BIOREACTOR DEVELOPMENT FOR THE PRODUCTION OF TISSUE-ENGINEERED CARTILAGE
Tanya Farooque, PhD
Tissue-engineered cartilage offers a promising and long-term treatment option for cartilage degradation due to trauma or disease. Mechanical forces (shear, perfusion, and compression) influence articular cartilage development. Bioreactors are the central processing unit for development of cartilage and other engineered tissues; delivering appropriate spatial and temporal nutrient transport and mechanical loading in a well-defined and controlled environment. A perfusion concentric cylinder (PCC) bioreactor has been developed to culture tissue-engineered cartilage constructs under orthogonal shear stresses. Applying both a low shear stress across the surface of cell-seeded scaffolds and perfusion through their thickness in the PCC bioreactor stimulated chondrocytes to undergo chondrogenesis and tissue development. The PCC bioreactor stimulated cartilage growth over the course of four weeks, supported by the appearance of glycosaminoglycan (GAG) and collagen type II, which are markers for articular cartilage. In vivo studies also led to an important observation that mechanical stimulation and cell density were important factors that maintained tissue-engineered cartilage maturation post implantation. When compared to a bioreactor that employed only shear stress over the surface of the constructs, the PCC bioreactor caused a significant increase in cellular proliferation, but not in extracellular matrix deposition, which was instead dependent on increased mechanical loading and low oxygen tension. Our results led to an important observation that the addition of convective flow affects cellular proliferation significantly, but not extracellular matrix deposition.