Skin substitutes and wound healing: Current status and challenges

Bioengineered skin substitutes have emerged over the post 20 years as the most carefully studied and proven of the advanced wound management technologies. While the initial impetus for their development was to replace autograft, allograft, and xenograft in burn applications, they have found even wider application in the treatment of chronic venous and chronic diabetic ulcers. The current review addresses the history of skin substitutes', surveys the landscape of existing Food and Drug Administration-approved products and other promising innovations that appear close to market, and discusses the reasoning and controversies associated with design of these products. While acellular biologic constructs are discussed, the authors focus on products that include autologous or allogeneic cells. The various clinical trials supporting the use of skin substitutes for different wound healing indications are reviewed. The preponderance of literature supports the cost effectiveness of using skin substitutes, in healing burn, autograft donor site, diabetic, and venous wounds. In addition, better methods for early identification of diabetic and venous ulcers that may not heal well with standard treatment should improve the process of triaging candidates for skin substitute therapy. In the future, attaining a more detailed understanding of the mechanisms by which skin substitutes induce accelerated healing, including a better appreciation of the roles of cytokines and cell scaffolds, may lead to product enhancements that increase efficacy. Ongoing progress toward overcoming issues, such as abbreviated shelf life and distribution difficulties, as well as high manufacturing costs, should enable broader implementation of skin substitutes in acute and chronic wound therapy.