Synergistic enhancement of peripheral nerve regeneration using electrospun polylactic acid conduits with leupeptin and methylprednisolone in rats

Peripheral nerve injuries pose significant clinical challenges, leading to sensory and motor impairments, neuralgia, and socioeconomic burdens due to suboptimal recovery. This study evaluated the efficacy of electrospun polylactic acid (PLA) conduits combined with leupeptin and methylprednisolone for nerve regeneration in a rat sciatic nerve defect model. Fifty adult male Sprague–Dawley rats were randomized into five groups (n = 10/group): control, saline, leupeptin (0.5 mg/mL), glucocorticoid (30 mg/mL methylprednisolone), and combined (leupeptin + methylprednisolone). A 10-mm sciatic nerve gap was created and bridged with PLA conduits filled with the respective treatments. Functional recovery was assessed via the sciatic functional index (SFI) from weeks 4–16 postsurgery. Histological analyses (hematoxylin–eosin, Masson, and Ponceau red staining) and immunofluorescence for collagen I/III were performed at week 16. The combined group showed significantly higher SFI scores (e.g., − 20.5 ± 4.2 at week 16 vs. − 45.3 ± 5.1 in saline; P < 0.001), enhanced regeneration, reduced fibrosis, and improved myelination compared to others. These results indicate that the combined approach optimizes the regenerative microenvironment, warranting further translational studies.