Yuan Peiqi, Luo Yilun, Luo Yu, Ma Lie
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
Biomater Sci. 2021 Apr 7;9(7):2553-2561. doi: 10.1039/d0bm02194f. Epub 2021 Feb 12.
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 (Ca) 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-α (TNF-α) 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.
鉴于巨噬细胞在组织修复和免疫治疗中的关键作用，设计能够在愈合过程中按需控制巨噬细胞表型的智能生物材料已成为一种有前景的策略。在此，制备了一种具有近红外（NIR）响应动态刚度的新型“三明治”细胞培养平台，用于原位极化骨髓来源的巨噬细胞（BMDM），以动态揭示巨噬细胞表型与底物刚度之间的关系。在近红外照射下，由于IR780的光热效应，钙离子（Ca）扩散穿过IR780混合相变材料（PCM）的中间层，通过透明质酸钠藻酸盐水凝胶（MA-HA&SA）上层的交联导致水凝胶刚度原位增加。分别通过免疫染色和酶联免疫吸附测定（ELISA）对诱导型一氧化氮合酶（iNOS）和肿瘤坏死因子-α（TNF-α）的上调进行定量，表明在动态刚度下巨噬细胞从抗炎表型向促炎表型的转变。核Yes相关蛋白（YAP）比率与巨噬细胞表型的转变呈正相关。在无细胞因子刺激的情况下通过刚度升高调节巨噬细胞表型，为操纵免疫反应以实现优化的愈合或治疗结果提供了一种有效且无创的策略。
