Conductive silk fibroin-based hydrogel composite conduit with anti-inflammatory and anti-scarring properties for peripheral nerve regeneration

Peripheral nerve injury (PNI) remains a major clinical challenge because of the limited regenerative capacity of nerve tissue and the formation of an unfavorable inflammatory and fibrotic microenvironment after injury. In this study, a multifunctional conductive hydrogel-composite nerve conduit was developed by integrating an electrospun silk fibroin/polycaprolactone (SF/PCL) hollow conduit loaded with ursolic acid (UA) and an injectable SF/hyaluronic acid (HA) conductive hydrogel containing polydopamine-modified polypyrrole (PDA–PPY) nanoparticles. The electrospun conduit provided structural support, balanced wettability, sustained UA release, and relatively slow degradation, while the conductive hydrogel created a hydrated three-dimensional microenvironment with tunable porosity, swelling behavior, and mechanical properties. PDA modification reduced the aggregation of PPY nanoparticles, improved their dispersion stability and interfacial compatibility within the hydrogel matrix, and promoted the formation of a more homogeneous conductive network, thereby significantly enhancing hydrogel conductivity. In vitro studies demonstrated good cytocompatibility toward Schwann cells, inhibition of fibroblast proliferation and collagen-related secretion, regulation of macrophage polarization under inflammatory conditions, and enhanced cellular activity under appropriate electrical stimulation. These findings indicate that the developed conductive hydrogel-composite conduit integrates structural support, electrical conductivity, and biological activity, providing a promising multifunctional platform for further investigation in peripheral nerve repair.