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两性离子聚合物涂层抑制体外和体内神经植入物的小胶质细胞包裹

Zwitterionic Polymer Coating Suppresses Microglial Encapsulation to Neural Implants In Vitro and In Vivo.

机构信息

Biomedical Science Tower 3, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA, 15232, USA.

McGowan Institute for Regenerative Medicine, University of Pittsburgh, 3025 East Carson Street, Pittsburgh, PA, 15219, USA.

出版信息

Adv Biosyst. 2020 Jun;4(6):e1900287. doi: 10.1002/adbi.201900287. Epub 2020 May 4.

Abstract

For brain computer interfaces (BCI), the immune response to implanted electrodes is a major biological cause of device failure. Bioactive coatings such as neural adhesion molecule L1 have been shown to improve the biocompatibility, but are difficult to handle or produce in batches. Here, a synthetic zwitterionic polymer coating, poly(sulfobetaine methacrylate) (PSBMA) is developed for neural implants with the goal of reducing the inflammatory host response. In tests in vitro, the zwitterionic coating inhibits protein adsorption and the attachment of fibroblasts and microglia, and remains stable for at least 4 weeks. In vivo two-photon microscopy on CX3CR1-GFP mice shows that the zwitterionic coating significantly suppresses the microglial encapsulation of neural microelectrodes over a 6 h observation period. Furthermore, the lower microglial encapsulation on zwitterionic polymer-coated microelectrodes is revealed to originate from a reduction in the size but not the number of microglial end feet. This work provides a facile method for coating neural implants with zwitterionic polymers and illustrates the initial interaction between microglia and coated surface at high temporal and spatial resolution.

摘要

对于脑机接口(BCI),植入电极的免疫反应是导致设备故障的主要生物原因。已证明生物活性涂层,如神经黏附分子 L1,可以改善生物相容性,但难以处理或批量生产。在这里,开发了一种合成两性离子聚合物涂层聚(磺基甜菜碱甲基丙烯酸酯)(PSBMA),用于神经植入物,以减少炎症宿主反应。在体外测试中,两性离子涂层抑制蛋白质吸附和成纤维细胞和小胶质细胞的附着,并且至少稳定 4 周。在 CX3CR1-GFP 小鼠的体内双光子显微镜下观察到,两性离子涂层在 6 小时的观察期内显著抑制了神经微电极的小胶质细胞包裹。此外,两性离子聚合物涂层微电极上小胶质细胞包裹程度的降低来源于小胶质细胞足突尺寸的减小,而不是数量的减少。这项工作提供了一种用两性离子聚合物涂覆神经植入物的简便方法,并以高时间和空间分辨率说明了小胶质细胞和涂层表面的初始相互作用。

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