Salmon fibrin gels for 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，鲑鱼衍生的纤维蛋白凝胶，它将桥接受损的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。在目标#1中，我们将测试鲑鱼衍生的纤维蛋白凝胶在CNS损伤的动物模型中的功效。使用大鼠背侧半部分、挫伤和流体冲击模型，我们将比较鲑鱼材料与人源性纤维蛋白凝胶的功效、炎症反应和可能的功能变化。在目标#2中，我们将寻求确定鲑鱼凝胶中涉及的生长促进因子。我们将确定是否有一个小的活性分子结合到纤维蛋白原，以及纤维蛋白原分子的哪些性质是重要的。在目标#3中，我们计划进行FDA批准鲑鱼纤维蛋白原和凝血酶所需的病毒清除、免疫原性和稳定性的临床前研究。我们将在蛋白质中掺入病毒，并确定加热和γ辐射的组合，以实现病毒减少，保持蛋白质功效，而不会导致免疫原性。将检查给药大鼠（目的#1）的组织的炎症反应，并采集血浆样品用于抗体研究。脊髓和脑损伤的费用和人类痛苦是一个主要的公共卫生问题。如果神经外科医生可以用一种促进神经元再生和连接的材料进行干预，那么对患者和社会的影响是巨大的。

DESCRIPTION (provided by applicant): Our objective is to develop a new biomaterial, a salmon-derived fibrin gel, which will bridge injured CNS tissue, support and promote axonal sprouting and growth, and deliver neurotrophic factors and cells. In Aim #1 we will test the efficacy of salmon-derived fibrin gels in animal models of CNS injury. Using the rat dorsal hemi-section, contusion, and fluid percussion models, we will compare the salmon material to human-derived fibrin gels for efficacy, inflammatory response, and possible functional changes. In Aim #2 we will seek to identify the growth-promoting factors that are involved in the salmon gels. We will determine if there is a small active molecule bound to the fibrinogen, and what properties of the fibrinogen molecule are important. In Aim #3 we plan pre-clinical studies of viral clearance, immunogenicity, and stability that are necessary for FDA approval of salmon fibrinogen and thrombin. We will spike the proteins with virus, and determine combinations of heat and gamma radiation that will achieve viral reduction, preserve protein efficacy, and not result in immunogenicity. Tissues from treated rats (Aim #1) will be examined for inflammatory response, and plasma samples taken for antibody studies. The cost of spinal cord and brain injury in both dollars and human suffering is a major public health issue. If the neurosurgeon could intervene with a material that promotes neuronal regrowth and connectivity, the impacts for the patient and for society are enormous.