A Biphasic Osteovascular Biomimetic Scaffold for Rapid and Self‐Sustained Endochondral Ossification

Abstract Regeneration of large bones remains a challenge in surgery. Recent developmental engineering efforts aim to recapitulate endochondral ossification (EO), a critical step in bone formation. However, this process entails the condensation of mesenchymal stem cells (MSCs) into cartilaginous templates, which requires long‐term cultures and is challenging to scale up. Here, a biomimetic scaffold is developed that allows rapid and self‐sustained EO without initial hypertrophic chondrogenesis. The design comprises a porous chondroitin sulfate cryogel decorated with whitlockite calcium phosphate nanoparticles, and a soft hydrogel occupying the porous space. This composite scaffold enables human endothelial colony‐forming cells (ECFCs) and MSCs to rapidly assemble into osteovascular niches in immunodeficient mice. These niches contain ECFC‐lined blood vessels and perivascular MSCs that dif…