CurrentUnitedHealthcarePolicy CS153NM.G

Skin and Soft Tissue Substitutes (for New Mexico Only)

Medical policy governing coverage and medical necessity criteria for skin and soft tissue substitute products for members in New Mexico, including specific covered products, not medically necessary items, and applicable billing codes.

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for New Mexico Only)

Policy CodePolicy CS153NM.G

Change TypeNo material change

Effective DateApril 1, 2026

Next Review Date

Key ActionDocument at least 4 weeks of prior standard wound care (debridement, moist dressings, offloading/compression) and objective perfusion measures before requesting coverage for EPIFIX/GRAFIX.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

NM onlystate-specific application

EPIFIX, GRAFIX, TransCytecovered products called out

manyproducts listed as unproven

4 wksSOC trial before change

100+Q-codes referenced

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 and Medical Necessity Criteria

Insufficient high-quality evidence - consolidated note

Insufficient high-quality evidence: the following summarizes the policy rationale and specific product-level determinations where evidence is limited, low quality, single-arm, industry‑funded, or otherwise insufficient to establish clinically meaningful benefit beyond standard of care.

Many commercially available skin and soft tissue substitute products have few or no high-quality clinical studies (randomized, controlled, blinded trials) demonstrating superiority to standard of care or durable clinical benefit. Systematic reviews and technology assessments (AHRQ, ECRI) highlight heterogeneity of study designs, short follow-up, limited reporting of long-term outcomes (recurrence, amputation, hospitalization), and potential publication or manufacturer funding biases.

Single-arm studies, small RCTs, or registry reports with substantial methodological limitations (small sample size, lack of blinding, short duration, heterogeneous wound types) do not provide sufficient evidence to establish medical necessity for routine use. Examples include products with only case series, pilot studies, or registry data.

Very-low-quality evidence (for some products) comes from single-arm studies or uncontrolled registries that cannot reliably attribute observed healing to the product rather than to concurrent standard wound care, debridement, offloading/compression, or natural history. When the body of evidence for a product is limited to such designs, the product is considered investigational / not medically necessary for general use.

Industry sponsorship and study conflicts of interest are common in the available literature; this raises concern for selective reporting and necessitates independent confirmation in larger, well-designed trials.

Where comparative RCT evidence is absent or limited to a single small trial, evidence is insufficient to determine superiority among products or to support expanded indications (for infected wounds, wounds with poor perfusion, wounds probing to tendon/bone, or indications outside chronic lower-extremity ulcers).

Billing and Code References

Applicable A codes (selection)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 19

1/2

Applicable Q and additional A codes (selection)HCPCS

A2026	Restrata MiniMatrix, 5 mg.
A2027	MatriDerm, per sq cm.
A2028	MicroMatrix Flex, per mg.
A2029	MiroTract Wound Matrix sheet, per cc.
A2030	Miro3D fibers, per mg.
A2031	MiroDry Wound Matrix, per sq cm.
Q4112	Cymetra, injectable, 1 cc.
Q4114	Integra flowable wound matrix, injectable, 1 cc.
Q4143	EpiFix, injectable, 1 mg.
Q4182	Transcyte, per sq cm.

1–10 of 13

1/2

Applicable Q-codes for skin substitutesHCPCS

Q4199	Cygnus matrix, per sq cm
Q4200	SkinTE, per sq cm
Q4201	Matrion, per sq cm
Q4202	Keroxx (2.5 g/cc), 1 cc
Q4203	Derma-Gide, per sq cm
Q4204	XWRAP, per sq cm
Q4205	Membrane graft or membrane wrap, per sq cm
Q4206	Fluid Flow or Fluid GF, 1 cc
Q4208	Novafix, per sq cm
Q4209	SurGraft, per sq cm

1–10 of 186

1/19

No explicit CPT/HCPCS/ICD codes listed in this sectionmixed

No codes listed

Codes referenced in this excerptmixed

No codes listed

No codes listed in this excerptmixed

No codes listed

Ankle-Brachial Index

Ankle-Brachial Index (ABI)Between 0.7 and 1.2 required to demonstrate adequate circulation

Pedal pulses / DopplerPalpable pedal pulses or pulses confirmed with Doppler may indicate adequate circulation

Alternative perfusion measuresTriphasic/biphasic Doppler waveforms at the ankle acceptable per trial criteria

Glycated hemoglobin (HbA1c)

HbA1c thresholdGlycated hemoglobin (HbA1c) < 12% (within the last 90 days; trials cite <12% within last 60–90 days)

Prior Authorization, Documentation, Step Therapy and Denial Risk

Prior Authorization

Prior authorization likely to require documentation of prior SOC and wound parameters

Prior authorization is likely required for many skin substitute products due to limited and heterogeneous evidence. Expect requests to include justification that standard of care (SOC) was tried and failed and to document wound-specific parameters (size, duration, percent area reduction during SOC run-in, perfusion/ABI or TcPO2, HbA1c where applicable, debridement and infection control). Authorization reviewers will often require evidence that SOC included appropriate debridement, moisture management, and offloading/compression as applicable.

SOC documentation: debridement, moist dressings, infection control, offloading/compression
Wound parameters: baseline size (cm2), duration (weeks), percent area reduction at 2–4 weeks (or 4 weeks for venous/diabetic ulcers)
Perfusion: ABI, TcPO2, or Doppler waveform documentation
Labs: HbA1c within 60–90 days where diabetes is relevant

Prior Authorization

Prior authorization likely required given limited evidence

Many products listed in this policy (including but not limited to numerous Q‑code and A‑code skin substitutes, amniotic/placental products, injectable forms, and newer biologics) have limited or mixed evidence; prior authorization is likely required and may require submission of clinical rationale and supporting literature when coverage is requested.

Key Definitions and Product Terms

Full-Thickness Thermal Burn

DefinitionFull-Thickness Thermal Burn: destruction of all layers of the skin, involving epidermal and dermal layers and possibly subcutaneous tissue

Clinical relevanceIndication context: products like TransCyte are used for surgically excised full-thickness burns prior to autografting

ReferenceDefinition adapted from Gomez and Cancio (2007) as cited in the policy

Partial-Thickness Thermal Burn

DefinitionPartial-Thickness Thermal Burn: involves epidermis and part of the dermis; deep partial-thickness involves most of the dermis

Clinical relevanceDeep partial-thickness burns may be treated with certain skin substitutes prior to autograft placement

Clinical Evidence Background and Literature Summary

Background: Thermal burns differ by depth of involvement. Partial‑thickness (second‑degree) burns involve the epidermis and part of the dermis, while full‑thickness (third‑degree) burns destroy all layers of the skin. Some skin and soft tissue substitutes (for example TransCyte) have specific proven indications for surgically excised full‑thickness or deep partial‑thickness thermal burns prior to autograft placement; most other products are evaluated as adjuncts for chronic or acute wound management and not in replacement of standard burn care.

Policy Revision History

April 1, 2026policy_effective_dateLatest

Policy effective date recorded in document header/metadata for CS153NM.G (New Mexico).

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for New Mexico Only)

Policy CodePolicy CS153NM.G

Change TypeNo material change

Effective DateApril 1, 2026

Next Review Date

Key ActionDocument at least 4 weeks of prior standard wound care (debridement, moist dressings, offloading/compression) and objective perfusion measures before requesting coverage for EPIFIX/GRAFIX.

SourceLink

On This Page

Measurement recencyDocument most recent HbA1c within 60–90 days per trial-derived eligibility

Denial risk if elevatedHbA1c ≥ 12% noted as an exclusion/denial risk in cited trial criteria

Standard of Care (SOC) duration prior to use

Minimum standard wound care durationAt least 4 weeks of standard wound care (debridement, moist dressings, offloading/compression) prior to adjunctive product use

Components requiredDebridement of necrotic tissue if present; application of dressings to maintain moist environment; offloading (DFU) or compression (VLU)

Run-in periods used in trialsSome trials used 2-week SOC screening prior to randomization; documentation of SOC response recommended

Conservative therapy trial

Conservative therapy trial length4 weeks of standard treatments

Response threshold prompting changeIf <50% reduction in wound size after 4 weeks, consider changing or adding therapies

SOC elements specifiedDebridement, moisture balance, infection prevention/control, offloading (DFU) or compression (VLU)

Common wound size inclusion range in trials

Common trial wound size rangeMost common inclusion range: 1 to 25 cm^2

Reported study variabilityStudy wound-size criteria varied widely (reported ranges 0.5 to 100 cm^2), but 1–25 cm^2 most frequent

Trial reporting noteWound size frequently used to stratify eligibility and outcomes; document baseline area

Common wound duration inclusion criterion

Common wound duration inclusionGreater than 4 weeks (most studies used >4 weeks as inclusion)

Trial variabilitySome studies allowed durations up to 52 weeks; many required chronic wounds >1 month

Documentation implicationRecord ulcer duration ≥4 weeks when seeking alignment with trial criteria

Recommended minimum study follow-up

Minimum study follow-up12 weeks minimum follow-up recommended for trials

Recurrence reporting suggestionSuggest reporting 6-month recurrence outcomes where possible

Run-in period recommendationUse of a 4-week run-in (or 2-week SOC screening in some RCTs) before enrollment improves interpretability

Perfusion and laboratory thresholds

Perfusion thresholdsABI > 0.7–0.75 or ABI 0.7–1.2; skin perfusion pressure or transcutaneous oximetry ≥ 30 mm Hg

Laboratory thresholdsHbA1c < 12% (recent) and serum creatinine < 3.0 mg/dL (per trial windows)

Trial exclusion contextParticipants with inadequate perfusion or active infection were generally excluded from trials

Wagner grade inclusion

Wagner grade noted in studiesWagner grade 3 or 4 included in DermACELL prospective study of large, complex DFUs

Clinical implicationDocument Wagner grade when applicable for large or deep DFUs considered for ADM use

Study limitationsUncontrolled design limits direct comparison with SOC; detailed wound descriptors recommended

Ulcer size

Ulcer size inclusion (trial-aligned)>= 1 cm2 and < 25 cm2 reported as typical RCT inclusion limits

Baseline size reportingTrials commonly required measurement/laser device documentation of wound area at baseline

Smaller baseline cutoffs noted>0.25 cm2 used as analytic baseline cutoff in some DFU analyses (Raspovic)

Ulcer duration

Ulcer duration (trial-aligned)>= 4 weeks duration commonly required for eligibility

Run-in requirementsSome RCTs included a 2-week run-in and required ≤25% closure during run-in to qualify

Exclusion for very chronic woundsIndex wound duration >52 weeks without intermittent healing often excluded

Transcutaneous oxygen

Transcutaneous oxygen (TCOM) thresholdTranscutaneous oxygen ≥ 30 mm Hg used to demonstrate adequate perfusion

Trial contextTCOM ≥30 mm Hg cited as an enrollment requirement in several RCTs for adequate circulation

Alternative perfusion testsABI or Doppler waveforms acceptable alternatives when TCOM not available

Ankle-Brachial Index (ABI)

Ankle-Brachial Index eligibility range0.7 to 1.2 commonly used for trial eligibility and documentation of adequate perfusion

Lower ABI limit in some trialsSome studies used ABI >0.75 as the lower acceptable threshold

Document methodABI measurement should be recent and documented in clinical record

HbA1c

HbA1c recent threshold for eligibilityHbA1c < 12% (within the last 60–90 days depending on trial) used in RCT eligibility

Documentation windowTrials referenced HbA1c within 60 days and policy criteria note within last 90 days; document most recent value

Exclusion if above thresholdHbA1c ≥12% was an exclusion criterion in several trials and a potential denial reason

Serum creatinine

Serum creatinine thresholdSerum creatinine < 3.0 mg/dL cited as an eligibility threshold in trials (recent measurement window applied)

Measurement windowSome trials specified creatinine within last 90 days to 6 months; document recent lab value

Exclusion if elevatedSerum creatinine ≥ 3.0 mg/dL listed as exclusion in several RCTs

Intermediate wound reduction predictor

Intermediate predictor of healing≥40% wound area reduction at 4 weeks predicts higher likelihood of complete healing by 12–24 weeks

Use in authorizationPercent area reduction at 4 weeks is commonly requested as part of documentation to predict outcome

Correlation evidenceRetrospective follow-up analyses demonstrated strong correlation between 4‑week PAR ≥40% and later complete healing

Baseline wound size inclusion for analysis

Baseline wound size analytic cutoff> 0.25 cm2 used as a baseline inclusion for DFU analysis in Raspovic retrospective study

Study implicationSmaller analytic cutoffs may be used for real-world datasets; document baseline measurements clearly

Use in cohort analysesAnalytic exclusions based on very small wounds (≤0.25 cm2) were applied in some observational studies

Standard of Care (SOC) screening period

SOC screening period used in some RCTs2-week SOC screening prior to randomization was used in at least one randomized trial

Purpose of run-inRun-in confirms inadequate response to SOC (e.g., ≤25% closure) before randomization to adjunctive product

Documentation implicationRecord SOC measures and percent area change during screening to match trial designs

Examples: products with limited published data or single-arm/registry evidence (see code list)
Injectable and newer formulations (e.g., EPIFIX Injectable) often have sparse publications and may need extra justification

Prior Authorization

Prior authorization for Q‑coded skin substitutes — verify product and indication

Specific verification is recommended for Q‑coded amniotic/placental skin substitutes (Q4199–Q4397 range shown in the code list). Prior authorization requests for these Q‑coded products should confirm the exact product (brand/formulation) and intended use and include documentation that the product matches an allowable, evidence-supported indication where applicable.

Verify HCPCS Q‑code maps to the product submitted
If code maps to an unproven indication, provide clinical justification and supporting evidence

Prior Authorization

Prior Authorization Likely for Products with Limited Evidence; CorMatrix prior review recommended

Products with especially limited or inconclusive evidence (for example, CaregraFT, CarePATCH, AMNIOMATRIX/BioDMatrix, EPIFIX Injectable, and many newer amniotic/placental formulations) commonly trigger prior review and may be routed to medical review or peer-to-peer discussion. For CorMatrix in cardiovascular uses, prior case review or authorization is recommended given mixed clinical cohort results and variable reintervention rates.

CorMatrix (cardiovascular): recommend case review or prior authorization
CaregraFT and CarePATCH: evidentiary insufficiency may prompt denial without strong justification
EPIFIX Injectable: limited published evidence — expect higher scrutiny

Prior Authorization

Prior authorization for amniotic/placental products

For amniotic and placental products (including dHACM, vCPM, hVWM, and other HAM/chorion/umbilical cord products), prior authorization is suggested to confirm product formulation, intended use, and that eligibility criteria similar to RCTs or guideline-supported SOC trials have been met (e.g., run-in period, perfusion thresholds, infection control).

Confirm formulation: cryopreserved vs dehydrated vs viable/cryopreserved (vCPM vs dHACM vs hVWM)
Document SOC run‑in: typical RCTs used 2–14 day to 4‑week run‑in and required failure of SOC prior to randomization
Perfusion eligibility: ABI, TcPO2, or Doppler criteria as used in trials

Prior Authorization

Prior authorization suggested for FSGs (Kerecis)

Some products with favorable randomized data (for example, intact fish skin grafts / FSGs such as Kerecis Omega3) may still require prior authorization to ensure SOC was attempted first and to document trial‑like eligibility; consider prior authorization suggested for FSGs to align use with RCT populations.

FSGs (Kerecis): recommend documentation of prior SOC trial (debridement, offloading/compression, moist dressings)
If wound penetrates to bone/tendon, confirm alignment with trial inclusion and offloading/antibiotic management where applicable

Note

Prior authorization requirements are not uniform — verify with payer

Prior authorization requirements vary by product and payer contract. Where requirements are not specified in this policy or in payer directives, providers should check payer-specific prior authorization rules and code mappings before submission to avoid claim denials.

If no PA requirement is posted by payer, submit documentation with claim to support medical necessity
Contact payer for code-to-product mapping when uncertain

Denial Risk

Denial risk for EPIFIX/GRAFIX when criteria unmet

Denial is likely when EPIFIX or GRAFIX criteria are not met — common denial triggers include inadequate perfusion documentation, HbA1c > allowed threshold (>12% in many trial criteria), lack of documented SOC trial (≥4 weeks for DFUs), or evidence of active infection/contraindication (Charcot, malignancy, probing to bone when excluded).

EPIFIX/GRAFIX denials: missing ABI/TcPO2, absent SOC documentation, HbA1c out of range
Provide clear timeline and objective wound measurements to avoid denial

Denial Risk

Denial risk for non‑covered indications

Services provided for non‑covered indications or outside the product's intended use (for example, TransCyte use other than presurgical placement for full‑thickness or deep partial‑thickness thermal burns) are at risk for denial. When submitting for less‑supported or off‑label indications, attach robust clinical justification and supporting literature.

TransCyte: covered for surgically excised full‑thickness and deep partial‑thickness thermal burns prior to autograft only
Non‑covered/off‑label uses: expect denial without strong supporting evidence

Denial Risk

Insufficient prior conservative treatment may lead to denial

Failure to document an adequate prior trial of conservative care (e.g., 4 weeks of SOC for DFUs with <50% reduction, 2–4 week run‑in for some RCTs, or 12 weeks for refractory venous ulcers in certain studies) increases the risk of denial. Ensure records show debridement, appropriate dressings, offloading/compression, infection management, and percent area change during the SOC period.

Document percent area reduction at 2–4 weeks and at 4 weeks where applicable
Specify offloading/compression type and frequency during SOC

Denial Risk

Evidence insufficiency may trigger coverage denial

Evidence insufficiency or heterogeneous/low‑quality studies may prompt denial or require additional peer review. For many products (single‑arm registries, small RCTs, or manufacturer‑sponsored trials), reviewers may request more rigorous justification or deny when trial‑like eligibility is not met.

Common denial reasons: small sample size, lack of blinding, short follow‑up, industry sponsorship without independent replication
Provide comparative evidence when available or detailed clinical rationale when using less‑studied products

Denial Risk

Contexts lacking evidence / trial exclusions may be denied

Contexts that fall outside trial inclusion criteria — such as infected ulcers, inadequate perfusion, wounds probing to muscle or bone when trials excluded those wounds, or patients with uncontrolled comorbidities — are commonly non‑eligible without strong supporting data. Prior authorization reviewers will compare the case to RCT exclusion criteria and may deny if discrepancies are found.

Common exclusions: infected ulcers, Charcot foot, ulcer probing to bone/tendon when excluded, HbA1c>12%, recent tobacco use as per specific trials

Denial Risk

Insufficient evidence may trigger denial

Repeatedly across product sections, insufficient evidence may lead to denial if the submitted clinical record fails to show trial‑like eligibility, SOC failure, or necessary objective measurements. Reviewers will expect precise documentation mirroring trial criteria when relying on RCT-based approvals.

When relying on RCT evidence, submit the same key elements: wound size, duration, run‑in findings, perfusion, comorbidity control

Prior Authorization

Use of EPIFIX Injectable has limited published evidence — expect scrutiny

EPIFIX Injectable has limited published data. Prior authorization for injectable forms should include clinical rationale, prior SOC documentation, and any available supporting studies; reviewers may subject injectable formulations to higher denial risk or require peer review due to sparse evidence.

Indicate if product is injectable EPIFIX and provide justification why sheet application is not feasible
Attach any available efficacy/safety publications

Prior Authorization

Evidence limitations may affect authorization

Evidence limitations (small samples, short follow‑up, heterogenous study designs, or manufacturer sponsorship) may affect authorization decisions. Authorization may be conditional (e.g., limited number of applications) or require prospective outcomes reporting to continue coverage.

Authorization may require documentation of percent area reduction at early time points (e.g., 4 weeks) and plan for subsequent therapy if inadequate response
Reviewer may limit number of allowed applications based on trial protocols

Denial Risk

Insufficient evidence or documentation may lead to denial

When submitted documentation is insufficient or evidence is lacking, denials are possible. Common deficits include missing SOC trial details, absent objective wound measurements, lack of perfusion data, or absence of exclusion/contraindication documentation.

Ensure the record includes objective wound measures (photography, measurements, PAR at defined intervals) and a clear SOC timeline to reduce denial risk

Documentation Required

Documentation required for TransCyte

TransCyte coverage requires documentation of a surgically excised full‑thickness or deep partial‑thickness thermal burn prior to autograft placement. For other burn depths or nonthermal wounds, TransCyte is generally unproven and may be denied.

Document surgical excision and indication for TransCyte prior to autografting
Non‑approved burn indications require supporting evidence for consideration

Documentation Required

Recommended clinical documentation elements

Recommended supporting documentation for prior authorization includes: wound etiology, baseline size and depth, duration, prior SOC treatments (dates and specifics), debridement status, offloading/compression details, perfusion studies, relevant labs (HbA1c, creatinine), photographic documentation, and prior advanced biologic use history.

Baseline wound measurements (cm2) and serial percent area reduction at run‑in and week 4
Perfusion: ABI, TcPO2, or Doppler waveforms; HbA1c within 60–90 days if diabetic

Documentation Required

Example clinical documentation elements from RCTs

RCTs and major trials provide example documentation elements that reviewers may request: eligibility run‑in results (percent area reduction during SOC run‑in), ABI/TcPO2 thresholds used in trials, HbA1c limits, wound size and depth inclusion thresholds, and infection status. Align submitted documentation to these trial elements when seeking authorization based on RCT evidence.

Example trial elements: 2–14 day to 4‑week run‑in percent area reduction thresholds, ABI >0.7 (trial‑specific ranges), HbA1c <12% in many RCTs

Documentation Required

Recommended Supporting Documentation for review

Recommended supporting documentation (registry and real‑world studies vary widely) should include objective wound outcomes and context: prior product applications, number of grafts used, wastage rates if reported, follow‑up duration, and any adverse events. Because registry evidence is heterogeneous, provide wound‑specific data to support treatment necessity.

Include prior advanced product use and outcomes, number of prior graft applications, and timeline of response

Documentation Required

Product formulation and indication should be specified

Clearly state the product formulation and intended indication in the request: cryopreserved vs dehydrated vs viable vs injectable forms have different evidence bases and may be adjudicated differently. Match the formulation to the trials or data cited in the clinical justification.

Identify product formulation (e.g., vCPM, dHACM, hVWM, FSG, ADM, ECM)
If requesting coverage based on a specific RCT, indicate that the product/formulation is the same as in the trial

Documentation Required

Trial‑type documentation useful for claims and prior authorization

When claims are submitted, trial‑type documentation useful for claims/appeals includes: dates of SOC run‑in and percent area change, photographic evidence with measurement scale, perfusion/lab results, and chart notes confirming debridement and offloading/compression. Keeping a consistent, trial‑like record will simplify PA review and appeals.

Attach dated wound photographs with measurement scale and provider notes for each SOC visit
Include percent area reduction calculations at defined timepoints (2, 4, and 12 weeks as applicable)

Documentation Required

Key trial inclusion criteria used in RCTs — often requested

Key trial inclusion criteria frequently cited in RCTs that may be requested by reviewers include: minimum wound duration (often ≥1 month or ≥4 weeks), wound size limits (commonly 1–25 cm2 or trial‑specific ranges), perfusion thresholds (ABI, TcPO2, or Doppler criteria), absence of infection, and documented failure to improve on SOC run‑in.

Typical thresholds: ABI 0.7–1.2 or TcPO2 ≥30 mm Hg, HbA1c <12% in many DFU trials
Run‑in: 2–14 days up to 4 weeks with documented percent area reduction

Step Therapy

Step therapy for EPIFIX/GRAFIX — SOC trial required

Step therapy: for EPIFIX and GRAFIX (noninjectable formulations) many RCTs and the policy require a prior trial of at least 4 weeks of standard wound care (debridement, moisture balance, infection control, and offloading/compression) with insufficient healing (commonly <50% area reduction) before advanced products are authorized. Align step therapy requirements with trial run‑in and SOC definitions.

4‑week SOC trial with documentation of interventions and percent wound area change
Require debridement, moist wound dressings, and offloading/compression as part of SOC

Step Therapy

Step approach: SOC before adjunctive skin substitute — SOC first

Step therapy expectation generally follows trial designs: SOC should be attempted and documented before adjunctive skin substitutes are used. For other product classes (amniotic/placental, injectable, FSGs), conservative therapy should be tried first and documented per the trial‑like run‑in period (2 weeks to 12 weeks depending on wound type and study design).

SOC first: debridement, infection control, moisture balance, and offloading/compression as indicated
Document SOC timeline and objective percent area reduction to meet step criteria

ReferenceDefinition adapted from Gomez and Cancio (2007) as cited in the policy

Class 1 — Skin substitute

Class 1 overviewClass 1: temporary impervious dressing materials, single-layer biological or synthetic membranes, bilayered tissue-engineered materials

Typical usesUsed as temporary biological dressings or protective covers (e.g., amniotic membrane) in acute or uninfected wounds

ExamplesIncludes single-layer amniotic membranes and temporary coverings; classification per Kumar & Gupta/Davison-Kotler frameworks

Class 1 (details)

Class 1 detailsTemporary impervious dressing materials (with or without negative pressure), single-layer biological membranes, bilayered tissue-engineered materials

Negative-pressure variantLimited access dressings with negative pressure examples included in Class 1 description

PurposeIntended to protect wound and facilitate initial healing phases prior to definitive closure

Class 2

Class 2 definitionSingle-layer durable substitutes including epidermal substitutes and dermal substitutes (e.g., bovine or porcine collagen sheets/matrices)

Clinical roleDurable substitutes intended to replace epidermal or dermal layers to support regeneration

ExamplesDermal collagen sheets/matrices used in chronic wound management and reconstructive contexts

Class 3

Class 3 definitionComposite skin substitutes: skin grafts (allograft, xenograft) and bioengineered skin constructs

CompositionMay include cellular components and multiple layers to more closely mimic full-thickness skin

Use casesOften used for definitive coverage or reconstruction when deeper tissue replacement is required

Acellular dermal substitute

Acellular dermal substitute definitionProducts primarily composed of extracellular matrix or dermal replacement materials from human placental membranes or animal tissues with cells removed

Common characteristicsProvide scaffold for cell migration and tissue regeneration; most commercially available substitutes fall into this category

Clinical indicationUsed to manage chronic wounds and support granulation and reepithelialization

Dermo-epidermal skin substitutes (DSSs)

Dermo-epidermal skin substitutes (DSSs)Cellular or acellular products that include dermal and epidermal components intended to restore skin integrity in chronic wounds

ExamplesEPIFIX, GRAFIX, and other dermo-epidermal constructs reviewed in trials for DFUs and VLUs

Clinical noteDSSs are typically used as adjuncts to SOC in well-perfused, uninfected chronic wounds

AlloWrap

ProductAlloWrap: a human amniotic membrane product designed to provide a biological barrier following surgical repair

Intended useProtective barrier following surgical repair; few published studies available

Evidence noteInsufficient published studies to determine clinical benefit per policy excerpt

AmchoPlast family

Product familyAmchoPlast / AmchoPlast EXCEL / AmchoPlast FD: dehydrated human amnion/chorion membrane allografts intended as protective barriers for acute and chronic wounds

Formulation notesAvailable in dehydrated/lyophilized forms preserving basement membrane and stromal matrix

Evidence statementFew published studies; benefit not established per policy excerpt

AmnioBand (dHACA)

AmnioBand (dHACA)Dehydrated human amnion and chorion allograft evaluated in randomized trials for chronic venous leg ulcers and DFUs

Trial evidenceMulticenter RCT (Serena et al. 2022) showed higher 12-week healing (75% vs 30%) for dHACA + SOC vs SOC alone in venous leg ulcers

Eligibility/limitsTrials excluded infected ulcers, ulcers due to nonvenous causes, and required adequate perfusion (ABI >0.75 or TCOM >30 mm Hg)

AmnioBind / DermaBind TL

AmnioBind / DermaBind TLTerminally sterilized, dehydrated, full-thickness placental membrane allograft containing amnion, chorion, and intermediate layer used as a protective barrier

Published evidenceFew published studies available; clinical benefit not established

Intended indicationsAcute and chronic wounds as a covering/barrier

AmnioCore

AmnioCoreDual-layer amniotic tissue allograft intended to reduce scar formation and modulate inflammation

Intended useBarrier and scaffold for acute and chronic wounds; few published outcome studies

Evidence noteInsufficient high-quality studies to determine broad clinical benefit

Amniocyte Plus

Amniocyte PlusMinimally manipulated amniotic fluid allograft intended for repair/reconstruction/supplementation of recipient tissue

EvidenceFew published studies; benefit not established per policy excerpts

Clinical roleUsed in soft tissue repair contexts; documentation recommended if considered

AmnioDefend FT Matrix

AmnioDefend FT MatrixMinimally manipulated human placental membrane containing amnion, intermediate, and chorion layers intended as a barrier for acute and chronic wounds

FormulationFull-thickness placental membrane preserving natural layers

Evidence statementFew published studies available; effect on health outcomes not established

AmnioExcel family

AmnioExcel familyDehydrated human amnion-derived tissue allografts (AmnioExcel / BioDExcel / AmnioExcel Plus) intended to advance soft tissue repair

Trial evidenceRCTs and systematic reviews report mixed/limited results; inclusion criteria often required ABI >0.7, HbA1c <12%, serum creatinine <3.0 mg/dL

RecommendationAdditional larger, multicenter RCTs with longer follow-up are needed to confirm effectiveness

AMNIOFIX

AMNIOFIXComposite amniotic tissue membrane available in sheet, particulate, wrap, and micronized injectable forms; used for soft tissue and surgical applications

EvidenceInsufficient evidence for many wound indications; micronized injectable forms have RCTs for plantar fasciitis showing short-term benefits

Clinical noteEPIFIX Injectable and other micronized forms have limited published studies; comparative effectiveness vs other therapies uncertain

dHACM / mDHACM / micronized dHACM

dHACM / mDHACM / micronized dHACMDehydrated human amnion/chorion membrane processed into micronized or injectable forms (examples include AMNIOFIX Injectable and mDHACM)

Clinical applicationsUsed both as topical sheet grafts (dHACM) and as injections (micronized) for soft tissue indications; evidence varies by indication

Evidence noteRCT evidence exists for plantar fasciitis (micronized dHACM) but long-term and comparative data limited

Dehydrated amniotic membrane grafts (patches)

Dehydrated amniotic membrane grafts (patches)Sterile, dehydrated amniotic membrane allograft products intended as wound coverings for chronic and acute wounds (examples: Amnio-Maxx, AmnioPlast)

Clinical roleApplied as patches or membranes to provide barrier and ECM support during healing

EvidenceMany products in this category lack robust controlled studies; evidence insufficient for routine coverage in many cases

Ascendion

AscendionMinimally manipulated, dehydrated human amnion (HAM) allograft designed as a wound covering for homologous use in DFUs, venous leg ulcers, and pressure ulcers

EvidenceFew published studies; benefit not established per policy excerpts

Intended useProtective barrier for compromised integumentary tissue

Artacent Cord

Artacent CordA wound healing patch comprising umbilical cord tissue intended for acute and chronic wounds including DFUs, venous ulcers, and burns

EvidenceFew published studies; observational analyses reported 65% closure at 12 weeks in a small cohort but require randomized confirmation

Use noteConsidered investigational/insufficient evidence for routine coverage absent stronger data

BIOVANCE (DDHAM)

BIOVANCE (DDHAM)Decellularized, dehydrated human amniotic membrane intended for treatment of acute and chronic wounds; available in single- and multi-layer configurations

Registry evidenceRegistry data showed ~50% closure in heterogeneous wounds (median 6.3 weeks) but evidence rated very low quality

RecommendationLarger RCTs needed to determine comparative effectiveness versus SOC

CaregraFT

CaregraFTDehydrated amnion and chorion membrane allograft intended as a barrier and protective coverage for acute and chronic wounds

EvidenceStudies lacking; not possible to conclude beneficial effect on health outcomes

Coverage stanceConsidered investigational/not medically necessary absent supporting peer-reviewed evidence

CarePATCH

CarePATCHDehydrated human amnion membrane allograft used as a wound cover or protective wound barrier

EvidenceFew published studies; clinical benefit not established per policy excerpts

Intended useProcessed to preserve native physical integrity for coverage of acute/chronic wounds

CorMatrix

CorMatrixPorcine small intestinal submucosal extracellular matrix used for cardiac and vascular surgical applications; available in envelope form

Evidence concernsSystematic review shows mixed clinical cohort results with widely variable reintervention rates (4.5%–87.5%); clinical applicability questioned

Use cautionCardiovascular applications require specialty-specific evidence; routine coverage may be restricted without strong supporting data

Corplex and packing variants

CorplexDehydrated human umbilical cord tissue used as a wound covering or barrier membrane

Corplex P / Theracor P / Allacor PSterile jelly allograft dehydrated into small pieces for packing into wound voids; not intended as a covering

ImplicationUse of packing products as coverings is outside intended use per policy note

DermACELL (and AWM variants)

DermACELL (D-ADM)Decellularized human dermal allografts intended for chronic nonhealing wounds and burns; studied in DFUs including Wagner grade 3–4 wounds

Study findingsProspective study reported rapid granulation and substantial wound-area reduction in large, complex DFUs but was uncontrolled; RCT evidence limited

Coverage implicationMay be considered in specific scenarios when trial-aligned criteria and documentation are met

Dermacyte AC Matrix / Dermacyte Amniotic Wound Care Matrix

Dermacyte AC Matrix / Dermacyte Amniotic Wound Care MatrixLyophilized full-thickness amnion/chorion allograft intended as protective covering/barrier

EvidenceFew published studies; clinical benefit not established per policy excerpts

Intended useSupport cell growth and provide protective coverage in various wound types

Derma-Gide (PRBM)

Derma-Gide (PRBM)Decellularized purified reconstituted bilayer matrix (collagen wound dressing) for covering and regenerating soft tissue defects

Pilot dataSmall observational pilot in DFUs showed promising closure rates; larger randomized studies needed

Clinical implicationMay be considered investigational pending higher-quality evidence

EPICORD

EPICORDMinimally manipulated, dehydrated, nonviable cellular umbilical cord allograft intended for chronic or acute wounds and burns

EvidenceSeveral published studies exist but have limitations; evidence inconclusive per ECRI review

Trial designsEPICORD trials included 14-day run-in with SOC in some RCTs; documentation of SOC response used for eligibility

EPIXPRESS

EPIXPRESSMinimally manipulated, lyophilized, nonviable cellular allograft derived from human amnion preserving ECM components

EvidenceFew published studies; clinical benefit not established

Intended useApplied as a protective covering for acute and chronic wounds

GRAFIX / vCPM / hVWM

GRAFIX (vCPM/hVWM)Cryopreserved placental membrane (viable cryopreserved placental membrane / human viable wound matrix) containing ECM, growth factors, and viable cells; studied in DFUs and VLUs

RCT evidenceLavery RCT showed higher 12-week closure with GRAFIX (62%) vs SOC (21%); observational and retrospective cohorts report favorable closure rates

Application frequencyApplied weekly in many study protocols; documentation of planned frequency recommended per trial alignment

GRAFIX product variants

GRAFIX product variantsGRAFIX Duo (dehydrated dual-layer), GRAFIX CORE (cryopreserved chorion matrix), GRAFIX Plus (lyophilized chorionic membrane) — limited published evidence for some variants

Evidence noteVariants have few studies; effectiveness not established for all product forms

Clinical implicationSpecify exact product variant when requesting coverage and provide supporting trial-like documentation

Acellular fish skin graft (FSG)

Acellular fish skin graft (FSG)Xenogenic decellularized fish skin (e.g., Kerecis Omega3) intended to accelerate wound healing by providing collagen, omega-3 fatty acids, and ECM components

RCT evidenceRCTs (e.g., Lullove, Kirsner) reported higher healing rates vs SOC or comparable products in DFUs and faster healing in acute biopsy wounds; evidence promising but limited

Trial screeningStudies used SOC run-in (2 weeks) and excluded wounds involving tendon/capsule/bone; document SOC failure and wound characteristics

Hyaluronic acid-based matrix (Hyalomatrix)

HyalomatrixHyaluronic acid–based scaffold with removable semipermeable silicone layer used to generate neodermis and support granulation in complex surgical wounds

EvidenceProspective noncomparative series report granulation and subsequent grafting success; controlled data limited

Use caseMay be combined with negative-pressure therapy in complex defects; larger studies required to determine comparative benefit

FSG (shorthand)

FSG (shorthand)Fish skin graft (FSG) — decellularized fish skin products (e.g., Kerecis) used for chronic DFUs and other wounds

Evidence summaryRCTs and meta-analyses show favorable healing rates in specific DFU populations; larger confirmatory trials recommended

DocumentationProvide prior SOC run-in response and wound parameters to align with trial eligibility when seeking coverage

dHACM (shorthand)

dHACM (shorthand)Dehydrated human amnion/chorion membrane allograft (dHACM) — includes EPIFIX and other dHACM products used in DFU and VLU trials

Evidence noteMultiple RCTs and observational studies support short-term healing benefits when added to SOC; long-term outcomes less well reported

Clinical implicationDocument wound size, duration, perfusion, and prior SOC failure to match trial contexts

ADM (acellular dermal matrix)

ADM (acellular dermal matrix)Acellular dermal matrix products intended to provide scaffold supporting cell migration and healing in acute or chronic wounds

ExamplesDermACELL, MatriDerm, Integra-derived matrices among those reviewed; evidence quality varies by product

Evidence implicationSome ADMs show promising results in limited RCTs/observational studies; document wound characteristics and trial-aligned criteria when requesting coverage