3D printed osteochondral lineage-specific biphasic scaffolds for functional repair of full-thickness articular cartilage defects in weight-bearing area

Abstract Functional repair of full-thickness defects in the weight-bearing articular cartilage has been one of the major challenges in orthopeadics. Whereas the advanced 3D printing technique allows the construction of bionic bioscaffolds that support in-situ tissue regeneration. Herein, we developed a sort of lineage-specific biphasic scaffolds for osteochondral regeneration, fabricated via consecutive 3D-printing and lyophilization. To facilitate osteogenesis and bone formation, a porous scaffold was 3D-printed fabricated using a composite ink consisting of gelatin methacrylate (GelMA) and hydroxyapatite (HAP). To synergistically stimulate chondrogenesis and hyaline cartilage regeneration, collagen was infused into the top layers of the 3D-printed GelMA/HAP construct. In vitro culture of bone marrow mesenchymal stem cells (BMSCs) showed that the top collagen layer preferentially promoted BMSCs chondrogenic differentiation, while the GelMA/HAP composite mostly contributed to their osteogenic differentiation. This customized biphasic scaffold was then examined within the defected weight-bearing regions of full-thickness articular cartilage in rabbits, in which neocartilage, bone formation and remodeling were identified at six and twelve weeks post-implantation. Consistently to the in vitro findings, the bottom GelMA/HAP scaffold facilitated bone formation, while the top-layer with preloaded collagen markedly augmented hyaline cartilage formation in vivo. Furthermore, it was evident that the biphasic scaffolds effectively modulated bone remodeling dynamics via inhibiting hyperactive osteoclast activities. Considering that such combinatorial biphasic scaffolds were easily prepared and successfully utilized for cartilage defect repair, this cell-free tissue-engineered strategy holds great promise in future clinical translation.