Salmon fibrin gels for CNS surgical applications

描述（由申请人提供）： 我们的目标是开发一种新的生物材料，鲑鱼纤维蛋白凝胶，将桥接受损的CNS组织，支持和促进轴突发芽和生长，并提供神经营养因子和细胞。目的#1是确定促进鲑鱼纤维蛋白凝胶中神经元存活和生长的生物化学和机械因素。由于其他蛋白质、FXIII、纤连蛋白和纤溶酶原与鱼纤维蛋白原相关或共纯化，因此将它们分离、纯化和耗尽或补充以优化凝胶组合物。这些蛋白质的生物活性将通过植入凝胶中的小鼠神经元的存活、神经元产生和神经突生长来评估。目的#2是确定在鲑鱼凝胶中大鼠原代神经元中的存活和神经突生长以及大鼠神经干细胞中的分化是否增加。大鼠是人类脊髓损伤的常见手术模型，也是II期体内研究的首选动物。目标#1的优化凝胶将植入大鼠神经细胞，并按照目标#1评估结果。促进移植或内源性神经元生长和连接的生物材料将是神经外科的重要工具。鉴定该材料中的生长促进分子可以为CNS损伤和疾病提供新的治疗方法。

DESCRIPTION (provided by applicant): Our objective is to develop a new biomaterial, a salmon fibrin gel, that will bridge injured CNS tissue, support and promote axonal sprouting and growth, and deliver neurotrophic factors and cells. Aim #1 is to determine the factors, biochemical and mechanical, that promote neuronal survival and outgrowth in salmon fibrin gels. Since other proteins, FXIII, fibronectin, and plasminogen are associated with or co-purify with fish fibrinogen, they will be separated, purified, and depleted or supplemented to optimize the gel composition. The bioactivity of these proteins will be assessed by survival, neuronal production, and neurite outgrowth of mouse neurons implanted in the gels. Aim #2 is to determine if survival and neurite outgrowth in rat primary neurons, and differentiation in rat neural stem cells is augmented in the salmon gels. Rats are a common surgical model of human spinal cord injury, and the animal of choice for Phase II in vivo studies. The optimized gel from Aim #1 will be implanted with rat neural cells, and results assessed as in Aim #1. A biomaterial that promotes growth and connectivity of transplanted or endogenous neurons would be an important tool in neurosurgery. Identification of the growth-promoting molecule(s) in that material could offer new therapies for CNS injury and disease.