Bone Morphogenetic Protein-2 and Cabozantinib for Temporomandibular Joint Cartilage Repair: Murine and Porcine Injury Models

Temporomandibular joint osteoarthritis (TMJ OA) is characterized by progressive degeneration of the fibrocartilaginous articular surface. We previously demonstrated that combined bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) inhibition promotes endogenous hyaline cartilage regeneration in appendicular joints. Whether this regenerative strategy can be extended to the specialized fibrocartilage of the TMJ remains unknown. In this study, we evaluated the regenerative potential of BMP-2 combined with cabozantinib, an FDA-approved multikinase inhibitor with activity against VEGF receptors, using complementary murine and porcine TMJ cartilage injury models. In mice, needle-induced abrasion of the mandibular condyle resulted in loss of the fibrocartilaginous articular surface and extracellular matrix; treatment with BMP-2 and cabozantinib was associated with improved cartilage architecture and increased fibrocartilage thickness. To examine translational feasibility, we developed a surgically accessible porcine TMJ cartilage defect model and demonstrated the technical feasibility of local BMP-2 and cabozantinib delivery with formation of repair tissue within the defect. Collectively, these findings provide preliminary evidence supporting further investigation of combined BMP-2 and cabozantinib for TMJ cartilage repair.