Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions.
Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions.
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DOI：
10.1038/s41467-020-19906-3
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发表时间：
2020-12-04
影响因子：
16.6
通讯作者：
Sofroniew MV
中科院分区：
文献类型：
--
作者：
OʼShea TM;Wollenberg AL;Kim JH;Ao Y;Deming TJ;Sofroniew MV
生物材料有望在中枢神经系统（CNS）的治疗应用。对于体内决定中枢神经系统异物反应（FBRs）的分子因素，以及这些反应如何影响生物材料的功能，我们知之甚少。在这里，我们使用易于修饰的可注射水凝胶平台在小鼠中探测这些因素，以呈现与宿主细胞具有不同物理化学性质的界面。我们发现，生物材料fbr模拟了外周组织中不存在的特化多细胞CNS伤口反应，可以隔离受损的神经组织并恢复屏障功能。我们发现，中枢神经系统fbr的性质和强度是由可定义的特性决定的，这些特性显著影响水凝胶的功能，包括在注入健康大脑或中风损伤时的吸收和分子传递。阳离子界面引起基质细胞浸润、外周源性炎症、神经损伤和淀粉样蛋白的产生。非离子和阴离子配方显示这些反应的最低水平，这有助于优越的生物活性分子传递。我们的研究结果确定了驱动CNS中fbr的特定分子机制，并对开发用于CNS应用的有效生物材料具有重要意义。植入式生物材料引起中枢神经系统的异物反应。作者比较了基于水凝胶的生物材料，以确定驱动不同类型的异物反应的细胞相互作用和分子机制，这些反应对生物材料的功能有不同的影响。
Biomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a platform of injectable hydrogels readily modified to present interfaces with different physiochemical properties to host cells. We found that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. We show that the nature and intensity of CNS FBRs are determined by definable properties that significantly influence hydrogel functions, including resorption and molecular delivery when injected into healthy brain or stroke injuries. Cationic interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amyloid production. Nonionic and anionic formulations show minimal levels of these responses, which contributes to superior bioactive molecular delivery. Our results identify specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications. Implantable biomaterials evoke foreign body responses in the central nervous system. The authors compare hydrogel-based biomaterials to identify cellular interactions and molecular mechanisms that drive different types of foreign body responses that have different effects on biomaterial function.
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影响因子：
16.6
作者：
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