Electroactive Dual-Drug Hydrogel-PLA Conduit for Nerve Regeneration

Peripheral nerve injury (PNI) remains a major clinical challenge due to the limitations of autologous nerve grafting. Herein, a multifunctional composite nerve conduit was developed by integrating an oriented collagen-grafted polylactic acid (PLA) electrospun scaffold with a conductive and anti-inflammatory hydrogel to enhance peripheral nerve regeneration. The hydrogel was fabricated by chemically cross-linking carboxymethyl chitosan (CMCS) and sodium carboxymethyl cellulose (CMC-Na), incorporating polyaniline (PANI) to impart electrical conductivity and loading rhein (RH) for sustained anti-inflammatory release. The PLA conduit was further modified with collagen and loaded with nerve growth factor (NGF), forming a structurally guided dual-drug delivery system. The modified conduit exhibited improved hydrophilicity (water contact angle reduced from 107.7° to 68.9°) and enhanced mechanical properties (Young's modulus of 9.88 MPa). Sustained NGF and RH release reached 81.53% and 76.37% within 30 days, respectively, with stable degradation over 72 days. The conductive hydrogel displayed a uniform porous structure with high porosity (> 70%) and an electrical conductivity of 12.19 mS/cm. The electrical conductivity of the composite nerve conduit is 3.27 mS/cm. In vitro experiments demonstrated enhanced Schwann cell adhesion, neurite outgrowth, neuronal differentiation, anti-inflammatory activity, and responsiveness to electrical stimulation. In vivo studies using a rat sciatic nerve defect model confirmed significantly accelerated nerve regeneration. Overall, this electrically responsive, dual-drug-loaded hydrogel-filled nerve conduit represents a promising alternative to autologous nerve grafts for peripheral nerve repair.