Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo
Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo
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DOI：
10.1016/j.matt.2020.03.018
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发表时间：
2020-06-03
期刊：
影响因子：
18.9
通讯作者：
Ghaemmaghami, Amir M.
中科院分区：
文献类型：
--
作者：
Rostam, Hassan M.;Fisher, Leanne E.;Ghaemmaghami, Amir M.
植入的医疗设备常常会引起不良的异物反应，巨噬细胞在其中起着中心作用。在这里，我们识别简单的聚合物，通过调节巨噬细胞的附着和极化到促炎(M1样)或抗炎(M2样)表型来指示不同的免疫反应。这些免疫指导性聚合物是通过体外高通量聚合物微阵列筛选不同的(甲基)丙烯酸酯和(甲基)丙烯酰胺文库发现的。这种具有生物指导性的聚合物功能在小鼠异物模型中得到了体内验证。涂覆在硅胶管上的聚合物的不同组织反应与体外巨噬细胞促炎和抗炎反应是一致的。使用机器学习对聚合物结构-细胞响应关系进行建模，以揭示用于描述免疫指导性聚合物的分子描述符。对从介质中吸附到聚合物上的蛋白质层的分析表明，较厚的蛋白质层可能与M1样的表型有关，而相反的则与M2样的反应有关。这种简单的聚合物很容易转化为免疫指导性生物材料，用于医疗器械和再生医学领域。
Implanted medical devices often elicit adverse foreign body responses whereby macrophages play a central role. Here, we identify simple polymers that instruct different immunological responses by modulating macrophage attachment and polarization to pro-inflammatory (M1-like) or anti-inflammatory (M2-like) phenotypes. These immune-instructive polymers were discovered using in vitro high-throughput polymer microarray screening of diverse (meth) acrylate and (meth)acrylamide libraries. The bioinstructive polymer function is validated in vivo within a murine foreign body model. Differential tissue response from polymers coated on silicone tubing is consistent with in vitro macrophage pro- and anti-inflammatory responses. Polymer structure-cell response relationships are modeled using machine learning to reveal molecular descriptors useful for describing immune-instructive polymers. Analysis of the protein layer adsorbed to polymers from media suggests that thicker layers may relate to M1-like phenotype whereas the reverse relates to M2-like response. Such simple polymers are readily translatable into immune-instructive biomaterials for application in the medical device and regenerative medicine fields.