Fig. 1: Mechano-bioactive hydrogel bioelectronics for mechanical-electrical-bioenergetic conversion and glia-modulating neural regeneration.

A BaTiO₃ piezoelectric hydrogel bioelectronics design and fabrication. The BaTiO₃ nanoparticles, synthesized via a solvothermal approach, were optimized for uniform particle size and single-domain structure to enhance piezoelectric properties. Post-synthesis surface modification with hydroxyl (-OH) groups improved the hydrophilicity of BaTiO₃ nanoparticles, facilitating their homogeneous dispersion and stability within COL-1 hydrogel matrix. This optimized BaTiO₃@COL-1 hydrogel bioelectronics was fabricated as an injectable system for neural repair. Under low-intensity ultrasound, the hydrogel bioelectronics exerted mechanoelectrical conversion. B Mechanical-electrical-bioenergetic energy conversion for energy-consuming neural repair. Ultrasound-driven piezoelectric hydrogel bioelectronics delivered mechanical stimulation to glia, which primarily sensed the stimulation through surface PIEZO ion channel proteins to mediate calcium ion influx. The calcium ion influx via PIEZO channels (PIEZO1 in astrocytes and PIEZO2 in Schwann cells) activated intracellular signaling pathways to promote mitochondrial fusion as a central bioenergetic hub and modulate glial-mediated neural repair in both central and peripheral nervous systems. C The therapeutic efficacy and biosafety of piezoelectric bioelectronics was verified in multiple animal models (mice, rats, Beagle dogs, and Rhesus monkeys) from peripheral and central nervous injuries, demonstrating its wide adaptivity and significant translational potential.