Piezoelectric composite hydrogel with wireless electrical stimulation enhances motor functional recovery of spinal cord injury

Electrical stimulation (ES) can restore motor function after spinal cord injury (SCI). However, traditional intraspinal ES has many disadvantages, such as the need for a complex circuitry device, an external power source, and a second surgery to remove the implant. Piezoelectric materials have received increasing attention due to their potential to convert ambient mechanical energy into ES without an external power source or implantation of electrodes. Herein, a novel polydopamine (PDA) coated barium titanate (BaTiO3) nanoparticles (BaTiO3@PDA) incorporated silk fibroin (SF) hydrogel (SFBT) was established. The SFBT hydrogel was crosslinked by horseradish peroxidase (HRP)/hydrogel peroxide (H2O2) to integrate the piezoelectric potency of BaTiO3 with the thermal sensitivity of HRP/H2O2 for SCI recovery. The hydrogel containing 5% (w/v) BaTiO3@PDA nanoparticles (SFBT-5), which was selected for in vivo study, exhibited a short gelation time (5 min), suitable storage modulus (925 ± 35 Pa), and wireless ES (average current of 124 nA). Moreover, Basso-Beattie-Bresnahan (BBB) scores test and footprint analysis demonstrated that the SFBT-5 hydrogel successfully enhanced motor functional recovery of SCI. In histopathological assessments, the SFBT-5 hydrogel significantly accelerated spinal cord healing, as indicated by smaller lesion cavities (∼16.7% of the SCI group). Meanwhile, the SFBT-5 hydrogel accelerated neurogenesis, facilitated axon regrowth and synapse formation, and promoted remyelination. Overall, this study highlights the potential of piezoelectric hydrogels for SCI regeneration.