Electrospun Composite PLLA‐PPSB Nanofiber Nerve Conduits for Peripheral Nerve Defects Repair and Regeneration

Abstract Peripheral nerve injury (PNI) is a common clinical problem and regenerating peripheral nerve defects remain a significant challenge. Poly(polyol sebacate) (PPS) polymers are developed as promising materials for biomedical applications due to their biodegradability, biocompatibility, elastomeric properties, and ease of production. However, the application of PPS‐based biomaterials in nerve tissue engineering, especially in PNI repair, is limited. In this study, PPS‐based composite nanofibers poly(l‐lactic acid)‐poly(polycaprolactone triol‐ co ‐sebacic acid‐ co ‐N,N‐bis(2‐hydroxyethyl)‐2‐aminoethanesulfonic acid sodium salt) (PLLA‐PPSB) are aimed to construct through electrospinning and assess their in vitro biocompatibility with Schwann cells (SCs) and in vivo repair capabilities for peripheral nerve defects. For the first time, the biocompatibility and bioactivity of PPS‐based nanomaterial are examined at the molecular, cellular, and animal levels for PNI repair. Electrospun PLLA‐PPSB nanofibers display favorable physicochemical properties and biocompatibility, providing an effective interface for the proliferation, glial expression, and adhesion of SCs in vitro. In vivo experiments using a 10‐mm rat sciatic nerve defect model show that PLLA‐PPSB nanofiber nerve conduits enhance myelin formation, axonal regeneration, angiogenesis, and functional recovery. Transcriptome analysis and biological validation indicate that PLLA‐PPSB nanofibers may promote SC proliferation by activating the PI3K/Akt signaling pathway. This suggests the promising potential of PLLA‐PPSB nanomaterial for PNI repair.