Transient Growth Factor Stimulation Improves Chondrogenesis in Static Culture and Under Dynamic Conditions in a Novel Shear and Perfusion Bioreactor

Abstract

Tissue engineering emerges as a viable method to replace cartilage damaged by osteoarthritis or trauma. A key element for cartilage tissue engineering is to elucidate growth factor exposure regimes that enhance cartilage production from multipotent progenitor cells. To address this, we identify growth factor conditions that promote chondrogenesis of human mesenchymal stem cells cultured under static conditions. We identified transient exposure to bone morphogenic protein-2 in the presence of transforming growth factor beta-1 as a viable condition that promotes expression of chondrogenic phenotype for human mesenchymal stem cells seeded onto polycaprolactone scaffolds. We then use this growth factor regime as a proof of concept to test a new shear and perfusion bioreactor. This novel bioreactor design applies shear stress stimulation on the surface of constructs while allowing tissue perfusion. Constructs harvested from the bioreactor after 8 days showed cartilage development primarily near the construct surface exposed to shear stress. By day 14, cells, collagen deposition and proteoglycan deposition is observed throughout the scaffold, indicative of cartilage development.