CurrentPremera BluecrossPolicy N/A

Bioengineered Skin and Soft Tissue Substitutes

Defines medical necessity, investigational uses, documentation, and coding for bioengineered skin and soft tissue substitutes including acellular dermal matrices, living cell therapies, biosynthetics, and specific named products for indications such as breast reconstruction, diabetic and venous lower-extremity ulcers, dystrophic epidermolysis bullosa, and deep dermal/full-thickness burns. Also reviews evidence for other reconstructive and soft-tissue uses (e.g., BEAR implant for ACL).

Policy Summary

PayerPremera Bluecross

PolicyBioengineered Skin and Soft Tissue Substitutes

Policy CodePolicy N/A

Change TypeReinstatement / coding and investigational list updates

Effective DateSep 1, 2025

Next Review DateN/A

Key ActionDocument wound assessment, prior standard wound therapy and applicable HDE or coding details to support coverage determinations.

POLICY UPDATE CHANGES

BEAR implant added to the list of investigational bioengineered tissue substitutes used in conjunction with anterior cruciate ligament repair.

Policy 7.01.582 reinstated replacing 7.01.113, effective July 3, 2025 following 90-day provider notification.

mVASC and TheraSkin added to medically necessary statement for diabetic lower-extremity ulcers.

GraftJacket and AlloMend removed from breast reconstruction policy statement (07/01/25).

Numerous HCPCS and CPT codes added and removed over multiple updates (2016-2026).

Wording changed from 'patient' to 'individual' throughout the policy for standardization.

6Named indications with Medical Necessity criteria

Coverage Summary

This policy defines coverage for bioengineered skin and soft tissue substitutes — including acellular dermal matrices, living cell therapies, biosynthetic and synthetic products — and specifies which products and clinical indications are considered medically necessary versus investigational (not eligible for coverage). It applies to indications such as breast reconstruction, diabetic and venous lower‑extremity ulcers, dystrophic epidermolysis bullosa, deep dermal/full‑thickness burns, and selected soft‑tissue repairs, and describes required documentation and coding. Effective date: Sep. 1, 2025; Last review: Jan. 1, 2026.

Quick facts and thresholds

Epicel TBSA threshold≥30% total body surface area (HDE-specified)

Conventional therapy duration for venous ulcers1 month of conventional ulcer therapy failed to promote healing before advanced therapy

Number of named medical-necessity indications6

Notable investigational implant (BEAR)BEAR (bridge-enhanced ACL repair) listed as investigational for use with ACL repair

Policy reinstatement / coding eventsPolicy reinstated 04/01/25 replacing prior policy; HCPCS C1763 added when BEAR added; multiple coding updates noted (A2030-A2034 added at reinstatement and further HCPCS changes through 2026)

Medical-Necessity Criteria

Covered when ALL of the following criteria for each indication are met as specified below:

ALL of the following

Allogeneic acellular dermal matrix products (e.g., AlloDerm, Cortiva/AlloMax, DermACELL, DermaMatrix, FlexHD, FlexHD Pliable) are used for breast reconstructive surgery.
Medical necessity for use
- There is insufficient tissue expander or implant coverage by the pectoralis major muscle and additional coverage is required.
- There are viable but compromised or thin postmastectomy skin flaps that are at risk of dehiscence or necrosis.

Not Medically Necessary / Investigational

Investigational / Not Medically Necessary

All other uses and all other bioengineered skin and soft tissue substitute products not listed above are considered investigational (Not Eligible for Coverage).

Product not specifically listed as medically necessary in this policy

Policy lists numerous specific products considered investigational; see product list

Investigational designation (selected)

Products are investigational (not eligible for coverage) when listed in the investigational section or when indication not met per policy; BEAR implant added to investigational list:

BEAR (bridge-enhanced anterior cruciate ligament repair) implant is listed as investigational bioengineered tissue substitute used in conjunction with anterior cruciate ligament repair

Added to investigational list effective with policy reinstatement 04/01/25 (policy replaces 7.01.113); HCPCS C1763 was added at that time

Coding

RECELL system CPT codesCPT

15011	Harvest of skin for skin cell suspension autograft; first 25 sq cm or less (use to report: The RECELL system)
15012	Harvest of skin for skin cell suspension autograft; each additional 25 sq cm or part thereof (use to report: The RECELL system)
15013	Preparation of skin cell suspension autograft; first 25 sq cm or less of harvested skin (use to report: The RECELL system)
15014	Preparation of skin cell suspension autograft; each additional 25 sq cm of harvested skin (use to report: The RECELL system)
15015	Application of skin cell suspension autograft to wound and donor sites; first 480 sq cm or less (use to report: The RECELL system)
15016	Application of skin cell suspension autograft; each additional 480 sq cm or part thereof (use to report: The RECELL system)
15017	Application of skin cell suspension autograft to face/scalp/genitalia/etc; first 480 sq cm or less (use to report: The RECELL system)
15018	Application of skin cell suspension autograft to face/scalp/..., each additional 480 sq cm or part thereof (use to report: The RECELL system)

Reviewed for Medical Necessity HCPCS / Add-on skin substitute codesHCPCS

A4100	Skin substitute, FDA cleared as a device, not otherwise specified (add-on, list separately in addition to primary procedure)
Q4100	Skin substitute, not otherwise specified. Investigational (Not Eligible for Coverage)
A2001	InnovaMatrix AC, per square centimeter
A2002	Mirragen Advanced Wound Matrix, per square centimeter
A2004	XCelliStem, per square centimeter
A2005	Microlyte Matrix, per square centimeter
A2006	NovoSorb SynPath dermal matrix, per square centimeter
A2007	Restrata, per square centimeter
A2008	TheraGenesis, per square centimeter
A2009	Symphony, per square centimeter

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1/5

Category III / C / Q / C9 HCPCS and other device codesmixed

C1763	Connective tissue, nonhuman (includes synthetic) (use to report: BEAR implant)
C1832	Autograft suspension, including cell processing and application, and all system components
C9353	Microporous collagen implantable slit tube (NeuraWrap Nerve Protector), per cm length
C9354	Acellular pericardial tissue matrix of nonhuman origin (Veritas), per square centimeter
C9356	TenoGlide Tendon Protector Sheet, per square centimeter
C9358	Dermal substitute, fetal bovine origin (SurgiMend), per 0.5 sq cm
C9360	Dermal substitute, neonatal bovine origin (SurgiMend), per 0.5 sq cm
C9363	Skin substitute (Integra Meshed Bilayer Wound Matrix), per square centimeter
C9364	Porcine implant, Permacol, per square centimeter

Q-codes for specific products (add-on)HCPCS

Q4103	Oasis Burn Matrix, per square centimeter
Q4104	Integra bilayer matrix wound dressing (BMWD), per square centimeter
Q4108	Integra Matrix, per square centimeter
Q4110	PriMatrix, per square centimeter
Q4111	GammaGraft, per square centimeter
Q4112	Cymetra, injectable, 1 cc
Q4113	Graftjacket Xpress, injectable, 1 cc
Q4115	AlloSkin, per square centimeter
Q4117	Hyalomatrix, per square centimeter
Q4118	MatriStem micromatrix, 1 mg

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ModifiersModifier

JC	Skin substitute used as a graft
JD	Skin substitute not used as a graft

FDA product codes mentionedmixed

FTM	FDA product code cited for various skin substitute products
OXF	FDA product code cited
KGN	FDA product code cited
FTL	FDA product code cited
PFC	FDA product code cited
OCE	FDA product code cited
ODS	FDA product code cited
QCZ	FDA product code for Recell autologous cell harvesting device
FRO	FDA product code cited
MDD	FDA product code cited

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1/2

HCPCS/CPT codes added in various updates (coding history)mixed

Q4166	HCPCS added (reference in 02/17/17 update)
Q4167	HCPCS added (reference in 02/17/17 update)
Q4169	HCPCS added (reference in 02/17/17 update)
Q4170	HCPCS added (reference in 02/17/17 update)
Q4171	HCPCS added (reference in 02/17/17 update)
Q4172	HCPCS terminated 1/1/19 (removed)
Q4179	HCPCS added to investigational section (01/01/20 and repeated)
Q4182	HCPCS added to investigational section (01/01/20 and repeated)
Q4238	HCPCS added under investigative section (06/25/2020)
C1849	HCPCS added (11/01/20), term date added 01/01/23

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1/7

Coding and code designations have changed repeatedly over time; codes must be applied consistent with the policy effective dates. The history documents numerous HCPCS and CPT additions and removals (for example, CPT 15011–15018 added 01/01/25 and HCPCS additions such as A2030–A2034 and C1763 with the 04/01/25 reinstatement), and the policy notes that reinstatement on 04/01/25 (effective 07/03/25) included many coding updates. Review the policy history and code group listings for the correct code to use for a product and indication by the policy effective date.

Provider Actions

Documentation Required

Wound assessment and comorbidities documentation

Document a detailed history and physical for wound care including associated medical comorbidities and a descriptive wound characterization (e.g., full thickness, deep dermal).

Documentation Required

Standard wound therapy documentation

Record the standard wound therapy provided and its duration and effectiveness or failure (for example, at least one month of conventional therapy failure for venous ulcers prior to advanced product application).

Background and Evidence

Bioengineered skin and soft tissue substitutes encompass products derived from human (autologous or allogeneic), nonhuman (xenogeneic), synthetic, or composite sources and include acellular dermal matrices, living cell therapies, autologous cell‑harvesting systems, biosynthetic matrices, and nerve wraps. They are used for a range of clinical situations — notably nonhealing wounds (diabetic foot ulcers, venous ulcers), breast reconstruction when tissue coverage is inadequate, second‑ and third‑degree burns, and selected soft‑tissue repairs — with evidence and regulatory status varying by specific product and indication.

Topic	Evidence Summary
Breast reconstruction evidence
Randomized controlled trials and systematic reviews show no difference in overall complication rates with acellular dermal matrices versus standard procedures, but higher rates of seroma, infection, and necrosis have been reported; possible reductions in capsular contracture and implant malposition—evidence sufficient to inform decision making when tissue coverage is limited.
Diabetic lower-extremity ulcers evidence
Randomized controlled trials with ≥12 weeks follow-up demonstrate efficacy of AlloPatch, Apligraf, Dermagraft, Integra, mVASC, and TheraSkin versus standard of care; evidence judged sufficient to show meaningful improvement in healing.
Venous ulcers evidence
RCTs demonstrate efficacy of Apligraf and Oasis Wound Matrix over standard of care for venous insufficiency ulcers; other products have mixed or insufficient evidence.
Deep dermal burns evidence
Epicel (HDE) and Integra Dermal Regeneration Template have RCT and comparative data showing improved outcomes for deep dermal/full-thickness burns; ReCell RCTs show comparable outcomes but overall evidence limited and heterogeneous.
BEAR implant evidence
Randomized trials and systematic reviews (Murray et al. 2020; Barnett 2021; systematic reviews) report similar patient-reported outcomes to autograft ACL reconstruction at 2 years, noninferiority on IKDC and laxity, but some studies report higher ipsilateral revision/rerupture rates (up to ~14%); evidence includes De Novo regulatory data and evolving reviews.
NICE recommendation
NICE (2023) recommends considering dermal or skin substitutes as an adjunct to standard care for diabetic foot ulcers only when healing has not progressed and on advice of a multidisciplinary foot care service.
CMS determination
CMS NCD states porcine skin dressings are covered as reasonable and necessary occlusive dressings for burns, donor sites, decubiti, and other ulcers; CMS has explored coding/payment changes for skin substitutes.
Recell PMA
ReCell was approved by FDA via PMA (BP170122) Sept 2018 with specified indications for autologous RES use in partial- and full-thickness burns and certain full-thickness defects/pediatric indications.
BEAR De Novo
BEAR implant received FDA De Novo classification DEN200035 (2020) indicated for skeletally-mature patients ≥14 years with complete ACL rupture and tibial stump present; FDA product code QNI.
Hayes review
Hayes, Inc. published an evolving evidence review for the BEAR implant (February 6, 2025) summarizing available RCTs and outcomes evidence.
Randomized trial
Murray MM et al. 2020 randomized clinical trial: BEAR not inferior to autograft ACL reconstruction at 2 years (PMID 32298131); other RCT data (Barnett 2021) report earlier symptom resolution but longer-term durability and revision differences noted.

Definitions

Skin substituteNo standard definition; includes acellular dermal matrices, cellular therapies, and biosynthetics; may or may not require FDA approval/clearance

HDEHumanitarian Device Exemption — FDA pathway for devices intended to benefit patients with conditions affecting fewer than 8,000 individuals per year

HCT/PHuman cells, tissues, and cellular- and tissue-based products regulated under section 361/PHS and 21 CFR Part 1271 when meeting minimal manipulation and homologous use criteria

ADM

Medicare Determinations

Name	Number	Type	Effective Date
Coverage of porcine skin dressings

NCD

Porcine Skin and Gradient Pressure Dressings
270.5
NCD

Revision History

04/01/25added

BEAR implant added to the list of investigational bioengineered tissue substitutes used in conjunction with anterior cruciate ligament repair. Detail: Added when policy 7.01.582 reinstated 04/01/25, effective July 3, 2025; C1763 HCPCS added.

04/01/25revised

Policy 7.01.582 reinstated replacing 7.01.113, effective July 3, 2025 following 90-day provider notification. Detail: Reinstatement included many coding updates (A2030-A2034 added) and investigational list changes.

06/01/24added

mVASC and TheraSkin added to medically necessary statement for diabetic lower-extremity ulcers. Detail: Added 06/01/24 annual review approved May 24, 2024.

Policy Summary

PayerPremera Bluecross

PolicyBioengineered Skin and Soft Tissue Substitutes

Policy CodePolicy N/A

Change TypeReinstatement / coding and investigational list updates

Effective DateSep 1, 2025

Next Review DateN/A

Key ActionDocument wound assessment, prior standard wound therapy and applicable HDE or coding details to support coverage determinations.

On This Page

Chronic diabetic lower-extremity ulcers (full-thickness)

Use of specified tissue-engineered skin substitute products (e.g., AlloPatch, Apligraf, Dermagraft, Integra Omnigraft, IntegraFlowable Wound Matrix, mVasc) is for chronic, non-infected, full-thickness diabetic lower-extremity ulcers.
Standard wound therapy has been documented and failed to achieve healing; documentation must include type, duration, and response to prior therapies.
Clinical records support the chronicity and non-infected status of the ulcer.

Venous insufficiency lower-extremity ulcers (partial or full-thickness)

Use of specified tissue-engineered skin substitute products (e.g., Apligraf, Oasis Wound Matrix) is for chronic, non-infected, partial- or full-thickness lower-extremity ulcers due to venous insufficiency.
A one-month period of conventional ulcer therapy has failed to promote healing (documentation required).
Clinical records support venous etiology and non-infected status of the ulcer.

Dystrophic epidermolysis bullosa (OrCel)

OrCel is used for treatment of dystrophic epidermolysis bullosa (e.g., mitten-hand deformity).
Standard wound therapy has failed for the treatment of the indicated deformity.
Use is provided in accordance with the humanitarian device exemption (HDE) specifications of the U.S. Food and Drug Administration and documentation demonstrates HDE-appropriate indications.

Second- and third-degree burns

Specified tissue-engineered skin substitute products (e.g., Epicel, Integra Dermal Regeneration Template) are used for treatment of second- and third-degree burns.
Use of Epicel only: treatment of deep dermal or full-thickness burns covering total body surface area >=30% and provided in accordance with FDA HDE specifications.>=30%
Epicel requires HDE compliance and documentation of total body surface area involved.
Use of Integra Dermal Regeneration Template: no additional criteria required beyond documentation of burn depth and extent.

Prior Authorization

Coverage dependent on policy criteria and coding

Confirm that coverage determinations follow the product-specific medically necessary vs investigational listings and use the correct HCPCS/CPT codes as designated with their effective dates.

Verify product placement on medically necessary vs investigational lists and confirm effective dates for HCPCS/CPT codes before billing.