Establishment of FK506-Enriched PLGA Nanomaterial Neural Conduit Produced by Electrospinning for the Repair of Long-Distance Peripheral Nerve Injury

Abstract

Peripheral nerve injury (PNI) is a serious complication of trauma. Autologous nerve transplantation is the gold standard for the treatment of long-distance peripheral nerve defects, but is often limited by insufficient donor sites, postoperative pain, and paresthesia at the donor site. Peripheral nerve tissue engineering has led to the development of neural conduits to replace autologous nerve grafts. This study aimed to evaluate a new type of electrospun nanomaterial neural conduit, enriched with tacrolimus (FK506), which is an FDA-approved immunosuppressant, for the repair of long-distance peripheral nerve injuries. Poly (lactic-co-glycolic acid) (PLGA) nanofibrous films, with FK506, were prepared by electrostatic spinning and rolled into hollow cylindrical nerve vessels with an inner diameter of 1 mm and length of 15 mm. Material characterization, mechanical testing, degradation, drug release, cytotoxicity, cell proliferation, and migration assays were performed in vitro. Long-distance sciatic nerve injuries in rats were repaired in vivo using electrospun nerve conduit bridging, and nerve regeneration and muscle and motor function recovery were evaluated by gait analysis, electrophysiology, and neuromuscular histology. Compared to PLGA, the PLGA/FK506 nanomaterial neural conduit showed little change in morphology, mechanical properties, and chemical structure. In vitro, PLGA/FK506 showed lower cytotoxicity and better biocompatibility and effectively promoted the proliferation, adhesion, and migration of Schwann cells. In vivo, PLGA/FK506 had a better effect on sciatic nerve index, compound muscle action potential intensity and delay time, and nerve regeneration quality 12 weeks post-transplantation, effectively promoting long-distance defect sciatic nerve regeneration and functional recovery in rats. FK506-enriched PLGA nanomaterial neural conduits offer an effective method for repairing long-distance peripheral nerve injury and have potential clinical applications.