Integration of articular cartilage and trabecular bone through the formation of a calcified interface

摘要

Articular cartilage is integral to the function of the musculoskeletal system by providing a load-bearing, near-frictionless surface that allows for efficient joint movement. Despite its complex structure, adult cartilage exhibits a limited ability to self-repair. Therefore, slight cartilage defects can lead to cartilage degeneration and the development of osteoarthritis. In native tissue, deep zone (DZ) articular cartilage is attached to bone through the zone of calcified cartilage (ZCC) and the subchondral bone plate (ScBP). The goal of this thesis was to develop and characterize an artificial cartilage-bone interface through the in vitro calcification and attachment of articular cartilage to a subchondral bone substrate. First, a double diffusion system (DDS) was implemented to calcify articular cartilage discs embedded in hydrogel over a 7-day period. Ultimately, mineralization was targeted within the cartilage DZ by orienting the cartilage surface towards the calcium reservoir and leveraging the cartilage negative fixed charge density to generate an artificial ZCC. Second, a devitalized trabecular bone substrate was placed adjacent to the articular cartilage disc DZ and encased in agarose hydrogel within the DDS. The optimal cartilage-bone interface position was determined, followed by the generation of engineered osteochondral constructs that exhibited hydroxyapatite mineralization in the cartilage DZ similar to the thickness (150microm) of the native ZCC and achieved 4.5% the strength and 40% the modulus of native calf controls. These studies implement a novel, in vitro calcification system to develop engineered osteochondral constructs containing a mineralized cartilage-bone interface.