Engineered Nanofiber‐Based Nerve Guidance Conduit Facilitates the Restoration of Peripheral Nerve Injury through Enhanced Vascularization

ABSTRACT Peripheral nerve injuries (PNI) can disrupt the innervation of target organs, leading to diverse dysfunctions. While autologous nerve grafts are often regarded as the gold standard for treatment, their use is limited by donor nerve availability and potential complications at the injury site. Therefore, nerve guidance conduits (NGCs) constructed from biomaterials are favoured as an alternative for nerve repair. Angiogenesis provides the necessary prerequisites and microenvironmental support for neural regeneration. In this study, the extracted endothelial cell‐derived matrix (ECd) was modified on the surface of polycaprolactone (PCL) nanofibers with oriented topology by electrospinning and electrospray techniques, ultimately constructing the ECd@PCL bionic scaffold. The scaffold mimicked the natural environment necessary for nerve regeneration by providing both physical guidance through its structure and biochemical signals. In vitro experiments investigated the regulatory effects of ECd@PCL scaffolds on axonal growth behavior. The results demonstrated that ECd@PCL scaffolds promoted axon extension in rat adrenal pheochromocytoma cells (PC12). Utilising the co‐culture model, it was determined that the ECd@PCL scaffold effectively enhanced intercellular communication. Furthermore, ECd@PCL NGCs remarkably accelerated myelin sheath formation and modified motor function. In conclusion, the ECd@PCL NGCs offer a novel concept for the development of bioactive nerve repair materials.