MSC-derived sEV-loaded hyaluronan hydrogel promotes scarless skin healing by immunomodulation in a large skin wound model

MSC-derived sEV-loaded hyaluronan hydrogel promotes scarless skin healing by immunomodulation in a large skin wound model
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MSC 衍生的 sEV 负载透明质酸水凝胶通过免疫调节在大皮肤伤口模型中促进无疤痕皮肤愈合

DOI:
10.1088/1748-605x/ac68bc
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发表时间:
2022-04
影响因子:
4
通讯作者:
Zhao Qiang
Zhao Qiang
中科院分区:
工程技术3区
文献类型:
--
作者:
Yang Sen;Jiang Huan;Qian Meng;Ji Guangbo;Wei Yongzhen;He Ju;Tian Hongyan;Zhao Qiang

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抽象。设计能够调节免疫细胞功能的基于水凝胶的结构为皮肤组织再生带来了希望。间充质干细胞(MSC)衍生的细胞外小泡(sEVs)由于其抗炎和促血管生成作用而引起越来越多的关注。在此,我们构建了一种生物功能水凝胶,其中MSC衍生的sEV被掺入到可注射的透明质酸水凝胶中,从而赋予水凝胶免疫调节作用。当植入到小鼠大面积皮肤损伤模型的伤口部位时,这种功能性水凝胶通过驱动巨噬细胞朝向抗炎和抗纤维化(M2c)表型促进伤口愈合并抑制瘢痕组织形成。进一步研究表明,MSC衍生的sEV诱导的M2c样表型显著抑制成纤维细胞的活化,这可能导致无瘢痕皮肤伤口愈合。总之,这些结果表明,调节免疫应答是预防纤维化瘢痕形成的有希望和有效的方法。
Abstract. Designing hydrogel-based constructs capable of adjusting immune cell functions holds promise for skin tissue regeneration. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have attracted increasing attention owing to their anti-inflammatory and proangiogenic effects. Herein, we constructed a biofunctional hydrogel in which MSC-derived sEVs were incorporated into the injectable hyaluronic acid hydrogel, thus endowing the hydrogel with immunomodulatory effects. When implanted onto the wound site in a mouse large skin injury model, this functional hydrogel facilitates wound healing and inhibits scar tissue formation by driving macrophages towards an anti-inflammatory and anti-fibrotic (M2c) phenotype. Further investigation showed that the M2c-like phenotype induced by MSC-derived sEVs markedly inhibited the activation of fibroblasts, which could result in scarless skin wound healing. Taken together, these results suggest that modulation of the immune response is a promising and efficient approach to prevent fibrotic scar formation.
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