Enhanced Cell Osteogenesis and Osteoimmunology Regulated by Piezoelectric Biomaterials with Controllable Surface Potential and Charges

Bone regeneration is a well-orchestrated process involving electrical, biochemical, and mechanical multiple physiological cues. Electrical signals play a vital role in the process of bone repair. The endogenous potential will spontaneously form on defect sites, guide the cell behaviors, and mediate bone healing when the bone fracture occurs. However, the mechanism on how the surface charges of implant potentially guides osteogenesis and osteoimmunology has not been clearly revealed yet. In this study, piezoelectric BaTiO₃/β-TCP (BTCP) ceramics are prepared by two-step sintering, and different surface charges are established by polarization. In addition, the cell osteogenesis and osteoimmunology of BMSCs and RAW264.7 on different surface charges were explored. The results showed that the piezoelectric constant d₃₃ of BTCP was controllable by adjusting the sintering temperature and rate. The polarized BTCP with a negative surface charge (BTCP-) promoted protein adsorption and BMSC extracellular Ca²⁺ influx. The attachment, spreading, migration, and osteogenic differentiation of BMSCs were enhanced on BTCP-. Additionally, the polarized BTCP ceramics with a positive surface charge (BTCP+) significantly inhibited M1 polarization of macrophages, affecting the expression of the M1 marker in macrophages and changing secretion of proinflammatory cytokines. It in turn enhanced osteogenic differentiation of BMSCs, suggesting that positive surface charges could modulate the bone immunoregulatory properties and shift the immune microenvironment to one that favored osteogenesis. The result provides an alternative method of synergistically modulating cellular immunity and the osteogenesis function and enhancing the bone regeneration by fabricating piezoelectric biomaterials with electrical signals.