CurrentUnitedHealthcarePolicy CS153PA.W

Skin and Soft Tissue Substitutes (for Pennsylvania Only)

Coverage and medical necessity criteria for skin and soft tissue substitute products for Pennsylvania members, including product-specific limits for EpiFix, Grafix, TransCyte, and an evidence-based stance on numerous other branded products.

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for Pennsylvania Only)

Policy CodePolicy CS153PA.W

Change TypeNo material changes

Effective DateNov 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and document ≥4 weeks of failed standard wound care plus perfusion and HbA1c criteria when requesting EpiFix or Grafix for diabetic foot ulcers.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

1 statepolicy applies to

up to 12 weeksEpiFix/Grafix application limit

4 weeksstandard treatment assessment

Extensiveunproven products listed

multipleHCPCS codes enumerated

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria and Product Conclusions

EpiFix/Grafix for diabetic foot ulcers

EpiFix or Grafix (non-injectable) are covered for diabetic foot ulcers when ALL of the following are met:

Adequate circulation to the affected extremity as indicated by one or more of: palpable pedal pulses or pulses confirmed with Doppler examination; ankle‑brachial index (ABI) between 0.7 and 1.2ABI 0.7-1.2

supporting perfusion documentation required

Glycemic control: Glycated hemoglobin (HgA1c) < 12% within the last 90 daysHgA1c <12%

lab documentation required

Prior standard wound care: Ulcer failed to demonstrate adequate healing after at least 4 weeks of standard wound care including moist dressings, debridement if present, and appropriate offloading>=4 weeks

document prior care; percent reduction during run‑in relevant

No contraindications: No known contraindications such as active Charcot deformity or major structural foot abnormalities; chronic infection at the ulcer site; known or suspected malignancy of the ulcer; or ulcer extending to tendon, muscle, capsule, or bone

clinical assessment required

Application limits: Applications limited to one application per week for up to 12 weeks; more frequent or longer use is not medically necessaryone/week, up to 12 weeks

see product application limits

TransCyte for thermal burns

TransCyte is covered when ALL of the following are met:

Indication: Treatment of surgically excised full‑thickness thermal burns and deep partial‑thickness thermal burn wounds prior to autograft placement

product‑specific indication

Products considered unproven/not medically necessary

Other listed skin and soft tissue substitutes are considered unproven and not medically necessary for any indication due to insufficient evidence of efficacy:

Unproven products list: Numerous named skin and soft tissue substitute products listed in this policy have few or no adequate published studies; their clinical benefit has not been established and they are considered investigational or not medically necessary for any indication unless robust supportive evidence is provided.insufficient published evidence

See product list in policy (chunks 6–10) for specific brand entries.

General coverage criteria for adjunctive use

Covered when used as an adjunct to standard of care for appropriate indications and after documentation of prior standard care efforts

threshold":"","note":"Adjunctive to SOC as described in trials","children":[]}

Prior standard care attempted: Standard of care measures (debridement, moisture balance, infection control/treatment, ischemia correction, compression for venous ulcers, offloading for diabetic foot ulcers) have been provided and documented; ulcer failed to demonstrate adequate healing (commonly defined as <50% reduction) after at least 4 weeks4 weeks without >=50% reduction

document prior care and response (run‑in data when available)

Coverage decision framework and product-level evidence grouping

Evidence synthesis and product-specific conclusions reflected in this section inform coverage decisions; product-level coverage depends on demonstrated clinical benefit and quality of evidence.

General evidence considerations: Coverage decisions require high‑quality comparative or randomized evidence demonstrating improved wound closure or clinically meaningful outcomes (commonly assessed at ~12 weeks), adequate reporting of wound size/duration consistent with trial criteria, and documentation that use aligns with studied populations and trial protocols.12-week assessment

Systematic reviews find biologic dressings often superior to SOC at 6–12 weeks but evidence is heterogeneous; consider trial design and endpoints.

Products supported by some RCT evidence: Products with randomized evidence showing benefit (for example specific HSAM or dHACM trials, Mirragen small RCT) may be considered for coverage when patient presentation matches trial populations and documentation supports prior SOC failure.statistical significance reported in RCT

Single small RCTs may support conditional coverage subject to prior authorization and documentation.

Products lacking sufficient evidence

General coverage stance for listed amniotic/placental membrane products in this excerpt

Insufficient evidence for listed products: For the majority of listed amniotic/placental membrane and related products (see policy product lists), published studies are few, of low quality, noncomparative, or absent; therefore clinical benefit cannot be concluded and these products are considered to have insufficient evidence to support routine coverage.insufficient published data

Individual product sections cite specific study limitations; prior authorization and detailed documentation expected if requested.

AmnioBand (dHACA) — RCT evidence and conditional consideration

Evidence summary and conditional consideration for AmnioBand/Guardian (dHACA)

RCT evidence for VLUs/DFUs: Randomized controlled trials (Serena et al. 2022; DiDomenico et al. 2016, 2018) evaluated dehydrated human amnion/chorion allograft (dHACA/AmnioBand) plus standard care versus standard care alone in chronic venous leg ulcers and diabetic foot ulcers with defined inclusion criteria (adequate perfusion thresholds, wound area limits, prior compression/offloading), reporting higher healing rates at 12 weeks for dHACA in these trials.trial inclusion criteria applied

Trials had limitations (lack of blinding, small samples, manufacturer funding).

RCT results summary: Serena et al. (VLU) reported 75% healed at 12 weeks with dHACA versus 30% with SOC (OR 8.7; p=0.001); DiDomenico reported up to 85% healing at 12 weeks in DFU RCTs versus lower SOC rates—findings suggest efficacy in trial populations.12-week healing rates reported

Adverse events reported but not graft‑related; interpret cautiously due to study limitations.

Covered when ALL trial-based criteria are met

Evidence-supported coverage considerations based on trial inclusion criteria

Inclusion-like criteria: Patient is an adult with a chronic DFU or VLU that has failed an adequate trial of standard of care (debridement, appropriate dressings, off‑loading or compression) and demonstrates adequate tissue perfusion (e.g., ABI > 0.75 or SPP > 30 mmHg or TCOM > 30 mmHg).as stated

Derived from multiple RCT inclusion criteria; payer may map to medical necessity rules

Wound characteristics: Wound area and depth are within ranges studied (examples: DFU 1–25 cm2 in some trials; VLU ≤2–20 cm2 in others); wounds are full‑thickness but not extending to muscle/tendon/bone, and are without clinical infection.as stated

Trials excluded infected wounds and certain advanced therapy requirements; document wound size/duration.

Supported/Investigational clinical findings

Evidence-supported uses (limited and specific):

AmnioFix injectable for plantar fasciitis: Randomized controlled trials report short‑ to intermediate‑term pain reduction and functional improvement with micronized dHACM injections for plantar fasciitis compared with placebo or corticosteroid in some studies; long‑term comparative effectiveness versus other advanced therapies is not established.short‑ to intermediate‑term follow‑up

Evidence limited to small RCTs and systematic reviews; comparative data lacking beyond 12 weeks.

Insufficient evidence / investigational

Products with insufficient evidence:

Multiple named products: Numerous listed products have few published studies or insufficient evidence to conclude benefit for wound treatment or other indications; these products are considered investigational or not medically necessary for routine use absent stronger evidence.insufficient published data

Examples include AMNIOMATRIX/BioDMatrix, Amnio‑Maxx, AmnioPlast, AMNIOREPAIR/AltiPly, Amniotext (and patch), Artacent variants, Architect, ArthroFLEX, Ascent, AxoBioMembrane, and many others (see policy list).

Artacent observational DFU data

Observational findings relevant to DFU:

Artacent DLAM observational DFU results: A small observational analysis (n=26) of a double‑layer amniotic membrane (Artacent) plus standard care reported 65% complete closure at 12 weeks in DFUs that failed to heal ≥50% after 2–4 weeks of SOC; sample size was small and trial was discontinued, so results are hypothesis‑generating and require validation in larger RCTs.per‑study outcomes

Baseline ulcers in the analysis were larger than typical DFU trials; interpret with caution.

Products with insufficient evidence

Covered when ALL of the following are met

Inconclusive evidence for listed products: For the named products in this section (e.g., Ascent; AxobioMembrane; Axolotl products; Barrera; BellaCell; bio‑ConneKt; BioDfence; Bioskin; Biovance variants; BioWound variants; CaregraFT; CarePATCH; Celera variants; Cellesta variants), available published studies are few and insufficient to conclude clinical benefit for wound treatment.

Registry or single‑arm studies cited for select products are low quality and heterogeneous, limiting conclusions.

Products with insufficient evidence / investigational

Products reviewed in this section are generally considered investigational/unproven due to insufficient evidence

General evidence‑based coverage stance: For each named product (e.g., Cellesta Duo, Cellesta Cord, ChoriPly, CLARIX, Cocoon, Cogenex, Coll‑e‑Derm, Corecyte, Corplex, Corplex P/Theracor P/Allacor P, Cryo‑Cord, Cygnus products), there are few published studies or insufficient evidence to conclude a beneficial effect on health outcomes; they are treated as investigational absent stronger evidence.evidence insufficient

Product‑specific intended uses are described but lack robust clinical trial support.

CorMatrix — insufficient evidence and specific concerns

CorMatrix specific findings

CorMatrix evidence summary: Available clinical studies of CorMatrix (porcine SIS‑ECM) are limited, mostly retrospective or small series, and report mixed outcomes including patch failure and reoperation in some cardiac applications; larger controlled studies are needed to establish safety and efficacy for intended uses.limited/low‑quality evidence

Reports include reoperation and recurrence tied to ECM patch failure; interpret cautiously.

Amniotic tissue-derived injections — plantar fasciitis evidence status

HAM injections for plantar fasciitis (Hayes review)

Hayes review conclusions: A low‑quality body of evidence suggests possible short‑term pain relief and improved function with human amniotic membrane (HAM) injections for plantar fasciitis, but studies lacked active comparators and had short follow‑up (≤12 weeks); comparative effectiveness and long‑term outcomes remain uncertain.short follow‑up

Higher‑quality double‑blind RCTs with active comparators and longer follow‑up are needed.

Coverage characterization by evidence level

Coverage stance varies by product based on available evidence; products in this section generally fall into two groups:

Products with insufficient evidence: Numerous named products (for example Cygnus family, Cytal, DermaBind variants, DermaPure, Dermacyte, Derm‑Maxx, Dual Layer products, DuoAmnion) have limited or no robust published evidence; routine coverage cannot be supported based on current data.evidence limited or lacking

Require case‑by‑case review if requested with strong supporting documentation.

Products with limited supportive evidence (DermACELL family): DermACELL and related acellular dermal matrices have some RCTs and meta‑analyses indicating higher healing rates in DFUs compared with SOC; evidence is limited by small sizes, heterogeneity, and potential industry sponsorship, and coverage may be considered when presentation matches studied populations and prior SOC failure is documented.RCTs/meta‑analysis present

Prior authorization and documentation recommended.

Evidence-based coverage summary

Summary of coverage-relevant evidence and product-specific conclusions from this section

Products with insufficient evidence: For many products (Dual Layer Impax Membrane, DuoAmnion, Duograft variants, E‑Graft, Emerge Matrix, Enclose TL Matrix, Enverse, EPIEFFECT, EpiFix Injectable), published studies are few or lacking; no conclusion of benefit can be made.

Statements derived from explicit 'studies are lacking' language.

Products with supportive but limited evidence: EpiFix/EpiCord (dHACM/dHACA) have multiple RCTs and systematic reviews showing higher proportions of complete healing and shorter time‑to‑heal in DFUs and some VLUs when used as adjuncts to SOC, though limitations (small trials, funding sources, heterogeneity) temper conclusions.

Reported 12‑week healing rates in trials ranged widely (eg, up to 97% in small trials); require careful application of trial criteria for coverage.

EpiFix/dHACM — studied indications

Evidence summary and situations where product use has been studied

EpiFix/dHACM evidence: Multiple randomized trials and observational studies report improved complete healing rates and faster time‑to‑heal for diabetic foot ulcers and venous leg ulcers when EpiFix/dHACM is applied as an adjunct to standard wound care; reported improvements at 12 weeks include higher proportions healed and shorter median time to closure in several trials.

Trials required run‑in with SOC, perfusion documentation, and excluded infected wounds; interpret within trial eligibility.

Comparative effectiveness and limitations

Comparative effectiveness findings

Comparative results: Some studies found EpiFix superior to standard care and to certain other advanced products (e.g., Apligraf) in selected trials for percent healed and time‑to‑heal; however, other real‑world retrospective analyses reported differing results favoring living cell constructs in observational data. Study limitations (small sizes, manufacturer funding, retrospective designs) limit generalizability.

Comparative conclusions should be made cautiously and require corroborating evidence.

Products lacking adequate clinical evidence

Products with insufficient evidence

Insufficient evidence products: EPIXPRESS, Esano family, Excellagen, E‑Z‑Derm, FlowerAmnioFlo/Patch, FlowerDerm and similar products have few or limited published clinical studies; therefore benefit for wound treatment cannot be concluded and routine coverage is not supported.

See individual product entries for details.

Grafix and related amniotic/placental membrane products

Evidence-based statements relevant to coverage determinations for Grafix and similar products

Grafix evidence summary: Randomized trials and observational studies suggest Grafix (cryopreserved viable placental membrane / hVWM) may improve healing rates versus standard care in DFUs and VLUs and may benefit wounds refractory to SOC; however, comparative data versus other advanced products are limited and sample sizes are modest.

Large, well‑designed comparative trials are needed to better define patient selection and comparative effectiveness.

Products lacking sufficient published evidence

Products with insufficient evidence

Limited evidence products: Many listed products (e.g., FlowerAmnioPatch, FlowerDerm, Fluid Flow, Foundation DRS Solo, GammaGraft, Genesis Amniotic Membrane, Grafix Core, GRAFIX PLUS, Helicoll) have few or limited published studies and lack robust clinical trial data to support routine coverage.

Individual assessment required if requested with supporting clinical documentation.

Products with limited/inconclusive evidence

Coverage stance for the following named products based on available evidence:

Insufficient evidence products: For each named product (GRAFIX PLUS, Helicoll, hMatrix, HHF10‑P, Hyalomatrix, InnovaMatrix AC/FS, Integra Flowable, InteguPly, Interfyl, Keramatrix, Kerasorb, Keroxx, Lamellas, MatriDerm, Matrion, MatriStem MicroMatrix), evidence is limited (small trials, noncomparative studies, or no studies) and definitive clinical benefit cannot be concluded.limited/inconclusive evidence

See product entries for study summaries and limitations.

Products with limited positive data

Where limited positive signals exist:

Products with small/suggestive studies: Some products (e.g., Integra Flowable Wound Matrix, MatriDerm, MatriStem MicroMatrix, Keramatrix) have small RCTs or case series reporting improved healing metrics versus control or favorable signals, but studies are limited by size, design, or interim reporting and are insufficient to establish broad coverage without additional evidence and case‑specific justification.small/suggestive studies

Clinical review and prior authorization recommended for these products.

Overall evidence-based coverage statement

Coverage stance based on evidence summary for listed products in this document segment

General coverage logic for products in this section: Most named products (Matrion through NeoMatriX and others) have few or limited published studies; therefore routine coverage is not supported unless convincing product‑specific high‑quality evidence is submitted to justify use.

Requests for such products should include detailed clinical justification, trial‑like documentation, and may require prior authorization or be denied without adequate evidence.

Mirragen (BBGFM) — limited positive RCT data

Product-specific favorable evidence (limited)

Mirragen: A small randomized controlled trial (Armstrong et al. 2022) showed Mirragen (BBGFM) plus SOC had higher 12‑week healing rates (70% vs 25%) and greater percent area reduction versus SOC alone in Wagner 1 DFUs, but findings require confirmation in larger studies before broad coverage without prior authorization.12 weeks

Suggestive benefit; require case‑by‑case review and documentation of SOC failure.

MatriStem MicroMatrix — interim RCT data

Product-specific inconclusive evidence

MatriStem MicroMatrix: Interim results from a multicenter RCT comparing MatriStem MicroMatrix to Dermagraft showed no statistically significant difference in healing at the interim analysis; results are interim and insufficient to support routine coverage without final analyses.interim analysis

Await full trial results for definitive conclusions.

Products with insufficient published evidence

General coverage stance based on evidence summaries in this section

Insufficient evidence for most products: For the majority of branded products listed (Myriad Morcells, NeoMatriX, NeoPatch, NEOX family, NeoStim family, Novachor, Novafix, NovoSorb SynPath, Omeza, ORION, Overlay SL Matrix, PalinGen, etc.), few or no published studies exist; therefore routine coverage is not supported absent robust supporting clinical evidence.

Expect prior authorization review and requirement for detailed documentation if coverage requested.

dACM evidence (NuShield)

Products with some randomized trial evidence

dACM (NuShield) for diabetic foot ulcers: A multicenter prospective RCT (Cazzell et al. 2024) of dehydrated amnion‑chorion membrane (NuShield/dACM) plus SOC versus SOC alone in DFUs reported statistically higher frequency of wound closure and shorter median time to closure at 12 weeks, though limitations included lack of blinding and controlled offloading; additional RCTs and real‑world studies are recommended.12 weeks

Evidence promising but requires replication and broader data for broad coverage.

Plantar fasciitis (injectable amniotic products)

Injectable amniotic products for plantar fasciitis

Small RCTs/pilot trials: Pilot and small randomized trials (Hanselman 2015; Zelen 2013; Cazzell et al. 2018) reported that cryopreserved or micronized dHACM injections may be safe and can improve pain and function for plantar fasciitis compared with placebo or corticosteroid in some measures; studies were small, short‑term, and underpowered for long‑term comparative effectiveness.short follow‑up, small samples

Comparative effectiveness versus other injectables or surgery remains uncertain.

EpiFix and Grafix (non-injectable) have explicit application and duration limits in this policy: use is limited to one application per week and only up to 12 weeks total. Requests exceeding these frequency or duration limits are described as not medically necessary. The policy also states that numerous other branded skin and soft-tissue substitute products are considered unproven or not medically necessary due to insufficient evidence of efficacy.

The policy limits use of skin substitutes to acute or uninfected chronic wounds and related soft-tissue indications; use for actively infected wounds is not supported by the trial-based indications summarized in the document. When considered for coverage, these products are intended as adjuncts to standard wound care and are appropriate only for wound types consistent with trial inclusion (for example, diabetic foot ulcers and venous leg ulcers that are full-thickness but not probing to tendon/muscle/bone and without clinical infection).

For a large number of named amniotic, placental, dermal, and other matrices the policy explicitly states that published studies are few or lacking and therefore it is not possible to conclude these products confer a beneficial effect on health outcomes. The document repeatedly summarizes individual product entries with near-identical language noting an absence of adequate clinical trial evidence; consequently these products are categorized as unproven or investigational for wound-healing indications.

Products for which only a few published studies exist or for which available studies are low quality are treated in the policy as having insufficient evidence. Such products are generally considered investigational or not medically necessary for wound-healing indications in the absence of higher-quality comparative randomized data or replication of positive findings.

The policy lists many specific products for which evidence is insufficient, including but not limited to: Abiomend Membrane and Hydromembrane (and Xplus variants), ACApatch, Acesso family (Acesso, Acesso AC/DL/TL), Activate Matrix, AdvoGraft products, AeroGuard/NeoGuard, AlloGen, alloPLY, AlloSkin/AlloWrap, AmchoPlast variants, AmnioBand/Guardian entries, AmnioBind/DermaBind, AmnioCore, Amnio-Maxx, AmnioPlast, AMNIOREPAIR/AltiPly, Amniotext and Amniotext Patch, Amnion Bio, AMNIPLY, Apis, Architect, Artacent variants, ArthroFLEX, Ascent, AxobioMembrane and many others. Each of these entries is described in the source as having few published studies or lacking sufficient data to conclude a clinical benefit.

Across the product entries the policy reiterates that single small trials, registry reports, or noncomparative case series frequently comprise the evidence base for many brands. Where studies exist they are often heterogeneous in patient mix, wound types, and application protocols; consequently the document emphasizes that such limited or inconsistent data do not establish reliable evidence of efficacy.

Biovance is given as an example of limited evidence: available data include small, heterogeneous registry studies and observational series with variable site practices and follow-up. The policy specifically notes limitations such as small sample sizes, lack of controls, incomplete outcome reporting, and heterogeneity of wound types and treatments, which together limit generalizability and preclude firm conclusions of benefit.

Corplex P/Theracor P/Allacor P are described as products intended to be packed into the wound environment rather than used as a surface covering or barrier membrane. The policy highlights this intended packing use to caution against treating these products interchangeably with topical coverings.

When no compelling comparative or randomized evidence is available for a product, the policy advises that the product should be considered investigational or unproven. Absent head-to-head trials or replicated RCTs demonstrating improved wound-closure or clinically meaningful outcomes, coverage should not be assumed and prior authorization review is likely required to justify use.

Trials commonly excluded wounds with active infection, inadequate perfusion, ulcers probing to tendon/muscle/capsule/bone, or ulcers caused by conditions other than the target indication. Patients whose wounds show signs of infection, insufficient circulation, or deep structural involvement therefore may not meet the trial-like eligibility criteria the policy relies on and such characteristics may preclude coverage absent specific supporting documentation.

Some comparative trials used control groups that did not receive other advanced therapies, which limits the ability to conclude superiority over alternative advanced products. The policy notes this limitation when interpreting trial results and when considering whether evidence justifies broader coverage.

Applicable Billing Codes

Applicable HCPCS Codes (A-codes)HCPCS

A2001	InnovaMatrix AC, per sq cm
A2002	Mirragen Advanced Wound Matrix, per sq cm
A2004	XCelliStem, 1mg
A2005	Microlyte Matrix, per sq cm
A2006	NovoSorb SynPath dermal matrix, per sq cm
A2007	Restrata, per sq cm
A2008	TheraGenesis, per sq cm
A2009	Symphony, per sq cm
A2010	Apis, per sq cm
A2011	Supra SDRM, per sq cm

1–10 of 29

1/3

Applicable HCPCS Q Codes (part 1)HCPCS

Q4100	Skin substitute, not otherwise specified
Q4110	PriMatrix, per sq cm
Q4111	GammaGraft, per sq cm
Q4112	Cymetra, injectable, 1 cc
Q4114	Integra flowable wound matrix, injectable, 1 cc
Q4115	AlloSkin, per sq cm
Q4117	HYALOMATRIX, per sq cm
Q4118	MatriStem micromatrix, 1 mg
Q4121	TheraSkin, per sq cm
Q4122	DermACELL, per sq cm

1–10 of 11

1/2

Applicable HCPCS Q Codes (part 2)HCPCS

Q4125	Arthroflex, per sq cm
Q4126	MemoDerm, DermaSpan, TranZgraft or InteguPly, per sq cm
Q4127	Talymed, per sq cm
Q4130	Strattice TM, per sq cm
Q4132	Grafix Core and GrafixPL Core, per sq cm
Q4133	Grafix PRIME, GrafixPL PRIME, Stravix and StravixPL, per sq cm
Q4134	HMatrix, per sq cm
Q4135	Mediskin, per sq cm
Q4136	E-Z-derm, per sq cm
Q4137	AmnioExcel, AmnioExcel Plus or BioDExcel, per sq cm

Products discussed (no billing codes listed in this segment)mixed

	GRAFIX PLUS - studies lacking; lyophilized human placental chorionic membrane-based skin substitute
	Helicoll - limited studies; acellular collagen matrix
	hMatrix - few published studies; acellular dermal matrix allograft
	Human Health Factor 10 Amniotic Patch (HHF10-P) - few published studies; single-layer amniotic allograft
	Hyalomatrix - several non-comparative studies; hyaluronic acid derivative pad
	InnovaMatrix AC or Innovamatrix FS - few published studies; porcine placenta ECM products
	InteguPly - few published studies; human acellular dermal matrix
	Interfyl - few published studies; decellularized placental disc
	MatriDerm - several studies with limitations; bovine collagen/elastin matrix
	MatriStem MicroMatrix - several studies with limitations; porcine urinary bladder ECM

inv-67: HgA1c

HgA1c< 12% (within the last 90 days)

inv-68: Ankle-Brachial Index (ABI)

Ankle-Brachial Index (ABI)0.7 - 1.2

inv-69: Initial trial of standard care

Initial trial of standard careAt least 4 weeks

inv-70: Recommended minimum study/follow-up period in trials

Recommended minimum study/follow-up period in trials12 weeks (report recurrence at 6 months)

Prior Authorization, Documentation, and Step Therapy

Prior Authorization

Prior Authorization Required for Listed Q-codes

Prior authorization is required for products billed with the Q-codes enumerated in the policy. Requests must include the product name, Q-code(s), indication, and complete clinical documentation as listed below to be considered. Absent required documentation, submissions may be returned or denied.

Prior authorization required for all listed Q-codes and associated brand names
Include product-level evidence and rationale when submitting

Prior Authorization

PA Should Reference Product-level Evidence

Prior authorization decisions will reference product-level evidence. Because comparative effectiveness and quality of evidence vary by brand, reviewers will consider randomized controlled trials, well-designed observational studies, registries, and systematic reviews specific to the named product when evaluating medical necessity.

Attach copies or citations of RCTs, pivotal trials, and relevant systematic reviews for the requested product
If relying on small or single-arm studies, provide justification for how the evidence supports use in the requested patient

Policy Background and Scope

This policy addresses the use of skin and soft tissue substitutes, including amniotic and dermal products, for wounds such as diabetic foot ulcers and thermal burns. It defines product classes and sets coverage logic that distinguishes a few supported uses (for example, EpiFix/EpiCord, Grafix, and TransCyte in defined indications) from a much larger group of products judged unproven due to limited or absent clinical evidence.

Key Definitions and Product Terms

inv-133: Full-Thickness Thermal Burn (Third Degree Burn) — definition entry

DefinitionA burn with destruction of all layers of the skin involving epidermal and dermal layers, with varying amounts of subcutaneous involvement.

Also calledThird-degree burn

Clinical implicationOften requires surgical management and possible grafting/autograft placement

inv-134: Partial-Thickness Thermal Burn (Second Degree Burn) — definition entry

DefinitionA burn involving the epidermis and only part of the dermis; deep partial-thickness burns involve most of the dermis and leave few intact skin appendages and nerve endings.

Also calledSecond-degree burn (partial-thickness)

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for Pennsylvania Only)

Policy CodePolicy CS153PA.W

Change TypeNo material changes

Effective DateNov 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and document ≥4 weeks of failed standard wound care plus perfusion and HbA1c criteria when requesting EpiFix or Grafix for diabetic foot ulcers.

SourceLink

On This Page

Products lacking adequate evidence: Many named products lack adequate randomized or comparative studies; absence of robust evidence may lead to noncoverage or coverage only within clinical trials or documented exceptions.no adequate RCTs or comparative studies

See product‑specific entries for details and citations.

Implication for coverage: dHACA (AmnioBand/Guardian) may be considered as an adjunct to standard of care for nonhealing DFUs or VLUs when patient and wound characteristics match trial inclusion criteria and prior conservative therapies have failed, but adoption should be cautious pending confirmatory, larger, blinded trials.match to trial criteria and documentation of SOC failure

Prior authorization recommended; require perfusion metrics and SOC documentation.

Products supported only by small observational studies:

Some products (e.g., Derma‑Gide, DermaPure, Dermacyte) have small observational or pilot studies suggesting possible efficacy but lack RCT‑level evidence; insufficient for routine coverage without stronger data.

observational/small studies

Clinical review required for individual cases.

inv-71: Perfusion and labs thresholds used in trials

Perfusion and labs thresholds used in trialsABI/SPP/TCOM thresholds; HbA1c and creatinine cutoffs noted in trial eligibility

Documentation Required

Document Standard of Care and Wound Eligibility

Prior authorization requests must document that appropriate standard of care (SOC) was attempted and the wound meets eligibility criteria used in pivotal trials. Include wound type, size, duration, percent change during SOC run-in, and exclusion criteria addressed in trials.

Document wound type (DFU, VLU, etc.), location, baseline area (cm2), and duration
Document SOC measures used (debridement, offloading, compression, dressings) and duration (typically ≥4 weeks)
Provide percent wound reduction during run-in (e.g., ≤25%–50% improvement thresholds used in some trials)

Documentation Required

Document Prior Conservative Therapy and Perfusion

Document prior conservative therapy and objective perfusion measures. Many trials required objective circulation assessment and excluded infected wounds. Provide recent vascular testing and relevant lab values.

Provide objective perfusion data: ABI (report value), TcPO2 (mmHg), or SPP (mmHg); acceptable thresholds used in trials (e.g., ABI 0.7–1.2; TcPO2 ≥30 mmHg; SPP >30 mmHg)
State presence or absence of infection and how infection is being managed
Report relevant comorbid labs: recent HbA1c (within 60–90 days), serum creatinine

Prior Authorization

Prior Authorization Likely for Limited-evidence Products

Prior authorization is likely required for many amniotic/placental-derived and other advanced matrices, especially products with limited or mixed evidence. Expect case-by-case review when evidence is sparse.

PA likely for products with limited published RCTs or only single-arm studies
Provide clinical rationale and any institutional outcome data if available

Prior Authorization

PA Recommended for CorMatrix Applications

For CorMatrix applications, prior authorization is recommended and reviewers may request site-specific outcome data or rationale because clinical results have been mixed and study quality limited.

Provide indication-specific rationale and any institutional outcomes if requesting CorMatrix use
Include pertinent surgical details and anticipated benefits over alternative materials

Prior Authorization

PA Recommended for Products with Limited RCT Evidence

When RCT evidence is limited (e.g., single small RCTs or single-arm studies), prior authorization is recommended and requests should include detailed wound metrics and prior SOC to support medical necessity.

For products supported by small RCTs (DermACELL, dACM examples), include wound size, depth, prior SOC details, and similarity to trial populations
If relying on registry or single-arm data, document why the patient matches the studied population

Documentation Required

PA Should Document Prior Conservative Therapy and Objective Wound Metrics

Prior authorization requests should document prior conservative therapy and objective wound metrics in a trial-like format. Reviewers expect the same essential elements used in clinical trials to assess eligibility and likely benefit.

Include baseline wound photographs, measurement method, and serial measurements (weekly preferred)
Document % area reduction during SOC run-in and reason for escalation to advanced therapy

Prior Authorization

PA Will Require Treatment History and Application Frequency

Prior authorization will require treatment history and planned application frequency/protocol. Many studies used weekly or biweekly applications and capped treatment duration; provide the intended schedule and maximum number of applications.

State proposed application frequency (weekly, biweekly) and total planned duration (e.g., up to 12 weeks where supported)
If requesting a different frequency or duration than studied, provide clinical justification and supporting evidence

Prior Authorization

PA Likely When Used as Adjunctive Therapy

When products are used adjunctively after failing SOC, prior authorization is likely required and reviewers will expect documentation showing refractory status to SOC before approving adjunctive therapies.

Demonstrate failure of appropriate SOC (duration and specific measures) prior to adjunctive product use
Provide timeline showing dates of SOC interventions and lack of adequate healing

Prior Authorization

PA Advised for Limited-evidence Advanced Matrices

For advanced matrices with limited evidence, prior authorization is advised. Requests should include objective wound data, prior SOC, and explicit rationale for selecting the requested product over alternatives.

Provide comparison to alternative advanced products and justification for product selection
If institutional protocols or registry outcomes support use, include those data

Prior Authorization

PA and Rationale

Provide a clear clinical rationale in the prior authorization request explaining why the requested product is medically necessary for this patient. When evidence is limited, a detailed rationale increases the likelihood of a favorable review.

State the unmet clinical need, prior therapies tried, and anticipated benefit of the requested product
Include details that align the patient with populations in supporting studies

Prior Authorization

PA Likely When Evidence Limited

Prior authorization is more likely to be required when published evidence is limited or conflicting. Submissions lacking supportive data or clinical rationale may be subject to additional review or denial.

If evidence is limited, expect requests to be scrutinized and for medical records to be requested
Provide any real-world outcomes or institutional data to support the request

Denial Risk

Requests That Do Not Meet Criteria May Be Denied

Requests that do not meet the documented criteria (including documented SOC failure, perfusion parameters, or exclusion of infection) may be denied. Pennsylvania exceptions (PARP) or case-by-case reviews do not guarantee approval.

Failure to provide required run-in SOC documentation (e.g., ≥4 weeks SOC and measured % reduction) may result in denial
Requests outside trial-supported indications, frequencies, or durations (e.g., >1 application/week or >12 weeks for EpiFix/Grafix) may be denied

Step Therapy

Failure to Meet SOC Prior to Adjunctive Therapy

Failure to meet standard of care prior to adjunctive therapy is a common reason for denial. Document the complete SOC package (debridement, infection control, offloading or compression) and trial duration before escalation.

List dates and types of SOC interventions and evidence of inadequate response
If any SOC component was not possible (e.g., contraindication to compression), document the clinical reason

Denial Risk

Risk for Products Lacking Evidence

Products lacking sufficient evidence are at risk for non-coverage. Submissions for such products should include protocolized documentation and, when available, product-specific supportive studies or institutional outcome data.

If requesting a product listed as investigational or with inconclusive evidence, justify with clinical need and any supportive data
Be prepared for additional documentation requests or peer-to-peer review

Denial Risk

Insufficient Evidence May Trigger Coverage Denial

Insufficient evidence may trigger coverage denial. Many products in the policy are considered investigational for wound uses unless robust, product-specific evidence is provided.

Common reasons for denial: lack of trial data, heterogeneity of wound populations, absence of long-term outcomes
Provide high-quality evidence and clear match between patient and study populations to mitigate denial risk

Denial Risk

Insufficient Evidence May Trigger Denial

Insufficient evidence or lack of required documentation may result in denial. Examples include products with only preliminary or single-arm data (e.g., Cellesta Duo) or uses not studied in trials.

If product has few published studies, include all available data and specific reasons why the product is clinically necessary for this patient
Consider alternative covered products with stronger evidence when possible

Documentation Required

Run-in and Eligibility Criteria May Affect Coverage

Run-in and trial eligibility criteria used in pivotal studies may affect coverage. Improvements during run-in (e.g., >25%–50% area reduction) sometimes precluded study enrollment; documentation of run-in results influences PA decisions.

Provide run-in period measurements and demonstrate failure to meet improvement thresholds required for study eligibility
If no run-in was performed, explain clinical rationale and provide serial wound data

Denial Risk

Documentation-dependent Coverage Risk

Coverage decisions are documentation-dependent. Inclusion thresholds referenced in trials (ABI, TcPO2, absence of infection) should be documented; absence of these data may lead to denial or requests for additional information.

Ensure vascular studies and infection assessments are included with the PA request
Document contraindications (e.g., active Charcot, malignancy at ulcer site) if present

Denial Risk

Evidence Limitations May Trigger Coverage Scrutiny

Evidence limitations may trigger additional scrutiny or requests for peer-to-peer review. Products with heterogeneous study designs or industry sponsorship may prompt extra documentation requests.

Anticipate requests for longer-term outcomes, recurrence rates, and adverse event reporting when evidence is limited
Provide follow-up plans and monitoring strategy if seeking approval

Denial Risk

Limited Evidence May Lead to Denial

Limited evidence may lead to denial for many products listed in the policy. When evidence is promising but limited, provide trial protocols, number of planned/used applications, and outcomes monitoring plans to support authorization.

If approved, consider documenting intended outcome measures and follow-up schedule to support medical necessity for continuation

Documentation Required

Suggested Clinical Documentation to Support Medical Necessity

Suggested clinical documentation to support medical necessity: provide a concise package including indication, prior treatments, objective wound metrics, perfusion data, comorbidities, and product-specific evidence.

Indication and diagnosis with ICD-10 code
Baseline wound size (cm2), depth, and location with dated photos
Duration of wound prior to request
SOC treatments and dates (debridement, offloading/compression, dressings) and % change during run-in
Perfusion studies (ABI, TcPO2, SPP) and recent HbA1c/creatinine
Planned application frequency, number of applications, and total course duration
Relevant product-specific studies or publications attached

Documentation Required

Relevant Clinical Documentation to Support Use

Relevant clinical documentation to support use includes matching the patient to trial populations (wound size, depth, duration) and supplying prior therapy history and outcome expectations.

Explain how the patient's wound aligns with inclusion criteria of supporting trials
If deviating from trial parameters, provide rationale and any supporting data

Documentation Required

Clinical Evidence Supporting Requests

Clinical evidence supporting requests should include indication, prior therapy, wound severity, and any observed outcomes if prior off-label or investigational treatments were used.

List prior advanced wound products used, dates, and responses
Provide objective outcome measures and photographs when available

Documentation Required

Suggested Documentation for Biovance Evaluations

For Biovance evaluations, include study limitations and a detailed clinical history; the evidence is inconclusive and reviewers will expect robust documentation when requesting coverage for Biovance formulations.

Attach ECRI or other independent assessments and explain how the patient fits or differs from studied cohorts
Provide complete SOC history and wound metrics

Documentation Required

Supporting Clinical Documentation

Supporting clinical documentation should mirror trial reporting: ulcer inclusion/exclusion criteria, run-in results, number of applications used in trials, protocolized follow-up, and outcome measures.

Number of applications used per healed wound in trials (report expected range)
Planned follow-up frequency and objective endpoints (e.g., % area reduction at 4 weeks, closure at 12 weeks)

Documentation Required

Typical Clinical Documentation Seen in Trials

Typical clinical documentation seen in trials includes inclusion/exclusion criteria, baseline wound characteristics, run-in period outcomes, and serial measurements. Replicate these elements in PA submissions.

Include trial-like data collection: dates, measurements, photos, debridement notes, offloading/compression details

Documentation Required

Suggested Supporting Documentation Elements

Suggested supporting documentation elements for PA include number of planned applications, application protocol, monitoring plan, and measurable outcome endpoints to align with trial evidence.

State planned number of applications, frequency, and criteria for discontinuation
Provide measurable endpoints and timeline for reassessment (e.g., re-evaluate at 4 and 12 weeks)

Documentation Required

Supportive Clinical Documentation for Limited-evidence Products

For products supported by limited evidence, include trial similarity and justification when relying on small studies or observational series. Show how the patient's wound and comorbidities compare to those in the supporting studies.

Map patient characteristics to trial cohorts (age, wound size, duration, comorbidities)
If extrapolating from a different wound type, provide rationale and evidence

Documentation Required

Documentation When Relying on Available Trial Evidence

When relying on available trial evidence, document the request population to match the trial population (wound type/size/duration) and include study citations to support the request.

Cite the specific trial(s) and note concordant inclusion/exclusion features between the patient and the study

Documentation Required

Document Wound Characteristics and Protocol

Document wound characteristics and the treatment protocol when requesting coverage for products with RCT evidence (e.g., NuShield, dACM). Include application counts, frequency, and outcome timelines used in the supporting trials.

Provide baseline wound metrics and planned adherence to the trial-derived protocol
State monitoring and criteria for discontinuation or alternative therapy

Step Therapy

Consider Step-up After Failed Standard Care

Consider step-up therapy after documented failure of standard care. Many trial designs implied stepwise escalation to advanced biologics after inadequate response to SOC; prior authorization will reflect this stepwise approach.

Document unsuccessful SOC and rationale for advancing to the requested product
If prior advanced biologics were used, include dates, products, and responses

Step Therapy

Step Therapy Implied (Conservative Care Before Allograft)

Step therapy is implied by trials that required conservative care before enrollment. PA requests must show conservative care efforts were made and failed before considering allografts or advanced products.

Show dates and descriptions of conservative measures and objective lack of sufficient healing

Step Therapy

Evidence of Prior Standard-of-Care Failure

Evidence of prior SOC failure should be documented (for example, <50% reduction after 2–4 weeks). Reviewers will use these thresholds to determine eligibility for advanced products.

Report percent reduction in wound area during SOC run-in and the duration of SOC attempted

Step Therapy

Stepwise Use Implied for Some Products

Stepwise use is implied for some products by trial designs that included prior use of SOC and sometimes other advanced therapies. Prior authorization requests should document prior steps taken and justify progression.

If prior advanced products were used, include trial-like documentation of their response and reason for switching

Step Therapy

Step from Standard of Care to Allograft in Trials

Clinical trials commonly used a step from SOC to allograft after documented failure. PA requests must make this step explicit: show SOC trial dates, response, and rationale for initiating allograft therapy.

Provide an explicit timeline: SOC start date, run-in measurements, date of decision to escalate, and planned allograft schedule

Step Therapy

Step Therapy / Prior Conservative Treatment

Step therapy and prior conservative treatment expectations: document debridement, offloading/compression, infection control, and moisture balance prior to coverage of advanced products.

List each SOC component and dates performed; if any SOC element was contraindicated, document the reason

Clinical implicationMay require specialized dressings or grafting depending on depth and healing potential

inv-135: Skin substitute — definition

DefinitionA biologic, synthetic, or biosynthetic material that provides temporary or permanent coverage of wounds to mimic normal skin properties and promote healing.

IncludesAcellular dermal matrices, human placental membranes (amnion), decellularized dermis, and bioengineered cellular products

PurposeProvides a matrix for cell migration and tissue regeneration to support wound closure

inv-136: Kumar classification (Class 1-3) — classification definition used in policy

Class 1Temporary dressings (single- or bi-layer) with/without negative pressure (e.g., amniotic membrane as biologic dressing)

Class 2Single-layer durable substitutes (epidermal or dermal substitutes)

Class 3Composite skin substitutes (grafts, bioengineered skin) — replace both epidermis and dermis

inv-137: placental membrane product — definition

DefinitionMinimally manipulated human placental membrane composed of amnion, chorion, and intermediate layers that serve as a biological barrier or wound cover.

FormulationDehydrated, cryopreserved, decellularized or other processed placental membrane products

Intended useProtective coverage for acute and chronic wounds as an adjunct to standard care

inv-138: amnion/chorion membrane allograft — definition

DefinitionDehydrated or processed layers of amnion and chorion intended to act as a protective barrier and cover for acute and chronic wounds.

CompositionTypically two amnion layers and one chorion layer in some products (example: ACApatch)

UseApplied as a wound covering to modulate inflammation and support healing

inv-139: AlloWrap — product definition entry

ProductAlloWrap: human amniotic membrane designed to provide a biologic barrier following surgical repair.

Intended useBiologic barrier/cover after surgical procedures

Evidence noteFew published studies available per policy review

inv-140: AmchoPlast (and variants) — product definition entry

Product familyAmchoPlast (and variants): minimally manipulated, dehydrated human amnion/chorion membrane allografts intended as protective wound covers.

VariantsAmchoPlast, AmchoPlast Excel, AmchoPlast FD

Evidence noteStudies are lacking to conclude benefit

inv-141: AmnioBand / Guardian — product definition entry

ProductAmnioBand / Guardian: human placental membrane allografts (dehydrated amnion/chorion) marketed under two names and evaluated in RCTs.

Clinical noteStudied in randomized trials for venous leg ulcers and diabetic foot ulcers

Evidence statusInsufficient evidence overall; larger studies needed

inv-142: dHACA / dHACM — definition for dehydrated human amnion/chorion allograft

DefinitiondHACA / dHACM: dehydrated human amnion and chorion allograft products used as skin/soft tissue substitutes.

FormsDehydrated sheets, particulates, or micronized forms reported in trials and injections

Clinical useApplied as adjunctive therapy in DFU and VLU trials with documented application schedules

inv-143: Placental membrane allograft (PM) — definition entry

DefinitionPlacental membrane allograft (PM): terminally sterilized or minimally manipulated placental membrane products containing amnion, chorion, and sometimes intermediate layers.

Intended effectBarrier or scaffold to support acute and chronic wound healing

ProcessingMay be terminally sterilized, dehydrated, decellularized, or cryopreserved

inv-144: dHACM / mDHACM — definition entry

TermdHACM / mDHACM: dehydrated human amnion/chorion membrane and micronized dehydrated human amnion/chorion membrane formulations used as patches or injectable products.

FormsMicronized/injectable and sheet/patch formats reported in studies

Evidence noteRCTs and reviews assess effectiveness for DFU and other indications with limited-duration follow-up

inv-145: DLAM — Double-layer amniotic membrane definition (Artacent)

DefinitionDLAM (Double-layer amniotic membrane): a placental-based patch (two amnion layers) intended to deliver growth factors and cover wounds (example: Artacent).

Clinical noteUsed in observational DFU analyses with weekly/biweekly application schedules

Evidence statusSmall observational data reported; larger trials planned

inv-146: Amniotic/placental allograft — general definition

DefinitionAmniotic/placental allograft: biologic wound covering derived from human amniotic or placental tissues processed as dehydrated, decellularized, cryopreserved, or flowable products.

PurposeProtect or support wound healing as adjuncts to standard care

Processing variabilityProduct processing and composition vary widely across manufacturers

inv-147: Collagen wound matrix (bio-ConneKt) — definition

ProductCollagen wound matrix (bio-ConneKt): reconstituted collagen derived from equine tendon for moderately to heavily exuding wounds.

Intended useDressing for exuding wounds and ulcers

Evidence noteFew published studies available

inv-148: CLARIX Regenerative Matrix — product definition

ProductCLARIX Regenerative Matrix: cryopreserved human amniotic membrane and umbilical cord allograft intended for wound healing and surgical coverings.

VariantQuick Peel version for reduced bulk in applications

Evidence noteFew published studies; evidence insufficient to conclude benefit

inv-149: CLARIX FLO — product definition

ProductCLARIX FLO: particulate form of CLARIX comprising amniotic membrane and umbilical cord products intended to facilitate tissue replacement or supplementation.

FormulationParticulate/flowable for injection or topical application

Evidence noteLimited published data; comparative effectiveness uncertain

inv-150: CorMatrix SIS-ECM — product definition

ProductCorMatrix SIS-ECM: non-cross-linked extracellular matrix from porcine small intestinal submucosa used in cardiac and surgical applications.

ConcernsMixed outcomes reported including reoperation and patch failure in some series; larger studies needed

Intended useCardiac patching, pericardial reconstruction, valve repair—site-specific applications

inv-151: Amniotic membrane allograft — definition

DefinitionAmniotic membrane allograft: dehydrated or preserved placental-derived membrane composed of amnion/chorion layers intended to act as a barrier and provide extracellular matrix components to support healing.

FormsDehydrated sheets, cryopreserved grafts, flowable particulates

UseApplied as wound coverings or surgical adjuncts

inv-152: Acellular dermal matrix (ADM) — definition

DefinitionAcellular dermal matrix (ADM): decellularized human dermis providing a structural scaffold for cell migration and tissue repair in chronic wounds and soft-tissue defects.

ExamplesDermACELL and related H‑ADM products analyzed in meta-analyses

Clinical noteSome RCTs/meta-analyses report higher healing rates vs SOC at 12 weeks but overall evidence limited

inv-153: Dual Layer Impax Membrane — definition

ProductDual Layer Impax Membrane: sterile dehydrated dual-layer human amniotic membrane allograft intended as a barrier or cover for acute and chronic wounds.

Evidence noteFew published studies available; benefit not established

Intended useBarrier/cover to protect wounds from environment

inv-154: DuoAmnion — definition

ProductDuoAmnion: a dehydrated allograft derived from donated human amniotic membrane serving as a barrier and protective coverage for wounds.

Evidence noteStudies lacking to conclude benefit

Intended useProtective wound coverage

inv-155: Duograft / duoGRAFT / triGRAFT — definition

ProductsDuograft / duoGRAFT / triGRAFT: dehydrated dual- or triple-layer placental/amniotic membrane allografts intended as protective barriers at injury or surgical sites.

VariantsDuograft AA, duoGRAFT AC, triGRAFT FT

Evidence noteFew published studies; clinical benefit unproven

inv-156: EpiCord / EpiFix — definition and product family

Product familyEpiCord / EpiFix: minimally manipulated, dehydrated umbilical cord (EpiCord) or amnion/chorion (EpiFix) allografts used to treat chronic and acute wounds.

EvidenceMultiple RCTs and systematic reviews report improved healing rates in DFUs when used adjunctively, though limitations exist

FormulationsNon-injectable sheets (EpiFix) and umbilical cord-derived products (EpiCord)

inv-157: EPIXPRESS — definition entry

ProductEPIXPRESS: lyophilized, non-viable cellular allograft derived from human amniotic membrane preserving extracellular matrix components.

Evidence noteFew published studies addressing clinical benefit

Intended useBarrier/cover for wound applications

inv-158: Esano (A/AAA/AC/ACA) — definition entry

Product familyEsano (A/AAA/AC/ACA): dehydrated or decellularized human amniotic membrane sheets/allografts with varying layers intended as wound coverings.

VariantsEsano A, Esano AAA, Esano AC, Esano ACA

Evidence noteFew published studies; benefit unestablished

inv-159: Excellagen — definition entry

ProductExcellagen: pharmaceutically formulated fibrillar Type I bovine collagen gel for wound care.

Intended useWound healing adjunct for chronic/acute wounds

Evidence noteFew published studies available

inv-160: E-Z-Derm — definition entry

ProductE-Z-Derm: porcine-derived biosynthetic xenograft intended for partial-thickness skin loss and ulcerations.

UsePartial-thickness wounds, donor sites, ulcerations

Evidence noteLimited studies available

inv-161: FlowerAmnioFlo / FlowerAmnioPatch / FlowerDerm — product definition entries

Product familyFlowerAmnioFlo / FlowerAmnioPatch / FlowerDerm: Flower Orthopedics products (liquid, patch, hydrated dermal matrix formats) intended for wound/burn treatment.

FormsFlowerAmnioFlo (liquid injectate), FlowerAmnioPatch (dehydrated patch), FlowerDerm (hydrated dermal matrix)

Evidence noteFew published clinical studies; benefit unproven

inv-162: Grafix (vCPM / hVWM) — product definition and characteristics

ProductGrafix (vCPM / hVWM): cryopreserved placental/amnion-derived viable wound matrix containing ECM, growth factors, and viable cells.

IndicationAdjunctive therapy for chronic wounds including DFUs; RCT data suggest improved healing vs SOC

Evidence noteRCTs and observational studies show potential benefit but additional comparative trials warranted

inv-163: Other named products — assorted product definitions in this segment

SummaryOther named products: a range of dehydrated, hydrated, cryopreserved, lyophilized, or collagen-based allografts/biologic dressings with varying compositions (amnion, dermis, chorion, animal collagen).

Evidence noteMost have few or limited published outcome data; benefit not established

ExamplesGrafix Core, GRAFIX PLUS, Helicoll, Genesis Amniotic Membrane, Fluid Flow, Foundation DRS Solo

inv-164: Acellular dermal matrix / extracellular matrix (ECM) — definition

DefinitionAcellular dermal matrix / extracellular matrix (ECM): biologic scaffolds derived from human or animal tissues processed to remove cells while retaining structural proteins to support wound healing.

ExamplesHuman‑derived ADMs, porcine bladder matrices, synthetic ECM scaffolds

Clinical noteSome ADMs have RCT/meta-analysis data suggesting benefit in DFUs; evidence generally heterogeneous

inv-165: Amniotic membrane / placental allograft — definition

DefinitionAmniotic membrane / placental allograft: human birth-tissue derived membranes (amnion/chorion) used as coverings or barriers to protect wounds and modulate inflammation.

FormsDehydrated sheets, cryopreserved grafts, injectable/micronized products

Clinical implicationWidely used as adjunctive therapy in DFU/VLU trials with varying reported outcomes

inv-166: Keratin-based dressing — definition

DefinitionKeratin-based dressing: dressings composed of keratin proteins (animal- or wool-derived) intended to support epithelialization and tissue regrowth.

UseIntended for partial- and full-thickness wounds to support epithelialization

Evidence noteSeveral studies exist but limitations noted; not conclusive

inv-167: Matrion — definition

ProductMatrion: decellularized human placental membrane available in membrane, injectable, and sponge configurations to modulate inflammation and enhance healing.

Intended useWound, tendon, and nerve application as barrier and regenerative adjunct

Evidence noteFew published studies; benefit unproven

inv-168: MatriStem MicroMatrix — definition

ProductMatriStem MicroMatrix: porcine urinary bladder–derived extracellular matrix intended for surgical wound care, pelvic floor support, burns, and wound healing.

Evidence noteSeveral studies including an interim RCT report; results inconclusive

Clinical noteInterim analyses reported without definitive superiority over comparators

inv-169: Mirragen Advanced Wound Matrix (BBGFM) — definition

ProductMirragen Advanced Wound Matrix (BBGFM): synthetic resorbable wound substitute of borate-based glass fibers/particulates providing scaffold for revascularization.

EvidenceOne small RCT reported higher 12-week healing rates versus SOC (suggestive benefit) but requires confirmation

Intended useAdjunct for DFUs and other chronic wounds

inv-170: Myriad Morcells — definition

ProductMyriad Morcells: ovine-derived extracellular matrix particulate scaffold intended to support cell infiltration and vascular ingrowth for wound healing.

FormatParticulate 'Morcells' scaffold

Evidence noteStudies lacking; benefit unproven

inv-171: NeoPatch — definition

ProductNeoPatch: dehydrated human placental membrane allograft composed of amnion and chorion intended as a wound covering.

Evidence noteFew published studies; benefit not established

Intended useProtective wound coverage

inv-172: NovoSorb SynPath — definition

ProductNovoSorb SynPath: synthetic porous biodegradable polymer dermal matrix used as a scaffold to support cellular repair and temporary wound closure (BTM).

Clinical useScaffold for tissue regeneration and temporary wound closure

Evidence noteFew published studies; benefit unproven

inv-173: NuShield — definition and product note

ProductNuShield: protective patch derived from amniotic membrane indicated as an adhesion barrier, wound covering, and adjunct to soft tissue healing.

EvidenceLimited studies; a recent RCT (dACM/NuShield) reported promising DFU results but additional data needed

UsesAdhesion barrier, tendon/nerve protection, wound covering