A Universal Classification System of Skin Substitutes Inspired by Factorial Design

The complexity of the dermal layer of skin means that damage to this section can result in permanent impairment of function. Partial or total dermal loss is a feature of deep burns and chronic wounds such as pressure sores or diabetic ulcers. The issues posed by traditional skin grafts have led to substantial research being carried out in the fields of tissue engineering and biomaterials science to develop a vast array of alternative skin substitutes. Given the large number of different materials, manufacturing methods, and techniques for implementation described for artificial skin substitutes, many classification systems have been created to simplify their categorization. Some of these systems are oriented toward clinicians while others toward researchers. However, none address the needs of both groups and none are intuitive. The creation of an effective classification system would be particularly helpful in the regulation, distribution, organization, and selection of skin substitutes. The aim of this review is to examine existing methods of classification of skin substitutes, and to propose a new system that uses an algorithm that is inspired by factorial design. Our system allows multiple factors to be simultaneously investigated or in this case, described, since all skin substitutes possess multiple characteristics: (1) cellularity (acellular or cellular), (2) layering (single layer or bilayer), (3) replaced region (epidermis, dermis, or both), (4) materials used (natural, synthetic, or both), and (5) permanence (temporary or permanent). The factors and levels are combined into an algorithm where all the possible combinations are shown. The multifactorial and palindromic structure of our system should enable all users to quickly understand the makeup of a selected skin substitute, or search for a skin substitute depending on their specific requirements. We feel that our proposed classification can be used by clinicians and biomedical researchers alike, which should be an advantage given the multidisciplinary nature of the tissue engineering field and the science that underpins the development of skin substitutes. We also touch upon some of the state-of-the-art skin substitutes that are commercially available or under development to demonstrate how our new method of classification might work.