CurrentUnitedHealthcarePolicy CS153NE.U

Skin and Soft Tissue Substitutes (for Nebraska Only)

UnitedHealthcare medical policy for Nebraska addressing coverage and medical necessity criteria for specific skin and soft tissue substitute products (notably EPIFIX/GRAFIX and TransCyte) and a long list of other products considered unproven/not medically necessary; includes applicable HCPCS/Q/A codes and A-codes for numerous products and clinical background/evidence summary.

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for Nebraska Only)

Policy CodePolicy CS153NE.U

Change TypeAdded/Removed/Revised product lists and codes

Effective DateApr 1, 2026

Next Review Date

Key ActionDocument adequate circulation, recent HbA1c <12%, and at least 4 weeks of standard wound care showing inadequate healing; document absence of listed contraindications when requesting coverage for EPIFIX/GRAFIX.

SourceLink

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; multiple products added and some names replaced.

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

Revised description for HCPCS code Q4130.

Updated Description of Services, Clinical Evidence, and References sections to reflect the most current information.

2Products with explicit proven indications in this part

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200+Products listed as unproven/not medically necessary (approx.)

MultipleApplicable HCPCS/Q-codes listed

majorityProducts with insufficient evidence

MultipleProducts with at least one RCT reported

Coverage Summary & Scope

This Nebraska-only policy addresses coverage and medical-necessity criteria for skin and soft tissue substitutes used as adjuncts in wound care and related soft-tissue indications. Primary chronic-wound indications reviewed include diabetic foot ulcers (DFU) and venous leg ulcers (VLU), and acute indications include partial- and full-thickness burns. The policy describes product classification (cellularity, layering, replaced region, materials, permanence) and standard wound care components, and it summarizes evidence and determinations for specific products (notably EPIFIX/GRAFIX and TransCyte). Overall coverage stance in this policy is mixed: some products have proven, indication-specific support while many others are judged unproven or not medically necessary based on available evidence.

Medical-Necessity Criteria (by product / indication)

EPIFIX or GRAFIX (Noninjectable) - Medical Necessity for Diabetic Foot Ulcer

EPIFIX or GRAFIX (Noninjectable) — Medical necessity for 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 within the range0.7–1.2
    ABI measured per standard practice
Glycated hemoglobin (HbA1c) < 12%<12%
Test within the last 90 days
- ALL of the following
  - Application of dressings to maintain a moist wound environment
  - Debridement of necrotic tissue if present
  - Offloading
- ANY of the following
  - Active Charcot deformity or major structural abnormalities of the affected foot
  - Chronic infection at the ulcer site
  - Known or suspected malignancy of the current ulcer being treated
  - Ulcer extends to tendon, muscle, capsule, or bone (exclusion)
Due to insufficient evidence of efficacy, EPIFIX and/or GRAFIX are unproven and not medically necessary for all other indications.

TransCyte - Medical Necessity for Burns

TransCyte — Medical necessity for burns. Covered when the following indication is met:

ALL of the following

TransCyte is proven and medically necessary for treating surgically excised Full-Thickness Thermal Burn wounds and deep Partial-Thickness Thermal Burn wounds prior to autograft placement.
TransCyte is unproven and not medically necessary for all other indications due to insufficient evidence of efficacy.

Products Considered Unproven / Not Medically Necessary

Evidence Summaries and Coverage Rationale

Randomized trials and systematic reviews show that several amniotic- and dermal-based products can increase healing rates versus standard of care, but the evidence is limited by small trials, heterogeneous designs, short follow-up, and frequent industry funding. For dehydrated human amnion/chorion membrane (dHACM, e.g., EPIFIX), multiple RCTs and meta-analyses report higher complete-healing rates and faster time to heal versus standard care in DFUs and some VLUs, but studies are often small and manufacturer-funded. Viable cryopreserved placental membrane (vCPM, GRAFIX) RCTs and observational series suggest improved healing versus standard care and noninferiority to some cellular products, but quality is low-to-moderate and comparative evidence is limited. Fish-skin grafts (Kerecis) have RCTs and meta-analyses showing higher closure rates versus standard care or collagen dressings in DFUs and some burns, though many trials are small and open-label. Other products with RCT evidence (Mirragen, TheraSkin, PriMatrix, TransCyte, certain acellular dermal matrices) show promising results in specific trials, but findings are inconsistent across products and settings. Across the body of evidence the main limitations are small sample sizes, heterogeneity of wound types and trial entry criteria, short-term follow-up with limited recurrence data, and potential publication or sponsor bias; additional large, blinded, comparative trials are needed to clarify comparative effectiveness.

EPIFIX (noninjectable dHACM): considered proven and medically necessary for DFUs when trial criteria are met — examples of trial-derived eligibility include ulcer area typically ≥ 1 cm² and < 25 cm², duration ≥ 4 weeks, adequate perfusion (eg, dorsum TcPO2 ≥ 30 mm Hg, ABI between 0.7 and 1.2, or triphasic/biphasic Doppler), HbA1c < 12%, and failure to heal after at least 4 weeks of standard wound care. RCTs/meta-analyses report higher rates of complete healing and shorter time-to-heal versus standard care for DFUs and improved healing when used adjunctively with compression for VLUs, but studies have limitations (small size, limited long-term data, manufacturer involvement).

GRAFIX (vCPM): evidence from RCTs and HTAs indicates potential benefit for chronic wounds including DFUs and VLUs (for example, randomized trials reporting higher closure rates vs standard care), but quality is low to moderate and additional independent RCTs are needed; product-specific trial eligibility criteria in published studies commonly required adequate perfusion and prior standard care run-in periods.

Applicable Codes (HCPCS / Q-codes / A-codes)

A-codes (HCPCS Axxx)HCPCS|mixed

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/A HCPCS-like codes (Q41xx, Q42xx, Q43xx)HCPCS

A4100	Skin substitute, FDA-cleared as a device, not otherwise specified
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	TheraSkin, per sq cm
Q4122	DermACELL, DermACELL AWM or DermACELL AWM Porous, per sq cm

1–10 of 72

1/8

Added HCPCS codes (Applicable Codes)HCPCS

A2036
A2037
A2038
A2039
Q4383	Axolotl Graft Ultra, per sq cm
Q4384	Axolotl DualGraft Ultra, per sq cm
Q4385	Apollo FT, per sq cm
Q4386	Acesso TrifACA, per sq cm
Q4387	NeoThelium FT, per sq cm
Q4388	NeoThelium 4L, per sq cm

1–10 of 19

1/2

Provider Actions — Documentation, Prior Authorization & Billing

Prior Authorization

Medical necessity documentation for EPIFIX/GRAFIX

EPIFIX/GRAFIX (including GRAFIX PL, GRAFIX PRIME, and GRAFIX PL PRIME) require prior authorization with documentation demonstrating medical necessity. Requests must include objective measures of perfusion, glycemic control, and prior standard of care (SOC) trial consistent with clinical trial enrollment criteria.

Circulation assessment: documented pedal pulses or Doppler confirmation, and at least one objective vascular test (e.g., ABI between 0.7 and 1.2, toe pressures or TcPO2 when available).
Glycemic control: HbA1c < 12% within the last 90 days.
Prior standard wound care: documentation of ≥ 4 weeks of SOC including dressings to maintain a moist environment, debridement if indicated, and appropriate offloading.
Wound description: location, size (length, width, depth and percent tissue types), duration, photographs, and confirmation ulcer does not extend to tendon/muscle/capsule/bone.
Contraindications: documentation that active Charcot deformity, chronic infection at the ulcer site, known/suspected malignancy at the ulcer, or other contraindications are not present.

Definitions

Key definitions used in the policy:

DFU: diabetic foot ulcer (term used throughout policy as primary chronic-wound indication).

VLU: venous leg ulcer.

dHACM: dehydrated human amnion/chorion membrane (example: EPIFIX).

dHACA: dehydrated human amnion/chorion allograft.

SOC (or SWC): standard of care or standard wound care (eg, debridement, offloading, moist dressings, compression for VLUs, infection control).

ADM: acellular dermal matrix.

BSA: bioactive split-thickness skin allograft (cryopreserved).

Full-Thickness Thermal Burn (Third-Degree Burn): destruction of all layers of the skin, involving epidermis and dermis with varying subcutaneous involvement.

Partial-Thickness Thermal Burn (Second-Degree Burn): involves epidermis and part of the dermis; deep partial-thickness involves most of dermis leaving few intact appendages/nerve endings.

Revision History

2026-04-01effective_dateLatest

Policy revision effective 04/01/2026 implemented multiple changes: removed prior application-frequency limitation for EPIFIX and GRAFIX; removed examples of unproven and not medically necessary indications for EPIFIX and GRAFIX; revised the list of skin and soft tissue substitutes judged unproven/not medically necessary (added multiple products and replaced some names); added numerous HCPCS/Q-codes (A2036–A2039 and Q4383–Q4397) to Applicable Codes; revised description for HCPCS code Q4130; and refreshed supporting information (Description of Services, Clinical Evidence, and References).

2026-04-01material_changeLatest

Removed language indicating EPIFIX and GRAFIX were limited to one application per week for up to 12 weeks (application-frequency limitation eliminated).

Policy Summary

PayerUnitedHealthcare

PolicySkin and Soft Tissue Substitutes (for Nebraska Only)

Policy CodePolicy CS153NE.U

Change TypeAdded/Removed/Revised product lists and codes

Effective DateApr 1, 2026

Next Review Date

SourceLink

On This Page

Trial eligibility/entry characteristics (general informational summary): many RCTs used run-in periods (eg, 2–4 weeks) to confirm inadequate healing, excluded infected ulcers or ulcers probing to tendon/muscle/bone, required perfusion thresholds (ABI or TcPO2), capped ulcer size (commonly 1–25 cm²), and set glycemic/renal limits (eg, HbA1c 12%, serum creatinine 3.0 mg/dL); these criteria guided trial enrollment and inform clinical selection.

FDA regulatory pathways: the policy's FDA section is provided for information only and notes that products may be regulated by HCT/P (minimally manipulated human tissue), 510(k), PMA, or Humanitarian Device Exemption pathways — this regulatory information is informational and not a basis for coverage decisions.

Documentation Required

TransCyte burn indication documentation

TransCyte is allowed only for the indicated burn types. Documentation should clearly state the burn depth and that the product is being used for surgically excised full-thickness thermal burns or deep partial-thickness thermal burns prior to autograft placement. Use for other wound types or burn depths is considered unproven.

Allowed indications: surgically excised Full-Thickness Thermal Burns and deep Partial-Thickness Thermal Burns prior to autograft placement.
Disallowed/Unproven: any other uses or burn indications without supporting evidence.

Documentation Required

Trial-derived inclusion/exclusion criteria and trial eligibility documentation

When applying clinical trial results to individual patients, consider the original trial inclusion and exclusion criteria. Use trial-derived thresholds to assess whether study outcomes are generalizable to the member.

Trial-derived inclusion/exclusion criteria to consider: wound type (e.g., diabetic foot ulcer), wound size ranges used in trials (document length × width and surface area), and chronicity/duration prior to enrollment.
Wound viability/perfusion thresholds: ABI 0.7–1.2 (or equivalent toe pressure/TcPO2 thresholds used in trials) to indicate adequate perfusion.
Trial eligibility documentation: for EPIFIX/dHACM studies, include wound size and duration consistent with published trials, documented perfusion measures, and HbA1c and serum creatinine values when applicable.
Laboratory thresholds referenced from trials: HbA1c < 12% and relevant renal function (document serum creatinine or eGFR if trial criteria required).
Venous ulcer treatment documentation: if treating venous leg ulcers, provide evidence of appropriate venous care (compression therapy, venous evaluation) consistent with trial or guideline-based care prior to advanced product use.

Billing Rule

HCPCS code additions

Billing updates — newly added HCPCS codes and a revised description are listed below. Use these codes per billing guidance and ensure documentation supports the billed code.

Newly added HCPCS: A2036, A2037, A2038, A2039
Newly added Q-codes: Q4383 through Q4397
Revised description: Q4130 description revised (verify latest claim coding guidance prior to billing)

Documentation Required

Evidence limitations, documentation needs, and case selection for less-studied products

Many skin and soft tissue substitute products lack sufficient high-quality evidence for effectiveness. When requesting coverage for less-studied or novel products, clinicians should provide detailed rationale, prior conservative care, and wound-specific information to enable case-by-case review.

Evidence limitations: list of many products considered insufficient evidence and generally not medically necessary unless exception criteria met.
Required justification for exceptions: clinician rationale for product selection, why preferred/covered products are not suitable, prior SOC and duration, and objective wound characteristics (size, depth, tissue types, infection status, perfusion).
Product-specific evidence considerations: include citations or summaries of peer-reviewed studies if available, and specify whether the product is FDA-cleared/approved for the intended indication.
Further study / case selection: document how the patient aligns with populations studied in trials (e.g., DFU enrollment criteria) or why trial criteria are not applicable.
Assess wound viability and infection status: include debridement status, culture results if infection suspected, and ongoing measures to address infection and perfusion prior to advanced product use.
Use evidence statements and guideline-based adjunctive therapy criteria to support coverage determinations: reference trial enrollment criteria, guideline-recommended adjuncts (e.g., offloading for DFU, compression for venous ulcers), and note that adherence to these is expected.

2026-04-01material_changeLatest

Removed list of examples of unproven and not medically necessary indications for EPIFIX and GRAFIX (examples deleted from policy).

2026-04-01material_changeLatest

Revised the 'Other Skin and Soft Tissue Substitutes' list: multiple products were added as unproven/not medically necessary (examples include 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 some product name entries were replaced (e.g., 'Dual Layer Impax' replaced with 'Dual Layer Impax Membrane'; 'Vendaje A' replaced with 'Vendaje AC').

2026-04-01material_changeLatest

Added HCPCS codes to Applicable Codes: A2036, A2037, A2038, A2039 and Q4383–Q4397; also noted Q4130 description was revised.

2026-04-01non_material_updateLatest

Supporting information refreshed: Description of Services, Clinical Evidence, and References sections updated to reflect current information.