Autogenous Biofabrication of Nativelike, Scaffold-Free Human Skin Equivalents Using a Smart, Enzyme-Degradable Tissue Templating Coating.

Abstract

In this study, we used tissue templating technology to direct human dermal fibroblasts to biofabricate large-area tissues that closely emulate the natural dermis. This technology also allowed the new tissues to promote their own release from the template surface, thus facilitating their recovery as self-sustained, scaffold-free dermal equivalents solely comprising human cells and their own extracellular matrix. The structure and composition of these dermal self-lifting autogenous tissue equivalents (SLATEs) were evaluated in detail and were shown to closely correlate to normal tissue function. Specifically, dermal SLATEs were shown to be composed of a dense collagen-based matrix interwoven with dermal-characteristic elastic fibers. In addition, the mechanical properties of these tissues (i.e., robustness, elastic modulus, and resistance to contraction and enzymatic degradation) were comparable to those of the natural human dermis. Furthermore, dermal SLATEs were capable of constituting tissues with a higher-order complexity by serving as a substrate to support the growth of keratinocytes into stratified epithelia with distinct layers of differentiation. This work thus illustrates the great potential of tissue templating technologies and how these can pave the way for the biofabrication of easily retrievable, scaffold-free human skin tissues with a structure, composition, and function suitable for both clinical and nonclinical applications.