Graphene foam/hydrogel scaffolds for regeneration of peripheral nerve using ADSCs in a diabetic mouse model

The functional recovery of peripheral nerve injury(PNI)is unsatisfactory,whereas diabetes mellitus(DM)and its related complications further attenuate the restoration of diabetic PNI(DPNI).Adipose-derived stem cells(ADSCs)are promising candidates for treatment of DPNI due to their abundant source,excellent differentiation and paracrine ability.Our results showed that ADSCs remarkably enhanced the proliferation and migration of Schwann cells and endothelial cells,and tube formation.Mechanistically,ADSCs could regulate Nrf2/HO-1,NF-κB and PI3K/AKT/mTOR signaling pathways,showing multiple functions in reducing oxidative stress and inflammation,and regulating cell metabolism,growth,survival,proliferation,angiogenesis,differentiation of Schwann cell and myelin formation.In current study,novel graphene foam(GF)/hydrogel-based scaffold was developed to deliver ADSCs for treatment of DPNI.GF/hydrogel scaffold exhibited excellent mechanical strength,suitable porous network,superior electrical conductivity,and good biocompatibility.In vitro results revealed that GF/hydrogel scaffold could obviously accelerate proliferation of Schwann cells.Moreover,in vivo experiments demonstrated that ADSCs-loaded GF/hydrogel scaffold significantly promoted the recovery of DPNI and inhibited the atrophy of targeted muscles,thus providing a novel and attractive therapeutic approach for DPNI patients.