Ultrasound-Responsive Composited Conductive Silk Conduits for Peripheral Nerve Regeneration

Abstract

Peripheral nerve injuries are challenging to repair clinically due to their limited regenerative capacity. Herein, a novel poly(3,4-ethylenedioxythiophene):poly(4-styrene sulfonate) (PEDOT:PSS) composited conductive silk conduit with ultrasound (US)-triggered active release for peripheral nerve regeneration is presented. The conduit is composed of silk fibroin inverse opal tubular scaffolds and the secondary hydrogel filler that contains thermosensitive material (poly(N-isopropylacrylamide), PNIPAM), PEDOT:PSS, and nerve growth factor (NGF). Benefiting from the integration of these functional materials and active factors, the silk fibroin conduits show excellent biocompatibility, flexibility, conductivity, and bioactivity. In particular, owing to the thermal effect of US and the temperature responsiveness of PNIPAM, the secondary filling hydrogel undergoes volume shrinkage upon US triggering, allowing the responsive NGF release. Besides, the electrical conductivity of PEDOT:PSS has been affirmed to promote neuron and axon outgrowth. Through in vivo experiments, the synergistic effect of PEDOT:PSS and US-triggered delivery of NGF on accelerating injured nerve repair are demonstrated. These results reveal the practical value of the proposed intelligent conductive silk conduits with US responsiveness for nerve regeneration in preclinical studies.