Self-powered biodegradable nerve conduits for synergistic ultrasound-driven electrical stimulation and smart drug release

Electrical stimulation (ES) is a promising strategy for nerve repair, motivating the use of piezoelectric biomaterials that generate charge under mechanical stress. Here, we aimed to develop a wireless, biodegradable electrospun conduit that couples piezoelectric stimulation with programmable drug delivery for enhanced neural regeneration. A hybrid scaffold composed of poly(lactic acid)/silk fibroin (PLA/SF) was fabricated and loaded with polydopamine-coated barium titanate (PDA-BTO) nanoparticles and retinoic acid (RA), yielding the PLA/SF/PDA-BTO/RA conduit. The scaffold exhibited robust piezoelectricity under low-intensity pulsed ultrasound (LIPUS), generating open-circuit voltages of 1.8–4.9 V, corresponding to electric fields of 44–122 V/cm, for varying LIPUS intensities, sufficient to exceed the thresholds for neurite outgrowth. Drug-release analysis revealed a sustained passive release of ∼32 % RA over 14 days, whereas LIPUS triggered on-demand release reaching ∼31 % within 4 h in pulsatile on/off cycles. In vitro, PC12 cells cultured on stimulated conduits showed ∼2.1-fold longer neurites and ∼ 1.8-fold higher calcium influx, along with upregulation of GAP43, TUBB3, and Piezo1 expression, compared to non-stimulated controls. Preliminary in vivo sciatic nerve implantation demonstrated favourable biocompatibility and improved functional recovery. Together, this work establishes a biodegradable, bioresorbable, LIPUS-responsive scaffold that integrates ES and drug delivery, demonstrating strong potential for neural tissue engineering and providing a promising foundation for next-generation neural tissue engineering and future clinical translations.