Martin Benton C, Minner Eric J, Wiseman Sherri L, Klank Rebecca L, Gilbert Ryan J
Regeneration and Repair Laboratory, Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931-1295, USA.
J Neural Eng. 2008 Jun;5(2):221-31. doi: 10.1088/1741-2560/5/2/013. Epub 2008 May 23.
Trauma sustained to the central nervous system is a debilitating problem for thousands of people worldwide. Neuronal regeneration within the central nervous system is hindered by several factors, making a multi-faceted approach necessary. Two factors contributing to injury are the irregular geometry of injured sites and the absence of tissue to hold potential nerve guides and drug therapies. Biocompatible hydrogels, injectable at room temperature, that rapidly solidify at physiological temperatures (37 degrees C) are beneficial materials that could hold nerve guidance channels in place and be loaded with therapeutic agents to aid wound healing. Our studies have shown that thermoreversible methylcellulose can be combined with agarose to create hydrogel blends that accommodate these properties. Three separate novel hydrogel blends were created by mixing methylcellulose with one of the three different agaroses. Gelation time tests show that the blends solidify at a faster rate than base methylcellulose at 37 degrees C. Rheological data showed that the elastic modulus of the hydrogel blends rapidly increases at 37 degrees C. Culturing experiments reveal that the morphology of dissociated dorsal root ganglion neurons was not altered when the hydrogels were placed onto the cells. The different blends were further assessed using dissolution tests, pore size evaluations using scanning electron microscopy and measuring the force required for injection. This research demonstrates that blends of agarose and methylcellulose solidify much more quickly than plain methylcellulose, while solidifying at physiological temperatures where agarose cannot. These hydrogel blends, which solidify at physiological temperatures naturally, do not require ultraviolet light or synthetic chemical cross linkers to facilitate solidification. Thus, these hydrogel blends have potential use in delivering therapeutics and holding scaffolding in place within the nervous system.
中枢神经系统受到的创伤是全球成千上万的人面临的一个使人衰弱的问题。中枢神经系统内的神经元再生受到多种因素的阻碍,因此需要采取多方面的方法。导致损伤的两个因素是受伤部位不规则的几何形状以及缺乏能够容纳潜在神经导向物和药物疗法的组织。在室温下可注射、在生理温度(37摄氏度)下迅速固化的生物相容性水凝胶是有益的材料,它可以固定神经导向通道,并负载治疗剂以促进伤口愈合。我们的研究表明,热可逆甲基纤维素可以与琼脂糖结合,形成具有这些特性的水凝胶混合物。通过将甲基纤维素与三种不同琼脂糖中的一种混合,制备了三种不同的新型水凝胶混合物。凝胶化时间测试表明,这些混合物在37摄氏度时比基础甲基纤维素固化得更快。流变学数据显示,水凝胶混合物的弹性模量在37摄氏度时迅速增加。培养实验表明,将水凝胶放置在解离的背根神经节神经元上时,神经元的形态没有改变。使用溶解测试、扫描电子显微镜评估孔径以及测量注射所需的力对不同的混合物进行了进一步评估。这项研究表明,琼脂糖和甲基纤维素的混合物比纯甲基纤维素固化得快得多,同时在琼脂糖无法固化的生理温度下固化。这些在生理温度下自然固化的水凝胶混合物不需要紫外线或合成化学交联剂来促进固化。因此,这些水凝胶混合物在神经系统中递送治疗剂和固定支架方面具有潜在用途。