Human reconstructed epidermis and vascularized bioprinted skin tissues as tissue-in-a-dish models for drug screening

Authors

• X Liu
• MJ Song
• S Michael
• M Ferrer

Abstract

In vitro cell assays and animal models are extensively used in early stage drug development for efficacy and toxicity testing. However, the lack of physiologically relevant human native tissue models result in limited predictive value of human response. Three-dimensional (3D) human skin equivalents are employed as an alternative method to animal testing for drug discovery. In this study, we first developed fully characterized reconstructed human epidermis (RHS) in a 96-well plate for in vitro skin corrosion testing following the OECD TG 431 guidelines. The results show RHE can correctly categorize and subcategorize corrosive substances. The tissue was then used to develop a new assay to predict both skin irritant and sensitizing chemicals. We further developed a physiologically accurate 3D bioprinted full-thickness human skin model with associated vasculature to enable preclinical drug development studies. Primary neonatal fibroblasts, pericytes, and iPSC-derived endothelial cells are suspended in a fibrinogen based bio-ink and bioprinted using HTS 24 transwell plate. In the dermis, confocal images of intact tissues stained with collagen IV and CD31 showed the 3D microvascular network and basement membrane of microvessels. Late epidermal differentiation markers further illustrated the epidermal layer was fully differentiated. These combined data demonstrate we have developed a rapid and robust 3D bioprinting platform faithfully recapitulating human native skin in microwell plate format. This 3D bioprinted skin tissue-in-a-dish assay platform is a major advance for studies in which vasculature is used to mimic systemic delivery of drugs, biological reagents like antibodies, immune cells, and viral vehicles for genomic editing.

Scientific Focus Area: Biomedical Engineering and Biophysics

This page was last updated on Friday, March 26, 2021