Sustained release of exosomes loaded into polydopamine-modified chitin conduits promotes peripheral nerve regeneration in rats

Abstract

Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation. On the basis of previously studied nerve conduits, we designed a polydopamine-modified chitin conduit loaded with mesenchymal stem cell-derived exosomes that release the exosomes in a sustained and stable manner. In vitro experiments revealed that rat mesenchymal stem cell-derived exosomes enhanced Schwann cell proliferation and secretion of neurotrophic and growth factors, increased the expression of Jun and Sox2 genes, decreased the expression of Mbp and Krox20 genes in Schwann cells, and reprogrammed Schwann cells to a repair phenotype. Furthermore, mesenchymal stem cell-derived exosomes promoted neurite growth of dorsal root ganglia. The polydopamine-modified chitin conduits loaded with mesenchymal stem cell-derived exosomes were used to bridge 2 mm rat sciatic nerve defects. Sustained release of exosomes greatly accelerated nerve healing and improved nerve function. These findings confirm that sustained release of mesenchymal stem cell-derived exosomes loaded into polydopamine-modified chitin conduits promotes the functional recovery of injured peripheral nerves.

Keywords

• exosome; mesenchymal stem cells; modification strategy; nerve conduits; peripheral nerve injury; peripheral nerve regeneration; polydopamine; reprogramming state; schwann cells; sustained release