Graphene oxide-doped chiral dextro-hydrogel promotes peripheral nerve repair through M2 polarization of macrophages

Dextro-chirality is reported to specifically promote the proliferation and survival of neural cells. However, applying this unique performance to nerve repair remains a great challenge. Graphite oxide (GO)-phenylalanine derivative hydrogel system was constructed through doping 5% GO into self-assembly dextro- or levo-hydrogels (named as dextro and levo group, respectively), which exhibited identical physical and chemical properties, cyto-compatibility, and mirror-symmetrical chirality. In vivo experiments using rat sciatic nerve repair models showed that the functional recovery and histological restoration of regenerating nerves in the dextro group were significantly improved, approaching that of autograft implantation. The doped GO promoted M2 polarization of macrophages, increasing the expression of platelet-derived growth factor BB chain and vascular endothelial growth factor, thereby improving angiogenesis in regenerating nerves. A mechanism is proposed for the facilitated nerve repair through the synergistic effect of GO and dextro-hydrogel, involving dextro-chirality selection of neural cells and GO-induced M2 polarization, which promotes microvascular regeneration and myelination. This study showcases the immense potential of chirality in addressing neurological issues by providing a compelling demonstration of the development of effective therapies that leverage the unique matrix chirality selection of nerve cells to promote peripheral nerve regeneration.