CurrentUnitedHealthcarePolicy CS153NJ.W

Skin and Soft Tissue Substitutes (for New Jersey Only)

State-specific UnitedHealthcare medical policy for skin and soft tissue substitutes in New Jersey, defining covered products/indications (EPIFIX/GRAFIX for diabetic foot ulcers; TransCyte for certain burns), products considered unproven/not medically necessary, definitions, background, evidence summaries, and an extensive list of applicable HCPCS A/Q codes and product-to-code mappings.

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for New Jersey Only)

Policy CodePolicy CS153NJ.W

Change TypeAdded/Removed product listings and HCPCS updates

Effective DateApr 1, 2026

Next Review Date

Key ActionDocument adequate circulation, A1c <12% within 90 days, and at least 4 weeks of standard wound care with inadequate healing before considering EPIFIX/GRAFIX.

POLICY UPDATE CHANGES

Removed language indicating EPIFIX and GRAFIX are limited to one application per week for up to 12 weeks.

Removed list of examples of unproven and not medically necessary indications for EPIFIX and GRAFIX.

Revised list of skin and soft tissue substitutes that are unproven and not medically necessary for any indication; added multiple products (list provided).

Added HCPCS codes A2036, A2037, A2038, A2039, Q4383-Q4397 to Applicable Codes.

Noted NJ Medicaid fee-schedule exception for newly added HCPCS codes.

Updated Description of Services, Clinical Evidence, and References sections.

2Approved indications called out (EPIFIX/GRAFIX; TransCyte)

Coverage Summary

This policy is UnitedHealthcare's New Jersey–specific coverage criteria for skin and soft tissue substitutes, effective 2026-04-01. It designates EPIFIX and GRAFIX (noninjectable forms) as proven and medically necessary for select diabetic foot ulcer (DFU) presentations when the specified clinical criteria are met, and designates TransCyte as proven and medically necessary for certain full- and deep partial-thickness thermal burns prior to autograft. Overall the policy's coverage stance is mixed: a small number of products/indications are covered under detailed criteria, while a very large, enumerated list of other skin and soft tissue substitutes are considered unproven and not medically necessary for any indication. For many products the policy provides guidance that evidence is insufficient and further high-quality comparative studies are needed.

Key thresholds and quick facts

Ankle-Brachial Index (ABI)0.7 - 1.2

Glycated hemoglobin (A1c)< 12% within the last 90 days

Standard wound care trial before adjunctive therapyAt least 4 weeks of standard wound care (moist dressings, debridement if present, and offloading) without adequate healing

Typical vCPM (GRAFIX) treatment metrics (real-world retrospective)Median treatment duration 42 days; median applications 4; closure at end of treatment 59.4%; probability of closure by week 12 = 71%

Typical dHACM (EPIFIX) trial 12-week closure examplesWeekly EPIFIX healed ~70% at 12 weeks; biweekly 92% at 6 weeks in cited RCTs

Medical Necessity & Indications

EPIFIX or GRAFIX (Noninjectable) (GRAFIX PL, GRAFIX PRIME, and GRAFIX PL PRIME)

EPIFIX or GRAFIX (Noninjectable) - Diabetic Foot Ulcer: Covered when ALL of the following are met:

ALL of the following

ANY of the following
- Pedal pulses palpable or pulses confirmed with Doppler examination.
- Ankle-Brachial Index (ABI) between 0.7 and 1.2.
Glycated hemoglobin (A1c) < 12% (within the last 90 days).
ALL of the following

Products Considered Unproven or Not Medically Necessary

Other Skin and Soft Tissue Substitutes

The following products are unproven and not medically necessary for any indication due to insufficient evidence of efficacy:

Unproven products list: Extensive list of named products considered unproven and not medically necessary; see mapped HCPCS/Q-code groups for product-to-code reference

Refer to policy product lists and code_groups for specific HCPCS/Q-code mappings

The policy classifies a long list of commercially available skin and soft tissue substitute products as unproven and not medically necessary because of insufficient evidence of efficacy (see the policy's extensive product lists). Those products are mapped to HCPCS codes in the Coding/Applicable Codes sections, and the policy notes that the full product list and code mappings appear across multiple sections of the document.

Evidence Summary and Clinical Interpretation

Evidence-based determination per product

Coverage conclusions based on available studies summarized per product (statements reflect insufficient evidence or limited evidence); each product entry states whether studies are lacking or insufficient.

General evidence determinations: Many products have 'studies are lacking' statements indicating insufficient evidence to determine beneficial effect on health outcomes; some products have few published studies and are inconclusive; a subset has RCT evidence suggesting improved healing but with limitations

See product-specific statements for examples

Coverage conclusions for named products in this section

Evidence statements in this section generally indicate insufficiency or few published studies:

Few or lacking studies: For Cohealyx, Coll-e-Derm, Complete AA/ACA/SL/FT, Conexa, Corecyte, Coretext/Protext, CorMatrix, Corplex variants, Cryo-Cord, CYGNUS products, Cymetra, Cytal, DermaBind variants, Dermacyte, Derma-Gide, DermaPure, EPICORD, EPIFIX (injectable), EPIFIX (noninjectable) and many others: studies are few or lacking and it is not possible to determine a beneficial effect on health outcomes

Guidelines & Regulatory Context

Guideline-based recommendations for adjunctive wound therapies

Summarized recommendations from major clinical guideline organizations:

SVS/APMA/SVM: Standard wound therapy for DFUs includes moist dressings, offloading, and debridement. For DFUs not improving (>50% area reduction) after minimum 4 weeks of SOC, consider adjunctive biologics (platelet-derived growth factor, living cellular therapy, extracellular matrix products, or amniotic membrane products); reevaluate vascular status, infection control, and offloading before adjunctive therapy (grade 1B). Consider living cellular therapy for recalcitrant DFUs (grade 2B). Consider extracellular matrix products as adjuncts (grade 2C).

WHS: Cellular bioengineered skin substitutes, ADM products, and human amniotic tissue membranes have evidence indicating increased incidence of healing and decreased time to heal (levels I-II); for venous ulcers bilayered living human skin equivalent with compression increases healing (level I).

Pre-application wound bed preparation and bioburden control recommended

NICE / IWGDF:

Applicable HCPCS / Coding Notes

State of New Jersey Medicaid fee-schedule exception notemixed

NOTE	Applicable HCPCS codes listed in the 'Applicable HCPCS codes added in 04/01/2026 revision' group may not be covered by New Jersey Medicaid per fee-schedule exception (asterisked codes in A-code list).

A-codes mapped to productsHCPCS

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 33

1/4

Q-codes and other HCPCS mapped to productsHCPCS

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
Q4173
Q4174
Q4175
Q4176
Q4177

1–10 of 172

1/18

HCPCS codes not on NJ Medicaid Fee ScheduleHCPCS

A2036	Cohealyx Collagen Dermal Matrix, per sq cm
A2037	G4Derm Plus, per ml
A2038	MariGen Pacto, per sq cm
A2039	InnovaMatrix FD, per sq cm
Q4383
Q4384
Q4385
Q4386
Q4387
Q4388

1–10 of 19

1/2

Applicable HCPCS codes A2036-A2039 and Q4383-Q4397 were added effective 04/01/2026 and may not be covered by New Jersey Medicaid per fee-schedule exception; see the "Applicable HCPCS codes added in 04/01/2026 revision" and the fee-schedule exception note above for details.

Provider Documentation & Billing Actions

Documentation Required

Key documentation required for EPIFIX/GRAFIX (summary of provider actions)

Document circulatory status, perfusion testing, glycemic control, standard wound care trial, and prior treatment details as described in the policy's provider_actions. Include ABI/TcPO2/Doppler findings; HbA1c (<12% within 90 days); documentation of ≥4 weeks of standard wound care (moist dressings, debridement if present, offloading) with run-in percent area reduction results; wound size (cm2), duration (weeks), depth, infection status, and prior use of cellular/tissue-based products.

Document circulatory status: palpable pedal pulses or Doppler confirmation, ABI 0.7–1.2, or TcPO2 ≥30 mm Hg.
Document A1c: HbA1c < 12% within the last 90 days.
Document prior standard wound care: at least 4 weeks of dressings to maintain moisture, debridement if present, and offloading; report percent area reduction during any run-in period.
Document wound details: wound area (cm2), duration (weeks), depth, presence/absence of infection, and prior use of cellular/tissue-based products.

Definitions

Term	Definition
DFU	Diabetic foot ulcer (DFU) — defined in policy context as a chronic wound of the lower extremity in persons with diabetes; policy uses DFU throughout evidence and criteria for adjunctive therapies, including EPIFIX/GRAFIX
SOC	Standard of care (SOC) — cleaning/debridement, moist dressings, offloading for DFUs, compression for venous ulcers, infection control and correction of ischemia as applicable
dHACM	Dehydrated human amnion/chorion membrane allograft (example: EPIFIX) — dehydrated placental membrane used as an extracellular collagen allograft adjunct to SOC
vCPM	Viable cryopreserved placental membrane (example: GRAFIX) — cryopreserved placental membrane containing extracellular matrix and viable cells used as a wound matrix
FSG	Fish skin graft (FSG) — acellular fish skin graft derived from cold-water fish (e.g., Kerecis Omega3) used as a xenograft wound coverage material
ADM	Acellular dermal matrix (ADM) — human- or animal-derived decellularized dermal matrix used as a scaffold for wound repair
Full-Thickness Thermal Burn	Full-Thickness Thermal Burn (Third-Degree Burn) — destruction of all layers of the skin involving epidermis and dermis with variable subcutaneous involvement (policy definition)
Partial-Thickness Thermal Burn	Partial-Thickness Thermal Burn (Second-Degree Burn) — involves epidermis and part of dermis; deep partial-thickness involves most of dermis leaving few intact appendages/nerve endings (policy definition)

Selected Evidence & Key Studies

Study/Source	Design & N	Key outcome(s)	Limitations
Sui et al. 2024 systematic review	Systematic review of 15 RCTs, 1,524 individuals	Dermal matrix + SOC shortened time to healing (MD 2.84 days reported) and increased complete healing (OR 0.40) and reduced amputation risk	Small sample sizes across trials, product heterogeneity, lack of blinding, variable follow-up
Alomairi et al. 2024	Systematic review/meta-analysis of 10 RCTs (633 individuals)	Human amniotic membrane accelerated ulcer closure vs SOC; high proportion healed at short-term follow-up (12–16 wks)	Short follow-up, heterogeneity in HAM preparation, small trials, participant demographics skewed
EPIFIX pooled RCTs	Multiple RCTs (examples: Tettelbach et al., Zelen et al.) — several trials, pooled analyses	EPIFIX + SOC showed higher complete healing rates and faster time to heal (examples: 70% healed at 12 weeks; biweekly arms with very high closure in small trials)	Most studies manufacturer-sponsored, small sizes, limited long-term data, lack of blinding in many trials
GRAFIX RCT (Lavery 2014)	Randomized controlled trial, n≈97 (GRAFIX n=50 vs SWC n=47)	Complete closure at 12 weeks: 62% GRAFIX vs 21% SWC; median time to heal 42 vs 69.5 days; fewer infections/adverse events with GRAFIX	Single RCT with modest sample size; needs confirmation in larger trials
Kerecis RCTs (Dardari 2024; Lullove 2021)	Multicenter RCTs (Dardari: 255 pts; Lullove: ~49 pts) comparing fish skin graft vs SOC or collagen alginate	Dardari: 44% vs 26% closure at 16 weeks (FSG vs SOC); Lullove: 67% vs 32% closure at 12 weeks; faster median time to heal	Open-label designs, manufacturer involvement, site heterogeneity, limited follow-up, some small trials
Mirragen Armstrong 2022	RCT in Wagner 1 DFUs, n=40 (BBGFM vs SOC)	12-week healing: 70% BBGFM vs 25% SOC; improved PAR and neuropathy scores	Small sample size, lack of investigator blinding, single study needing replication
Cazzell 2024 NuShield (dACM) RCT	Multicenter RCT, n=218 (dACM+SOC vs SOC)	dACM showed higher wound closure rates at weeks 4–12 (50% vs 35% at week 12; p=0.04); hazard ratio 1.48 favoring dACM	Lacked blinding, offloading not standardized, conducted under controlled conditions; further real-world studies needed
Sui/pooled evidence summary (general synthesis)	Multiple RCTs/meta-analyses summarized across products	Across products some RCTs show improved healing vs SOC (EPIFIX, GRAFIX, fish skin, Mirragen, dACM), but results vary by product and trial	Common limitations: small/moderate sample sizes, industry funding, heterogeneity in SOC/run-in criteria, short follow-up, limited blinding

Revision History

2026-04-01addedLatest

Applicable HCPCS code list expanded — HCPCS A-codes A2036–A2039 and Q-codes Q4383–Q4397 were added to the policy's Applicable Codes.

2026-04-01clarifiedLatest

Notation added that the newly added HCPCS codes A2036–A2039 and Q4383–Q4397 are not on the State of New Jersey Medicaid Fee Schedule and therefore may not be covered by NJ Medicaid.

2026-04-01removed

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for New Jersey Only)

Policy CodePolicy CS153NJ.W

Change TypeAdded/Removed product listings and HCPCS updates

Effective DateApr 1, 2026

Next Review Date

Key ActionDocument adequate circulation, A1c <12% within 90 days, and at least 4 weeks of standard wound care with inadequate healing before considering EPIFIX/GRAFIX.

On This Page

ANY of the following

Active Charcot deformity or major structural abnormalities of the affected foot (contraindication).
Chronic infection at the ulcer site (contraindication).
Known or suspected malignancy of the current ulcer being treated (contraindication).
Ulcer that extends to tendon, muscle, capsule, or bone (note: EPIFIX/GRAFIX indicated when ulcer does NOT extend to these structures).

EPIFIX or GRAFIX — Not Medically Necessary for Other Indications

EPIFIX or GRAFIX — Other Indications:

ANY of the following

Use of EPIFIX and/or GRAFIX for indications other than a diabetic foot ulcer meeting the criteria above is considered unproven and not medically necessary due to insufficient evidence of efficacy.

Evidence Synthesis & Applicability

Evidence synthesis and applicability:

ALL of the following

Clinical evidence includes randomized controlled trials and observational studies demonstrating improved healing outcomes with EPIFIX/GRAFIX in diabetic foot ulcers when standard wound care and selection criteria are met; applicability is limited to lower-extremity diabetic foot ulcers that meet the circulation, glycemic control, and prior standard-care requirements.
TransCyte evidence supports use as a temporary biologic dressing for indicated full-thickness and deep partial-thickness thermal burns prior to definitive autografting; evidence for other indications is insufficient.

Clinical Evidence-Based Determinations & Product Conclusions

Clinical evidence-based determinations and product-specific conclusions:

ALL of the following

EPIFIX/GRAFIX: Clinical studies suggest benefit in chronic diabetic foot ulcers refractory to adequate standard care; therefore EPIFIX/GRAFIX are considered medically necessary only when the specific clinical criteria in this policy are met.
TransCyte: Clinical data support its role as a temporary biologic dressing in surgically excised full-thickness and deep partial-thickness thermal burns prior to autograft placement; other uses lack sufficient evidence and are considered not medically necessary.
Other skin and soft tissue substitutes listed in this policy lack sufficient high-quality evidence of efficacy for any indication and are considered unproven and not medically necessary.

Guideline Recommendations & Policy Implications

Guideline recommendations and policy implications (informational):

ALL of the following

Providers should ensure documentation of failed standard wound care (including duration and components), objective vascular assessment (pulses, Doppler, or ABI), and recent glycemic control (A1c) when requesting coverage for EPIFIX/GRAFIX for diabetic foot ulcers.
Prior authorization and supporting clinical documentation may be required; absence of required documentation or failure to meet the stated criteria may result in denial as not medically necessary.
Use of TransCyte should follow burn-care guidelines that prioritize definitive coverage for indicated burn depths prior to autografting; other product uses should be supported by peer-reviewed evidence to justify coverage consideration.
This policy aligns coverage decisions with available evidence and guideline recommendations; clinicians should reference the Clinical Evidence section for product-specific trial data and the Definitions section for burn-depth terminology when applying criteria.

Coverage / Evidence conclusions (per product)

Coverage/evidence implications when considering these products for wound care:

Interpretation: Products have limited or variable published evidence; for many products studies are few or lacking; where RCT evidence exists it often has limitations (small size, lack of blinding, manufacturer funding); additional larger and comparative studies are needed before definitive conclusions

EPIFIX and GRAFIX have multiple RCTs or trials but limitations are noted; Kerecis FSGs and Mirragen have some RCT data but require confirmation

The evidence synthesis includes multiple systematic reviews and meta-analyses and selected RCTs showing that some product classes and individual products have trial data suggesting improved healing versus standard of care (for example, pooled RCT/meta-analytic signals favoring dHACM/EPIFIX, positive RCT outcomes for some dHACM trials and for certain H-ADM and BSA products). Specific trials/analyses cited include pooled RCT/meta-analyses reporting higher healing rates with amniotic/dermal matrices, RCTs showing superior DFU healing with dHACM/EPIFIX, RCTs and cohort data for GRAFIX (vCPM) suggesting higher closure rates versus standard care, and randomized and systematic evidence for Kerecis fish skin grafts indicating higher closure rates in some trials. The policy also notes pervasive limitations across the evidence base — notably small sample sizes, heterogeneity of study designs and wound types, short follow-up, and frequent manufacturer funding — which restrict confidence and generalizability and motivate the conclusion that many products remain unproven.

NICE: dermal/skin substitutes are adjuncts to SOC for DFUs only when healing has not progressed and per multidisciplinary foot service. IWGDF (2023): generally suggests not using cellular or acellular skin substitutes routinely as adjuncts to SOC for DFUs (conditional; low); consider placental-derived products when SOC has failed (conditional; low); do not use autologous skin graft substitutes (strong; low).

FDA regulatory pathways (informational)

Regulatory classification mechanisms for skin substitutes noted for information only:

FDA pathways (informational): Devices may be regulated via PMA (requires clinical data); devices may be cleared via 510(k) if substantially equivalent to predicate devices; HCT/P pathway (21 CFR 1270 & 1271) applies to minimally manipulated human tissue such as amniotic membrane and allows marketing without clinical efficacy testing but with tissue-handling regulations

Humanitarian Device Exemption (HDE) also exists for small population/rare conditions

Background clinical care discussed in the policy emphasizes that treatment of chronic wounds relies on established standard-of-care elements: repeated debridement, maintaining moisture balance, infection prevention/control, correction of ischemia, and offloading or compression as appropriate (e.g., offloading for DFUs, compression for venous leg ulcers). The policy also explains that there is no universal classification system for skin substitutes and references commonly used classification approaches (Davison‑Kotler; Kumar & Gupta), reflecting the heterogeneous product types and mechanisms.

Documentation Required

Application frequency considerations for EPIFIX

When aligning treatment with the clinical trials cited for EPIFIX, document planned application frequency as weekly. The policy notes trials used weekly EPIFIX applications (and some compared weekly vs biweekly) and indicates weekly application was associated with faster healing in reported studies.

If following trial protocols, plan and document weekly EPIFIX application.
If using a different frequency (eg, biweekly), document rationale and note that some studies directly compared weekly vs biweekly schedules.

Billing Rule

HCPCS code additions and New Jersey Medicaid fee-schedule exception

The policy added HCPCS codes effective 04/01/2026 and flags a New Jersey Medicaid fee-schedule exception. Billing staff should note which new codes may not be on the NJ Medicaid Fee Schedule and may not be covered.

Affected HCPCS codes (added 04/01/2026): A2036, A2037, A2038, A2039
Added Q-codes: Q4383, Q4384, Q4385, Q4386, Q4387, Q4388, Q4389, Q4390, Q4391, Q4392, Q4393, Q4394, Q4395, Q4396, Q4397
Note: Codes marked with an asterisk in the policy are not on the State of New Jersey Medicaid Fee Schedule and therefore may not be covered by NJ Medicaid.

Documentation Required

Reference federal/state/contractual benefit requirements for coverage determinations

Reference and follow applicable federal, state, or contractual benefit plan requirements when determining coverage. The policy states that federal/state/contractual rules govern in the event of conflict and to check applicable rules before use.

Verify federal, state, and contractual benefit plan requirements before use or billing.
If policy language conflicts with benefit plan terms, the federal/state/contract governs and should be followed.

2026-04-01revisedLatest

Revised the 'Other Skin and Soft Tissue Substitutes' unproven/not medically necessary product list — multiple products were added (for example: Acelagraft; Acesso TrifACA; AmnioPlast Double; Apollo FT; Ascendion; Axolotl DualGraft Ultra/Axolotl Graft Ultra; Cohealyx Collagen Dermal Matrix; G4Derm Plus; GRAFIX Duo; InnovaMatrix FD; MariGen Pacto; Natalin; NeoThelium FT/4L/4L Plus; Summit AAA; SurGraft AC/ACA) and naming updates applied (e.g., 'Dual Layer Impax' replaced by 'Dual Layer Impax Membrane™', 'Vendaje A' replaced by 'Vendaje AC®').