Cerium Oxide Nanoparticle-Decorated Dual-Layer Nanofibrous Conduits Incorporating Schwann Cells and Fibrin Gel Enhance Peripheral Nerve Regeneration Publisher



Saremi J ; Zarei Behjani Z ; Ogle B M ; Farahani M S ; Nahanmoghadam A ; Lotfibakhshaiesh N ; Ai J ; Ebrahimi Barough S
Source: Journal of Drug Delivery Science and Technology Published:2027

Abstract

Peripheral nerve injury often results in long-term sensory and motor dysfunction, and the limitations of autologous nerve grafting have encouraged the development of alternative nerve guidance conduits. In this study, we evaluated a multifunctional dual-layered nanofibrous conduit incorporating cerium oxide nanoparticles, fibrin hydrogel, and allogeneic Schwann cells for its potential to promote peripheral nerve regeneration (PNR). The dual-layered conduits were fabricated by electrospinning, consisting of longitudinally aligned silk fibroin nanofibers as the inner layer to guide axonal growth and randomly oriented silk fibroin/polycaprolactone nanofibers as the outer layer to provide structural stability to the conduits. The conduit lumen was filled with a fibrin hydrogel containing Schwann cells and cerium oxide nanoparticles. Conduits with or without nanoparticles and Schwann cells were implanted to bridge a 12-mm sciatic nerve defect in rats. Functional recovery, electrophysiological performance, muscle reinnervation, and histological regeneration were assessed using walking footprint analysis, hot plate testing, electromyography, gastrocnemius muscle wet-weight measurement, and histological and immunohistochemical analyses. The dual-layered conduits demonstrated good biocompatibility and supported Schwann cell survival. In vivo results showed that conduits containing both cerium oxide nanoparticles and Schwann cells significantly improved axonal regeneration, functional recovery, and electrophysiological outcomes compared with untreated injury control. Among all experimental groups, conduits incorporating 1% nanoparticles within the scaffold and 2% nanoparticles in the fibrin gel combined with Schwann cells produced the most pronounced regenerative effects, although the outcomes remained inferior to those of autograft. Overall, these findings indicate that the combined use of aligned and random nanofibrous architectures with cerium oxide nanoparticles, fibrin hydrogels, and Schwann cells supports peripheral nerve regeneration, suggesting that this multifunctional dual-layer conduit offers a promising integrated strategy that may serve as an alternative to autografts following further optimization. © 2026 Elsevier B.V.