Biomimetic engineered cartilage: Recreating the in vivo collagen network and depth-dependent inhomogeneity

Osteoarthritis is the debilitating wearing down of the articular cartilage in diarthrodial joints. The poor natural healing of articular cartilage and the limitations of current treatments have motivated research in cartilage tissue engineering. This dissertation aimed to improve the bio-mimesis of engineered cartilage by (1) improving the overall collagen network and (2) incorporating a depth-dependent cellular and mechanical inhomogeneity similar to native cartilage.; Recent efforts can produce an engineered cartilage with physiologic GAG content and compressive stiffness. These constructs, however, possess sub-physiologic collagen content and dynamic compressive properties and may not be able to withstand in vivo mechanical stresses. The research in this dissertation discovered that amino acid supply and nutrient/waste transport in free-swelling culture are not major limitations to collagen synthesis by chondrocytes in engineered cartilage. Using growth factors and collagen hydrolysate as anabolic chemical signals, it was found that the temporal exposure of chemical factors can greatly influence the synthetic outcome of the chondrocytes, though a physiologic collagen network was not achieved. These findings imply that a proper stimulatory signal with appropriate temporal exposure may be the key in stimulating collagen synthesis in engineered cartilage.; The depth-varying cellular and mechanical aspects of articular cartilage lend to a variety of functional properties, including low friction, wear and cartilage-cartilage adhesion. There has been little research aimed at replicating the mechanical inhomogeneity found in the native tissue. It was found that seeding zonal chondrocyte populations into a scaffold with initially inhomogeneous material properties would eventually lead to a cartilage tissue with both depth-dependent cellular and mechanical inhomogeneity qualitatively similar to the native cartilage. This result shows that intelligent scaffold design combined with cell selection can lead to a more biomimetic engineered cartilage.; The research in this biomedical engineering dissertation have combined techniques and principles of biology and engineering to greatly contribute to our understanding of mechanisms belying the limited collagen synthesis observed in engineered cartilage along with providing guidelines and methodology to improve the bio-mimesis of the engineered tissue. These findings will aid and improve the functional tissue engineering of articular cartilage and advance it towards a clinical treatment.