Synchronised regeneration of osteochondral defects via spatially patterned implants of stable and hypertrophic cartilage organoids

Here, we present a scaffold-free, modular strategy that spatially bioassembles iPSC-derived chondrocytes (iChon) organoids with human periosteum-derived cell (hPDC) organoids to engineer zonated osteochondral assembloids.

The resulting iChon+hPDC assembloids exhibit intrinsic spatial organization, forming chondral- and osteo-like zones with an intermediate interface without exogenous scaffolds. In vitro characterization confirmed layered glycosaminoglycan-rich cartilage and collagen I-rich bone-like domains, with an intermediate interface emerging through self-directed matrix organization. Upon implantation into full-thickness osteochondral defects, iChon+hPDC assembloids promoted robust hyaline cartilage restoration, subchondral bone reconstruction, and partial restoration of collagen fiber anisotropy.