The origins of the “skin substitutes” as a term referring to bioengineered substitutes predates its current syntax. Prior to the advent of bioengineering, the term “skin substitutes” was often used interchangeably with words like “graft” or “wound dressing” to refer to any biologic or synthetic wound covering. Essentially, anything used to apply natural or synthetic protection over an exposed wound was referred to as a skin substitute. However, beginning in the mid-1970s, the meaning of the term started to evolve as scientific progress, led by researchers such as Rheinwald, Green, O’Connor and their teams of colleagues, made advances in using cultured cell lines as barrier protections for exposed wounds. From that time until now, products and devices used to dress wounds and promote healing have grown significantly in both complexity and variety; however, the tendency to use the phrase “skin substitutes” as it was originally used has persisted, and this has had negative consequences in terms of muddling cross-communication between researchers, providers, suppliers, and payers.
According to the ASTM standards, a skin substitute is defined as a, “biomaterial, engineered tissue, or combination of biomaterials and cells or tissues that can be substituted for a skin allograft, a skin autograft, an epidermal autograft, or a dermal autograft in a clinical procedure”. Additionally, it defines a cellular and/or tissue-based product (CTP) as a, “product… comprising cells and/or the extracellular components of tissue… which may contain cells (viable or nonviable), tissues, proteins, and other materials for which there is a rationale for benefit beyond that achievable with conventional wound coverings”. Simply put, the ASTM defines CTPs primarily by their composition, and it defines skin substitutes by its function –i.e. in serving as a substitute, temporary or permanent, for traditional skin grafts. While it is tempting to use these terms interchangeably, the wound care industry has objected strongly to this tendency as they believe the term skin substitutes inaccurately implies these products are capable of fulfilling the functions of healthy skin (e.g. innervation, thermal regulation, oil production, and pigmentation).
Additionally, it objects to their classification as dressings as this term has “low-tech” connotations, which consequently have negative impacts in terms of reimbursement and coverage for patients and providers. The Alliance for Woundcare Stakeholders, a non-profit inter-professional trade association which serves as an “umbrella” organization for other wound care organizations, had fought hard to change the vocabulary associated with skin substitutes.
How are they regulated?
When synthetic and biologic combinations of wound healing products first started to present to the FDA for pre-market approval in the 1980s, the issue of what to call these devices was compounded by the issue of how to classify and regulate them. In response to this growing complexity, the FDA established Division IV of Committee F04 for Medical Devices through the ASTM. This committee responded to the need to clarify the classification of products colloquially referred to as “skin substitutes” with several standards. Concurrent with the challenge of naming and defining these products, the FDA faced the challenge of deciding which regulatory center would be responsible for reviewing these products. Initially, the FDA had three centers responsible for monitoring human medical devices: the Center for Devices and Radiologic Health (CDRH), the Center for Biologics Evaluation and Research (CBER), and the Center for Drug Evaluation and Research (CDER), but in 2002 it also established the Office of Combination Products. Additionally, the FDA established guidelines to help guide the regulatory process when there was confusion about which center was appropriate for reviewing the product –especially when review was required by more than one center.