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

Patrícia Zoio,Sara Lopes-Ventura,Abel Oliva

doi:10.3390/micro2010013

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.

Highlights

The global topical drug delivery market is growing fast due to the increasing prevalence of chronic skin diseases [1]
We have developed a 3D full-thickness SoC model based on a fibroblast-derived matrix
Human fibroblasts are stimulated to produce their extracellular matrix, which deposits onto the scaffold structure, resulting in a fully human dermal compartment

Summary

Introduction

The global topical drug delivery market is growing fast due to the increasing prevalence of chronic skin diseases [1]. Animal models have been used worldwide to test the efficacy and toxicity of topical drugs. There is a lack of accuracy of the animal-to-human extrapolation, with approximately 90% of the drug candidates that appear safe and effective in animal studies failing to win approval when tested in humans [5–7]. These factors resulted in an increasing need to replace and/or complement animal testing with physiologically relevant reconstructed human skin models suitable for topical drug delivery and disease modeling [8,9]

Methods

Discussion

Conclusion