The Combination of Aligned PDA-Fe@PLCL Conduit with Aligned GelMA Hydrogel Promotes Peripheral Nerve Regeneration

Abstract

Biomaterial-assisted therapeutic strategies enable precise modulation to direct endogenous cellular responses and harness regenerative capabilities for nerve repair. However, achieving effective cellular engagement during nerve remodeling remains challenging. Herein, a novel composite nerve guidance conduit (NGC), the GelMA/PLys@PDA-Fe@PLCL conduit is developed by combining aligned poly(l-lactide-co-caprolactone) (PLCL) nanofibers modified with polydopamine (PDA), ferrous iron (Fe³⁺), and polylysine (PLys) with aligned methacrylate-anhydride gelatin (GelMA) hydrogel nanofibers. PDA films exhibit strong adhesion and metal coordination properties, allowing Fe³⁺ irons to chelate with phenolic hydroxyl groups of dopamine derivatives, forming a metal-phenolic network on PLCL. PLys molecules are then grafted onto PDA-Fe³⁺ coating via Schiff base and Michael addition reactions. This multifunctional coating enhances surface roughness and zeta potential of PLCL nanofibers, imparts superhydrophilicity with anisotropic wetting behavior, and maintains wet tensile properties of substrates. In vitro studies show that the PLys@PDA-Fe coating significantly promotes aligned distribution of Schwann cells, improves cell adhesion and differentiation, and demonstrates notable antioxidant and anti-inflammatory properties. When implanted into nerve defects in rats, the multifunctional coating conduit combined with aligned GelMA hydrogel effectively accelerates axonal regeneration, remyelination, and angiogenesis, leading to enhanced motor function recovery. Overall, the GelMA/PLys@PDA-Fe@PLCL conduit presents a promising strategy for advancing peripheral nerve repair.