Salmon fibrin gels for surgical applications

描述(申请人提供)：我们的目标是开发一种新的生物材料，三文鱼衍生的纤维蛋白凝胶，将桥接受损的中枢神经组织，支持和促进轴突萌发和生长，并提供神经营养因子和细胞。在目标1中，我们将测试鲑鱼来源的纤维蛋白凝胶在中枢神经系统损伤动物模型中的疗效。使用大鼠背侧半切伤、挫伤和流体冲击模型，我们将比较鲑鱼材料和人源性纤维蛋白凝胶在疗效、炎症反应和可能的功能变化方面的差异。在目标2中，我们将寻求确定鲑鱼凝胶中涉及的促进生长的因素。我们将确定是否有一个小的活性分子与纤维蛋白原结合，以及纤维蛋白原分子的哪些性质是重要的。在目标3中，我们计划进行病毒清除、免疫原性和稳定性的临床前研究，这是FDA批准鲑鱼纤维蛋白原和凝血酶所必需的。我们将在蛋白质中加入病毒，并确定热辐射和伽马辐射的组合将实现病毒减少，保持蛋白质效力，并不产生免疫原性。将对治疗大鼠的组织(目标1)进行炎症反应检查，并采集血浆样本进行抗体研究。脊髓和脑损伤的代价是美元和人类痛苦，这是一个重大的公共卫生问题。如果神经外科医生能够用一种促进神经元再生和连接的材料进行干预，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.