A sustainable strategy for generating highly stable human skin equivalents based on fish collagen

Tissue engineered skin equivalents are increasingly recognized as potential alternatives to traditional skin models such as human ex vivo skin or animal skin models. However, most of the currently investigated human skin equivalents (HSEs) are constructed using mammalian collagen which can be expensive and difficult to extract. Fish skin is a waste product produced by fish processing industries and identified as a cost-efficient and sustainable source of type I collagen. In this work, we describe a method for generating highly stable HSEs based on fibrin fortified tilapia fish collagen. The fortified fish collagen (FFC) formulation is optimized to enable reproducible fabrication of full-thickness HSEs that undergo limited contraction, facilitating the incorporation of human donor-derived skin cells and formation of biomimetic dermal and epidermal layers. The morphology and barrier function of the FFC HSEs are compared with a commercial skin model and validated with immunohistochemical staining and transepithelial electrical resistance testing. Finally, the potential of a high throughput screening platform with FFC HSE is explored by scaling down its fabrication to 96-well format.