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.