Development of a novel RNAi therapy:Engineered miR-31 exosomes promoted the healing of diabetic wounds

Rationale:Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment.Exosome therapy is an extension of stem cell therapy,and RNA interference(RNAi)-based therapy is a type of advanced precision therapy.Based on the discovery of chronic wound-related genes in diabetes,we combined exosome therapy and RNAi therapy through an engineering approach for the treatment of diabetic chronic wounds.Methods:We combined exosome therapy and RNAi therapy to establish a precision therapy for diabetes-associated wounds via an engineered exosome approach.Results:First,chronic diabetic wounds express low levels of miR-31-5p compared with nondiabetic wounds,and an miR-31-5p mimic was shown to be effective in promoting the proliferation and migration of three wound-related cell types in vitro.Second,bioinformatics analysis,luciferase reporter assays and western blotting suggested that miR-31-5p promoted angiogenesis,fibrogenesis and reepithelization by inhibiting factor-inhibiting HIF-1(HIF1AN,also named FIH)and epithelial membrane protein-1(EMP-1).Third,engineered miR-31 exosomes were generated as a miR-31-5p RNAi therapeutic agent.In vivo,the engineered miR-31 exosomes promoted diabetic wound healing by enhancing angiogenesis,fibrogenesis and reepithelization.Conclusion:Engineered miR-31 exosomes are an ideal disease pathophysiology-initiated RNAi therapeutic agent for diabetic wounds.

Forsterite-hydroxyapatite composite scaffolds with photothermal antibacterial activity for bone repair

Bone engineering scaffolds with antibacterial activity satisfy the repair of bacterial infected bone defects,which is an expected issue in clinical.In this work,3D-printed polymer-derived forsterite scaffolds were proposed to be deposited with hydroxyapatite(HA)coating via a hydrothermal treatment,achieving the functions of photothermal-induced antibacterial ability and bioactivity.The results showed that polymer-derived forsterite scaffolds possessed the photothermal antibacterial ability to inhibit Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli)in vitro,owing to the photothermal effect of free carbon embedded in the scaffolds.The morphology of HA coating on forsterite scaffolds could be controlled through changing the hydrothermal temperature and the pH value of the reaction solution during hydrothermal treatment.Furthermore,HA coating did not influence the mechanical strength and photothermal effect of the scaffolds,but facilitated the proliferation and osteogenic differentiation of rat bone mesenchymal stem cells(rBMSCs)on scaffolds.Hence,the HA-deposited forsterite scaffolds would be greatly promising for repairing bacterial infected bone defects.