Optimized piezoelectric bone regeneration through inhibiting sympathetic nerve-bone interaction

Electrical cues are crucial for osteogenesis. To tackle critical-sized bone defects, piezoelectric materials noninvasively generate electrical stimuli via ultrasonic excitation, imitating natural bone's piezoelectricity. Twodimensional piezoelectric nanomaterials, with their flexibility and cellular interactions, effectively improve osteogenic outcomes. Yet, the concurrent electrical and injury signals may overly activate sympathetic nerves, causing excessive norepinephrine release, which hinders osteogenic differentiation by targeting mesenchymal stem cells' beta 2-receptors. Addressing this, we developed a sophisticated drug carrier, encapsulating piezoelectric zinc sulfide (ZnS) in a polydopamine (PDA) coating with the beta blocker propranolol (PRO), creating ZnS@PDAPRO. This nanocarrier generates electrical signals and releases Zn2+ to promote osteogenic differentiation, while PRO mitigates sympathetic nerve inhibition, enhancing the regeneration of critical-sized bone defects.