Department of Burn and Plastic surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China.
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
J Nanobiotechnology. 2022 Jun 21;20(1):294. doi: 10.1186/s12951-022-01503-9.
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-γ activated macrophage cell membrane. After defining physicochemical properties of the nanofibers modified by LPS/IFN-γ 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-γ 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-γ 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.
糖尿病性伤口是导致非创伤性截肢的主要原因，其中氧化应激和慢性炎症是影响伤口愈合的主要因素。虽然间充质干细胞（MSCs）作为活的材料可以促进皮肤再生，但它们仍然容易受到氧化应激的影响，这限制了它们的临床应用。在这里，我们制备了（聚乳酸-共-羟基乙酸）（PLGA）纳米纤维，这些纳米纤维是用电纺法将脂多糖/干扰素-γ激活的巨噬细胞膜包裹制成的。在确定了用脂多糖/干扰素-γ激活的小鼠 RAW264.7 细胞衍生的细胞膜（RCM-纤维）修饰的纳米纤维的理化性质后，我们证明了在体外氧化应激条件下，RCM-纤维可以改善 BMMSC 的增殖和角质形成细胞的迁移。此外，骨髓来源的间充质干细胞（BMMSCs）负载 RCM-纤维（RCM-纤维-BMMSCs）可加速实验性糖尿病伤口愈合中的伤口闭合，伴有快速的再上皮化、胶原重塑、抗氧化应激和血管生成。转录组分析显示，当与 RCM-纤维共培养时，BMMSCs 中与伤口愈合相关的基因上调。RCM-纤维-BMMSCs 活材料的增强愈合能力部分是通过 CD200-CD200R 相互作用介导的。同样，脂多糖/干扰素-γ激活的 THP-1 细胞膜包被的纳米纤维（TCM-纤维）也表现出对体内糖尿病伤口愈合的人 BMMSCs（hBMMSCs）的类似改善。因此，我们的研究结果表明，脂多糖/干扰素-γ激活的巨噬细胞膜修饰的纳米纤维可以原位免疫刺激 BMMSCs 的生物功能，使这种新型活材料在人类糖尿病伤口修复中具有广阔的应用前景。
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