Immuno-activated mesenchymal stem cell living electrospun nanofibers for promoting diabetic wound repair

Diabetic wound is the leading cause of non-traumatic amputations in which oxidative stress and chronic inflammation are main factors affecting wound healing. Although mesenchymal stem cells (MSCs) as living materials can promote skin regeneration, they are still vulnerable to oxidative stress which limits their clinical applications. Herein, we have prepared (polylactic-co-glycolic acid) (PLGA) nanofibers electrospun with LPS/IFN-gamma activated macrophage cell membrane. After defining physicochemical properties of the nanofibers modified by LPS/IFN-gamma activated mouse RAW264.7 cell derived membrane (RCM-fibers), we demonstrated that the RCM-fibers improved BMMSC proliferation and keratinocyte migration upon oxidative stress in vitro. Moreover, bone marrow derived MSCs (BMMSCs)-loaded RCM-fibers (RCM-fiber-BMMSCs) accelerated wound closure accompanied by rapid re-epithelialization, collagen remodeling, antioxidant stress and angiogenesis in experimental diabetic wound healing in vivo. Transcriptome analysis revealed the upregulation of genes related to wound healing in BMMSCs when co-cultured with the RCM-fibers. Enhanced healing capacity of RCM-fiber-BMMSCs living material was partially mediated through CD200-CD200R interaction. Similarly, LPS/IFN-gamma activated THP-1 cell membrane coated nanofibers (TCM-fibers) exhibited similar improvement of human BMMSCs (hBMMSCs) on diabetic wound healing in vivo. Our results thus demonstrate that LPS/IFN-gamma activated macrophage cell membrane-modified nanofibers can in situ immunostimulate the biofunctions of BMMSCs, making this novel living material promising in wound repair of human diabetes.

Automated summary

Through modification of nanofibers with activated macrophage cell membrane, we have enhanced the biological functions of mesenchymal stem cells (MSCs) and promoted wound healing in diabetes. Experimental results showed that the modified nanofibers improved MSC proliferation and keratinocyte migration, resulting in accelerated wound closure and tissue regeneration.