BMSC‐NFMC Model for Vascular Regulation and Interface Integration in Osteochondral Regeneration

Abstract The core challenge in osteochondral tissue engineering is achieving the dual objectives of precise vascularization regulation and effective interface integration. Current tissue‐engineering strategies have limitations in addressing these challenges. This study has regulated BMSC differentiation by optimizing the GT/PCL ratio and topological structure of nanofibrous materials, systematically comparing three different materials (r5G5P, a5G5P, and a7G3P), and employing a “rolling and folding” method in order to construct BMSC‐NFMC composite structures. This approach achieves effective vascular isolation between the bone and cartilage layers. After implantation in nude mice, the a5G5P group exhibits distinct natural osteochondral tissue structural characteristics, which become more stable after 8 weeks of in vivo culture. Transcriptome sequencing analysis reveals that under ischemic conditions, the a5G5P group effectively regulates cartilage formation by inhibiting the Rap1 pathway and subsequently activating the ERK pathway. In rabbit articular osteochondral defect repair experiments, the a5G5P group successfully regenerates complete articular osteochondral structures similar to those of the adjacent natural tissues. The BMSC‐NFMC structure can be used for both local and long‐segment osteochondral defect repair, providing broader possibilities for clinical applications.