BMSC-Based Cartilage Regeneration Units Enable Efficient Mandibular Defect Repair via Endochondral Ossification

Abstract The repair of mandibular bone defects remains a significant clinical hurdle, and tissue engineering offers an alternative strategy for reconstructive therapy. Nevertheless, conventional direct ossification is heavily dependent on a permissive microenvironment, which severely limits the regenerative outcome in large-scale bone defects. Endochondral ossification (EO)-based approaches, together with bone organoid microcarrier technology, have emerged as potential resolutions to this limitation. In the present work, cartilage regeneration units (CRUs) were fabricated by seeding decellularized bone matrix microparticles (DBM/COL-MPs) with bone marrow-derived mesenchymal stem cells (BMSCs), followed by chondrogenic priming in vitro. Upon implantation into mandibular defects in rabbits, these CRUs yielded a bone volume fraction (BV/TV) of 51.6% at 4 weeks—a value 1.5-fold higher than that of the control group. Moreover, the CRUs promoted vascular infiltration and accomplished robust and durable bone regeneration alongside satisfactory osseointegration through the EO pathway, both in ectopic and orthotopic mandibular defect settings. Collectively, this strategy furnishes a viable solution for the regenerative restoration of mandibular bone defects.