Presentation by Dr. Ruogang Zhao, Ph.D., Associate Professor, Department of Biomedical Engineering, University at Buffalo at the Regional Respirology Rounds, Division of Respirology, McMaster University January 26th, 2021
Fibrosis is a severe health problem characterized by progressive stiffening of tissues which causes organ malfunction and failure. Current development of anti-fibrosis drugs is facing major obstacles as most candidate drugs that were selected in pre-clinical animal studies failed in human clinical trials. In this talk, I will present engineering approaches to model fibrosis- associated biomechanical properties of the alveolar tissue and the use of such in vitro models for the development of anti-fibrosis drugs.
The engineered microtissue is able to model key biomechanical events occurred during lung fibrogenesis including progressive stiffening of alveolar tissue, decline in alveolar compliance and macrophage-induced alveolar contraction. With these capabilities, we provide proof of principle for using this fibrotic tissue array for phenotypic analysis of the therapeutic efficacy of two anti-fibrosis drugs recently approved by the FDA.
Preventative treatments with Pirfenidone and Nintedanib reduce the tissue contractility and prevent the decline in tissue compliance. In a therapeutic treatment regimen, both drugs restore tissue compliance. These results highlight the pathophysiologically relevant modeling capability of the novel fibrotic microtissue system.