A Photoresponsive Hyaluronan Hydrogel Nanocomposite for Dynamic Macrophage Immunomodulation
A Photoresponsive Hyaluronan Hydrogel Nanocomposite for Dynamic Macrophage Immunomodulation
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DOI：
10.1002/adhm.201801234
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发表时间：
2018-12
影响因子：
10
通讯作者：
Haoyu Wang;Renee-Tyler T Morales;Xin Cui;Jiongxian Huang;Weiyi Qian;Jie Tong;Weiqiang Chen
中科院分区：
文献类型：
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作者：
Haoyu Wang;Renee-Tyler T Morales;Xin Cui;Jiongxian Huang;Weiyi Qian;Jie Tong;Weiqiang Chen
巨噬细胞是一种主要的免疫细胞群体，其驱动炎症反应并在疾病和修复中的组织重塑期间表现出表型和功能的转变。因此，工程化免疫调节生物材料对于解决炎症具有重要意义。在这里，设计了一种仿生和光响应性透明质酸（HA）水凝胶纳米复合材料，其具有可调的3D细胞外基质（ECM）粘附位点，用于动态巨噬细胞免疫调节。利用光降解性烷基苯甲酰甲基基聚碳酸酯（APP）纳米复合材料，允许用户控制Arg-Gly-Asp（RGD）粘附肽释放并与HA基ECM偶联，用于真实的整合素激活封装在3D HA-APP纳米复合材料水凝胶中的巨噬细胞。已证明光控3D ECM-RGD肽缀合可激活巨噬细胞的αvβ3整联蛋白，并且周期性αvβ3整联蛋白激活可增强抗炎性M2巨噬细胞极化。总之，仿生，光响应和生物活性HA-APP纳米复合水凝胶的新兴用途被强调用于控制3D细胞-ECM相互作用以调节巨噬细胞极化，这可能揭示先天免疫中的细胞-ECM相互作用并激发新的基于生物材料的免疫调节疗法。
Macrophages are a predominant immune cell population that drive inflammatory responses and exhibit transitions in phenotype and function during tissue remodeling in disease and repair. Thus, engineering an immunomodulatory biomaterial has significant implications for resolving inflammation. Here, a biomimetic and photoresponsive hyaluronan (HA) hydrogel nanocomposite with tunable 3D extracellular matrix (ECM) adhesion sites for dynamic macrophage immunomodulation is engineered. Photodegradative alkoxylphenacyl‐based polycarbonate (APP) nanocomposites are exploited to permit user‐controlled Arg–Gly–Asp (RGD) adhesive peptide release and conjugation to a HA‐based ECM for real‐time integrin activation of macrophages encapsulated in 3D HA–APP nanocomposite hydrogels. It is demonstrated that photocontrolled 3D ECM–RGD peptide conjugation can activate αvβ3 integrin of macrophages, and periodic αvβ3 integrin activation can enhance anti‐inflammatory M2 macrophage polarization. Altogether, an emerging use of biomimetic, photoresponsive, and bioactive HA–APP nanocomposite hydrogel is highlighted to command 3D cell–ECM interactions for modulating macrophage polarization, which may shed light on cell–ECM interactions in innate immunity and inspire new biomaterial‐based immunomodulatory therapies.