Nerve guidance conduit promotes nerve regeneration under a combination of electrical stimulation and RSCs combined with stem cell differentiation

Abstract

The Nerve Guide Conduit (NGC)offers a promising alternative to traditional methods for regenerating peripheral nerves. The efficacy of nerve regeneration and functional recovery is heavily dependent on the electrical, chemical, and physical properties of the NGC. A bionic Melt electrowriting (MEW) NGC loaded with Placental derived mesenchymal Stem Cells (PDMSCs) has been developed. Our study introduces a novel approach by utilizing Schwann cells induced from placental mesenchymal stem cells (PDMSCs), showcasing their potential in enhancing nerve regeneration when integrated with conductive nerve guidance conduits. Schwann cells (SCs) are crucial for nerve regeneration, and while various stem cells, including Bone Marrow Stromal Cells (BMSCs), have been investigated as sources of SCs for NGC loading, they are often limited by ethical concerns and restricted availability. PDMSCs, however, offer the advantages of widespread sourcing and the unique ability to differentiate into SCs, making them an attractive alternative for NGC applications. This NGC utilizes of an electrostatic direct writing technique employing Polycaprolactone (PCL) for the sheath and acrimped fiber scaffold made of polypyrrole (PPY) incorporating PDMSCs for itsinternal structure. The bionic PC-NGC loaded with PDMSCs, exhibits favorable characteristics including permeability, mechanical stability, and electrical conductivity. The PPY component effectively transmitsphysiological nerve signals, thereby promoting nerve regeneration, while the PDMSCs differentiateinto Schwann cells, creating a conducive environment for nerve regeneration. This research innovatively combines PDMSCs, known for their wide availability and SC differentiation potential, with a bionic NGC to enhance the treatment of peripheral nerve injuries (PNI). In vitro evaluations have confirmed the excellent biocompatibility of the materials used. Animal experiments usinga rat model with sciatic nerve injury demonstratedthat the PC-NGC significentlyfacilitated peripheral nerve regeneration. This was evidenced by improvements in axonal myelination, increased musclemass, enhanced sciatic nerve function index, and positive electrophysiologicalfindings. These outcomes arecomparable to those achieved through autologous transplantation. Characterized by its layered oriented fibers, the bionic PC-NGC integrates multi-scale and multifunctional biomaterials with PDMSCPDMSCs to effectively address peripheral nerve injuries (PNI). The useof thisprinted NGC stimulatesneuronal cell growth, thereby accelerating nerve regeneration. This innovative approach in tissue engineering presentsa promising clinical treatment strategy for PNI.