230 active-duty military personnel who underwent treatment with the collagen meniscal implant. A total of 51 complications occurred in 46 (21.1%) participants, including a secondary tear or extrusion (9%). The authors reported that 10 participants (4.4%) f20 participants (0.9%) subsequently underwent total knee arthroplasty. After implantation, 50 participants (22%) underwent knee-related military discharge at a mean of 2.49 years postoperatively. They concluded that while there were low reoperation and revision rates, their investigation indicated that 22% of participants who received implants were unable to return to military duty due to persistent knee limitations at short-term follow-up.

Menaflex was originally cleared by the FDA in the 510(k) process. Subsequent to further review by the FDA, this clearance was revoked. The manufacturer, ReGen Biologics, Inc. went bankrupt shortly thereafter. The Menaflex device is currently not marketed in the U.S.

Mirragen (Engineered Tissue Solutions, Rolla, MO) is a product composed of borate-based bioactive glass fiber matrix and cleared by the FDA in the 510K process. It is intended for use in the management of wounds, including partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds (donor sites/grafts, post-Moh's surgery, post laser surgery, podiatric, wound dehiscence), trauma wounds (abrasions, lacerations, first and second degree burns, skin tears) and draining wounds.

Armstrong (2022) published the results of a single-blinded RCT involving 40 participants with DFUs assigned to treatment with Mirragen plus standard care with collagen alginate dressing or standard care alone (n=20 in each group). All participants were followed for 12 weeks or until 2 weeks following wound closure, whichever came first. Re-application of Mirragen was performed at weekly intervals. Final adjudication of wound healing was conducted by a panel of wound experts blinded to group assignment. Both the treating providers and participants were aware of group assignment. The primary endpoint was the proportion of completely healed wounds at 12 weeks. The secondary endpoints included percent area reduction at 12 weeks, safety, and differences between scores for pain, Semmes-Weinstein, and w-QoL12 (wound quality of life) at 12 weeks. A total of 17 (85%) participants in the Mirragen and 8 (40%) participants in the control group completed the study (overall loss to follow-up 53%). The intent to treat analysis included all 40 participants. Of the Mirragen participants, 1 withdrew due to adverse events and 2 were withdrawn for having less than 50% wound healing at 6 weeks. In the control group, 5 participants withdrew due to adverse events, 6 were withdrawn due to having failed to achieve at least 50% healing at 6 weeks, and 1 was withdrawn due to wound reopening. The authors noted that at 12 weeks, 14 of 20 wounds (70%) in the Mirragen group had healed compared with 5 of 20 (25%) wounds in the control group (unadjusted p=0.004). Additionally, at 12 weeks the wound percent area reduction was 79% in the Mirragen group compared to 37% in the control group (unadjusted p=0.009; adjusted p=0.027). The mean change in neuropathic score (Semmes-Weinstein) at 12 weeks was 2.0 in the Mirragen group compared to -0.6 in the control group (unadjusted p=0.002; adjusted p=0.008). No significant difference between groups was noted with regard to w-QOL (unadjusted p=0.43; adjusted p=0.86) or pain (unadjusted p=0.84; adjusted p=0.86). The mean number of applications or Mirragen was 6. In the Mirragen group there were 4 adverse events reported, including 3 serious adverse events. The serious adverse events included cellulitis requiring hospitalization, diabetic ketoacidosis and methicillin resistant S. aureus (MRSA) infection requiring hospitalization, and exacerbation of an existing chronic heart failure condition that also required hospitalization. The control group experienced 9 adverse events, including 7 serious adverse events. The serious adverse events included an abscess, cellulitis, and osteomyelitis of a wound requiring hospitalization; a wound infection requiring amputation; a wound infection requiring hospitalization; swelling and cellulitis of the knee and ankle requiring aspiration and hospitalization; an infection of a non-index ulcer; and 2 falls requiring hospitalization. The authors concluded that the significantly better results in the Mirragen group compared control group for the primary endpoint, with the odds of healing over 11 times better compared to the control group, indicated the superiority of the Mirragen treatment. They also pointed to the reduction in the Semmes-Weinstein score and fewer infections in the Mirragen group compared with the control group, as indicating the superiority of Mirragen. However, these results are limited by multiple factors, including the significant loss to follow-up in both groups and especially in the control group, lack of investigator and participant blinding, and small sample size that does not allow generalizability. Further studies with robust trial design and execution are needed to fully understand the clinical utility of Mirragen for the treatment of DFUs.

In another study by Armstrong (2025), the authors reported on a multicenter, single-blind randomized controlled trial that evaluated the effectiveness Mirragen as an adjunct to standard of care in the treatment of chronic, non-infected Wagner Grade 1 DFUs. A total of 148 individuals were randomized to receive Mirragen plus standard of care or standard of care alone for up to 12 weeks. At 6 weeks a total of 53 individuals from both groups were lost to follow-up. In the modified intent-to-treat analysis, significantly more ulcers healed with Mirragen plus standard of care than with standard of care alone (48% vs. 24% at 12 weeks, p=0.007), and healing occurred faster in the Mirragen group. Similar benefits were observed in the per-protocol population, with 73% healing in the Mirragen group versus 42% with standard of care (p=0.007). Safety outcomes were consistent with expectations for a high-risk DFU population, with no unexpected adverse events attributable to the product. Limitations include the single-blind design (lack of investigator blinding), early withdrawal of non-responding wounds at 6 weeks, which may underestimate later healing potential, and restriction to Wagner Grade 1, non-infected, non-ischemic ulcers, limiting generalizability to deeper or more complex wounds. Additionally, variability across multiple sites and a relatively high withdrawal rate introduce potential heterogeneity. Further trials are needed to evaluate durability of healing, effectiveness in more severe DFUs and other wound types.

Miro3D Wound Matrix (Reprise Medical, Plymouth MN) is a sterile, single use, non-crosslinked porcine acellular wound dressing. The Miro3D porous scaffold provides a protective environment for wound healing. The device is packaged dry, terminally sterilized in its packaging by e-beam irradiation, and is rehydrated with sterile saline or lactated Ringer’s solution prior to use. Miro3D Wound Matrix is provided in four sizes that may be cut to fit a wound size prior to application. Miro3D is indicated for partial and full thickness wounds, pressure ulcers, venous ulcers, chronic vascular ulcers, diabetic ulcers, tunneled, undermined wounds, trauma wounds (abrasions, lacerations, partial-thickness burns, and skin tears), draining wounds, and surgical wounds (donor sites/grafts, post-Mohs' surgery, post-laser surgery, podiatric, wound dehiscence). Miro3D is cleared through the FDA’s 510(k) process (K223257).

In a retrospective case series by Abdo (2024), 11 individuals with type 2 diabetes and 13 deep or tunneling foot ulcers present for at least 4 weeks underwent surgical debridement and application of Miro3D. One individual also underwent are with the Miro3D Fibers Wound Matrix product. Over the 4-week study period, 62% (8/13) of ulcers achieved at least 50% area reduction by 4 weeks, and 54% (7/13) closed fully by 12 weeks, with all ulcers ultimately healing in an average of 13.1 weeks (range 2.0-22.3 weeks). Participants with larger initial volumes and poor offloading adherence tended to take longer to heal. However, no new infections, readmissions, or adverse events linked to Miro3D were reported. The concluded that the results suggest that Miro3D Wound Matrix effectively creates a protective environment for managing deep or tunneling DFUs, with early improvements in depth and volume. However, the study’s retrospective design and relatively small sample size and other methodological issues limit broader generalizability, and further research is needed.

MiroTract (Reprise Medical, Plymouth MN) is a porcine-derived collagen wound matrix compressed on a guidewire and expands when hydrated to fit the wound bed. It is a porous three dimensional structure indicated for partial and full thickness wounds, pressure ulcers, venous ulcers, chronic vascular ulcers, diabetic ulcers, tunneled, undermined wounds, trauma wounds (abrasions, lacerations, partial-thickness burns, and skin tears), draining wounds, and surgical wounds (donor sites/grafts, post-Mohs' surgery, post-laser surgery, podiatric, wound dehiscence). MiroTract is cleared through the FDA’s 510(k) process (K231614).

Myriad Matrix and Myriad Morcells are comprised of processed ovine forestomach matrix. Myriad Morcells are intended to cover, protect, and provide a moist wound environment. The products are indicated for the management of partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds (donor sites/grafts, post-Moh's surgery, post-laser surgery, podiatric, wound dehiscence), trauma wounds (abrasions, lacerations, partial-thickness burns, and skin tears), and draining wounds. The products are cleared through the FDA’s 510(k) process (K200502).

Two studies published in 2023 are the first to address the clinical utility of Myriad. Cormican (2023) reported the results of a retrospective pilot case series involving 10 participants with 13 contaminated lower-extremity defects undergoing surgical reconstruction with Myriad Matrix (n=3), Myriad Morcells (n=4), or both (n=6). All participants had at least 1 significant comorbidity with the potential to complicate their healing trajectory. Mean defect age was 3.5 ± 5.6 weeks and mean area was 217.3 ± 77.9 cm². Most defects had exposed structures (85%), and all defects were Centers for Disease Control and Prevention grade 2 or higher. Mean time to 100% granulation tissue formation was 23.4 ± 9.2 days, with a median product application of 1.0. Staged reconstruction was used in 7 of 13 defects, with the remainder (6 of 13) left to heal via secondary intention using standard wound care protocols. Mean follow-up was 7.4 ± 2.4 weeks, with 4 wounds (30%) lost to follow up ≤ 5 weeks. No major postoperative infections or adverse events were reported. The small sample size, and high loss to follow-up do not allow reasonable, generalizable conclusions regarding the clinical utility of these products

Bosque (2023) described the results of a similar retrospective case series study involving 50 participants with complex lower-extremity defects undergoing surgical reconstruction with Myriad Matrix (n=41), Myriad Morcells (n=3), or both (n=6). The participants had heterogenous etiologies, including diabetic foot ulcers (DFUs) (48%), half of which were complicated by a necrotizing soft-tissue infection (50%). Additionally, in the total population, 34% of participants had exposed bone, 10% had exposed tendon, 18% had both exposed tendon and bone, and 4% had exposed capsule. Ten participants (20%) were lost to follow-up before complete closure of the defect, but after 100% granulation tissue had formed. Where Myriad products were used for dermal regeneration (n=47), the median time to 100% granulation tissue was 17 days (mean, 26 ± 22.2 days; range, 7-120 days). A total of 38 participants (76%) were closed by secondary intention, with an overall median time to close of 14 weeks (mean, 14.0 ± 5.9 weeks; range, 1-27 weeks). The overall time to closure from the initial surgical procedure to closure across defects (n=40) was 13 weeks (mean, 13.7 ± 6.9 days; range, 2-29 weeks). This study involving these two Myriad products is promising, but the results are limited by multiple factors, including significant loss to follow-up, heterogeneity of wound etiologies, and use of multiple versions of the product used.

NeoMatriX (NeXtGen Biologics, Alachua, FL) is a sterile collagen wound dressing fabricated from the decellularized dermal extracellular matrix of the axolotl, an aquatic salamander. It is intended for management of wounds that include partial and full-thickness wounds, pressure ulcers, VSUs, DFUs, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds, trauma wounds, and draining wounds. NeoMatriX is cleared through the FDA’s 510(k) process (K181330).

Malueg (2026) reported on a preliminary single-center observational study that reports early clinical experience using NeoMatriX for wound management after neurosurgical procedures in a high-risk population. Included in the study were 23 individuals (mean age 61 years), most with comorbidities known to impair wound healing, who underwent primary or secondary wound closure with NeoMatriX following a wide range of cranial and spinal procedures. Over the observed follow-up period, postoperative wound infection or dehiscence requiring revision occurred in 2 individuals (8.7%), and scarring was subjectively minimal in all cases. The author highlighted the theoretical advantages of axolotl dermis which include low immunogenicity, regenerative and antifibrotic properties, and avoidance of mammalian xenograft concerns and conclude that the patch demonstrated acceptable safety and promising feasibility for neurosurgical wound management in complex clinical scenarios. Limitations include the small sample size, retrospective analysis of a prospectively maintained database, single-center design, and absence of a control or comparator group, making it impossible to determine whether outcomes are superior to standard closure techniques or other biologic matrices. Larger, controlled, and ideally randomized studies are required to establish comparative efficacy, define optimal indications, and clarify the clinical value of axolotl-derived dermal matrices in neurosurgical wound care.

NEOVEIL Tube/Sheet (Gunze Limited, Kyoto, Japan) is a synthetic surgical mesh made from bioabsorbable polyglycolic acid (PGA), designed for use in surgical procedures that require reinforcement of soft tissue transection or resection with staples or sutures. NEOVEIL is indicated for use in surgical procedures in which soft tissue transection or resection with suture or staple line reinforcement is needed. The product can be used for reinforcement of suture or staple lines during lung resection, liver resection, bronchial, bariatric, colon, colorectal, esophagus, gastric, mesentery, pancreas, and small bowel procedures. NEOVEIL has received clearance under the FDA 510(k) process (K130997).

Neox is an ed ultra-thick human umbilical cord-derived amniotic membrane allograft regulated by the FDA under HCT/P process as human tissue for transplantation.

Caporusso (2025), reported on a multicenter, randomized controlled trial that evaluated Neox 1K as an adjunct to standard of care for complex diabetic foot ulcers with exposed bone, tendon, muscle, or joint capsule, including those with controlled osteomyelitis. A total of 220 individuals were randomized to receive Neox + standard of care or standard of care alone, with follow-up extending to 50 weeks. Healing rates were numerically higher in the Neox group at 26 weeks (66.1% vs. 59.8%, p=0.4) and 50 weeks (77.1% vs. 71.6%, p=0.29), but differences were not statistically significant, and time to wound closure was similar between groups. Safety outcomes, including adverse events and amputation rates, were comparable across treatment arms. Key limitations include the open-label design, variability in investigator-driven reapplication and debridement practices, and higher baseline partial wound closure with sutures in the standard of care group, which likely contributed to the unexpectedly strong standard of care healing rates. As a result, while Neox was safe and effective, the study did not demonstrate superiority over high-quality standard of care, highlighting the need for further controlled studies to clarify incremental benefit.

NeuraGen 3D Nerve Guide Matrix (Integra LifeSciences Corporation, Plainsboro, N.J.) is a resorbable implant for the repair of peripheral nerve discontinuities. NeuraGen 3D is composed of bovine Type I collagen conduit and a porous inner matrix comprised of collagen and glycosaminoglycan (chondroitin‐6‐sulfate). NeuraGen 3D is supplied sterile, non‐pyrogenic, for single use. NeuraGen 3D provides a protective environment for peripheral nerve repair after injury, and is designed to isolate and protect the nerve and to create a conduit for axonal growth across a nerve gap. The NeuraGen 3D is indicated for the repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity. The device is cleared through the FDA’s 510(k) process (K163457).

In an unblinded RCT of Neuragen 44 participants with ulnar or median nerve lacerations were assigned to treatment with Neuragen (n=23) compared to direct fascicular repair or nerve grafting (n=21) (Boeckstyns, 2013). The authors reported that data for only 36 participants (81%) were available at the 24-month follow-up visit. However, they do not provide information regarding which groups the dropouts were from. At 24 months no significant differences between groups were reported with regard to amplitudes, latencies and conduction velocities. With regard to comparison to the contralateral hand, both groups remained significantly deficient on all electrophysiological measures. No surgical complications were reported. These results may indicate some benefit from the use of Neuragen, but the generalizability is hampered by missing information regarding participants at 24 months, as well as methodological flaws such small study population and lack of blinding.

In addition to this study, several unblinded non-randomized controlled trials and multiple case series studies addressing the use of Neuragen have been published, with most involving small numbers of participants (Ashley, 2006; Bushnell; Distinct, 2013; Erakat 2013; Farole, 2008; Haug 2013; Huber 2017; Karup, 2017; Lohmeyer, 2014; Rbia, 2019; Schmauss 2014; Taras, 2011; Wangensteen, 2010; Wilson, 2016). These studies do not adequately control bias and the clinical utility and generalizability of their conclusions is limited.

Subsequently, Ilyas (2024) reported a multicenter US based RCT that included 220 participants with digital nerve injuries, treated either with type I bovine collagen conduit (NeuraGen) or a Avance Nerve Graft. Inclusion criteria were individuals 18- to 69-years with 5 to 25 mm digital nerve gaps within 24 weeks of injury. Participants were randomized (1:1) to Avance or NeuraGen repairs. Cold Intolerance Symptom Severity (CISS) scores and sensory function testers were assessed at first visit (FPV), 1-, 3-, 6-, 9-, and 12-months post-surgery, both participants and assessors blinded to treatment. One hundred eighty-three participants completed the last evaluable visit (LEV) of 6 months or more of follow-up; of these, 91 received Avance repair and 92 had NeuraGen repair. No significant differences were observed in demographics, gap length, time to repair, or injury mechanism between the groups. The average gap lengths were 13.6 mm for the Avance group and 13.0 mm for the NeuraGen group. The average time to repair was 28.2 and 23.4 days for repairs, respectively. Both groups reported a reduction in the CISS over time, indicative of improved cold intolerance symptoms. The mean CISS score for the entire cohort decreased from 31.15 ± 29.25 at FPV to 23.42 ± 22.16 at the LEV. The reduction in CISS score was numerically greater but not statistically different in the Avance group (10.39 points) compared with the NeuraGen group (5.23 points). A sub-analysis showed more participants improved from severe/extremely severe cold intolerance to mild cold intolerance for Avance compared with NeuraGen at 1 month and LEV (p< 0.05). The CISS scores also correlated with sensory function testing. The authors concluded that Avance had improved cold tolerance outcomes for participants with more severe cold intolerance at FPV relative to nerves repaired with NeuraGen. The study was limited by a loss to follow-up at later timepoints in the study. At the 1-month timepoint, the study had a total of 178 participants, but by 12 months, only 149 were available for evaluation. Target follow-up for the study was 12 months, however, participants were assessed at or greater than 6 months, which included up to 15 months out from repair. The study did not include a sub-analysis of participants who concomitantly underwent vascular repair. This was due to a low overall number of participants with vascular injury requiring repair, which is likely a result of the exclusion criteria of the study as well as study design limitations. This limits the generalizability of this study to individuals with nerve injuries who do not require vascular repair.

Neuro-Patch device (B. Braun Medical Inc., Bethlehem, PA) is a synthetic fabric composed of fine-fibered microporous polyester urethane fleece. Neuro-Patch is indicted as a dura mater substitute in neurological procedures for soft tissue reconstruction of damaged, impaired or missing tissue. It is cleared through the FDA’s 510(k) process (K960470).

A non-randomized comparative study was published by Wales (2024), involving 11 participants, (6 who prospectively received treatment with Neuro-Patch and 5 retrospective participants treated with autologous grafts). In the Neuro-Patch group, the authors reported no cerebrospinal fluid leaks, need for lumbar drains, or hearing loss by the 6 month follow-up. Discharge occurred within 48 hours in all participants in this group, with no readmissions. By contrast, the control group had a higher rate of complications, including two instances of CSF leak with lumbar drains placement. They reported an average inpatient stay or 91.2 hours (range: 48-120 h), with three participants having stays of 5 days.

Yang (2025) reported on a single-center retrospective cohort study that analyzed 125 individuals with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC) who underwent periarterial divestment (PAD) to achieve tumor clearance without arterial resection with Neuro-Patch use for arterial reinforcement for postpancreatectomy hemorrhage (PPH) prevention. Neuro-Patch was applied in 51 individuals, at the surgeon’s discretion. Overall perioperative outcomes were acceptable for this high-risk population, with a 90-day mortality of 3.2%, median hospital stay of 10 days, and a median overall survival of 20.6 months; neoadjuvant chemotherapy emerged as an independent predictor of improved survival, while venous invasion predicted worse outcomes. The authors reported that Neuro-Patch use was independently associated with a significant reduction in PPH (p=0.031), without increasing arterial stenosis, thrombosis, or infection during follow-up, suggesting a potential protective role in reinforcing skeletonized arteries after PAD. Limitations included the retrospective, non-randomized design, single high-volume center experience, and selection bias, as Neuro-Patch was preferentially used in individuals perceived to be at higher risk of bleeding. The modest sample size limits statistical power, and the study cannot establish causality or define optimal indications, technique, or long-term safety. Additionally, quality-of-life outcomes and external generalizability were not assessed. Larger, prospective randomized controlled trials are required to confirm the efficacy and safety of Neuro-Patch.

NeuraWrap Nerve Protector (Integra LifeSciences Corporation, Plainsboro, N.J.) is an absorbable collagen implant that provides a non-constricting encasement for injured peripheral nerves for protection of the neural environment. NeuraWrap is designed to be an interface between the nerve and the surrounding tissue, when hydrated, NeuraWrap is a pliable, nonfriable, porous collagen conduit with a longitudinal slit that allows NeuraWrap to be spread open for placement over the injured nerve. NeuraWrap is sterile, non-pyrogenic, for single use only. The device is cleared through the FDA’s 510(k) process (K041620).

At this time, the available peer-reviewed published data addressing the clinical utility of NeuraWrap is limited to a small number of studies (Hibner, 2012; Kokkalis, 2016; Soltani, 2014). Additional evidence addressing the clinical utility of this product from large, well-designed, and conducted trials is needed to fully assess the clinical utility of this product.

NovoSorb Biodegradable Temporizing Matrix (BMT) (PolyNovo Biomaterials Pty Ltd., Victoria, AU) is composed of porous biodegradable polyurethane foam bonded with a polyurethane adhesive layer to a fenestrated one-sided transparent sealing membrane. The sealing membrane is designed to physiologically close the wound by limiting evaporative water loss during integration of the foam. The adhesive layer and sealing membrane are to be removed and discarded when appropriate leaving only the foam layer to biodegrade. NovoSorb is indicated for use in the management of wounds including: partial and full thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic and vascular ulcers, surgical wounds (donor sites/grafts, post-Moh’s surgery, post-laser surgery, podiatric, wound dehiscence), trauma wounds (abrasions, lacerations, second-degree burns, and skin tears) and draining wounds. The device is for single use only. NovoSorb is cleared through the FDA’s 510(k) process (K172140).

At this time there is a reasonable number of studies published in the medical literature addressing the use of NovoSorb for a variety of conditions including burns, treatment of necrotizing fasciitis, DFUs, and chronic complex wounds (Solanki, 2020; Schlottmann, 2022; Li, 2021; Lo, 2022; Austin, 2023; Kidd, 2023; Lo, 2023; Betar, 2023; and Guerrico, 2023). However, due to several factors, including a nongeneralizable sample and other factors, the results cannot be generalized to the wider population. Larger studies in the form of well-designed and conducted trials are needed to assess the clinical utility and efficacy of NovoSorb.

Tsang (2025) reported on a retrospective, cross-sectional review that examined NovoSorb use over a 12-month period in 12 individuals with complex non-burn wounds, with particular emphasis on reconstructive salvage following partial or complete free-flap failure. Wound etiologies included trauma, cancer resection, necrotising fasciitis, and chronic wounds, many involving circumferential soft-tissue defects with exposed bone or tendon. Overall, NovoSorb integration followed by successful split-thickness skin grafting occurred in 83% of cases, with a mean interval of approximately 33 days between NovoSorb placement and grafting. Three detailed case vignettes demonstrated how NovoSorb enabled limb salvage and durable wound closure after failed free flaps in situations where revision free tissue transfer was deemed high risk or unacceptable to individuals, potentially avoiding amputation or further donor-site morbidity. The author highlighted NovoSorb role as an “off-the-shelf” salvage option that can stabilize hostile wound beds, allow infection control, and create a graftable neodermis in scenarios traditionally requiring complex microsurgical reconstruction. Limitations included a small sample size, single-center retrospective design, and absence of a comparator group, with outcomes largely descriptive rather than quantitative. Selection bias is likely, as BTM was reserved for particularly challenging cases and functional outcomes, and individual-reported measures were not systematically assessed. Larger comparative studies are needed to better define indications, long-term outcomes, and the role of BTM relative to revision free flaps in complex reconstructive algorithms.

ologen Collagen Matrix (Aeon Astron Europe B.V., Leiden, CH) is a biodegradable material composed of collagen obtained from porcine collagen and glycosaminoglycans (GAG). The device is gamma sterilized for single use only. ologen Collagen Matrix is intended for the management of wounds including surgical wounds, trauma wounds, draining wounds, second degree burns, partial and full-thickness wounds, pressure ulcers, venous ulcers, vascular ulcers, diabetic ulcers, oral wounds and sores. ologen is cleared through the FDA’s 510(k) process (K173223). The use of this product has been proposed for a variety of ophthalmological indications.

The most rigorous trial to date was an open label, non‑randomized, prospective study involving 93 participants undergoing phacotrabeculectomy assigned to receive treatment with mitomycin C (n=53) or ologen (n=40). The authors reported that after 12 months follow-up there were no significant differences between groups with regard to best corrected visual acuity (p=0.151), intraocular pressure (p=0.254), mean number of medications used (p=0.91) or overall procedure success (p=0.745). No reported repeat procedures, blebitis or endophthalmitis were reported. This study indicates equal outcomes from the use of mitmycin C compared to ologen during phacotrabeculectomy. However, the study was not designed as a non-inferiority trial and contained several methodological flaws that limit the generalizability of the reported findings. Further investigation in the form of well-designed and conducted studies is needed (Chelerkar, 2021).

Park (2022) published a retrospective analysis of 72 individuals with glaucoma who underwent XEN gel stent implantation with (n=42) and without (n=30) ologen collagen matrix augmentation. Surgical success, defined as intraocular pressure (IOP) reduction greater than 20% than preoperative IOP, and the percentage of postoperative complications were compared between the ologen implant augmented group and the non-augmented group. The surgical success rate at 6 months postoperatively was not different between the groups (56.4% compared to 43.3%, p>0.05). Neither was the prevalence of postoperative hypotony, 5-fluorouracil injections, use of anti-glaucoma medications, bleb needling, and additional glaucoma surgeries different between the groups at 6 months. The authors concluded that all groups showed IOP reduction after XEN gel stent implantation, however there was no significant difference between the Ologen implant augmented and non-augmented groups in surgical outcomes.

Bhatkoti (2023) and Khairy (2023) also published small studies that assessed the use of ologen implant in place of or in combination with trabeculotomy. Bhatoki (n=43) demonstrated a similar success rate between trabeculectomy and ologen implant in treating primary open angle glaucoma. However, there was a lower complication rate and faster visual recovery in the trabeculectomy-only group compared to the ologen group. Khairy (n=21) compared the use of Mitomycin C or ologen implant as an adjunct to combined trabeculotomy-trabeculectomy in the treatment of primary congenital glaucoma. Complete success was achieved in 17 eyes (81.0%) in combined trabeculotomy-trabeculectomy group, 18 eyes (85.7%) in Mitomycin-C group, and 17 eyes (81.0%) in the ologen group. Qualified success, defined as IOP < 21 with or without antiglaucoma medications, was achieved in 85.7% in both the combined trabeculotomy-trabeculectomy and the ologen groups, and 90.5% in the Mitomycin C group. The ologen group had the lowest success probability at 3 months (85.7%). The authors concluded that combined trabeculotomy-trabeculectomy is a safe and effective primary surgical treatment in individuals with primary congenital glaucoma without the need for implant augmentation, and that the use of ologen implant should be preserved for use in recurrent cases. Additional larger studies are needed to assess the safety and clinical efficacy of ologen in ophthalmic applications.

Jacobson (2025) reported on a retrospective interventional case series that evaluated Ologen augmentation of Ahmed glaucoma drainage devices (OAGD) in children with refractory glaucoma, reporting outcomes with 2-6 years of follow-up. In the study, 40 eyes from 28 pediatric individuals (median age 2.6 years), most with complex or previously operated glaucomas, underwent Ahmed valve implantation with adjunctive placement of a biodegradable collagen matrix. At a median follow-up of 3.6 years, intraocular pressure decreased significantly from a median of 27 mmHg to 15 (p<0.0001), and glaucoma medication burden was markedly reduced from a median of 3 to 0 (p<0.0001). Complete success, defined as IOP control without medications or additional surgery, was achieved in 55% of eyes, while qualified success, defined as with or without medications, was achieved in 75%, with Kaplan-Meier survival rates of 75% and 87% at 3 years, declining to 57% and 67% at 5 years, respectively. Early complications were uncommon. Limitations include the retrospective, noncomparative design, single-surgeon experience, heterogeneous glaucoma etiologies, small sample size, and variable follow-up duration, which introduce selection bias and limit generalizability.

Omeza Complete Matrix (Omeza LLC, Sarasota, FL) is a combination wound care matrix composed primarily of hydrolyzed fish peptides infused with cod liver oil. Its intended uses are for management of dermal wounds. It is not indicated for third degree burns. Omeza was cleared through the FDA’s 510(k) process (K211972).

Dhillon (2025) reported on an open-label, prospective, real-world evidence study that evaluated Omeza in individuals with refractory chronic wounds of multiple etiologies who had failed prior standard and advanced therapies and would typically be excluded from randomized trials. Among 53 evaluable wounds (including DFUs, VLUs, pressure injuries, surgical wounds, and wounds of unclassified etiologies) in a population with extensive comorbidities, the objective response rate was 42% (≥40% area reduction at 4 weeks), with a mean percentage area reduction of 34% at 4 weeks and 66% at 12 weeks, and 34% of wounds achieving complete closure by week 12. Significant reductions in wound size over time were observed across wound types, suggesting that Omeza may help shift stalled, nonhealing wounds onto a healing trajectory in a highly complex, real-world population. Safety findings were consistent with expectations for this high-risk cohort; most adverse events were unrelated to the product, with only one event definitively attributed to Omeza (localized pain on application). However, interpretation is limited by the lack of a control group, open-label design, and modest sample size, which preclude causal inference and direct comparison with standard care or alternative advanced therapies. Additional limitations include heterogeneity of wound etiologies, variability in prior treatments, attrition and missing data, and inconclusive individual-reported quality-of-life outcomes, likely confounded by extensive comorbidities. Controlled comparative studies are needed to confirm effectiveness and durability.

Simman (2024) reported on an open-label, single-arm clinical study that evaluated the use of Omeza as part of a structured treatment protocol for chronic, stalled diabetic foot ulcers (DFUs). For the study, 19 individuals with Wagner grade 1-2 DFUs (median ulcer duration 36 weeks, including several ulcers present for greater than 1 year) were enrolled after a screening phase that excluded wounds showing at least 30% spontaneous improvement. Among individuals completing follow-up, treatment with Omeza plus offloading resulted in a mean percentage area reduction of 62% at 4 weeks, a threshold predictive of healing, and 94% percentage area reduction at 12 weeks, with 57% (8/14) achieving complete closure by week 12. All remaining ulcers continued to improve, with no wounds enlarging during the study, and several long-duration ulcers achieved complete healing. Safety findings were favorable, with no product-related adverse events reported while one serious event (death due to comorbidities) was deemed unrelated to treatment. Limitations included a small sample size, open-label, non-comparative design, single health-system setting, and high attrition due to offloading non-adherence, which introduce selection and performance bias. The study was not powered for statistical inference, relied on descriptive analyses only, and included a relatively homogeneous population, limiting generalizability. Larger randomized controlled trials comparing MWM with standard care and other advanced therapies are needed to confirm efficacy and durability of healing.

Pelvicol is a porcine-derived ADM intended for use as a soft tissue patch to reinforce soft tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue membranes. It is specifically indicated for plastic and reconstruct surgery of the face and head. It is cleared through the FDA’s 510(k) process (K013625).

The use of Pelvicol was evaluated in 132 participants with pelvic organ prolapse. This RCT involved 64 participants who underwent anterior and posterior colporrhaphy and 68 who received colporrhaphy with Pelvicol. At 3 months follow-up, there were significantly more surgical failures and recurrences in the Pelvicol group, but by the 3-year follow-up period recurrence rates were similar. No significant differences were noted with regard to symptom resolution, sexual activity, or complications rates. The authors conclude that, “Pelvicol did not provide advantages over conventional colporrhaphy in recurrent pelvic organ prolapse concerning anatomical and subjective outcomes.”

Kahn (2015) published the results of an RCT involving 201 participants undergoing surgical treatment for stress urinary incontinence. Participants received treatment with either tension-free vaginal tape (TVT), autologous fascial sling (AFS), or Pelvicol. The authors reported that 162 (80.6%) participants were available for follow-up at a median follow-up of 10 years. They reported the 1 year “success rates”, defined as being completely dry or improved, as 93% in the TVT group, 90% in the AFS group and 61% in the Pelvicol group. There were no significant differences between groups at 10 years. Comparing the 1- and 10-year success rates, there were significant reductions in the TVT and AFS groups (p<0.05 for both), but not for the Pelvicol group (p=1.0). Similar results were reported with the rates of “dry” participants at 1 and 10 years, with rates for TVT reported as being 55% and 31.7%, 48% and 50.8% for AFS, and 22% and 15.7% for Pelvicol. These rates significantly favored AFS (p<0.001 vs. Pelvicol and p=0.001 vs. TVT). The Pelvicol arm of the study was discontinued by the data monitoring group after it was clear that the Pelvicol group had significantly poorer results compared to TVT and AFS. The results of this study indicate that the use of Pelvicol for the treatment of stress urinary incontinence may present a significant risk of harm compared to other available treatments, and further investigation may be warranted.

Peri-Strips Dry (Bio-Vascular, Inc. St. Paul, MN) is a surgical mesh product derived from decellularized bovine pericardium that is crosslinked with glutaraldehyde. Peri-Strips Dry is indicated to reinforce staple lines during lung and bronchus resections including: wedge resections, blebectomies, lobectomies, bullectomies, bronchial resections and other lung incisions and excision of lung and bronchus. It can also be used for the reinforcement of the gastric staple line during bariatric surgical procedures and gastric bypass and gastric banding. Per-Strips Dry is cleared through the FDA’s 510(k) process (K971048).

At this time there are only a limited number of peer-reviewed published articles addressing the use of this product. Stamou compared the use of Peri-Strips Dry (n=96) to standard care (n=91) in staple line reinforcement during sleeve gastrectomy procedures (2011). The authors reported that the use of Peri-Strips Dry significantly reduced the incidence of staple line bleeding (p=0.012) and intra-abdominal collections (p=0.026), however, the leak rate was not significantly reduced.

A similar study was conducted by Shah and others (2014) involving 100 participants undergoing sleeve gastrectomy procedures and assigned to surgery with either Peri-Strips Dry staple line reinforcement (n=51) or standard care (n=49). Participants were followed up for 30 days post procedure. No intra- or postoperative leaks were reported in either group. Staple line bleeds were reported to occur less in the Peri-Strips group compared to controls (45.1% vs. 79.6%, p=0.0005). Overall BMI did not impact staple line bleeds (p_interaction=0.072). However, participants with BMI < 43 were significantly more likely to have staple line bleeds compared to participants with BMI ≥ 43 (79.3% vs. 33%, p=0.0015). Participants in the Peri-Strips group had less severe staple line bleeding compared to controls, with moderate to severe bleeding occurring in 2 Peri-Strips group participants compared to 6 controls (p=0.0002). Peri-Strips participants also had shorter procedure times (58.8 minutes vs. 72.8 minutes, p=0.0153) as well as fewer hemostatic clips or sutures (19.6% vs. 67.3%, p<0.0001).

Permacol Surgical Mesh (Tissue Science laboratories, PLC. Hants, UK) is an ADM product derived from porcine pericardium and elastin. Permacol is intended for use as a soft tissue patch to reinforce soft tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue membranes. It is specifically indicated for use in the following types of soft tissue repair procedures: abdominal, inguinal, diaphragmatic, femoral, scrotal, umbilical, and incisional hernia, colon, rectal, urethral and vaginal prolapse, muscle flap reinforcement, reconstruction of the pelvic floor, sacrocolsuspension, and urethral sling. Permacol is cleared through the FDA’s 510(k) process (K992556).

Mitchell (2008) published a retrospective, nonrandomized controlled study of 37 participants undergoing congenital diaphragmatic hernia repair. Participants received treatment with either Permacol (n=29) or synthetic Gore-Tex (n=8), with a median follow-up of 57 months for Gore-Tex and 20 months for Permacol. Overall recurrences were reported in 8 (28%) Gore-Tex participants with a median time to recurrence of 12 months. There were no recurrences reported in the Permacol group. These results are interesting, but due to the small sample size, retrospective nature and lack of randomization, it is not possible to generalize the results to other populations.

Kalaiselvan (2020) performed a retrospective analysis of 13 participants who had abdominal wall defect repair with bridging Permacol over a 5-year period. Twelve of these (92%) participants developed abdominal wall defects (AWD) and enterocutaneous fistulation following complications of previous surgery. Six participants underwent fistula takedown and abdominal wall repair with Permacol, of which 5 (83%) recurred. Seven participants had already undergone similar procedures in their referring hospitals and had also recurred. Median time to fistulation after Permacol treatment was 17 days. In all cases, Permacol was used to bridge the defect and placed in direct contact with bowel. At reconstructive surgery for refistulation, it was inseparable from multiple segments of small intestine, necessitating extensive bowel resection. Histological examination confirmed that Permacol almost completely integrated with the seromuscular layer of the small intestine. The study raised concerns regarding intraperitoneal use due to the fact that Permacol may become inseparable from the serosa of the small intestine and was associated with recurrent intestinal fistula formation and treatment failure.

Rashid (2020) examined rotator cuff repair augmented with either GraftJacket (n=4), Permacol (n=3) or standard of care (n=3). The study addressed histological and proinflammatory changes in the native supraspinatus tendon in both Permacol groups. The authors reported increased friability of the matrix, and lack of parallel oriented collagen fibers. In the standard of care group, which was a conventional repair without patch augmentation, the tissue resembled normal tendon. The Permacol-treated sections, however, demonstrated more disruption of the extracellular matrix when compared to sections treated with GraftJacket. They reported that one participant in the Permacol group experienced adverse tissue reaction characterized by extensive infiltration of pro-inflammatory cells. The authors concluded use of Permacol augmentation in rotator cuff repair lacks clinical efficacy and may potentially cause harm.

Roman (2021) reported the results of a retrospective case-control study of 209 participants undergoing complete excision of large rectovaginal endometriotic nodules treated with (n=167) or without Permacol (n=42) mesh. No significant differences were reported in the rate of postoperative rectovaginal fistula formation (OR, 1.6) and the authors concluded that the use of Permacol mesh may not impact the rate of rectovaginal fistula formation compared to no mesh.

Vahtsevanos (2021) reported the results of a retrospective case-control study of 73 participants who had undergone 76 parotidectomy procedures with (n=32) and without Permacol (n=44) to evaluate the impact on the incidence of Frey’s syndrome. At a mean follow-up of 26.3 months the incidence of Frey’s syndrome was significantly lower in the Permacol group (6.7% vs. 31.8%, respectively, p=0.031). The incidence of severe Frey’s syndrome was 3.12% in the Permacol group compared to 31.82% in the control group (p=0.002). The results of this study should be confirmed in a prospective trial.

Ball (2022) conducted a parallel, dual-arm, double-blind randomized controlled trial involving adults (n=94) undergoing complex abdominal wall reconstruction with a biologic mesh (2017-2020). Participants were randomized in a 1:1 ratio to receive either Strattice or Permacol biologic meshes. The incidence of complications between groups was not statistically significant (46.0% vs. 64.6%; p=0.06). A total of 14 (14.9%) participants experienced a hernia recurrence, with no differences between groups (n=6 in the Permacol group and n=8 in the Strattice group).

Promogran Matrix Wound Dressing is a sterile primary dressing comprised of (Johnson & Johnson Medical, Ltd., North Yorkshire, UK) is an ADM product of bovine origin. Program is indicated for the management of exuding wounds including, diabetic foot ulcers, venous ulcers, ulcers caused by mixed vascular etiologies, full thickness and partial thickness wounds, donor sites and other bleeding surface wounds, abrasion, traumatic wounds healing by secondary intention, and dehisced surgical wounds. Promogran is cleared through the FDA’s 510(k) process (K014129).

The use of Promogran has been evaluated in two RCTs. The first, by Veves and others, involved 276 participants with DFUs randomized to receive treatment with either Promogran (n=138) or moistened gauze (control group; n=138) (2002). At 12 weeks of treatment, there was no statistically significant difference between groups with regard to complete wound closure (p=0.12), in healing for either the subgroup of participants with wounds of less than 6 months duration (p=0.056), or the group with wounds of at least 6 months duration (p=0.83). No differences were seen in the safety measurements between groups. The other study by Vin involved 73 participants with VSUs randomly allocated to receive either Promogran (n=37) or a non-adherent dressing (Adaptic) (n=36). Only 29 participants completed the 12-week study period (39.7%). No intent-to-treat analysis was provided. Because of this, the data reported is not particularly useful.

PuraPly antimicrobial wound matrix is an ADM product composed of a purified collagen matrix of bovine origin containing polyhexamethylenebiguanide (PHMB). PuraPly AM is intended for the management of wounds and as an effective barrier to resist microbial colonization within the dressing and reduce microbes penetrating through the dressing. PluraPly may be used for the management of: partial and full thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds (donor sites/grafts, post-Moh's surgery, post-laser surgery, wound dehiscence), trauma wounds (abrasions, lacerations, second-degree bums, and skin tears) and draining wounds. PuraPly is cleared through the FDA’s 510(k) process (K051647).

Lintzeris (2018) published a case series involving 8 participants with chronic wounds with a variety of etiologies including trauma (n=1), DFUs (n=1), pressure ulcers (n=3), venous stasis ulcers (VSUs) (n=1), surgical wounds (n=1), and calciphylaxis ulcers (n=1). PuraPly AM was applied once weekly after debridement. The authors reported a mean of 5.8 PuraPly applications were used. A total of 6 wounds had complete healing at an average time to closure of 10 weeks. The 3 wounds that did not completely heal demonstrated improved wound appearance with 100% granulation with an average area reduction of 61.4%.

Bain (2020) published the results of the Real-World Effectiveness Study of PuraPly AM on Wounds (RESPOND) registry, a prospective cohort study involving 307 participants with wounds with a variety of etiologies including VSUs (n=67), DFUs (n=62), pressure ulcers (n=45), surgical wounds (n=54), and other wounds (n=79) treated with PuraPly AM. Participants were followed for 32 weeks. The authors reported the mean number of PuraPly AM applications as 5.2. Full wound closure was 52% at 20 weeks, 62% at 26 weeks, and 73% at 32 weeks. Complete wound closure for VSUs was 73%, for DFUs was 51%, for pressure ulcers 62%, for surgical wounds 96% and 67% for other wounds. No adverse events or serious adverse events attributable to PuraPly were reported.

Koullias and others (2022) completed a secondary analysis of the RESPOND registry examining the effects of PuraPly AM treatment in the subgroup of participants with VSUs (n=67) over 32 weeks. The use of PuraPly resulted in successful healing defined as > 60% reduction from baseline in wound area and depth, as well as the incidence of wounds demonstrating > 75% reduction from baseline in wound volume. This resulted in successful healing in 73% of participants as demonstrated by reduction in area, depth, and volume. A limitation of the study was the participants included were predominantly white (87%) females (58%).

Menack (2022) also completed a secondary analysis of the RESPOND registry in a subgroup of participants with pressure injuries (PI) (n=45). The participants were primarily elderly, with large deep wounds of long duration. The use of PHMB in the management of PI resulted in 91% PAR and 62% rate of healing.

Regeneten (Rotation Medical, Inc. Plymouth, MN) is an ADM product composed of bovine collagen. Regenten is indicated for the management and protection of tendon injuries in which there has been no substantial loss of tendon tissue. It has been cleared through the FDA’s 510(k) process (K222501).

Clinical use of the Regeneten graft has been described in several studies. The first, published by Bokor and others (2016) described a case series study of 13 participants with intermediate- to high-grade partial thickness rotator cuff tears who were followed for 2 years. At the end of the study 10 participants with evaluable tears had demonstrable improvement in tear appearance on MRI, with 7 completely healed. The remaining 3 participants had continued tears, but with continued improvement. No evidence of tear progression was reported. Clinical symptoms were shown to improve significantly in overall Constant-Murley shoulder scores (p≤0.01) and Constant-Murley pain score, (p≤0.001), as well as American Shoulder and Elbow Society (ASES) total score (p≤0.001), and ASES pain score (p≤0.001). No postoperative infections and no adverse events associated with the product were reported.

Schlegel reported the results of a prospective case series study involving 33 participants with intermediate-grade or high-grade partial-thickness tears of the supraspinatus tendon treated with Regeneten and followed for 1 year. Intermediate-grade tears were reported in 12 participants and or high-grade tears in 21. Of these, 11 were articular, 10 were bursal, 4 were intrasubstance, and 8 were hybrid). At 12 months, a total of 8 participants (24%) had no visible defect on MRI, 23 participants (70%) had a decrease in tear size by at least 1 grade. Only 1 participant (3%) had a tear that remained unchanged. No tears progressed to full-thickness tears in the participants who followed the postoperative rehabilitation protocol. No revision procedures were reported. Overall, tendon thickness increased significantly (p<0.0001) based upon MRI evidence of new tissue growth over the bursal surface of the supraspinatus tendon. The ASES pain score improved significantly at 1 year, as did the ASES shoulder function score and ASES shoulder index score (p<0.001 for all). No device-related significant adverse events were reported.

McIntyre (2019) published the results of a retrospective case series study involving data from participants with partial- and full-thickness cuff tears treated with Regeneten reported in the REBUILD registry. The registry included 203 participants and 173 (85%) had complete 1 year follow-up data. Overall, 90 participants had partial-thickness tears and 83 had full-thickness tears. Of the partial tear group, 16.7% were grade I tears, 37.8% grade II, and 45.5% grade III. Of the full-thickness tears, 4.8% were small, 50.6% medium, 30.1% large, and 14.5% massive. Other surgical procedures were conducted in conjunction with the graft placement, including acromioplasty (89.0%), acromioclavicular joint resection (39.9%), capsular release (12.1%), and biceps surgery (55.6%). At 12 months, the partial-thickness group has a statistically significant improvement with regard to outcomes on the single-assessment numeric evaluation (SANE), Veterans RAND 12-Item (VR-12) physical component, ASES, and Western Ontario Rotator Cuff (WORC) measures (p<0.05 for all). For the VAS pain and ASES scores, improvement was 84% and 83%, respectively, which met or exceeded each measure’s minimal clinically important difference (MCID). In the full-thickness group, a statistically significant improvement was reported at the 12 month point on the VAS, SANE, VR12 physical component, ASES, and WORC measures (p<0.05 for all). MCIDs were met or exceeded on the VAS and ASES tools in 72% and 77% of participants, respectively. Revision surgery for complications was required in 8 participants (4.6%). Indications included progression of a partial thickness tear to a full thickness tear, deep vein thrombosis and adhesive capsulitis, loose mobile graft remnant in the joint, recurrent effusions, and failure to heal. In the partial thickness group, 29 participants (32.2%) required corticosteroid injections in the postoperative period for pain control, and 9 participants (10.8%) in the full-thickness group required injections. The majority of post-operative steroid injections administered in the study were done in 2 centers accounting for 76% of injections. Nine sites did not administer any steroid injections.

Thon (2019) reported on the results of a prospective case series study of 23 participants with large (n=11) or massive (n=12) full-thickness rotator cuff tears treated with Regeneten. In addition to complete rotator cuff repair, participants underwent subacromial decompression (n=19), distal clavicle excision (n=17), biceps tenodesis/tenotomy (n=12), and suprascapular nerve release (n=5). Mean time to postoperative MRI was 13 months, and the final ultrasound evaluation was 24 months. Complete healing on both measurements was reported to be 96%, with 2 treatment failures. No difference was found between the two tear groups with regard to final ASES scores (p=0.69). There were no postoperative infections or adverse events associated with the device.

Delgado and colleagues (2025) reported on a prospective, multicenter observational study that evaluated biologic augmentation with a Regeneten in individuals undergoing revision arthroscopic repair of rotator cuff retears after a prior failed repair. There were 21 individuals who were followed for a median of approximately 26 months, with tendon integrity assessed by Magnetic Resonance Imaging (MRI) at 12 months and clinical outcomes assessed up to 24 months. The study found an overall retear rate of 28.6%, which is lower than many rates reported historically for revision rotator cuff repair, and notably, half of the retears were smaller than the original tears. Clinically, individuals experienced significant improvements in pain and shoulder function, with meaningful gains in Constant Murley, American Shoulder and Elbow Surgeons (ASES), and Single Assessment Numeric Evaluation (SANE) scores and a marked reduction in Visual Analog Scale (VAS) pain scores with only one individual requiring further revision surgery. No intraoperative complications, infections, stiffness, or implant-related adverse events were reported, supporting the short-term safety of the bioinductive implant in this challenging revision setting. However, interpretation is limited by the small sample size, absence of a non-augmented control group, and observational study design, which precludes definitive conclusions regarding causality or comparative effectiveness. In addition, the cohort was relatively selective (younger individuals, mostly small-to-medium tears, limited muscle atrophy), potentially underestimating retear risk, and the follow-up period does not capture longer-term durability. Controlled comparative studies with larger, more heterogeneous populations are needed.

Genuth and Iselin (2025) reported on a retrospective single-surgeon case series that evaluated the use of Regeneten as an adjunct to standard surgical treatment for insertional Achilles tendinopathy (IAT) associated with Haglund deformity. There were 8 individuals who underwent open Achilles tendon debridement, Haglund resection, and tendon reattachment augmented with the bioinductive scaffold, with outcomes assessed clinically and by Magnetic Resonance Imaging (MRI). At a mean follow-up of approximately 10 months, AOFAS) hindfoot scores improved significantly from a preoperative mean of 62.3 to 89.6 (p<0.05) at six months. All individuals returned to full preoperative activity by a mean of nine months, and MRI demonstrated complete tendon healing in all cases by six months. No scaffold-related complications, infections, or wound-healing problems were reported, and one delayed wound issue following trauma confirmed complete scaffold resorption and durable tendon attachment at reoperation. Overall, the findings suggest that augmentation with Regeneten may enhance tendon healing and functional recovery in surgically treated IAT without increasing short-term complication risk. However, interpretation is limited by the very small sample size, single-surgeon and single-center design, absence of a control or comparator group, and short follow-up duration, which restrict generalizability and preclude causal inference. In addition, reliance on the AOFAS score, which lacks robust individual-reported outcome measures, limits assessment of individual-perceived benefit. Larger, controlled studies and longer-term follow-up are needed to determine whether Regeneten provides incremental benefit over standard surgical repair alone.

Kimmeyer and colleagues (2025) reported on a single-center case series evaluated arthroscopic posterosuperior rotator cuff repair augmented with Regeneten in 30 individuals considered at high risk for retear, including revision cases and individuals with multiple biological, radiological, and intraoperative risk factors. At 12 months, MRI demonstrated complete tendon healing in 56.7%, partial healing in 16.7%, and insufficient healing in 26.7%, with higher non-healing rates observed in revision compared with primary repairs. Despite this high-risk profile, individuals experienced significant and clinically meaningful improvements in pain, shoulder function, and range of motion, with Subject Shoulder Value (SSV), ASES, and Constant scores all exceeding minimally clinically important differences by 1 year (45.3 to 83.5 [p<0.001], 40.6 to 77.8 [p=0.002], and 36.6 to 71.7 [p<0.001], respectively). Importantly, clinical improvement was observed even in individuals with incomplete tendon healing, suggesting a potential functional benefit independent of full structural integrity. Complication rates were low, with secondary shoulder stiffness in 6.7% and no revision surgeries related to the rotator cuff repair or implant. Limitations included a non-comparative design, small sample size, short follow-up duration, and highly selected population, which restrict generalizability and preclude conclusions about comparative effectiveness versus standard repair. Larger, controlled studies with extended follow-up are needed to better define selection criteria and long-term structural benefit of Regeneten.

A case-controlled cohort study evaluated whether arthroscopically inserted Regeneten improve outcomes after revision rotator cuff repair in a particularly high-risk population, workers’ compensation individuals, with a minimum follow-up of 2 years (Lau, 2025). There were 40 individuals analyzed (n=16 with Regeneten, n=24 matched controls), matched for age and tear size. The study found no significant difference in repair integrity, with high retear rates in both groups at a median 2.3 years (50% with Regeneten vs. 38% controls; p=0.52), and no difference in Kaplan-Meier survival of the repair. Although individuals in the bioinductive group demonstrated within-group improvements over time in pain frequency, abduction strength, and forward flexion, these gains did not translate into superior outcomes compared with controls, as individual-reported and examiner-measured outcomes were similar between groups at 2 years or more. No implant-related adverse reactions were observed, supporting the safety of the device, but the findings indicate that Regeneten augmentation does not meaningfully improve long-term healing or function in revision rotator cuff repairs within this challenging cohort. Key limitations include the non-randomized, post hoc matched design, small sample size with limited statistical power, loss to follow-up, and restriction to workers’ compensation individuals, which limits generalizability to broader revision populations.

In a retrospective, propensity-matched cohort study Rab and colleagues (2025) compared primary arthroscopic repair of full-thickness supraspinatus rotator cuff tears with Regeneten compared to without augmentation in individuals considered at elevated risk for retear. There were 46 matched individuals (n=23 per group) with comparable demographic, biological, radiographic, and tear-related risk factors who were evaluated with clinical outcomes and MRI at 1 year. The study found no reduction in retear rates with Regeneten (21.7% with BCI vs. 13.0% without; p=0.72), and no significant differences in functional or individual-reported outcomes, including Constant Score, ASES, Subjective Shoulder Value, pain, or range of motion. Complication rates were similar between groups, and no clear clinical advantage of BCI augmentation was demonstrated despite targeting a high-risk population. Limitations included the retrospective design, small matched sample size, potential residual selection bias despite propensity matching, and heterogeneity in surgical techniques and concomitant procedures (for example, subscapularis repair, single- vs. double-row fixation). Follow-up was limited to one year, which may not capture longer-term differences in tendon durability, and the study may have been underpowered to detect modest differences in retear rates. Larger randomized controlled trials with longer follow-up are needed to define whether specific subgroups may benefit from Regeneten.

The results of these studies are all promising, but the methodology used limit the generalizability of this data to larger populations. Additional studies are warranted to better understand the clinical utility of Regeneten for rotator cuff repair surgery.

Relese (StimLabs^® LLC, Rosewell, GA) is a fenestrated dehydrated complete human placental membrane allograft with preserved three native placental layers (amnion, intermediate layer, and chorion) along with key extracellular matrix proteins and bioactive components. It is intended for use on acute and chronic wounds such as dermatologic wounds, DFUs, pressure ulcers, surgical wounds, traumatic wound and VSUs. Relese is regulated by the FDA under HCT/P process as human tissue for transplantation.

A retrospective, multicenter real-world audit evaluated Relese as an adjunct to standard of care for hard-to-heal lower-extremity ulcers, primarily diabetic foot and neuropathic ulcers (Freeland, 2025). There were 23 individuals with 26 chronic ulcers that had failed at least 4 weeks of standard care. In the intent-to-treat population, 54% of ulcers achieved complete closure, increasing to 78% in the per-protocol cohort, with a median time to closure of 49 days and a median of 5.5 applications. By 12 weeks, mean percentage area reduction was 56%, with 77% of wounds achieving at least 50% percentage area reduction, an early indicator of healing trajectory. Safety outcomes were consistent with expectations for a high-risk population: 30% of individuals experienced wound-related adverse events, most commonly local infection or inflammation, with no serious adverse events attributed to the product. Limitations included the retrospective, observational design, small sample size, absence of a comparator arm, and variable documentation and follow-up across sites. Wound assessments were performed in routine practice without centralized verification, and missing data were handled conservatively, which may underestimate outcomes. As a result, these findings are descriptive rather than causal, and larger prospective controlled studies are needed to confirm effectiveness, durability of healing, and comparative value versus other advanced wound therapies.

Seamguard (W.L. Gore and Associated, Flagstaff, AZ) is a synthetic product composed of polytetrafluroethylene. The device is intended for use as a prosthesis for surgical repair of soft tissue deficiencies using linear surgical staplers. The device can be used to reinforce staple lines during lung resections, abdominal and thoracic wall repairs, gastric banding, muscle flap reinforcement, rectal and vaginal prolapse, pelvic floor reconstructions, urethral sling, and diaphragmatic, femoral, incision, inguinal, lumbar, paracolostomy, scrotal and umbilical hernias. Seamguard is cleared through the FDA’s 510(k) process (K955364).

Salgado (2011) published a randomized controlled trial evaluating the use of Seamguard compared to extraluminal suturing or fibrin glue for open bariatric surgical procedures (2011). Twenty participants were assigned to each group; however, enrollment in the fibrin glue group was stopped due to serious complications, including leaks requiring surgical intervention. The authors report that no significant differences were found between the Seamguard group and the suturing group. This study was not designed or powered to be a non-inferiority study, so these findings are not particularly useful in understanding the safety and efficacy of Seamguard.

Albanopoulos (2012) published a study comparing Seamguard to staple line suturing in laparoscopic sleeve gastrectomy procedures. This study enrolled 90 participants, 48 who were assigned to the Seamguard group and 42 to the suturing group. As with the Salgado study, the authors reported no significant differences in measured outcomes. One exception to this was a 6.2% complication rate in the Seamguard group compared to no complications in the suturing group.

In 2013, Wallace published the results of a nonrandomized controlled study of 36 participants undergoing pancreatectomy with the addition of Seamguard to the stapled stump closure. This group was compared to 18 historical controls undergoing the same procedure without Seamguard. Postoperative leak rate was reported in 8% in the experimental group compared to 39% in the control group. This study is limited due to its small population, use of historical controls and other methodological issues.

Guerrier and others (2018) published the results of a retrospective review of 256 participants undergoing laparoscopic sleeve gastrectomy. Participants received treatment with staple line reinforcement with oversewing (n=28), reinforcement with Seamguard (n=115), or no staple line reinforcement (n=111). Intraoperative staple line bleeding was significantly reduced in the reinforcement group (22.3 vs. 37.8%, p=0.003). Gastric leaks were reported in 9 participants (3.52%), with no difference between any reinforcement method (2.7 vs. 2.1%, p=0.54). The authors did note that oversewing of the staple line was associated with higher incidence of stenosis, a serious complication with significant morbidity and mortality (p<0.01). The authors concluded that their study demonstrated that staple line reinforcement does not provide significant leak reduction but does reduce intraoperative staple line bleeding. However, this must be viewed in light of the increased risk of stenosis development.

In a 5-year, single-center retrospective case-control study, Vitiello (2024) analyzed 626 individuals undergoing laparoscopic sleeve gastrectomy, comparing 450 procedures reinforced with GORE SeamGuard to 176 procedures without any staple line reinforcement. The no-reinforcement group experienced a 2.26% rate of leaks or bleeding, whereas the GORE SeamGuard group recorded 0% staple line complications (p<0.05). In addition, 13 external cases of staple line complications treated at the same center all involved laparoscopic sleeve gastrectomy performed without reinforcement.

Suprathel is a synthetic copolymer consisting mainly of DL-lactide (>70%), trimethylenecarbonate, and e-caprolactone and was cleared under the FDA’s HTC/P process.

An RCT involving 22 participants with burn injuries treated with STSG was reported by Schwarze in 2007. Each donor site was randomly selected and was treated with Suprathel or Jelonet. There was no significant difference between the two materials tested regarding healing time and re-epithelization, but a significantly lower pain score was reported for the participants treated with Suprathel (p=0.0002). The same group reported the results of another RCT study involving 30 participants with burn injuries (Schwarze, 2008). Wounds from each participant were randomly selected and partly treated with Omniderm and partly treated with Suprathel. There was no significant difference between the two products regarding healing time and re-epithelization. There was a significantly lower pain score for participants treated with Suprathel (p=0.0072).

Rashaan (2017) reported the use of Suprathel in a population of 21 children with partial thickness burns. The authors reported a median reepithelialization time of 13 days (range 7-29), and 3 participants required treatment with split skin grafts. There were 7 (33%) participants with wound colonization before application of Suprathel, which increased to 12 (57%) during treatment. Only 1 participant developed a wound infection.

Nischwitz (2021) published the results of a prospective case series study involving 22 participants with chronic leg wounds treated with Suprathel and followed for 8 weeks. Out of the original participant pool, 19 participants completed the trial. No significant difference in average wound size was reported between baseline and 4 weeks (p=0.074). The wound size changed significantly between 4 and 8 weeks (p=0.031). Overall, the average wound size between baseline and 8 weeks decreased significantly (p=0.006). One wound was reported as healed at 4 weeks (5.3%) and two at 8 weeks (15.79%). When stratified by wound age < 12 months and > 12 months, the overall wound size had a significant reduction for both old and young wounds (p=0.002 and 0.03, respectively). Similar findings were reported for both diabetic (p=0.014) and non-diabetic wounds (p=0.028). No adverse event associated to the intervention had occurred in the study period.

Heitzmann (2023) published a prospective intra-individual clinical study in 23 individuals with burn injuries aged 18 to 85 years that compared Suprathel and Jelonet in the treatment of deep dermal burns after enzymatic debridement. Individuals had sustained partial-thickness-to-deep-thickness flame, scald, or contact burns of their hands or feet, with more than 0.3% of TBSA. The outcomes measured were wound healing, participant comfort, and pain. Wounds were divided in 2 areas, one treated with Suprathel and the other with Jelonet. Suprathel was placed on the wounds and gradually cut back as the re-epithelialization progressed until the dressings were completely detached. The Jelonet dressings were changed every 2 days. Wound closure was documented with a mean of 18.44 days for wounds treated with Suprathel, and 18.81 days with Jelonet (p=0.58), with no significant difference in final wound healing time, only 1 individual had a second debridement followed by skin grafting. Less pain was reported during the dressing changes with Suprathel compared to Jelonet on day 2 (p<0.001) and day 4 (p<0.0). Additionally, the wound areas treated with Suprathel showed less exudation and bleeding. The authors concluded that both dressings achieve safe and rapid healing after the enzymatic debridement of deep dermal burns of the hands and feet. However, the results of this study require further investigation in the form of more robust and well-designed trials.

Karlsson (2023) reported a retrospective, single center study of 58 pediatric individuals with burns comparing Suprathel (n=30) to Mepilex^® Ag (n=28). The outcomes measured were healing time, burn wound infection, need for operations and number of dressing changes. The results showed that healing within 14 days occurred in 17 Suprathel group participants and 15 in Mepilex Ag group participants. A total of 10 participants from each group received antibiotics for suspected burn wound infection, and 2 from each group had skin grafting. The median number of dressing changes was 4 in each group. The authors concluded that the results were similar with both Suprathel and Mepilex Ag dressings. However, they noted that these results to be interpreted with caution due to the retrospective study design, and the fact that burns were significantly larger in the Mepilex Ag group.

In a randomized controlled trial involving 40 individuals undergoing split-thickness skin graft procedures for non-melanoma skin cancer, donor sites were dressed in either Suprathel or Hypafix adhesive tape (Cussons, 2024). Of the original 40 participants, only 16/20 (80%) of participants in the Suprathel group and 14/20 (70%) in the Hypafix group completed the trial, resulting in a loss to follow-up of 70% . The results showed no statistically significant difference in mean time to healing (31.7 vs. 27.3 days, p=0.182), pain, itch, or final scar outcomes at 13 weeks, as measured by the Patient and Observer Scar Assessment Scale. Neither group had postoperative infections. Although these findings suggest that Suprathel may not provide clear advantages for older individuals with small-area donor sites, the trial’s methodological limitations prevent further conclusions. Further high-quality research with larger populations is warranted.

In a retrospective, single-center study by Delgado-Miguel (2024) involving 378 individuals under 18 years old, three skin substitutes (Suprathel [n=92], EZ-derm [n=179], and Biobrane [n=107]) were compared for short- and long-term outcomes in pediatric partial-thickness burns. Although the groups had similar demographics and burn characteristics, the Suprathel group exhibited a significantly shorter median hospital stay (p<0.01), lower escharectomy and grafting rates (p=0.018), and fewer long-term reoperations (p=0.031). No differences in long-term complications were observed between groups. While these findings suggest Suprathel may offer distinct advantages, the single-center, retrospective study design may limit generalizability. Further high-quality, multicenter research is warranted.

Van de Warenburg (2025) published the results of a single-center 10-year retrospective cohort study that evaluated the usability and clinical effectiveness of Suprathel for the treatment of pediatric partial-thickness burns. The study included 92 children (mean age 4 years) with superficial, deep, or mixed partial-thickness burns (predominantly scald injuries). The median time to wound healing was 12.5 days, consistent across age groups, with low rates of progression to split-thickness skin grafting (5%). The authors reported that Suprathel demonstrated good adherence to the wound bed, required relatively few dressing changes, and was associated with no increase in wound infection rates, even when premature detachment occurred. Outcomes were not significantly influenced by timing of application, wound location, wound bed preparation, or use over joints, supporting its versatility in mobile anatomical areas such as the hands. Most scars observed at follow-up were atrophic, with hypertrophic scarring occurring in a minority and associated with longer healing times and older age. Limitations included the retrospective, non-comparative design, single-center setting, and reliance on chart-based documentation, which constrained objective assessment of pain and quality-of-life outcomes. The absence of a control group and standardized scar assessment tools limits conclusions regarding superiority over alternative dressings, and prospective randomized trials are needed to confirm comparative effectiveness and long-term scar outcomes.

SURGISIS Biodesign Tissue Graft (Cook Biotech Inc., West Lafayette, IN), is a product composed of decellularized intestinal porcine mucosa. SURGISIS is intended to be implanted to reinforce soft tissues where weakness exists, and is purported to minimize tissue attachment to the device in cases of direct contact with viscera. Several forms of Surgisis/Biodesign are available, including Anal Fistula Plug (AFP), 4-Layer Tissue Graft, Dural Graft, Hernia Graft, and others. Cook Medical, the manufacturer of this product changed the name of Surgisis products to Biodesign in 2008. However, the medical literature continues to refer to these products by their former name. Indications for use include the repair of a hernia or body wall defect. SURGISIS is cleared under the FDA’s 510(k) process (K073391).

At this time, there are a large number of case series studies published on the use of the Surgisis anal fistula plug (AFP) (Champagne, 2006; Cintron, 2013; Ellis, 2010; Ky, 2008; O’Connor, 2006; Schwandner, 2009; Thekkinkattil, 2009). The vast majority of these involve very small sample sizes and short follow-up times. The uncontrolled nature of these studies minimizes the scientific value of this data.

Several RCTs are currently available addressing the use of Surgisis for the treatment of anal fistulae. The first study, reported by Ortiz et al., involved 43 participants randomized to receive either endorectal advancement flap surgery or insertion of an anal fistula plug (2009). The drop-out rate was greater than 20% for each group. The authors reported that the relative risk for recurrence was 6.4 for those who received the plug intervention during the 1-year follow-up. Additionally, of the 16 who had previous fistula surgery, 9 had recurrence and 8 of these were from the plug group. Overall, the authors concluded that the anal fistula plug was associated with a low rate of fistula healing, especially in individuals with a history of fistula surgery. The second study included 60 participants with perianal fistulas who were randomly assigned to receive treatment with Surgisis (n=31) or a mucosal advancement flap (n=29) (van Koperen, 2011). Both participants and investigators were blinded to group assignment. At a follow-up of 11 months, the recurrence rates were 71% (n=22) in the Surgisis group compared to 52% (n=15) in the mucosal advancement flap group, which was not significantly different. Additionally, no significant differences were reported with regard to postoperative pain, pre- and postoperative incontinence scores, soiling, and quality of life. Senéjoux (2016) reported the results of an open-label, randomized controlled trial comparing seton removal alone (n=52) compared to Surgisis (n=54) in 106 participants with Crohn’s disease and at least one ano-perineal fistula tract drained for more than 1 month. The authors reported that fistula closure at week 12 was achieved in 31.5% of participants in the Surgisis group compared to 23.1 % in the control group (p=0.19). No interaction in treatment effect was found when data was analyzed to control for case complexity (p=0.45). Adverse events at week 12 were reported in 17 participants in the Surgisis group compared to 8 controls (p=0.07). The authors concluded that the use of Surgisis was not more effective than seton removal alone. In 2017, Bondi and others published the results of an RCT involving 94 participants with cryptogenic trans-sphincteric anal fistulas assigned to treatment with either Surgisis (n=48) or mucosal advancement flap (n=46). The authors reported that the recurrence rate at 12 months was 66% in the Surgisis group and 38% in the flap group (p=0.006). While anal pain was reduced after operation in both groups, anal incontinence did not change in the follow-up period for either. No differences between the groups were reported with regard to pain, incontinence, or quality of life. The authors concluded that there was a considerably higher recurrence rate after the anal fistula plug procedure than following advancement flap repair.

Several studies have reported on the results from nonrandomized controlled, retrospective trials. Ellis described the results of a study that involved 95 control participants who had trans-sphincteric or rectovaginal fistulas repaired via advancement flap repair (2007). The experimental group included only 18 participants who received treatment with Surgisis. The results indicated a significant benefit to the Surgisis procedure. Another study included 80 participants who received treatment with either anal fistula plug or endorectal advancement flap (Christoforidis, 2009). The results of this trial demonstrated that treatment success was close to over twice as likely with the flap procedure compared to treatment with a fistula plug after a mean follow-up period of 56 months. Chung (2009) reported on the results of a retrospective study that involved 245 participants who underwent anal fistula repair surgery with either Surgisis (n=27), fibrin glue (n=23), Seton drain (n=86), or an endorectal advancement flap procedure (n=96). The results indicate that the rate of success was similar between the Surgisis group and the endorectal advancement flap group. Hyman and others conducted a study that involved 245 participants who received one of seven procedures, including the Surgisis plug (n=43), endorectal advancement flap (n=4), Seton drain (n=34), fibrin glue (n=5), fistulotomy (n=156), and other unspecified procedures (n=3) (2009). In contrast to the findings of the Chung study, the authors reported that the Surgisis plug demonstrated the lowest success rate, with only 32% healed at 3 months compared to 87% for the fistulotomy group. In 2014, Blom reported on a case series study involving 126 participants with anal fistulae treated in four different hospitals. After a median of 13 months, 30 (24%) of the fistulae had closed with no discomfort or secretion reported. The outcomes in the four hospitals varied from 13% to 33% with similar numbers of participants in each hospital. A success rate of 12% was observed for participants with anterior fistula compared with 32% for those with posterior tracks [HR for successful healing, 2.98] and 41% for those with a lateral internal opening (HR, 3.76). The authors concluded that their study demonstrated low success rates after the first plug-insertion procedure and that anterior fistulae were much less likely to heal compared with fistulae in other locations.

Jayne (2019) reported on the results of an RCT involving 304 participants with anal fistula treated with either Surgisis or ‘surgeon’s choice” (e.g., fistulotomy, cutting seton, advancement flap or ligation of intersphincteric fistula tract [LIFT] procedure). The authors reported clinical evidence of fistula healing in 66 participants (54%) in the Surgisis group compared to 66 participants (55%) in the control group at 12 months. Furthermore, MRI data showed fistula healing in 54 participants (49%) in the Surgisis group compared to 63 participants in the control group. Overall, 12-month clinical healing rates were 55% in the Surgisis group compared to 64%, 75%, 53%, and 42% in the cutting seton, fistulotomy, advancement flap and LIFT procedure groups, respectively. The authors commented that overall, there was no significant difference between the use of Surgisis and other procedures.

A meta-analysis was reported by Lin (2019) that included 11 studies comparing the use of Surgisis to rectal advancement flap (RAF) for anal fistula repair in 810 participants. They reported that the pooled analysis indicated that there was no significant difference between the use of Surgisis and RAF in terms of healing rate, recurrence rate and incidence of fistula complications. However, the pooled results of the 4 RCTS and 1 series study with long-term follow-up revealed that the RAF group had a significantly higher healing rate (OR, 0.32; p=0.01) and lower recurrence rate (OR, 4.45; p=0.009) than the AFP group. These results appear to support the use of RAF over Surgisis for anal fistula repair.

Jayne (2021) published the results of an open-label RCT involving 304 participants undergoing anal fistula repair. Participants were assigned to treatment with either Surgisis anal fistula plug (n=152) or surgeon’s preference (advancement flap, cutting seton, fistulotomy, Ligation of the Intersphincteric Fistula Tract procedure, n=152). At 12 months, the authors reported no significant differences between groups with regard to rate of clinical healing (54% in the Surgisis group compared to 55% in the surgeon’s preference group, p=0.83). Similar findings were reported with regard to MRI-confirmed healing (49 vs. 57%, respectively, no p-value provided). Additionally, no significant differences between groups were reported at 12 months on the St. Mark’s incontinence score (p=0.48), complication rate (23% vs. 20%, p=0.6), or rate of reintervention (23%. vs. 22%, p=0.96). These results indicate that the use of Surgisis is equivalent to other surgical approaches to anal fistula repair.

Unlike the anal fistula plug product discussed above, Surgisis Gold is provided in larger sheets. Sarr and others (2014) conducted an RCT involving 380 participants with body mass index (BMI) ≥ 35 kg/m² scheduled to undergo open Roux-en-Y gastric bypass surgery. Participants were randomized to receive standard suture closure alone or Surgisis Gold as a reinforcing adjunct. The authors reported that complications were more common in the Surgisis Gold group with significantly more wound events and seroma formation compared with the suture closure alone group. At final follow-up of 2 years post-procedure, 32 of 185 (17%) participants in the Surgisis Gold group and 38 of 195 (20%) in the control group developed an incisional hernia (p=0.6). Based on these findings, it would seem that the use of Surgisis Gold is not warranted, and further investigation is needed regarding the safety and efficacy of this product.

Korwar (2019) retrospectively reported the treatment of PEH in 154 consecutive participants who underwent standardized laparoscopic suture repair of the hiatus with Surgisis reinforcement. Follow-up barium swallow was performed in 122 participants (79.22%). Symptomatic recurrence was noted in 25 participants (28.73%), and recurrence on barium swallow was noted in 25 participants (20.4%). Both symptomatic and barium swallow recurrence were reported in 10 participants (12.98%). The reoperation rate was 3.25%. The authors concluded that the use of Surgisis Biodesign for PEH repair is safe. They further commented that there was a high recurrence rate in long-term follow-up, but that the majority of recurrences are small, asymptomatic, and the reoperation rate is very low.

Surgisis Biodesign was also described in the repair of pelvic floor reconstruction following levator abdominoperitoneal excision of the rectum (Thomas, 2019). This retrospective case series study involved 100 participants, for whom 1-, 2-, and 5-year mortality rates were 3, 8 and 12%, respectively. The authors reported that 33 perineal wounds had not healed by 1 month, but no mesh was infected, and no mesh needed to be removed. Only 1 participant developed a symptomatic perineal hernia requiring repair. On review of imaging, an additional 7 asymptomatic perineal hernias were detected. At 4 years the cumulative radiologically detected perineal hernia rate was 8%.

Ravo (2019) described the results of a trial of 104 participants with inguinal hernia repair with a continuous suture of transversalis to transversalis fascia repair reinforced with Surgisis. Long term follow-up was scheduled at 1 week, 1 month, 1 year, 3 years, 7 years, and 10 years, and was achieved in 100%, 100%, 99%, 93%, 89% and 85% of the participants, respectively. The authors reported a recurrence rate of 1.9% (2 participants, one at 1 week in a participant with bilateral IH and one at 7 years). The mean recovery time was 1.2 days (range 1-5 days). Mortality was 0(0%).

In 2021 Alexandridis and others reported the results of a retrospective case series involving 155 participants with pelvic organ prolapse treated with Surgisis. A total of 138 (89.0%) participants completed the 3-month clinical visit, with 12 of the 17 participants not seen being contacted by telephone and included in the analysis of complications. At 3 months, 22 participants (15.9%) had Pelvic Organ Prolapse Qualification system (POP0Q) stage ≥ 2. The overall recurrence rate for Surgisis-treated defects was 11.6%. Reoperations were reported in 13 (8.4%) participants due to prolapse. Additionally, 7 participants experienced prolapse-related symptoms postoperatively, but had no record of reoperation. This data represents a subjective failure rate of 12.9%. Perioperative and postoperative complications occurred in 56% of participants. The most common complications were urinary (n=28) and pain (n=18). Major complications were reported in 8 participants (5.3%). Persistent complications at 3 months were reported in 28% of participants, including vaginal deformations, dyspareunia, stress urinary incontinence, urge urinary incontinence, and pain. Statistical analysis for recurrence identified a significant effect only for previous prolapse surgery at the same compartment as the Surgisis application (p=0.028). Other significant predictors for complications included lower age (p=0.034), smoking (p=0.022) and longer duration of surgery (p=0.003). The authors concluded, “The relatively high recurrence rates do not suggest a clear benefit from SIS graft use.”

Talymed (Marine Polymer Technologies, Inc., Danvers, MA) is a synthetic sterile wound matrix product composed of poly-N-acetyl glucosamine (pGIcNAc) isolated from microalgae. Talymed is indicated for the management of wounds including diabetic ulcers, venous ulcers, pressure wound, ulcers caused by mixed vascular etiologies, full thickness and partial thickness wounds, second degree burns, surgical wounds-donor sites/grafts, post-Moh’s surgery, post-laser surgery, and other bleeding surface wounds, abrasions, lacerations, traumatic wounds healing by secondary intention, chronic vascular ulcers, and dehisced surgical wounds. Talymed and is cleared under the FDA’s 510(k) process (K102002).

At this time, only a single RCT is available addressing the use of Talymed (Kelechi, 2011). In this reviewer-blinded trial, 82 participants with VSUs were randomized to receive either standard care (n=20) or to 1 of 3 groups that received standard treatment combined with different treatment frequencies with Talymed: (1) applied only once, (2) applied once every other week, or (3) applied once every third week. Seven participants were lost to follow-up, 5 from the 1 application group and 2 from the every 3-week group. Additionally, another 4 participants were withdrawn from the study, 3 from the 1 application group and 1 from the every 3 weeks group. This left 62 participants in the experimental group and 20 in the control group. At 20 weeks, the authors report that 45.0% (n=9 of 20) of participants receiving standard care alone had complete healing, while 45.0% (n=9 of 20), 86.4% (n=19 of 22), and 65.0% (n=13 of 20) of participants receiving Talymed only once, every other week, and every 3 weeks, respectively, had complete healing. This single study is insufficient to allow proper evaluation of the safety and efficacy of Talymed.

TAPESTRYRC (Zimmer Biomet, Warasaw, IN) is a composite implant composed of poly DL-lactide (PDLLA) and non-crosslinked bovine collagen. It is designed to function as a non-constricting, protective layer between the tendon and surrounding tissues. TAPESTRY is indicated for managing and protecting tendon injuries where there is no significant loss of tendon tissue. The implant was cleared by the FDA through the 510(k) process (K201572).

TIGR Matrix Surgical Mesh (Novus Scientific AB, Paradise Valley, AZ) is a synthetic absorbable polymer made of lactide, glycolide, and trimethylene carbonate. It is a surgical mesh for soft tissue repair, including hernia repair. e TIGR is indicated for use in the reinforcement of soft tissue, where weakness exists in individuals undergoing plastic and reconstructive surgery, or for use in procedures involving soft tissue repair, such as for the repair of hernias or other fascial defects that require the addition of a reinforcing material to obtain the desired surgical result. TIGR is cleared under the FDA’s 510(k) process (K191749).

Hansson (2020) reported a prospective, single-blind, clinical trial of 24 individuals (n=48 breasts) with bilateral mastectomy and immediate breast reconstruction. Participants were randomized to receive biological Veritas Collagen Matrix on one side and synthetic TIGR Matrix Surgical Mesh on the other side. During the 12‐month follow-up the 2 meshes yielded significantly different esthetic results and asymmetry. Due to this finding, recruitment to the study was terminated. No participants were lost to follow‐up at 12 months and 24 breasts in each group had an analysis of complications at 1 year postoperatively. All mastectomies were nipple‐sparing. The most common complication was seroma formation (38% in the Veritas group compared to 3.8% in the TIGR group, p=0.011). All TIGR meshes were completely integrated during the exchange to a permanent implant, the Veritas meshes were poorly integrated in the participants with seroma. The frequency of total implant loss (stage I + II) in the Veritas mesh group was 8.5% compared to 2% in the TIRG group (p=0.083). There were 2 implant losses and reoperations which were suspected to have been caused by penetration due to thin mastectomy flaps in the same participant. The authors concluded that there is a higher risk for complications, particularly seroma and implant loss, with Veritas compared to TIGR. However, more robust studies with larger sample sizes are needed to confirm these finding with a high degree of certainty.

Paganini (2022) reported the results of a blinded, randomized, prospective trial that compared participant-reported outcomes after immediate breast reconstruction with TIGR mesh and Veritas mesh using the compared materials in the same participant. Twenty-four participants were recruited and all had a prophylactic bilateral mastectomy and a dual-plane reconstruction. There were no capsular contractures in either group at 5 years. No significant differences between groups were reported with regard to reported outcomes. The authors stated that the two products resulted in different types of reconstructed breasts, but concluded that the study was limited by its small sample size, varying surgical techniques, and variability in the meshes used, therefore more studies are needed to generalize the findings.

A retrospective single-center study reported early clinical outcomes of immediate implant-based breast reconstruction using TIGR^® Matrix in 76 individuals (100 breasts) undergoing direct-to-implant reconstruction following mastectomy (Caddia, 2025). Over a mean follow-up of approximately 17 months, the authors observed an overall grade III complication rate of 21%, including infections (10%), seromas (2%), hematomas, and wound dehiscence, with implant loss occurring in 10% of reconstructions. These complication rates were considered comparable to or lower than those reported for ADM and within the expected range for synthetic meshes in real-world practice. No individual- or surgery-related variables were identified as significant predictors of complications, although an inverse association was noted between mastectomy specimen weight and complication risk, with smaller mastectomies paradoxically showing higher complication rates. A majority of reconstructions required secondary lipofilling to optimize cosmetic outcomes, particularly in prepectoral cases, highlighting the importance of adjunctive fat grafting in achieving satisfactory aesthetics. Limitations include the retrospective design, absence of a direct control group, single-center experience, and heterogeneity in indications, surgical techniques, and adjuvant therapies. Additionally, reliance on literature-based comparisons rather than internal controls, limited standardized aesthetic or individual-reported outcome measures, and relatively short follow-up for long-term implant-related outcomes constrain generalizability. Prospective randomized studies are needed to better define comparative efficacy, durability, and individual-centered outcomes of TIGR Matrix in breast reconstruction.

Shauly (2025) reported on a retrospective, multi-institutional study that evaluated early outcomes of TIGR Matrix, a long-term resorbable synthetic mesh, used for immediate direct-to-implant (DTI) breast reconstruction following mastectomy. The analysis included 71 individuals (109 breasts) with at least short-term follow-up and encompassed nipple-sparing, skin-sparing, and Goldilocks mastectomies, with the majority of implants placed in the prepectoral plane. Early postoperative outcomes showed an acceptable complication profile, with major complications including hematoma (5.5%), seroma (2.8%), infection (1.8%), and implant explantation (2.8%), and a reoperation rate of 10.1%. Minor complications such as delayed wound healing or eschar occurred in 17.4% of breasts. No thromboembolic events were reported, and overall major complication rates were comparable to or lower than those reported for ADMs in similar direct to implant (DTI) cohorts. Limitations include retrospective design, small sample size, short follow-up period, and lack of a comparator group, which precludes conclusions about superiority or equivalence relative to ADM. Additionally, variability in surgeon technique, mastectomy type, and risk factors across institutions may confound outcomes. The study does not address long-term endpoints such as capsular contracture, aesthetic durability, or individual satisfaction reports. Larger, prospective comparative studies with longer follow-up are needed to define the long-term safety, effectiveness, and optimal selection for TIGR Matrix in breast reconstruction.

TUTOMESH(RTI Biologics, Inc., Alachua, FL) is a bovine pericardium surgical mesh processed with the Tutoplastsolvent dehydration process followed by gamma irradiation. TUTOMESH is comprised of collagenous connective tissue with three-dimensional intertwined fibers. Tutomesh is indicated for use in general and plastic surgery applications. These products are intended for repair of pericardial structures and for use as a prosthesis for the surgical repair of soft tissue deficiencies which include: gastric banding, muscle flap reinforcement, rectal and vaginal prolapse, reconstruction of the pelvic floor, and hernias (including diaphragmatic, femoral, incisional, inguinal, lumbar, paracolostomy, scrotal, and umbilical hernias). TUTOMESH is cleared under the FDA’s 510(k) process (K081538).

A retrospective review with 41 participants who underwent 52 breast reconstructions using ADMs was reported by Paprottka (2017). Participants received treatment with either EpiFlex (not available in the US, n=15), Strattice (n=21), or Tutomesh (n=16). Follow-up was 36 months (range 12-54). Overall complication rate was 17%, and 7% for the EpiFlex group, 14% for the Strattice group, and 31% for the Tutomesh group. Capsular contracture occurred in 6%, more frequently in this study compared to the current literature. The authors recommended the use of human derived grafting materials (EpiFlex) over those from porcine of bovine sources.

Eichler (2017) published a retrospective, nonrandomized comparative trial involving 54 participants undergoing breast reconstruction procedures using either SurgiMend (n=18) or Tutomesh (n=27) (Eichler, 2017). No difference in complications rates was noted, consistent with other previous reports.

Tutopatcha product made from bovine pericardium and indicated for implantation to repair, reinforce and/or supplement soft tissue in general and plastic surgery applications. Tutopatch is cleared under the FDA’s 510(k) process (K091142).

Teixidor-Rodríguez (2025) reported the results of a single-center pilot cohort study comparing a unspecified human acellular dermal matrix with Tutopatch for duraplasty in adult Chiari malformation surgery following posterior fossa decompression. There were 2 groups, with 19 individuals in each. Each group underwent surgery by the same senior neurosurgeon, with the hADM cohort followed prospectively and the Tutopatch cohort assessed retrospectively. Baseline clinical characteristics, symptom profiles, tonsillar descent, and postoperative clinical improvement were broadly comparable between groups. However, postoperative complications occurred exclusively in the Tutopatch group (7/19, 37%), including aseptic meningitis and pseudomeningocele, with 2 individuals requiring reoperation, whereas no complications, CSF leaks, meningitis, or reoperations were observed in the acellular dermal matrix group. The acellular dermal matrix group also required significantly fewer dural sealants, suggesting a more reliable watertight closure. Limitations included the small sample size, non-randomized design, age imbalance between groups, and different follow-up durations, as well as the single-surgeon, single-center experience, which restrict generalizability. Larger multicenter randomized trials with longer follow-up are needed to confirm superiority and assess long-term durability.

Vascu-Guard is a decellularized product derived from bovine pericardium cleared under the FDA’s 510(k) process. Please see the section for Gore^® Acuseal Cardiovascular Patch above.

Veritas is an implantable surgical patch comprised of decellularized bovine pericardium, it is purported to minimize tissue attachment to the device in cases of direct contact with the viscera. Veritas is intended for use as an implant for the surgical repair of soft tissue deficiencies; this includes but is not limited to the following: buttressing and reinforcing staple lines during lung resection, and other incision and excision of the lung and bronchus, reinforcement of the gastric staple line during the bariatric surgical procedures, and gastric banding, abdominal and thoracic wall repair, muscle flap reinforcement, rectal prolapse excluding rectocele, reconstruction of the pelvic floor excluding transvaginal organ prolapse repair, and repair of hernia. Veritas is cleared under the FDA’s 510(k) process (K06295).

Guerette (2009) published an RCT of 94 participants assigned to treatment with either anterior colporrhaphy alone compared to colporrhaphy reinforced with Veritas bovine pericardium graft. This study had significant loss to follow-up, with only 72 of 94 (76.6%) participants at the 1-year time point and 59 of 92 (64.1%) at the completion of the study at 2 years. The authors report no significant differences between groups.

Quah (2019) published the results of a retrospective, non-randomized controlled trial involving 215 participants undergoing mastectomy and implant-based reconstruction procedures with either Veritas (n=36) or TiLOOP^® Bra (n=179), a product not currently approved for use in the U.S. In the Veritas group, 22 participants underwent unilateral procedures and 7 underwent bilateral procedures. In the TiLOOP group 61 participants underwent unilateral procedures and 59 participants underwent bilateral procedures. The authors reported that the Veritas group had a higher rate of postoperative complications when compared with the TiLOOP group (54% vs. 14%, respectively; p<0.01). This included higher rates of seroma (51.4% vs. 1.7%, p<0.01), nonintegration of mesh (51.4% vs. 1.6%, p<0.01), implant rotation (16.2% vs. 1.6%, p<0.01), infection (18.9% vs. 2.1%, p<0.01), and wound breakdown (10.8% vs. 0.5%, p<0.01). Additionally, when compared to the TiLOOP group, the Veritas group also had a higher rate of major interventions (35.1% vs. 7.8%, p<0.01), minor interventions (18.9% vs. 2.2%, p<0.01), implant loss (8.1 vs. 1.7%, p=0.05), and unplanned return to theater (27% vs. 6.1%, p<0.01). The results of this trial indicate that Veritas, at least when compared to TiLOOP Bra, results in significantly poorer outcomes.

VICRYL Mesh (polyglactin 910) Mesh (Ethicon, Inc., Summerville, NJ) is a synthetic absorbable sterile copolymer made from glycolide and L-lactide. VICRYL may be used wherever temporary wound or organ support is required (kidney, liver, spleen), and may be cut to the shape or size desired for each specific application. VICRYL mesh was approved via the FDA’s 510(k) process in 2019 (K191373).

Messer (2025) reported on a large retrospective multicenter study evaluated outcomes of abdominal wall closure using fascial bridging with Vicryl mesh in non-trauma laparotomy individuals when primary fascial closure was not feasible. Among 202 individuals treated for a median follow-up 47 months. The cohort was characterized as a complex surgical population, with most cases involving contaminated or dirty fields, bowel resection, multiple reoperations, and significant comorbidity burden. Over at least 6 months of follow-up, enterocutaneous or enteroatmospheric fistulas occurred in 8.4% of individuals, and no interventions for small bowel obstruction were required within the period when the mesh was present, suggesting that Vicryl mesh did not confer excess bowel-related risk compared with other closure strategies reported in similarly ill populations. Wound morbidity was high including surgical site infection (48.5%), wound dehiscence (27.2%), and soft-tissue necrosis (9.9%). These complications were largely attributed to the severity of underlying disease, contamination, and repeated operations rather than the mesh itself. Despite frequent wound dehiscence, bowel evisceration was uncommon (2%). Limitations include a retrospective, single-arm design, absence of a comparator group, and performance in a high-volume tertiary center, which may limit generalizability. There was a lack of data on mesh size or extent of fascial bridging. The study could not definitively attribute complications to Vicryl mesh versus individual or operative factors.

Xelma consists of amelogenin proteins purified from porcine teeth, propylene glycol alginate (PGA), and water. It has not yet received marketing approval or clearance by the FDA. Amelogenin is a cell adhesion protein, and when suspended in a gelatinous matrix has been proposed to promote cellular growth. The use of Xelma was reported in a single-blind randomized trial involving 123 participants with VSUs (Vowden, 2006). Participants were assigned to receive treatment with either Xelma plus compression therapy (n=62) compared to a mixture of PGA and water plus compression therapy (n=61) and were followed for 12 weeks. The authors of this study state that Xelma outperformed the control group in multiple factors, including percentage of wound size reduction. However, no statistical analysis is presented to support these claims. No data on complication rates was provided.

XenMatrix (C.R. Bard, Warwick, RI) is an acellular, sterile, non-pyrogenic, dermal collagen product of bovine origin. XenMatix is intended for implantation to reinforce soft tissue where weakness exists and for surgical repair of damaged or ruptured soft tissue, including: abdominal plastic and reconstructive surgery; muscle flap reinforcement; hernia repair including abdominal, inguinal, femoral, diaphragmatic, scrotal, umbilical, and incisional hernias. The product is cleared through the FDA’s 510(k) process (K140501).

Ilahi (2023) reported the results of a prospective case series study involving 75 participants undergoing ventral/incisional midline hernia repair using XenMatrix. The authors reported on surgical site occurrence in the first 45 days post-implantation and length of stay, return to work, hernia recurrence, reoperation, quality of life, and surgical site occurrence at 1, 3, 6, 12, 18, and 24 months. A total of 16 participants (21%) did not complete the study, resulting in complete data for 59 participants (79%). Overall, hernia recurrence was reported to be 5.8%. Device-related adverse events occurred in 4.0% of cases, and reoperation in 10.7%. Only one case of mesh infection was reported (1.3%) and no graft removal was needed. Surgical site occurrence requiring intervention within 45 days post-implantation was reported in 14.7% of participants, and 20.0% > 45 days post-implantation. Surgical complications were evaluated according to the Clavien-Dindo system, with very few grade IVa, IVb, and V hernia-related complications (3%). Complications judged to be grade IIIa or IIIb occurred 37% of participants. The most common hernia-related complications seroma (n=14), bowel obstruction (n=9), pain (n=8), Ileus (n =4), incisional cellulitis (n=4), and surgical site infections (n=4). This study is impaired by several factors, including low power, lack of blinding and comparison groups, and others. Further, the significant loss of complete data makes these results difficult to interpret.

Other studies involving the use of XenMatrix are discussed elsewhere in this document for abdominal wall defect repair (Huntington, 2016; Rosen 2013). Those results are not generalizable to a wider population.

Xcellistem (StemSys LLC, Sunrise, FL) is a multi-tissue extracellular matrix powder derived from decellularized xenogeneic or allogeneic tissues. It is intended for use on surgical wounds, trauma wounds, tunneled/undermined wounds, partial and full-thickness wounds, pressure, DFUs, VSUs, and second-degree burns. Xcellistem is cleared through the FDA’s 510(k) process (K172593).

Irfan (2025) reported on a retrospective case series that examined the feasibility and early outcomes of XcelliStem as an adjunct to standard wound care for severe ballistic and blast-related injuries treated under extreme resource constraints in Gaza. There were 15 individuals, predominantly young males with high-energy trauma and frequent exposure of bone or tendon, who received Xcellistem powder following serial surgical debridement, often in combination with topical vancomycin. Granulation tissue developed in 12 of 15 individuals within 7 days, and 13 wounds progressed to definitive closure via skin grafting, flap coverage, or secondary intention within weeks, despite contamination, malnutrition, and limited access to negative-pressure wound therapy. No adverse reactions attributable to the Xcellistem were reported, and clinicians observed consistent wound-bed stabilization and readiness for closure across diverse injury patterns. Limitations include a small sample size, retrospective and uncontrolled design, heterogeneity of injuries and adjunctive treatments, and short, variable follow-up, which preclude causal inference or comparative effectiveness conclusions. Outcomes likely reflect the combined effects of aggressive debridement, antibiotics, and natural healing in addition to XcelliStem use, and longer-term functional results were not assessed. Prospective comparative studies are needed.

Several nationally recognized organizations have published recommendations or statements addressing the use of soft tissue grafting products for a variety of conditions.

The American Diabetes Association’s (ADA) published the following recommendation in their Standards of Care in Diabetes-2026:

12.32 For chronic diabetic foot ulcers that have failed to heal with optimal standard care alone, adjunctive treatment with randomized controlled trial- proven advanced agents should be considered (e.g., negative-pressure wound therapy, several skin substitutes, or topical oxygen therapy). A

They follow that statement with the following text, which is supportive of an evidence-based approach to the use of skin substitute products based on their scientific and clinical merits:

If DFUs fail to heal despite appropriate standard or surgical wound care, adjunctive advanced therapies should be instituted and are best managed in an interprofessional manner. Those products with grade A evidence to support their efficacy should be considered over those with less robust or no evidence at all. FDA-approved products for DFUs include living, bioengineered skin substitutes like Apligraf and Dermagraft, along with growth factor products like becaplermin. Once healed, all individuals should be enrolled in a formal comprehensive prevention program focused on reducing the incidence of recurrent ulcerations and subsequent amputations (122,133,169). These principles are outlined in the above section, foot care education for people with diabetes.

Allogeneic: A product derived from humans, other than the individual being treated.

Autologous: A product derived from the individual’s own body or body products.

Equine-derived decellularized collagen products (e.g., OrthADAPT and Unite): This is a type of product derived from purified tissues which are derived from horses. It has been proposed that this type of technology may be used for the repair and reinforcement of soft tissues such as tendons and ligaments, as well as the treatment of skin wounds.

Hernia meshes of non-biologic origin: These products are either synthetic or biosynthetic:

Biosynthetic: Mesh products are made from resorbable synthetically derived meshes with resorption profiles between 6 and 36 months. Theoretically, this allows native collagen deposition for wound strength and durability while reducing the risks of chronic mesh infection affiliated with permanent synthetic alternatives.
Synthetic: Mesh products are made from either woven extruded monofilament (for example, polypropylene or polyester) or created from expanded polytetrafluoroethylene. They may be subcategorized by; weight/density, material, composition, pore characteristics, and mechanical parameters. Products in this category are permanent and are not absorbed by the body.

Nerve conduits: A bioengineered product used in the repair of traumatic peripheral nerve injuries. The product is used in the reconstruction of a gap defect by placing proximal and distal nerve stumps into a tubular construct. Conduits are intended to replace the need for nerve autograft harvest.

Nerve wraps: A bioengineered sheet of material used in the repair of traumatic peripheral nerve injuries. The product is formed into a tube around approximated nerve stumps, it’s purpose is to minimize fibrosis and scarring, and provide a narrow gap to facilitate bridging across the repair site.

Vancouver scar scale: An objective and validated method for describing burn scars that includes a summation of scar characteristics including pigmentation [0-2], vascularity [0-3], pliability [0-5], and height [0-3], normal skin is given a score of 0 for each category.

WHCRA: The Women’s Health and Cancer Rights Act of 1998 (WHCRA) is federal legislation that provides that any individual, with insurance coverage who is receiving benefits in connection with a mastectomy covered by their benefit plan (whether or not for cancer) who elects breast reconstruction, must receive coverage for the reconstructive services as provided by WHCRA. This includes reconstruction of the breast on which the mastectomy has been performed, surgery and reconstruction of the other breast to produce a symmetrical appearance and prostheses and treatment of physical complications of all stages of the mastectomy including lymphedemas. If additional surgery is required for either breast for treatment of physical complications of the implant or reconstruction, surgery on the other breast to produce a symmetrical appearance is reconstructive at that point as well. The name of this law is misleading because: 1) cancer does not have to be the reason for the mastectomy; and 2) the mandate applies to men, as well as women. WHCRA does not address lumpectomies. Some states have enacted similar legislation, and some states include mandated benefits for reconstructive services after lumpectomy.

Xenographic: A product derived from non-human organisms (e.g., cows, pigs, horses, etc.).

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary for application of products listed below:

Index

Bilaminate Skin Substitute
Culture-Derived Human Skin Equivalent
Graves’ Disease
Human Skin Equivalent
Wound Healing
Xenograft

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status	Date	Action
Revised	02/19/2026	Medical Policy & Technology Assessment Committee (MPTAC) review. Removed Avance Nerve Graft, Cymetra, and VersaWrap from document. Added new products to INV and NMN list. Added “Summary for Members and Families” section. Revised Description, Rationale, References, and Websites sections. Revised Coding section including 04/01/2026 and prior HCPCS updates to add codes A2036-A2042, A2045, G0681-G0684, Q4368, Q4370-Q4373, Q4375-Q4380, Q4382-Q4390, Q4392-Q4409, Q4411-Q4429, Q4435-Q4440 and Q4431-Q4433 replacing Q4100; removed C5271-C5278 deleted as of 1/1/2026, and removed 31574, Q4112 no longer addressed, also updated with 07/01/2026 CPT changes to add codes 1044T-1049T.
Revised	08/07/2025	MPTAC review. Removed Via Disc and Viable Allograft Supplemental Disc Regeneration (VAST) from document. Revised name of Duragen XS to Duragen Dural Graft Matrix. Added new products to INV and NMN list. Revised Description, Rationale, and Reference sections. Revised Coding section, removed 0627T, 0628T, 0629T, 0630T no longer addressed.
Revised	05/08/2025	MPTAC review. Revised Description/Scope. Removed AmnioBand particulate and ReNu injection from INV and NMN list. Added MiroTract^® Wound Matrix to INV and NMN list. Revised Rationale, Definitions, References, and Websites sections. Revised Coding section, removed Q4168 no longer addressed.
	04/16/2025	Updated Coding section to add missing descriptor for A2034 and missing NOC A4100. Note that history section below should indicate addition of NOC 29999 instead of 20999.
Revised	02/20/2025	MPTAC review. Revised Title and Scope. Removed content related to MN products and transitioned that content to CG-SURG-127. Added new products to INV and NMN statement. Revised Rationale, References, and Websites sections. Revised Coding section to include 04/01/2025 HCPCS changes, added A2030-A2035, Q4354-Q4367 and removed Q4231 deleted as of 04/01/2025; also added NOC 20999 and HCPCS C1763; removed codes 15011-15018, 65778, 65779, 65780, C1832, C8002, C9358, C9360, C9363, Q4101, Q4102, Q4104, Q4105, Q4106, Q4107, Q4110, Q4115, Q4116, Q4121, Q4122, Q4124, Q4128, Q4130, Q4133, Q4136, Q4151, Q4154, Q4158, Q4160, Q4186, Q4187, Q4283, Q4334, Q4335, V2790 now addressed in CG-SURG-127.
	01/30/2025	Updated Coding section with 01/01/2025 CPT and HCPCS changes, added 15011-15018, C8002, Q4346, Q4347, Q4348, Q4349, Q4350, Q4351, Q4352, Q4353.
	10/01/2024	Updated Coding section with 10/01/2024 HCPCS changes, revised descriptor for A2024 and added A2027, A2028, A2029, Q4334, Q4335, Q4336, Q4337, Q4338, Q4339, Q4340, Q4341, Q4342, Q4343, Q4344, Q4345.
Revised	05/09/2024	Medical Policy & Technology Assessment Committee (MPTAC) review. Revised ocular indications, including addition of SurSight to MN and NMN section and added new MN criterion addressing non-healing or persistent corneal epithelial defects. Removed VersaWrap from INV and NMN statement. Removed Phasix Mesh from INV and NMN statement. Added Phasix Mesh and Phasix ST Mesh to MN and NMN statements. Updated Rationale, References, and Websites sections. Updated Coding section with 07/01/2024 HCPCS changes to add Q4311-Q4333 and remove Q4210, Q4277 deleted as of 07/01/2024; also revised Coding section for ocular indications including removing Q4290, and added Phasix to NOC codes.
	02/15/2024	MPTAC review. Revised MN statement to include Cortiva and SurgiMend for breast reconstruction. Revised MN statement to include EPICEL, Integra Omnigraft Dermal Regeneration Template, and ReCell for the treatment of partial and deep thickness burns. Revised MN statement to include Biovance and Oasis for the treatment of diabetic foot ulcers. Revised NMN statement to align with revisions to MN statements. Added new products to the INV and NMN statement. Updated Definitions, Background, Discussion, References, and Websites sections. Updated Coding section to include 04/01/2024 HCPCS changes, added Q4310 replacing Q4244 deleted as of 04/01/2024, also added A2026, C9796, Q4305, Q4306, Q4307, Q4308, Q4309.
	12/28/2023	Updated Coding section with 01/01/2024 HCPCS changes, added Q4279, Q4287, Q4288, Q4289, Q4290, Q4291, Q4292, Q4293, Q4294, Q4295, Q4296, Q4297, Q4298, Q4299, Q4300, Q4301, Q4302, Q4303, Q4304 and revised descriptor for Q4225.
	09/27/2023	Updated Coding section with 10/01/2023 HCPCS changes to add A2022, A2023, A2024, A2025, Q4285 and Q4286; also added HCPCS code C1832.
	06/28/2023	Updated Coding section with 07/01/2023 HCPCS changes, added Q4272, Q4273, Q4274, Q4275, Q4276, Q4277, Q4278, Q4280, Q4281, Q4282, Q4283, Q4284. Updated URL for HCT/Ps information site.
Revised	02/16/2023	MPTAC review. Revised MN statement to include SimpliDerm for breast reconstruction. Revised MN statement to include Kerecis and TheraSkin for diabetic foot ulcers. Revised MN statement to include AmnioBand for venous stasis ulcers. Revised MN statement to include OviTex for complex abdominal wall wounds. Revised formatting in several MN statements. Revised NMN statement to align with revisions to MN statements. Added new products to the INV and NMN statement. Updated Rationale, Coding and References sections. Updated Coding section with 04/01/2023 HCPCS changes; added A2019, A2020, A2021, Q4265, Q4266, Q4267, Q4268, Q4269, Q4270, Q4271.
	12/28/2022	Updated Coding section with 01/01/2023 HCPCS changes; added Q4262, Q4263, Q4264, and added Q4236 (code reactivated).
	09/28/2022	Updated Coding section with 10/01/2022 HCPCS changes; revised descriptor for Q4128 and added A2014, A2015, A2016, A2017, A2018.
Revised	05/12/2022	MPTAC review. Revised INV and NMN statement for products with MN indications. Updated Rationale and References sections. Updated Coding section, including 07/01/2022 HCPCS changes; added Q4259, Q4260, Q4261 and revised A2004 descriptor.
Revised	02/17/2022	MPTAC review. Moved StrataGraft from INV and NMN section to MN section for burns. Added mVASC to MN section for treatment of DUFs. Clarified product terminology regarding AlloDerm products. Added new products to INV and NMN statement. Updated Rationale and References sections. Updated Coding section to include MN indications for StrataGraft and mVASC (NOC codes) and 04/01/2022 HCPCS updates to add A2011, A2012, A2013, A4100, Q4224, Q4225, Q4256, Q4257, Q4258.
Revised	11/11/2021	MPTAC review. Updated title and scope to include bioengineered products. Reorganized MN section by indication. Simplified criteria for treatment of DFUs and venous stasis ulcers. Incorporated position statement addressing bioengineered autologous skin-derived products from MED.00110. Added new products to INV and NMN statement. Updated Description/Scope, Rationale, Background, and References sections. Updated Coding section with 01/01/2022 HCPCS changes to add A2001-A2002, A2004-A2010 and Q4199 effective 01/01/2022, also added Q4200, Q4226 previously addressed in MED.00110.
	10/01/2021	Updated Coding section with 10/01/2021 HCPCS changes; added Q4251, Q4252, Q4253 effective 10/01/2021 and removed Q4228, Q4236 deleted 09/30/2021.
Revised	11/05/2020	MPTAC review. Added new MN statement for TheraSkin for treatment of lower extremity dermal wounds. Revised note addressing fresh frozen unprocessed allograft skin products. Revised several statements to begin with the name of the product. Revised IVN and NMN statement for products which have MN indications. Added new products to INV and NMN statement. Updated Scope, Rationale, and References sections. Updated Coding section to include 01/01/2021 CPT changes adding 0627T-0630T.
	10/01/2020	Updated Coding section with 10/01/2020 HCPCS changes to add Q4249, Q4250, Q4254, Q4255, and also 10/01/2020 ICD-10-CM changes adding H18.599 replacing H18.59 deleted 09/30/2020.
	07/01/2020	Updated Coding section with 07/01/2020 HCPCS changes to add Q4227-Q4242, Q4244-Q4248 and revised descriptor for Q4176; also removed C1878, L8607 now addressed in MED.00132.
Revised	11/07/2019	MPTAC review. Moved AmbioDisk from INV and NMN statement to the MN statement addressing of allogeneic amniotic membrane-derived grafts or wound coverings. Added Artacent Ocular to MN statement addressing of allogeneic amniotic membrane-derived grafts or wound coverings. Added new products to INV and NMN statement. Updated Rationale and References sections.
	10/01/2019	Updated Coding section with 10/01/2019 HCPCS changes; added Q4205-Q4206, Q4208-Q4222, revised descriptors for Q4122, Q4165, Q4184; also added C1878.
	06/18/2019	Correction to MN statement addressing amniotic membrane-derived products for conjunctival and corneal indications made. Kerasys removed and replaced by AmnioGraft.
Revised	06/06/2019	MPTAC review. Added new MN and INV and NMN statements addressing amniotic membrane-derived products for conjunctival and corneal indications. Added new products to INV and NMN statement. Updated Rationale, Coding and References sections.
Revised	01/24/2019	MPTAC review. Added new MN statements for EpiCord, Grafix PRIME, and the sheet or membrane form of AmnioBand. Revised INV and NMN statements regarding those products. Added EpiBurn to INV and NMN statement. Updated Coding, Rationale, and References sections.
	12/27/2018	Updated Coding section with 01/01/2019 HCPCS changes; removed Q4131, Q4172 deleted 12/31/2018.
Revised	09/13/2018	MPTAC review. Added several products to the INV and NMN section. Updated Rationale, Coding and References sections.
Revised	01/25/2018	MPTAC review. Revised criteria for EpiFix and Integra Bilayer Matrix Wound Dressing. Deleted statement regarding TransCyte. Moved several products from the INV and NMN section to the MN section. Updated Rationale and References sections. Updated Coding section to include removing Q4182 no longer addressed.
	12/27/2017	The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Coding section with 01/01/2018 HCPCS changes; added codes Q4176-Q4182, descriptor revisions for Q4132, Q4133, Q4148, Q4156, Q4158, Q4162, Q4163.
Revised	08/03/2017	MPTAC review. Added new products to INV and NMN list. Removed Perlane and Restylane from Inv and NMN list. Updated Rationale, Coding and References sections.
Revised	02/02/2017	MPTAC review. Made minor typographical revisions to Position Statement. Added new products to INV and NMN list. Updated Rationale and References sections.
	01/01/2017	Updated Coding section with 01/01/2017 CPT and HCPCS changes; removed codes C9349, Q4119, Q4120, Q4129 deleted 12/31/2016.
Revised	05/05/2016	MPTAC review. Added AlloDerm Ready to Use as MN for the same indications as AlloDerm Regenerative Tissue Matrix. Added FlexHD as MN for breast reconstruction surgery. Clarified INV and NMN statement regarding fresh frozen allograft products. Added new products to the INV and NMN list. Updated Rationale, Coding, and References sections.
Revised	11/05/2015	MPTAC review. Added Restlyane and Perlane to investigational and not medically necessary list. Updated Rationale and References sections. Updated Coding section with 01/01/2016 HCPCS changes; also removed ICD-9 codes.
	07/01/2015	Updated Coding section with 07/01/2015 HCPCS change to descriptor for C9349.
Revised	05/07/2015	MPTAC review. Added new medically necessary position statement regarding the use of fresh, frozen, unprocessed skin allograft products for the treatment of full-thickness or deep partial-thickness burns when criteria are met. Added new products to investigational and not medically necessary section. Updated Rationale, Coding, and References sections.
Revised	02/05/2015	MPTAC review. Added new medically necessary position statement regarding the use the sheet or membrane form of EpiFix. Revised investigational and not medically necessary statement to differentiate between the sheet or membrane form of EpiFix and the particulate or injectable form of EpiFix. Added new products to investigational and not medically necessary section. Updated Rationale, Background, Coding, and References sections. Revised position statements were finalized in a follow-up vote on 03/04/2015.
	01/01/2015	Updated Coding section with 01/01/2015 HCPCS changes.
Revised	02/13/2014	MPTAC review. Clarified nomenclature of AlloDerm product in medically necessary section. Added new products to investigational and not medically necessary section. Updated Rationale, Background, and References sections.
	01/01/2014	Updated Coding section with 01/01/2014 CPT and HCPCS changes.
Revised	08/08/2013	MPTAC review. Added new products to Investigational and Not Medically Necessary list. Updated Rationale and References sections.
Revised	05/09/2013	MPTAC review. Added new products to Investigational and Not Medically Necessary list. Updated Rationale, Coding, and Reference sections.
	01/01/2013	Updated Coding section with 01/01/2013 HCPCS changes; removed C9366, C9368, C9369 deleted 12/31/2012.
Revised	05/10/2012	MPTAC review. Deleted “autologous” from title. Split off growth factors, silver-based products and autologous tissues for wound treatment and soft tissue to a new policy (MED.00110). Reorganized position statement section. Clarified Medically necessary statement for Apligraf regarding number of applications and deleted corresponding investigational and not medically necessary statement. Added new products to investigational and not medically necessary position statement. Revised Rationale, Background, References, and Index sections. Updated Coding section to include 07/01/2012 HCPCS changes.
	01/19/2012	Updated Coding section with correct diagnosis coding for Apligraf; removed HCPCS codes G0440, G0441 deleted 12/31/2011.
	01/01/2012	Updated Coding section with 01/01/2012 CPT and HCPCS changes; removed codes 15170, 15171, 15175, 15176, 15330, 15331, 15335, 15336, 15340, 15341, 15360, 15361, 15365, 15366, 15400, 15401, 15420, 15421, 15430, 15431, C9365 deleted 12/31/2011; also removed CPT 15150, 15151, 15152, 15155, 15156, 15157.
Revised	05/19/2011	MPTAC review. Added synthetic soft-tissue grafting materials as investigational and not medically necessary to Section I. Added xenographic-related or derived products as investigational and not medically necessary to Section IV. Updated Rationale, References, and Index sections. Updated Coding section with 07/01/2011 HCPCS changes.
Revised	02/17/2011	MPTAC review. Added use of cryopreserved allogeneic human skin to the Allogeneic section as investigational and not medically necessary. Updated Rationale, Coding, References, and Index sections.
	01/01/2011	Updated Coding section with 01/01/2011 HCPCS changes; removed Q4109 deleted 12/31/2010.
Revised	08/19/2010	MPTAC review. Added use of synthetic fistula plugs to synthetic products section as investigational and not medically necessary. Expanded investigational and not medically necessary statement for Dermagraft to cover all indications not listed as medically necessary. Revised language in xenographic investigational and not medically necessary statement. Updated list of xenographic products, including Menaflex^™ Collagen Meniscus Implant. Added new section addressing composite autologous / allogeneic / xenographic products. Updated Rationale, Background, Coding, and References sections.
	07/01/2010	Updated Coding section with 07/01/2010 CPT and HCPCS changes.
	01/01/2010	Updated Coding section with 01/01/2010 CPT changes; removed CPT 0170T deleted 12/31/2009.
Revised	08/27/2009	MPTAC review. Added Platelet Rich Plasma as investigational and not medically necessary. Updated coding and Index sections.
Reviewed	05/21/2009	MPTAC review. Added note stating that this document does not address the use of meshes or patches of non-biologic origin when used for standard hernia repair procedures. Updated Index section. Updated coding section with 07/01/2009 HCPCS changes.
Revised	02/26/2009	MPTAC review. Added Investigational and Not Medically Necessary statements for C-QUR and Strattice.
Revised	11/20/2008	MPTAC review. Added AlloDerm as medically necessary for breast reconstruction and complex abdominal wall wound closure. Updated Rationale and Reference sections. Updated coding section with 01/01/2009 HCPCS changes; removed C9357, J7340, J7341, J7342, J7343, J7344, J7346, J7347, J7348, J7349 deleted 12/31/2008.
Revised	08/28/2008	MPTAC review. Added Vitagel to Investigational and Not Medically Necessary statement of Section II Autologous Products. Added Cymetra to Investigational and Not Medically Necessary statement of Section III Allogeneic Products. Updated Background. Coding section updated to include 10/01/2008 ICD-9 changes.
Revised	05/15/2008	MPTAC review. Changed title from “Wound Healing: Skin Substitutes and Blood-Derived Growth Factors” to “Autogous, Allogeneic, Xenographic, Synthetic and Composite Products for Wound Healing and Soft Tissue Grafting.” Reorganized Position Statement section. Added position statements regarding the following products: Actisorb, Avaulta Plus, Collamend, CuffPatch, Mediskin, Neoform Dermis, Pelcvicol, Pelvisoft, Silversorb, and Unite. Revised Rationale, Coding, Background, Definitions, References, and Index sections. Deleted information regarding Procuren^®. Updated Coding section with 07/01/2008 HCPCS changes.
Revised	02/21/2008	MPTAC review. Added position statements for Integra^™ Matrix Wound Dressing, Primatrix, and TissueMend. Expanded investigational and not medically necessary statement for Surgisis, Autogel and Safeblood to include all indications. Updated Rationale, Background, Definitions, and References sections.
	01/01/2008	Updated Coding section with 01/01/2008 HCPCS changes; removed HCPCS C9351, J7345 deleted 12/31/2007. The phrase “investigational/not medically necessary” was clarified to read “investigational and not medically necessary.” This change was approved at the November 29, 2007 MPTAC meeting.
Revised	05/17/2007	MPTAC review. Added the use of AlloDerm for breast reconstruction or augmentation to investigational/not medically necessary statement. Updated Rationale and References sections.
	01/01/2007	Updated Coding section with 01/01/2007 CPT/HCPCS changes.
Revised	09/14/2006	MPTAC review. Added position statement for Surgisis^®; updated rationale, background and reference sections. Coding updated; removed CPT 15342, 15343 deleted 12/31/05, HCPCS Q0182, Q0183 deleted 12/31/04.
Revised	03/23/2006	MPTAC review. Added position statement for AlloDerm^® and GraftJacket^™.
	01/01/2006	Updated Coding section with 01/01/2006 CPT/HCPCS changes
	11/22/2005	Added reference for Centers for Medicare and Medicaid Services (CMS) - National Coverage Determination (NCD).
Revised	07/14/2005	MPTAC review. Revision based on Pre-merger Anthem and Pre-merger Wellpoint Harmonization.

Pre-Merger Organizations	Last Review Date	Document Number	Title
Anthem, Inc.	04/28/2005	SURG.00011	Wound Healing: Tissue Engineered Skin Substitutes and Growth Factors
WellPoint Health Networks, Inc.	04/28/2005	3.02.03	Human Skin Equivalent Grafts
	09/23/2004	8.01.08	Autologous Blood Derived Preparations for Wound Healing

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member’s contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.

No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan.

© CPT Only – American Medical Association

The requirements below are specific to the Florida Medicaid Managed Care Plan and are not a part of the Medical Policy or Clinical UM guideline approved by Elevance Health's Medical Policy and Technology Assessment Committee.

If the Florida Medicaid Managed Care Plan intends to deny coverage on the basis that a diagnostic test, therapeutic procedure, or medical device or technology is experimental or investigational, the Managed Care Plan shall submit a request for coverage determination to the Agency in accordance with rule 59G-1.035, F.A.C and Core SMMC Contract, Attachment II, Section VI.G.4.d.

Below is a list of the materials the plans are required to submit when they deny coverage as experimental/investigational:

Subject: Products for Wound Healing and Soft Tissue Grafting: Investigational
Document #: SURG.00011	Publish Date: 04/01/2026
Status: Revised	Last Review Date: 02/19/2026

CPT
46707	Repair of anorectal fistula with plug (eg, porcine small intestine submucosa [SIS])

ICD-10 Diagnosis
	All diagnoses

CPT
15150	Tissue cultured skin autograft, trunk, arms, legs; first 25 sq cm or less
15151	Tissue cultured skin autograft, trunk, arms, legs; additional 1 sq cm to 75 sq cm
15152	Tissue cultured skin autograft, trunk, arms, legs; each additional 100 sq cm, or each additional 1% of body area of infants and children, or part thereof
15155	Tissue cultured skin autograft, face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits; first 25 sq cm or less
15156	Tissue cultured skin autograft, face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits; additional 1 sq cm to 75 sq cm
15157	Tissue cultured skin autograft, face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits; each additional 100 sq cm, or each additional 1% of body area of infants and children, or part thereof
15271	Application of skin substitute graft to trunk, arms, legs, total wound surface area up to 100 sq cm; first 25 sq cm or less wound surface area
15272	Application of skin substitute graft to trunk, arms, legs, total wound surface area up to 100 sq cm; each additional 25 sq cm wound surface area, or part thereof
15273	Application of skin substitute graft to trunk, arms, legs, total wound surface area greater than or equal to 100 sq cm; first 100 sq cm wound surface area, or 1% of body area of infants and children
15274	Application of skin substitute graft to trunk, arms, legs, total wound surface area greater than or equal to 100 sq cm; each additional 100 sq cm wound surface area, or part thereof, or each additional 1% of body area of infants and children, or part thereof
15275	Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area up to 100 sq cm; first 25 sq cm or less wound surface area
15276	Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area up to 100 sq cm; each additional 25 sq cm wound surface area, or part thereof
15277	Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area greater than or equal to 100 sq cm; first 100 sq cm wound surface area, or 1% of body area of infants and children
15278	Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area greater than or equal to 100 sq cm; each additional 100 sq cm wound surface area, or part thereof, or each additional 1% of body area of infants and children, or part thereof
15777	Implantation of biologic implant (eg, acellular dermal matrix) for soft tissue reinforcement (ie, breast, trunk)
17999	Unlisted procedure, skin, mucous membrane and subcutaneous tissue [when specified as implantation of biologic implants for soft tissue reinforcement in tissues other than breast and trunk]
29999	Unlisted procedure, arthroscopy [when specified as a tendon repair using BioBrace implant]
	Note, the following CPT codes will be effective 7/1/2026:
1044T	Harvest of full-thickness skin for autologous heterogeneous skin-construct graft, including direct closure of donor site; first 5 sq cm or less
1045T	Harvest of full-thickness skin for autologous heterogeneous skin-construct graft, including direct closure of donor site; each additional 5 sq cm, or part thereof
1046T	Autologous heterogeneous skin-construct graft application, trunk, arms, legs; first 50 sq cm or less, or 0.5% of body area of infants and children
1047T	Autologous heterogeneous skin-construct graft application, trunk, arms, legs; each additional 50 sq cm, or each additional 0.5% of body area of infants and children, or part thereof
1048T	Autologous heterogeneous skin-construct graft application, face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits; first 50 sq cm or less, or 0.5% of body area of infants and children
1049T	Autologous heterogeneous skin-construct graft application, face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits; each additional 50 sq cm, or each additional 0.5% of body area of infants and children, or part thereof

HCPCS
G0681	Application of a premarket approval (PMA), 510(k), 361 human cells, tissues or cellular and tissue-based products (HCT/P) non-sheet form skin substitute for a wound surface area up to 100 sq cm; first 25 sq cm or less of wound surface area
G0682	Application of a premarket approval (PMA), 510(k), 361 human cells, tissues or cellular and tissue-based products (HCT/P) non-sheet form skin substitute for a wound surface area up to 100 sq cm; each additional 25 sq cm wound surface area, or part thereof
G0683	Application of a premarket approval (PMA), 510(k), 361 human cells, tissues or cellular and tissue-based products (HCT/P) non-sheet form skin substitute graft for a wound surface greater than or equal to 100 sq cm; first 100 sq cm wound surface area, or 1% of body area of infants and children
G0684	Application of a premarket approval (PMA), 510(k), 361 human cells, tissues or cellular and tissue-based products (HCT/P) non-sheet form skin substitute graft for a wound surface greater than or equal to 100 sq cm; each additional 100 sq cm wound surface area or part thereof, or each additional 1% of body area of infants and children, or part thereof

ICD-10 Diagnosis
	All diagnoses

HCPCS
A2001	Innovamatrix AC, per square centimeter
A2002	Mirragen advanced wound matrix, per square centimeter
A2004	Xcellistem, 1mg
A2005	Microlyte matrix, per square centimeter
A2006	Novosorb synpath dermal matrix, per square centimeter
A2007	Restrata, per square centimeter
A2008	TheraGenesis, per square centimeter
A2009	Symphony, per square centimeter
A2010	Apis, per square centimeter
A2011	Supra SDRM, per square centimeter
A2012	Suprathel, per square centimeter
A2013	InnovaMatrix FS, per square centimeter
A2014	Omeza Collagen Matrix or Omeza Complete Matrix, per 100 mg
A2015	Phoenix Wound Matrix, per sq cm
A2016	PermeaDerm B, per square centimeter
A2017	PermeaDerm Glove, each
A2018	PermeaDerm C, per square centimeter
A2019	Kerecis omega3 MariGen Shield, per square centimeter
A2020	Ac5 advanced wound system (Ac5)
A2021	NeoMatriX, per square centimeter
A2022	InnovaBurn or InnovaMatrix XL, per square centimeter
A2023	InnovaMatrix PD 1 mg
A2024	Resolve Matrix or xenoPATCH, per square centimeter
A2025	Miro3D, per cubic centimeter
A2026	Restrata MiniMatrix, 5 mg
A2027	Matriderm, per square centimeter
A2028	MicroMatrix Flex, per mg
A2029	MiroTract Wound Matrix sheet, per cubic centimeter
A2030	Miro3D fibers, per milligram
A2031	MiroDry wound matrix, per square centimeter
A2032	Myriad matrix, per square centimeter
A2033	Myriad morcells, 4 milligrams
A2034	Foundation DRS Solo, per square centimeter
A2035	Corplex P or Theracor P or Allacor P, per milligram
A2036	Cohealyx collagen dermal matrix, per square centimeter
A2037	G4Derm Plus/Suprello, per milliliter
A2038	Marigen Pacto, per square centimeter
A2039	Innovamatrix FD, per square centimeter
A2040	Microlyte Painguard, per square centimeter
A2041	Foundation DRS+ Duo, per square centimeter
A2042	Foundation DRS+ Solo, per square centimeter
A2045	NovaShield or NovoGen wound matrix, per square centimeter
A4100	Non-sheet form skin substitute, FDA-cleared as a device, not otherwise specified [when describing a product with no specific code indicated as investigational and not medically necessary]
C1763	Connective tissue, non-human (includes synthetic) [when specified as BioBrace Implant]
C9352	Microporous collagen implantable tube (NeuraGen Nerve Guide), per centimeter length
C9353	Microporous collagen implantable slit tube (NeuraWrap Nerve Protector), per centimeter length
C9354	Acellular pericardial tissue matrix of non-human origin (Veritas), per square centimeter
C9355	Collagen nerve cuff (NeuroMatrix), per 0.5 centimeter length
C9356	Tendon, porous matrix of cross-linked collagen and glycosaminoglycan matrix (TenoGlide Tendon Protector Sheet), per square centimeter
C9361	Collagen matrix nerve wrap (NeuroMend Collagen Nerve Wrap), per 0.5 centimeter length
C9364	Porcine implant, Permacol, per square centimeter
C9399	Unclassified drugs or biologicals [when describing a product with no specific code indicated as investigational and not medically necessary]
C9796	Repair of enterocutaneous fistula small intestine or colon (excluding anorectal fistula) with plug (e.g., porcine small intestine submucosa [sis])
G0428	Collagen meniscus implant procedure for filling meniscal defects (e.g., CMI, collagen scaffold, Menaflex)
Q4103	Oasis Burn Matrix, per square centimeter
Q4108	Integra Matrix, per square centimeter
Q4111	Gammagraft, per square centimeter
Q4113	Graftjacket Xpress, injectable, 1 cc
Q4114	Integra Flowable Wound Matrix, injectable, 1 cc
Q4117	Hyalomatrix, per square centimeter
Q4118	Matristem micromatrix, 1 mg
Q4123	AlloSkin RT, per square centimeter
Q4125	ArthroFlex, per square centimeter
Q4126	Memoderm, dermaspan, tranzgraft or integuply, per square centimeter
Q4127	Talymed, per square centimeter
Q4132	Grafix CORE and GrafixPL CORE, per square centimeter
Q4134	hMatrix, per square centimeter
Q4135	Mediskin, per square centimeter
Q4137	AmnioExCel, AmnioExCel plus or BioDExCel, per square centimeter
Q4138	BioDfence Dryflex, per square centimeter
Q4139	AmnioMatrix or BioDMatrix, injectable, 1 cc
Q4140	BioDfence, per square centimeter
Q4141	Alloskin AC, per square centimeter
Q4142	XCM Biologic Tissue Matrix, per square centimeter
Q4143	Repriza, per square centimeter
Q4145	Epifix, injectable, 1 mg
Q4146	TenSIX, per square centimeter
Q4147	Architect, Architect PX, or Architect FX, extracellular matrix, per square centimeter
Q4148	NEOX Cord 1k, NEOX Cord RT, or Clarix Cord 1k, per square centimeter
Q4149	Excellagen, 0.1 cc
Q4150	Allowrap DS or Dry, per square centimeter
Q4152	DermaPure, per square centimeter
Q4153	Dermavest and Plurivest, per square centimeter
Q4155	NeoxFlo or ClarixFlo, 1 mg
Q4156	NEOX 100 or Clarix 100, per square centimeter
Q4157	Revitalon, per square centimeter
Q4159	Affinity, per square centimeter
Q4161	Bio-connekt wound matrix, per square centimeter
Q4162	WoundEx Flow, BioSkin Flow, 0.5 cc
Q4163	WoundEx, BioSkin, per square centimeter
Q4164	Helicoll, per square centimeter
Q4165	Keramatrix or Kerasorb, per square centimeter
Q4166	Cytal, per square centimeter [formerly Matristem wound/burn matrix]
Q4167	TruSkin, per square centimeter
Q4169	Artacent Wound, per square centimeter
Q4170	CYGNUS, per square centimeter
Q4171	Interfyl, 1 mg
Q4173	PalinGen or PalinGen Xplus, per square centimeter
Q4174	PalinGen or ProMatrX, 0.36 mg per 0.25 cc
Q4175	Miroderm, per square centimeter
Q4176	NeoPatch or Therion, per square centimeter
Q4177	FlowerAmnioflo, 0.1 cc
Q4178	FlowerAmniopatch, per square centimeter
Q4179	FlowerDerm, per square centimeter
Q4180	Revita, per square centimeter
Q4181	Amnio Wound, per square centimeter
Q4183	Surgigraft, per square centimeter
Q4184	Cellesta or Cellesta Duo, per square centimeter
Q4185	Cellesta flowable amnion (25 mg per cc); per 0.5 cc
Q4188	Amnioarmor, per square centimeter
Q4189	Artacent AC, 1 mg
Q4190	Artacent AC, per square centimeter
Q4191	Restorigin, per square centimeter
Q4192	Restorigin, 1 cc
Q4193	Coll-e-derm, per square centimeter
Q4194	Novachor, per square centimeter
Q4195	Puraply, per square centimeter
Q4196	PuraPly AM, per square centimeter
Q4197	PuraPly XT, per square centimeter
Q4198	Genesis amniotic membrane, per square centimeter
Q4199	Cygnus matrix, per square centimeter
Q4200	Skin TE, per square centimeter
Q4201	Matrion, per square centimeter
Q4202	Keroxx (2.5g/cc), 1cc
Q4203	Derma-gide, per square centimeter
Q4204	Xwrap, per square centimeter
Q4205	Membrane graft or Membrane wrap, per square centimeter
Q4206	Fluid flow or Fluid GF, 1 cc
Q4208	Novafix, per square centimeter
Q4209	SurGraft, per square centimeter
Q4211	Amnion bio or AxoBioMembrane, per square centimeter
Q4212	AlloGen, per cc
Q4213	Ascent, 0.5 mg
Q4214	Cellesta cord, per square centimeter
Q4215	Axolotl Ambient or Axolotl Cryo, 0.1 mg
Q4216	Artacent cord, per square centimeter
Q4217	Woundfix, BioWound, Woundfix Plus, BioWound Plus, Woundfix Xplus or BioWound Xplus, per square centimeter
Q4218	Surgicord, per square centimeter
Q4219	SurgiGRAFT-Dual, per square centimeter
Q4220	BellaCell HD or Surederm, per square centimeter
Q4221	Amniowrap2, per square centimeter
Q4222	Progenamatrix, per square centimeter
Q4224	Human health factor 10 amniotic patch (hhf10-p), per square centimeter
Q4225	Amniobind or DermaBind TL, per square centimeter
Q4226	MyOwn Skin, includes harvesting and preparation procedures, per square centimeter
Q4227	AmnioCore, per square centimeter
Q4229	Cogenex amniotic membrane, per square centimeter
Q4230	Cogenex flowable amnion, per 0.5 cc
Q4232	Corplex, per square centimeter
Q4233	SurFactor or NuDyn, per 0.5 cc
Q4234	Xcellerate, per square centimeter
Q4235	Amniorepair or AltiPly, per square centimeter
Q4236	CarePATCH, per square centimeter
Q4237	Cryo-cord, per square centimeter
Q4238	Derm-Maxx, per square centimeter
Q4239	Amnio-Maxx or Amnio-Maxx Lite, per square centimeter
Q4240	CoreCyte, for topical use only, per 0.5 cc
Q4241	PolyCyte, for topical use only, per 0.5 cc
Q4242	AmnioCyte Plus, per 0.5 cc
Q4245	Amniotext, per cc
Q4246	Coretext or Protext, per cc
Q4247	Amniotext patch, per square centimeter
Q4248	Dermacyte Amniotic Membrane Allograft, per square centimeter
Q4249	Amniply, for topical use only, per square centimeter
Q4250	AmnioAMP-MP, per square centimeter
Q4251	Vim, per square centimeter
Q4252	Vendaje, per square centimeter
Q4253	Zenith Amniotic Membrane, per square centimeter
Q4254	Novafix DL, per square centimeter
Q4255	REGUaRD, for topical use only, per square centimeter
Q4256	MLG-complete, per square centimeter
Q4257	Relese, per square centimeter
Q4258	Enverse, per square centimeter
Q4259	Celera dual layer or celera dual membrane, per square centimeter
Q4260	Signature Apatch, per square centimeter
Q4261	TAG, per square centimeter
Q4262	Dual Layer Impax Membrane, per square centimeter
Q4263	SurGraft TL, per square centimeter
Q4264	Cocoon membrane, per square centimeter
Q4265	NeoStim TL, per square centimeter
Q4266	NeoStim membrane, per square centimeter
Q4267	NeoStim DL, per square centimeter
Q4268	SurGraft FT, per square centimeter
Q4269	SurGraft XT, per square centimeter
Q4270	Complete SL, per square centimeter
Q4271	Complete FT, per square centimeter
Q4272	Esano A, per square centimeter
Q4273	Esano AAA, per square centimeter
Q4274	Esano AC, per square centimeter
Q4275	Esano ACA, per square centimeter
Q4276	Orion, per square centimeter
Q4278	EPIEFFECT, per square centimeter
Q4279	Vendaje AC, per square centimeter
Q4280	Xcell amnio matrix, per square centimeter
Q4281	Barrera SL or Barrera DL, per square centimeter
Q4282	Cygnus Dual, per square centimeter
Q4284	DermaBind SL, per square centimeter
Q4285	NuDYN DL or NuDYN DL mesh, per square centimeter
Q4286	NuDYN SL or NuDYN SLW, per square centimeter
Q4287	DermaBind DL, per square centimeter
Q4288	DermaBind CH, per square centimeter
Q4289	RevoShield + Amniotic Barrier, per square centimeter
Q4290	Membrane Wrap-Hydro, per square centimeter
Q4291	Lamellas XT, per square centimeter
Q4292	Lamellas, per square centimeter
Q4293	Acesso DL, per square centimeter
Q4294	Amnio Quad-Core, per square centimeter
Q4295	Amnio Tri-Core amniotic, per square centimeter
Q4296	Rebound Matrix, per square centimeter
Q4297	Emerge Matrix, per square centimeter
Q4298	AmnioCore Pro, per square centimeter
Q4299	AmniCore Pro+, per square centimeter
Q4300	Acesso TL, per square centimeter
Q4301	Activate Matrix, per square centimeter
Q4302	Complete ACA, per square centimeter
Q4303	Complete AA, per square centimeter
Q4304	Grafix Plus, per square centimeter
Q4305	American amnion AC tri-layer, per square centimeter
Q4306	American amnion AC, per square centimeter
Q4307	American amnion, per square centimeter
Q4308	Sanopellis, per square centimeter
Q4309	VIA Matrix, per square centimeter
Q4310	Procenta, per 100 mg
Q4311	Acesso, per square centimeter
Q4312	Acesso AC, per square centimeter
Q4313	DermaBind FM, per square centimeter
Q4314	Reeva FT, per square centimeter
Q4315	RegeneLink Amniotic Membrane allograft, per square centimeter
Q4316	AmchoPlast, per square centimeter
Q4317	VitoGraft, per square centimeter
Q4318	E-Graft, per square centimeter
Q4319	SanoGraft, per square centimeter
Q4320	PelloGraft, per square centimeter
Q4321	RenoGraft, per square centimeter
Q4322	CaregraFT, per square centimeter
Q4323	alloPLY, per square centimeter
Q4324	AmnioTX, per square centimeter
Q4325	ACApatch, per square centimeter
Q4326	WoundPlus, per square centimeter
Q4327	DuoAmnion, per square centimeter
Q4328	MOST, per square centimeter
Q4329	Singlay, per square centimeter
Q4330	TOTAL, per square centimeter
Q4331	Axolotl Graft, per square centimeter
Q4332	Axolotl DualGraft, per square centimeter
Q4333	ArdeoGraft, per square centimeter
Q4336	Artacent C, per square centimeter
Q4337	Artacent Trident, per square centimeter
Q4338	Artacent Velos, per square centimeter
Q4339	Artacent VeriClen, per square centimeter
Q4340	SimpliGraft, per square centimeter
Q4341	SimpliMax, per square centimeter
Q4342	TheraMend, per square centimeter
Q4343	Dermacyte AC matrix amniotic membrane allograft, per square centimeter
Q4344	Tri-membrane wrap, per square centimeter
Q4345	Matrix HD allograft dermis, per square centimeter
Q4346	Shelter DM Matrix, per square centimeter
Q4347	Rampart DL Matrix, per square centimeter
Q4348	Sentry SL Matrix, per square centimeter
Q4349	Mantle DL Matrix, per square centimeter
Q4350	Palisade DM Matrix, per square centimeter
Q4351	Enclose TL Matrix, per square centimeter
Q4352	Overlay SL Matrix, per square centimeter
Q4353	Xceed TL Matrix, per square centimeter
Q4354	PalinGen dual-layer membrane and dual-layer PalinGen X-membrane, per square centimeter
Q4355	Abiomend Xplus membrane and abiomend Xplus hydromembrane, per square centimeter
Q4356	Abiomend membrane and abiomend hydromembrane, per square centimeter
Q4357	Xwrap Plus, per square centimeter
Q4358	Xwrap Dual, per square centimeter
Q4359	Choriply, per square centimeter
Q4360	AmchoPlast FD, per square centimeter
Q4361	EpiXpress, per square centimeter
Q4362	Cygnus Disk, per square centimeter
Q4363	Amnio Burgeon Membrane and Hydromembrane, per square centimeter
Q4364	Amnio Burgeon Xplus Membrane and Xplus Hydromembrane, per square centimeter
Q4365	Amnio Burgeon Dual-Layer Membrane, per square centimeter
Q4366	Dual Layer Amnio Burgeon X-Membrane, per square centimeter
Q4367	AmnioCore SL, per square centimeter
Q4368	AmchoThick, per square centimeter
Q4370	AeroGuard, per square centimeter
Q4371	NeoGuard, per square centimeter
Q4372	AmchoPlast EXCEL, per square centimeter
Q4373	Membrane Wrap-Lite, per square centimeter
Q4375	Duograft AC, per square centimeter
Q4376	Duograft AA, per square centimeter
Q4377	Trigraft FT, per square centimeter
Q4378	Renew FT Matrix, per square centimeter
Q4379	AmnioDefend FT matrix, per square centimeter
Q4380	AdvoGraft One, per square centimeter
Q4382	AdvoGraft dual, per square centimeter
Q4383	Axolotl Graft Ultra, per square centimeter
Q4384	Axolotl Dualgraft Ultra, per square centimeter
Q4385	Apollo FT, per square centimeter
Q4386	Acesso TrifACA, per square centimeter
Q4387	NeoThelium FT, per square centimeter
Q4388	NeoThelium 4L, per square centimeter
Q4389	NeoThelium 4L plus, per square centimeter
Q4390	Ascendion, per square centimeter
Q4392	Grafix duo, per square centimeter
Q4393	SurGraft AC, per square centimeter
Q4394	SurGraft ACA, per square centimeter
Q4395	Acelagraft, per square centimeter
Q4396	Natalin, per square centimeter
Q4397	Summit AAA, per square centimeter
Q4398	Summit AC, per square centimeter
Q4399	Summit FX, per square centimeter
Q4400	Polygon3 membrane, per square centimeter
Q4401	Absolv3 membrane, per square centimeter
Q4402	Xwrap 2.0, per square centimeter
Q4403	Xwrap Dual Plus, per square centimeter
Q4404	Xwrap Hydro Plus, per square centimeter
Q4405	Xwrap Fenestra Plus, per square centimeter
Q4406	Xwrap Fenestra, per square centimeter
Q4407	Xwrap Tribus, per square centimeter
Q4408	Xwrap Hydro, per square centimeter
Q4409	AmnioMatrixF3X, per square centimeter
Q4411	AmnioMatrixF4X, per square centimeter
Q4412	Choriofix, per square centimeter
Q4413	Cygnus Solo, per square centimeter
Q4414	SimpliChor, per square centimeter
Q4415	AlexiGuard SL-T, per square centimeter
Q4416	AlexiGuard TL-T, per square centimeter
Q4417	AlexiGuard DL-T, per square centimeter
Q4418	BioLab Membrane Wrap Flow, per square centimeter
Q4419	BioLab Membrane Wrap Lite Flow, per square centimeter
Q4420	Nuform, per square centimeter
Q4421	BioLab Membrane Wrap Solo, per square centimeter
Q4422	A/C wrap, per square centimeter
Q4423	BioLab Tri-Membrane Wrap Flow, per square centimeter
Q4424	Revive FT, per square centimeter
Q4425	Revive TL, per square centimeter
Q4426	DermaBind TL + or Dermabind TL X, per square centimeter
Q4427	DermaBind DL N or DermaBind DL + or DermaBind DL X, per square centimeter
Q4428	DermaBind SL N or DermaBind SL + or DermaBind SL X, per square centimeter
Q4429	DermaBind CH N or DermaBind CH X, per square centimeter
Q4431	PMA skin substitute product, not otherwise specified [when describing a product with no specific code indicated as investigational and not medically necessary]
Q4432	510(k) skin substitute product, not otherwise specified [when describing a product with no specific code indicated as investigational and not medically necessary]
Q4433	361 HCT/P skin substitute product, not otherwise specified [when describing a product with no specific code indicated as investigational and not medically necessary]
Q4435	Renati membrane, per square centimeter
Q4436	Renati AC membrane, per square centimeter
Q4437	Revival AC, per square centimeter
Q4438	Pretect, per square centimeter
Q4439	InstaGraft, per square centimeter
Q4440	Curamatrix, per square centimeter

ICD-10 Diagnosis
	All diagnoses