Koss K M, Churchward M A, Nguyen A T, Yager J Y, Todd K G, Unsworth L D
Department of Chemical and Materials Engineering, University of Alberta, 11487-89 Ave., Edmonton, AB, Canada, T6G 2M7; National Institute for Nanotechnology, NRC, 11421 Saskatchewan Dr NW, Edmonton, AB, Canada, T6G 2M9.
Neurochemical Research Unit, Department of Psychiatry, University of Alberta, 11487-89 Ave., Edmonton, AB, Canada, T6G 2M7.
Acta Biomater. 2016 Apr 15;35:127-37. doi: 10.1016/j.actbio.2016.02.001. Epub 2016 Feb 2.
(RADA)4-based nanoscaffolds have many inherent properties making them amenable to tissue engineering applications: ease of synthesis, ease of customization with bioactive moieties, and amenable for in situ nanoscaffold formation. There is a dearth in the literature on their biocompatibility in brain tissues; where the glia response is key to regulating the local host response. Herein, nanoscaffolds composed of (RADA)4 and (RADA)4-IKVAV mixtures were evaluated in terms of their effect on primary microglia in culture and general tissue (in vivo) biocompatibility (astrocyte and migroglia). Laminin-derived IKVAV peptide was chosen to promote beneficial cell interaction and attenuate deleterious glial responses. Microglia remained ramified when cultured with these nanoscaffolds, as observed using TNF-α and IL-1β, NO, and proliferation assays. Evidence suggests that cultured microglia phagocytise the matrix whilst remaining ramified and viable, as shown visually and metabolically (MTT). Nanoscaffold intracerebral injection did not lead to microglia migration or proliferation, nor were glial scarring and axonal injury observed over the course of this study. IKVAV had no affect on microglia activation and astrogliosis. (RADA)4 should be advantageous for localized injection as a tuneable-platform device, which may be readily cleared without deleterious effects on tissue-resident microglia.
Self-assembling nanoscaffolds have many inherent properties making them amenable to tissue engineering applications: ease of synthesis, ease of customization with bioactive moieties, and amenable for in situ nanoscaffold formation. A dearth of literature exists on their biocompatibility in brain tissues; where the glia response is key to regulating the local host response. Herein, nanoscaffolds composed of the peptides (RADA)4 and (RADA)4-IKVAV mixtures were evaluated in terms of their effect on microglia cells in culture and general tissue (in vivo) biocompatibility (astrocyte and migroglia). Laminin-derived IKVAV peptide was chosen to promote beneficial cell interaction and attenuate deleterious glial responses. (RADA)4 nanoscaffolds showed no adverse effect from these cell types and should be advantageous for localized injection as a tuneable-platform device.
基于（RADA）4的纳米支架具有许多固有特性，使其适用于组织工程应用：易于合成、易于用生物活性部分进行定制，并且适合原位形成纳米支架。关于它们在脑组织中的生物相容性，文献中存在不足；其中神经胶质细胞反应是调节局部宿主反应的关键。在此，评估了由（RADA）4和（RADA）4 - IKVAV混合物组成的纳米支架对培养的原代小胶质细胞和一般组织（体内）生物相容性（星形胶质细胞和小胶质细胞）的影响。选择层粘连蛋白衍生的IKVAV肽来促进有益的细胞相互作用并减弱有害的神经胶质细胞反应。使用TNF-α、IL-1β、NO和增殖测定法观察到，当与这些纳米支架一起培养时，小胶质细胞保持分支状。有证据表明，培养的小胶质细胞吞噬基质，同时保持分支状和活力，这在视觉和代谢方面（MTT）都有显示。在本研究过程中，纳米支架脑内注射未导致小胶质细胞迁移或增殖，也未观察到神经胶质瘢痕形成和轴突损伤。IKVAV对小胶质细胞活化和星形胶质细胞增生没有影响。（RADA）4作为一种可调节平台装置，对于局部注射应该是有利的，它可以很容易地被清除，而不会对组织驻留小胶质细胞产生有害影响。
自组装纳米支架具有许多固有特性，使其适用于组织工程应用：易于合成、易于用生物活性部分进行定制，并且适合原位形成纳米支架。关于它们在脑组织中的生物相容性，文献中存在不足；其中神经胶质细胞反应是调节局部宿主反应的关键。在此，评估了由肽（RADA）4和（RADA）4 - IKVAV混合物组成的纳米支架对培养的小胶质细胞和一般组织（体内）生物相容性（星形胶质细胞和小胶质细胞）的影响。选择层粘连蛋白衍生的IKVAV肽来促进有益的细胞相互作用并减弱有害的神经胶质细胞反应。（RADA）4纳米支架对这些细胞类型没有显示出不利影响，作为一种可调节平台装置，对于局部注射应该是有利的。
