Bioengineered Skin and Soft Tissue Substitutes
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 healing lower-extremity ulcers and severe burns. The gold standard for surgical wound repair is to use a skin graft harvested from the patient’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.
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:
Any product utilized for this procedure must have FDA approval specific to the indication, otherwise it will be considered investigational.
See also: Human Amniotic Membrane Grafts and Amniotic Fluid Injections
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 including each of the following: AlloDerm® Regenerative Tissue Matrix; AlloMax™ Surgical Graft; AlloMend®; DermMatrix™; FlexHD®; 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:
Integra® Dermal Regeneration Template
Treatment of chronic, non-infected, partial- or full-thickness lower extremity skin ulcers due to venous insufficiency, which have not adequately responded following a 30 day period of conventional ulcer therapy, using ANY ONE of the following tissue-engineered skin substitutes:
Oasis™ Wound Matrix
Treatment of dystrophic epidermolysis bullosa using OrCel™ for individuals with mitten-hand deformity when ALL of the following criteria are met:
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™
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, the express terms of the health plan will govern.
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. Therefore, many of these products remain investigational.
Agency for Healthcare Research and Quality (AHRQ). (2012, December). Skin substitutes for treating chronic wounds. Retrieved January 27, 2014 from: http://www.ahrq.gov.
American Society of Plastic Surgeons. (2013, March). Evidenced-based clinical practice guideline: Breast reconstruction with expanders and implants. Retrieved January 27, 2014 from: http://www.plasticsurgery.org.
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2017) Amniotic membrane and amniotic fluid injections (7.01.149). Retrieved May 30, 2017 from BlueWeb. (26 articles and/or guidelines reviewed)
BlueCross BlueShield Association. Medical Policy Reference Manual. (1:2017). Bio-engineered skin and soft tissue substitutes (7.01.113). Retrieved May 19, 2017 from BlueWeb. (62 articles and/or guidelines reviewed)
Cahaba Government Benefit Administrators, LLC. (2017, February). Local Coverage Determination (LCD): Surgery: Bioengineered skin substitutes for the treatment of diabetic and venous stasis ulcers of the lower extremities (L34285) Retrieved February 3, 2017 from: http://www.cms.gov.
Code of Federal Regulations. (2017) Title 21: Food and Drugs. PART 1271 - Human cells, tissues, and cellular and tissue based products. Received February 7, 2017 from http://www.ecfr.gov/cgi-bin/text.
Davila, A. A., Seth, A. K., Wang, E., Hanwright, P., Bilimoria, K., Fine, N., et al. (2013). Human acellular dermis versus submuscular tissue expander breast reconstruction: A multivariate analysis of short-term complications. Archives of Plastic Surgery, 40 (1), 19-27. (Level 1 evidence - Industry sponsored)
DiDomenico, L., Landsman, A., Emch, K. and Landsman, A. (2011, July) A prospective comparison of diabetic foot ulcers treated with either a cryopreserved skin allograft or a bioengineered skin substitute. Wounds. 2011:23(7):184-9. Abstract retrieved February 20, 2017 from PubMed database.
Driver, V., Lavery, L., Reyzelman, A., Dutra, T., Dove, C., Kotsis, S., et. al. (2015, August) A clinical trial of Integra Template for diabetic foot ulcer treatment. Wound Repair and Regeneration(2015) 23 891–900. (Level 1 evidence)
Frykberg, R., Gibbons, G., Walters, J., Wukich, D., and 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. Vol. 4, No. 9; 434-444. (Level 4 evidence - Industry sponsored)
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.
Johnson, E., Marshall, J., and Michael, G. (2017, January) A comparative outcomes analysis evaluating clinical effectiveness in two different human placental membrane products for wound management. Wound Repair and Regeneration. Retrieved February 14, 2017 from: http://onlinelibrary.wiley.com. (Level 3 evidence)
Landsman, A.S., Cook, J., Cook, E., Landsman, A.R., Garrett, P., Yoon, J., et. al., (2011, February) A retrospective clinical study of 188 consecutive patients to examine the effectiveness of a biologically active cryopreserved human skin allograft (TheraSkin®) on the treatment of diabetic foot ulcers and venous leg ulcers. Foot & Ankle Specialist; 4(1):29-41. Abstract retrieved July 11, 2016 from PubMed database.
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-centre, controlled, randomised, blinded, clinical trial. International Wound Journal ISSN 1742-4801. (Level 2 evidence - Industry sponsored)
Letendre, S., LaPorta, G., O’Donnell, E., Dempsey, J., and Leonard, K. (2009, April) Pilot trial of Biovance® collagen-based wound covering for diabetic ulcers. Advanced Wound Care. Abstract retrieved March 23, 2016 from PubMed Database.
National Institute for Health and Clinical Excellence (NICE). (2015, August). Diabetic foot problems: prevention and management. Retrieved March 23, 2016 from http://www.nice.org.uk.
Regulski, M., Jacobstein, J., Petranto, R., Migliori, V., Nair, G., and Pfeiffer, H. (2013, December) A retrospective analysis of human cellular repair matrix for the treatment of chronic wounds. Ostomy Wound Management. 2013; 59(12):38-43. (Level 4 evidence)
Sanders, L., Landsman, A., Landsman, A., Keller, N. Cook, J., Cook, J., et. al., (September, 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)
Serena, T., Carter, M., Lam, T., Sabo, M., & DiMarco, D., (September, 2014) A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. Wound Repair and Regeneration.22 688-692. (Level 2 evidence - Industry sponsored)
Sheikh, E. S., Sheikh, E. S., & Fetterolf, D. E. (2013). Use of dehydrated human amniotic membrane allografts to promote healing in patients with refractory non healing wounds. International Wound Journal, 1-7. (Level 4 evidence)
Smiell, J., Treadwell, T., Hahn, HD., and Hermans, M. (2015, June) Real-world experience with a decellularized dehydrated human amniotic membrane allograft. Wounds; 27(6):158-69. Abstract retrieved March 23, 2016 from PubMed database.
U. S. Food and Drug Administration. (2001, August). Center for Devices and Radiological Health. OrCel™ Bilayered Cellular Matrix - P010016. 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. 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. Clinical Research Response. (2017, February). Tissue expanders for breast reconstruction. Retrieved February 7, 2017 from www.Hayesinc.com/subscribers. (5 articles and/or guidelines reviewed)
Zelen, C. M., Gould, L., Serena, T., Carter, M., Keller, J. & Li, W. (2014) A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers. International Wound Journal. ISSN 1742-4801. (Level 2 evidence - Industry sponsored)
Zelen, C. M., Serena, T., Denoziere, G., & Fetterolf, D. (2013, October). A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers. International Wound Journal, 10 (5), 502-507. (Level 2 evidence - Industry sponsored)
ORIGINAL EFFECTIVE DATE: 8/11/2012
MOST RECENT REVIEW DATE: 11/1/2017
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.
This document has been classified as public information.