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A 'sandwich' cell culture platform with NIR-responsive dynamic stiffness to modulate macrophage phenotypes

机译:一种“三明治”细胞培养平台,具有循环响应动态刚度来调节巨噬细胞表型

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摘要

Considering the key roles of macrophages in tissue repair and immune therapy, designing smart biomaterials able to harness macrophage phenotypes on demand during the healing process has become a promising strategy. Here, a novel "sandwich" cell culture platform with near-infrared (NIR) responsive dynamic stiffness was fabricated to polarize bone marrow-derived macrophages (BMDMs) in situ for revealing the relationship between the macrophage phenotype and substrate stiffness dynamically. Under NIR irradiation, calcium ions (Ca2+) diffused through the middle layer of the IR780-mixed phase change material (PCM) due to the photothermal effect of IR780, resulting in an increase of hydrogel stiffness in situ by the crosslinking of the upper layer of the hyaluronic acid-sodium alginate hydrogel (MA-HA&SA). The up-regulation of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) was quantified by immunostaining and enzyme-linked immune sorbent assay (ELISA), respectively, indicating the transformation of macrophages from the anti-inflammatory to pro-inflammatory phenotype under dynamic stiffness. The nuclear Yes-associated-protein (YAP) ratio positively correlated with the shift of the macrophage phenotype. The modulation of macrophage phenotypes by stiffness-rise without the stimuli of cytokines offers an effective and noninvasive strategy to manipulate immune reactions to achieve optimized healing or therapeutic outcomes.
机译:考虑到巨噬细胞在组织修复和免疫疗法中的关键作用,设计能够在治疗过程中满足巨噬细胞表型的智能生物材料,已成为一个有希望的策略。这里,制造具有近红外(NIR)响应性动态刚度的新型“夹心”细胞培养平台,以原位偏振骨髓衍生的巨噬细胞(BMDMS),以揭示巨噬细胞表型和衬底刚度之间的关系。在鼻辐射下,由于IR780的光热效应,通过IR780-混合相变材料(PCM)的中间层扩散的钙离子(CA2 +)扩散,导致通过上层的交联升高水凝胶刚度透明质酸 - 藻酸钠水凝胶(MA-HA&SA)。通过免疫染色和酶联免疫吸附剂测定(ELISA)分别通过免疫染色和酶联免疫吸附剂测定(ELISA)来定量诱导型一氧化氮合酶(InOS)和肿瘤坏死因子-α(TNF-α)的上调,表明抗炎巨噬细胞的转化动态刚度下的促炎表型。核是相关蛋白(YAP)与巨噬细胞表型的偏移呈正相关。通过细胞因子刺激的刚度上升的巨噬细胞表型的调节提供了一种有效和无侵入性的策略来操纵免疫反应,以实现优化的愈合或治疗结果。

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  • 来源
    《Biomaterials Science》 |2021年第7期|共9页
  • 作者单位

    Zhejiang Univ MOE Key Lab Macromol Synth &

    Functionalizat Dept Polymer Sci &

    Engn Hangzhou 310027 Peoples R China;

    Zhejiang Univ MOE Key Lab Macromol Synth &

    Functionalizat Dept Polymer Sci &

    Engn Hangzhou 310027 Peoples R China;

    Zhejiang Univ MOE Key Lab Macromol Synth &

    Functionalizat Dept Polymer Sci &

    Engn Hangzhou 310027 Peoples R China;

    Zhejiang Univ MOE Key Lab Macromol Synth &

    Functionalizat Dept Polymer Sci &

    Engn Hangzhou 310027 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
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