Smooth muscle extracellular matrix modified small intestinal submucosa conduits promote peripheral nerve repair

Challenges still exist to develop an ideal cell-free nerve guidance conduit (NGC) providing a favorable microenvironment for rapid and successful nerve regeneration. Proteomic analysis revealed that extracellular matrix (ECM) derived from smooth muscle cells (SMCs) was abundant in nerve-related active proteins and significantly enriched signaling pathways involved in nerve regeneration. However, whether NGCs based on SMCs-derived ECM modification strategy promote nerve regeneration remains unclear. In the study, we investigated the neuroregenerative effect of SMCs-derived ECM and developed a novel NGC (MyoNerve) by coating small intestinal submucosa (SIS) with SMCs-derived ECM. The SMCs-ECM was rich in neurotrophic factors, which endowed MyoNerve with remarkable neuroregenerative capabilities by promoting the expression of genes implicated in aspects of neuronal maintenance and activating signaling pathways involved in nerve regeneration. In vitro, MyoNerve exhibited excellent bioactivity for accelerating angiogenesis, regulating macrophages polarization, promoting the proliferation, migration and elongation of Schwann cells, enhancing differentiation of PC12 cells, and inducing the neurite outgrowth of dorsal root ganglia. In the model of rat sciatic nerve 10 mm defect, MyoNerve showed great potential for functional nerve regeneration by promoting angiogenesis, proliferation and migration of Schwann cells and neuron, axonal regeneration, remyelination, and neurological functional recovery.