Bio-inspired zonal-structured matrices for bone-cartilage interface engineering.

Design and development of scaffold structures for osteochondral (OC) interface regeneration is a significant engineering challenge. Recent efforts are aimed at recapitulating the unique compositional and hierarchical structure of an OC interface. Conventional scaffold fabrication techniques often have limited design control and reproducibility, and the development of OC scaffolds with zonal hierarchy and structural integrity between zones is especially challenging. In this study, a series of multi-zonal and gradient structures were designed and fabricated using three-dimensional bioprinting. We developed OC scaffolds with bi-phasic and tri-phasic configurations to support the zonal structure of OC tissue, and gradient scaffold configurations to enable smooth transitions between the zones to more closely mimic a bone-cartilage interface. A biodegradable polymer, polylactic acid, was used for the fabrication of zonal/gradient scaffolds to provide mechanical strength and support OC function. The formation of the multi-zonal and gradient scaffolds was confirmed through scanning electron microscopy imaging and micro-computed tomography scanning. Precisely controlled hierarchy with tunable porosity along the scaffold length established the formation of the bio-inspired scaffolds with different zones/gradient structure. In addition, we also developed a novel bioprinting method to selectively introduce cells into desired scaffold zones of the zonal/gradient scaffolds via concurrent printing of a cell-laden hydrogel within the porous template. Live/dead staining of the cell-laden hydrogel introduced in the cartilage zone showed uniform cell distribution with high cell viability. Overall, our study developed bio-inspired scaffold structures with structural hierarchy and mechanical integrity for bone-cartilage interface engineering.