Recombinant human bone morphogenetic protein-2-engineered piezoplatform synergistically promotes bone regeneration through bone morphogenetic protein receptor activation.

Bone morphogenetic protein-2 (BMP-2) is a potent cytokine that promotes bone formation in orthopedic procedures. However, the delivery of recombinant human BMP-2 (rhBMP-2) with sustained release kinetics, while maximizing osteogenic potential, remains a challenge. In this study, we constructed a novel rhBMP-2-engineered piezoplatform for sustained release of rhBMP-2 and synergistic enhancement of osteoinductive activity. The piezoelectric signals are capable of initiating rapid biomineralization and promoting the early adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs), as well as enabling efficient immobilization and sustained release of rhBMP-2 through electrostatic interactions. Notably, piezoelectric stimulation synergizing with rhBMP-2 enhances osteogenesis-related protein production. This is achieved by amplifying the expression of BMP-2 receptors (Bmpr1a and Bmpr2) in BMSCs by approximately three-fold, which in turn reinforces the regenerative capacity of rhBMP-2. The rat femur defect model further confirms the osteogenic efficacy of the rhBMP-2-engineered piezoplatform. These findings are expected to advance the development of biopiezoelectric implants incorporating growth factor therapy for tissue engineering.