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

IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Biomedical materials Pub Date : 2022-04-20 DOI:10.1088/1748-605X/ac68bc
Sen Yang, Hua Jiang, Meng Qian, Guangbo Ji, Yongzhen Wei, Ju He, H. Tian, Qiang Zhao
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引用次数: 13

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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在大型皮肤伤口模型中,msc衍生的sev负载透明质酸水凝胶通过免疫调节促进无疤痕皮肤愈合
设计能够调节免疫细胞功能的水凝胶结构为皮肤组织再生带来了希望。间充质干细胞(MSC)衍生的小细胞外囊泡(sev)因其抗炎和促血管生成的作用而受到越来越多的关注。在此,我们构建了一种生物功能水凝胶,将msc衍生的sev掺入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。当植入小鼠大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向抗炎和抗纤维化(M2c)表型发展,促进伤口愈合并抑制疤痕组织形成。进一步研究表明,mscs衍生的sev诱导的m2c样表型显著抑制成纤维细胞的激活,从而导致无疤痕皮肤伤口愈合。综上所述,这些结果表明,调节免疫反应是预防纤维化瘢痕形成的一种有希望和有效的方法。
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来源期刊
Biomedical materials
Biomedical materials 工程技术-材料科学:生物材料
CiteScore
6.70
自引率
7.50%
发文量
294
审稿时长
3 months
期刊介绍: The goal of the journal is to publish original research findings and critical reviews that contribute to our knowledge about the composition, properties, and performance of materials for all applications relevant to human healthcare. Typical areas of interest include (but are not limited to): -Synthesis/characterization of biomedical materials- Nature-inspired synthesis/biomineralization of biomedical materials- In vitro/in vivo performance of biomedical materials- Biofabrication technologies/applications: 3D bioprinting, bioink development, bioassembly & biopatterning- Microfluidic systems (including disease models): fabrication, testing & translational applications- Tissue engineering/regenerative medicine- Interaction of molecules/cells with materials- Effects of biomaterials on stem cell behaviour- Growth factors/genes/cells incorporated into biomedical materials- Biophysical cues/biocompatibility pathways in biomedical materials performance- Clinical applications of biomedical materials for cell therapies in disease (cancer etc)- Nanomedicine, nanotoxicology and nanopathology- Pharmacokinetic considerations in drug delivery systems- Risks of contrast media in imaging systems- Biosafety aspects of gene delivery agents- Preclinical and clinical performance of implantable biomedical materials- Translational and regulatory matters
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