Bioengineered Skin and Soft Tissue Substitutes
DESCRIPTION
Bio-engineered skin and soft tissue substitutes may be derived from human tissue (autologous or allogeneic), nonhuman tissue (xenographic), synthetic materials, or a composite of these materials. Bioengineered skin and soft tissue substitutes are being evaluated for a variety of conditions, including breast reconstruction and to facilitate healing of lower-extremity ulcers and severe burns. The gold standard for surgical wound repair is to use a skin graft harvested from the individual’s own skin (autograft). However, autologous tissue grafting is an invasive and painful procedure, and the extent of damaged skin can be too large to be covered by an autologous graft alone.
While there are many proposed applications for these products the evidence on any single product is extremely limited. FDA approval is obtained as premarket approval, 510(k) clearance, humanitarian device exemption (HDE) or regulated as banked human tissue depending on the source of the product.
Note: Please see Human Amniotic Membrane Grafts and Amniotic Fluid Injections medical policy for all products using human amniotic membrane or amniotic fluid.
POLICY
Bioengineered skin and soft tissue substitutes are considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
All other uses of bio-engineered skin and soft tissue substitutes are considered investigational.
All other skin and soft tissue substitutes, including, but not limited to the following, are considered investigational:
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Any product utilized for this procedure must have FDA approval specific to the indication, otherwise it will be considered investigational.
MEDICAL APPROPRIATENESS
Bioengineered skin and soft tissue substitutes are considered medically appropriate if ANY ONE of the following criteria are met:
Treatment for breast reconstructive surgery using allogenic acellular dermal matrix products (i.e., AlloDerm® Regenerative Tissue Matrix; Cortiva®, [AlloMax™ Surgical Graft]; AlloMend®; DermACELL™; DermMatrix™; FlexHD®; FlexHD Pliable®; or GraftJacket®) if ANY ONE of the following criteria are met:
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
The infra-mammary fold and lateral mammary folds have been undermined during mastectomy and re-establishment of these landmarks is needed
Treatment of chronic, non-infected, full-thickness diabetic lower extremity ulcers using ANY ONE of the following tissue-engineered skin substitutes:
AlloPatch® Pliable
Apligraf®
Dermagraft®
Integra® Dermal Regeneration Template or
Integra Omnigraft™ Dermal Regeneration Matrix
Integra® Flowable Wound Matrix
Treatment of chronic, non-infected, partial- or full-thickness lower extremity skin ulcers and ALL of the following:
Skin ulcers are due to venous insufficiency
Conventional wound therapy has failed after a 30-day period
Tissue-engineered skin substitute to be used is ANY ONE of the following:
Apligraf®
Oasis™ Wound Matrix
Treatment of dystrophic epidermolysis bullosa when ALL of the following criteria are met:
Individual with mitten-hand deformity
Tissue-engineered skin substitute being used is OrCel™
Standard wound therapy has failed
Provided in accordance with the Humanitarian Device Exemption (HDE) specifications of the FDA
Treatment of second- and third-degree burns using ANY ONE of the following tissue-engineered skin substitutes:
Epicel® when ALL of the following criteria are met:
For the treatment of deep dermal or full-thickness burns comprising a total body surface area of greater than or equal to 30%
Provided in accordance with the Humanitarian Device Exemption (HDE) specifications of the FDA
Integra Dermal Regeneration Template™
IMPORTANT REMINDERS
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
ADDITIONAL INFORMATION
Overall, the number of bio-engineered skin and soft-tissue substitutes is large, but the evidence is limited for any specific product. Relatively few products have been compared with the standard of care (SOC), and then only for some indications.
SOURCES
Agency for Healthcare Research and Quality (AHRQ). (2020, February). Skin substitutes for treating chronic wounds. Retrieved March 5, 2020 from http://www.ahrq.gov.
BlueCross BlueShield Association. Evidence Positioning System. (2:2023). Bio-engineered skin and soft tissue substitutes (7.01.113). Retrieved April 3, 2023 from http://www.evidencepositioningsystem.com. (64 articles and/or guidelines reviewed)
Campitiello, F., Mancone, M., Della Corte, A., Guerniero, R., & Canonico, S. (2017). To evaluate the efficacy of an acellular Flowable matrix in comparison with a wet dressing for the treatment of patients with diabetic foot ulcers: a randomized clinical trial. Updates in Surgery, 69 (4), 523-529. Abstract retrieved March 15, 2018 from PubMed database.
Centers for Medicare & Medicaid Services. CMS.gov. NCD for porcine skin and gradient pressure dressings (270.5). Retrieved January 21, 2021 from http://www.cms.gov.
Chang, E. and Liu, J. (2017). Prospective unbiased experience with three acellular dermal matrices in breast reconstruction.Journal of Surgical Oncology, 116 (3), 365-370. Abstract retrieved March 15, 2018 from PubMed database.
Code of Federal Regulations. (2023). Title 21: Food and Drugs. PART 1271—Human cells, tissues, and cellular and tissue based products. Received April 4, 2023 from http://www.ecfr.gov/cgi-bin/text.
Driver, V., Lavery, L., Reyzelman, A., Dutra, T., Dove, C., Kotsis, S., et. al. (2015). A clinical trial of Integra Template for diabetic foot ulcer treatment. Wound Repair and Regeneration, 23, 891–900. (Level 1 evidence)
Frykberg, R., Gibbons, G., Walters, J., Wukich, D., & Milstein, F. (2016) A prospective, multicentre, open-label, single-arm clinical trial for treatment of chronic complex diabetic foot wounds with exposed tendon and/or bone: positive clinical outcomes of viable cryopreserved human placental membrane. International Wound Journal ISSN, 1742-4801. (Level 2 evidence)
Gibbons, G. (2015). Grafix® a cryopreserved placental membrane for the treatment of chronic/stalled wounds. Advances in Wound Care, 4 (9), 434-444. (Level 4 evidence)
Gordon, AJ., Alfonso, AR., Nicholson, J., & Chiu, ES. (2019). Evidence for healing diabetic foot ulcers with biologic skin substitutes: A systematic review and meta-analysis. Annals of Plastic Surgery, S31-S44. Abstract retrieved March 13, 2020 from PubMed database.
Holmes, J.H., Molnar, J.A., Carter, J E., Hwang J., Cairns, B A., King, B T., et al. (2018). A comparative study of the ReCell® device and autologous split-thickness meshed skin graft in the treatment of acute burn Injuries. Journal of Burn Care & Research, 39 (5), 694-702. (Level 3 evidence)
Holmes, J.H., Molnar, J.A., Shupp, J.W., Hickerson, W.L., King, B.T., Foster, K.N., et al. (2018). Demonstration of the safety and effectiveness of the RECELL® System combined with split-thickness meshed autografts for the reduction of donor skin to treat mixed-depth burn injuries. Burns: Journal of the International Society for Burn Injuries, 45 (4), 772-782. (Level 3 evidence)
Infectious Diseases Society of America. (2012, June). 2012 Clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Retrieved January 27, 2014 from http://www.guidelines.gov.
Lavery, L., Fulmer, J., Shebetka, K., Regulski, M., Vayser, D., Fried, D, et al. (2014). The efficacy and safety of Grafix® for the treatment of chronic diabetic foot ulcers: results of a multi-center, controlled, randomized, blinded, clinical trial. International Wound Journal, ISSN 1742-4801. (Level 2 evidence)
National Institute for Health and Clinical Excellence (NICE). (2015, August)). ReCell ® spray-on skin system for treating skin loss, scarring and depigmentation after burn injury: A NICE Medical Technology Guidance. Retrieved April 3, 2023 from http://www.nice.org.uk.
National Institute for Health and Clinical Excellence (NICE). (2014, November; last update search October 2019). Diabetic foot problems: prevention and management. Retrieved January 20, 2021 from http://www.nice.org.uk.
Pittman, T., Fan, K., Knapp, A., Frantz, S., & Spear, S. (2017). Comparison of Different Acellular Dermal Matrices in Breast Reconstruction: The 50/50 Study. Plastics & Reconstructive Surgery, 139 (3), 521-528. Abstract retrieved March 15, 2018 from PubMed database.
Sanders, L., Landsman, A., Landsman, A., Keller, N. Cook, J., Cook, J., et al. (2014). A prospective, multicenter, randomized controlled clinical trial comparing a bioengineered skin substitute to a human skin allograft. Ostomy Wound Management, 60 (9), 26-38. (Level 2 evidence)
Towler, M., Rush, E., Richardson, M., and Williams, C. (2018). Randomized, prospective, blinded-enrollment, head-To-head venous leg ulcer healing trial comparing living, bioengineered skin graft substitute (Apligraf) with living, cryopreserved, human skin allograft (TheraSkin). Clinics in Podiatry Medicine & Surgery, 35 (3), 357-365. Abstract retrieved February 25, 2019 from PubMed database.
U. S. Food and Drug Administration. (2001, August). Center for Devices and Radiological Health. Cellular Matrix - P010016 (OrCel™ Bilayered). Retrieved January 31, 2014 from http://www.accessdata.fda.gov.
U. S. Food and Drug Administration. (2006, July). Center for Devices and Radiological Health. Premarket Approval Database. P950032/S016 (Apligraf®). Retrieved January 31, 2014 from http://www.accessdata.fda.gov.
U. S. Food and Drug Administration. (2007, October). Center for Devices and Radiological Health. Epicel® (cultured epidermal autografts) - H990002. Retrieved January 31, 2014 from http://www.accessdata.fda.gov.
Winifred S. Hayes, Inc. Medical Technology Directory. (2019, January; last update search February 2022). Comparative effectiveness review of human acellular dermal matrix for breast reconstruction. Retrieved April 4, 2023 from www.Hayesinc.com. (3 articles and/or guidelines reviewed)
Winifred S. Hayes, Inc. Medical Technology Directory. (2020, July; last update search August 2022). Skin substitutes for venous leg ulcers in adults. Retrieved April 4, 2023 from www.Hayesinc.com. (44 articles and/or guidelines reviewed)
Winifred S. Hayes, Inc. Medical Technology Directory. (2020, March; last update search March 2022). Cellular skin substitutes for chronic foot ulcers in adults with diabetes mellitus. Retrieved April 4, 2023 from www.Hayesinc.com. (48 articles and/or guidelines reviewed)
Winifred S. Hayes, Inc. Medical Technology Directory. (2020, May; last update search April 2022). Acellular skin substitutes for chronic foot ulcers in adults with diabetes mellitus. Retrieved April 4, 2023 from www.Hayesinc.com. (50 articles and/or guidelines reviewed)
ORIGINAL EFFECTIVE DATE: 8/11/2012
MOST RECENT REVIEW DATE: 5/11/2023
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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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