Functionalized Microscaffold–Hydrogel Composites Accelerating Osteochondral Repair through Endochondral Ossification

Osteochondral regeneration remains a key challenge because of the limited self-healing ability of the bone and its complex structure and composition. Biomaterials based on endochondral ossification (ECO) are considered an attractive candidate to promote bone repair because they can effectively address the difficulties in establishing vascularization and poor bone regeneration via intramembranous ossification (IMO). However, its clinical application is limited by the complex cellular behavior of ECO and the long time required for induction of the cell cycle. Herein, functionalized microscaffold–hydrogel composites are developed to accelerate the developmental bone growth process via recapitulating ECO. The design comprises arginine–glycine–aspartic acid (RGD)-peptide-modified microscaffolds loaded with kartogenin (KGN) and wrapped with a layer of RGD- and QK-peptide-comodified alginate hydrogel. These microscaffolds enhance the proliferation and aggregation behavior of the human bone marrow mesenchymal stem cells (hBMSCs); the controlled release of kartogenin induces the differentiation of hBMSCs into chondrocytes; and the hydrogel grafted with RGD and QK peptide facilitates chondrocyte hypertrophy, which creates a vascularized niche for osteogenesis and finally accelerates osteochondral repair in vivo. The findings provide an efficient bioengineering approach by sequentially modulating cellular ECO behavior for osteochondral defect repair.