Optimized piezoelectric bone regeneration through inhibiting sympathetic nerve-bone interaction

Abstract

Electrical cues are crucial for osteogenesis. To tackle critical-sized bone defects, piezoelectric materials non-invasively generate electrical stimuli via ultrasonic excitation, imitating natural bone's piezoelectricity. Two-dimensional 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' β2-receptors. Addressing this, we developed a sophisticated drug carrier, encapsulating piezoelectric zinc sulfide (ZnS) in a polydopamine (PDA) coating with the β blocker propranolol (PRO), creating ZnS@PDA-PRO. 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.