Biomimetic osteochondral regeneration of the TMJ condyle: integrating BMP-2 osteoinduction, MSC-mediated fibrochondrogenesis, and gradient 3D-printed scaffolds

Background Biological and biomaterial-based approaches for temporomandibular joint (TMJ) condylar reconstruction have advanced substantially, yet no unified regenerative strategy currently reproduces the native osteochondral unit, particularly the fibrocartilage–bone hierarchy and its biomechanical demands. Methods An integrative evidence synthesis was performed across four translational domains relevant to biomimetic condylar regeneration: (1) ultra-low-dose rhBMP-2 osteoinduction, (2) bilaminar osteochondral scaffolds, (3) MSC/TGF-β3–driven chondrogenesis, and (4) zonal or gradient 3D-printed constructs. Evidence was interpreted through mechanistic plausibility, scaffold design, safety constraints, and translational readiness for oral and maxillofacial surgery. Results Convergent findings support the feasibility of biomimetic osteochondral regeneration. Controlled BMP-2 delivery enables potent osteoinduction when spatially confined and dose-restricted. Bilaminar constructs reproducibly generate stratified cartilage–bone organization and improve interface integrity. MSC/TGF-β3 approaches promote fibrocartilage-like matrix formation, particularly when combined with instructive scaffolds. Gradient 3D printing enhances anatomical fidelity and transitional biomechanics, improving construct coherence across zones. Conclusions A multimodal regenerative framework integrating controlled osteoinduction, scaffold-based interface engineering, and biologically guided fibrocartilage regeneration may represent a promising translational pathway toward biologically engineered TMJ condylar reconstruction, although current evidence remains predominantly preclinical.