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Preprints

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

Gao S, Chen T, Wang Z, Ji P, Xu L, Cui W, Wang Y.
Preprint from
Research Square
8 March 2022
PPR
PPR464998
Abstract
Diabetic wound is the leading cause of non-traumatic amputations in which oxidative stress and chronic inflammation are main factors affecting wound healing. Although conventional mesenchymal stem cells (MSCs) living material can promote skin regeneration, they are still vulnerable to oxidative stress which limits their clinical applications. Here, we have prepared (lactic-co-glycolic acid) (PLGA) nanofibers electrospun with LPS/IFN-γ activated macrophage cell membrane with the capacity to immunostimulate bone marrow derived mesenchymal stem cells (BMMSCs) and investigated the effects of this living material on diabetic wound healing. After defining the physic-chemical properties of LPS/IFN-γ activated RAW264.7 cell(a mouse M1 macrophage cell line model) membrane modified nanofibers (RCM-fibers), including surface molecule, diameter, hydrophilicity and degradation rate, we demonstrated that the RCM-fibers not only improved BMMSC proliferation and keratinocyte migration upon oxidative stress in vitro, but also accelerated BMMSCs-mediated wound closure with rapid re-epithelialization, collagen remodeling, immunoregulation, antioxidant stress and angiogenesis in experimental diabetic wound healing in vivo. Transcriptome analysis revealed the up-regulation of genes related to wound healing in BMMSCs upon RCM-fiber immune-stimulation. Enhanced healing capacity of RCM-fiber-BMMSCs living material was partially mediated through CD200-CD200R interaction. Similarly, LPS/IFN-γ activated THP-1 cell(a human M1 macrophage cell line model) membrane coated nanofibers (TCM-fibers) exhibited the similar improvement of human BMMSCs (hBMMSCs) on the diabetic wound healing in vivo. Our results thus demonstrate that LPS/IFN-γ activated macrophage cell membrane-modified nanofibers can in situ promote the biofunction of BMMSCs, making this novel living material promising in wound repair for human diabetes.