Biomimetic Full-Thickness Skin-on-a-Chip Based on a Fibroblast-Derived Matrix

Abstract

Current commercially available in vitro skin models do not fully reproduce the structure and function of the native human skin, mainly due to their use of animal-derived collagen and their lack of a dynamic flow system. In this study, a full-thickness skin-on-a-chip (SoC) system that reproduces key aspects of the in vivo cellular microenvironment is presented. This approach combines the production of a fibroblast-derived matrix (FDM) with the use of an inert porous scaffold for the long-term, stable cultivation of a human skin model. The culture of a dermal compartment under fluid flow results in the increased synthesis and deposition of major FDM proteins, collagen I, and fibronectin, compared to tissues cultured under static conditions. The developed SoC includes a fully differentiated epidermal compartment with increased thickness and barrier function compared to the controls. Contrary to other SoC platforms that include a collagen-based matrix, the described model presents superior stability and physiological relevance. Finally, the skin barrier function was quantitatively evaluated via in situ transepithelial electrical resistance (TEER) measurements and in situ permeation tests. The SoC model presents a significantly higher TEER and lower permeability to FITC-dextran. In the future, this innovative low-cost platform could provide a new in vitro tissue system compatible with long-term studies to study skin diseases and evaluate the safety and efficacy of novel drugs and technologies.