Constructing Nerve Guidance Conduit using dECM‐Doped Conductive Hydrogel to Promote Peripheral Nerve Regeneration

Abstract Peripheral nerve injury often leads to the loss of neurological functions due to the slow regeneration rate and inefficient functional reconstruction. Current clinical treatments using nerve guidance conduits (NGCs) still face challenges in providing a biomimetic microenvironment to promote nerve repair. Herein, decellularized extracellular matrix (dECM) is obtained from porcine Achilles tendon and crosslinked with 3‐amino‐4‐methoxybenzoic acid grafted gelatin (PAMB‐G) to obtain conductive hydrogels. Then, a novel nerve guidance conduit is developed by assembling poly(vinyl alcohol) (PVA) conduit and conductive ECM@PAMB‐G hydrogel. This bioengineered ECM@PAMB‐G/PVA conduit demonstrated excellent cytocompatibility, electrical conductivity, mechanical properties, and biodegradability. In vitro experiments confirmed that the ECM@PAMB‐G hydrogel significantly promotes the proliferation and migration of PC12 cells and primary Schwann cells, as well as the growth of dorsal root ganglion (DRG) axons. Furthermore, in vivo studies in a rat sciatic nerve model exhibited improvements in axonal regeneration, Schwann cell migration, myelin sheath formation, and functional recovery mediated by the ECM@PAMB‐G/PVA conduit. This work demonstrates the synergistic effects of extracellular matrix and electrical cues in enhancing peripheral nerve regeneration. The ECM@PAMB‐G/PVA nerve guidance conduit shows potential as an alternative to autografts for supporting peripheral nerve reconstruction.