Fibrin-based scaffolds for spinal cord injury

描述（由申请人提供）：该提案的统一假设是，生物材料支架的使用对于脊髓损伤成功治疗的发展至关重要。在缺乏可以帮助桥接损伤部位的生物材料支架的情况下，损伤的脊髓中缺乏再生促进基质限制了生长因子递送和细胞移植方法的功效。我们假设，在长时间内（数周）从纤维蛋白为基础的生物材料支架单独或与胚胎干细胞衍生的神经谱系细胞（ESNLC）的控制释放生长因子是需要实现脊髓损伤后的显着再生。这一假设将通过解决以下具体目标进行系统测试，所有这些都是实现脊髓再生目标所必需的。本提案的目的是：（1）在大鼠脊髓损伤模型中，与不受控制的生长因子释放相比，检验基于纤维蛋白的生物材料支架能够充分控制生长因子（神经营养素-3）的释放以增强短期和长期再生的假设。(2)为了检验以下假设：从基于纤维蛋白的生物材料支架递送生长因子将使胚胎干细胞衍生的神经谱系细胞（ESNLC）在体外环境中存活并分化为神经元，与传统分化方案观察到的结果相当或更好。(3)在脊髓损伤的情况下，与单独的胚胎干细胞来源的神经谱系细胞（ESNLC）（无支架）相比，在体内从基于纤维蛋白的生物材料支架递送生长因子将能够增强胚胎干细胞来源的神经谱系细胞（ESNLC）向神经元的存活和分化。

DESCRIPTION (provided by applicant): The unifying hypothesis of this proposal is that the use of biomaterial scaffolds is critical to the development of successful therapies for spinal cord injury. In the absence of a biomaterial scaffold that can help to bridge the injury site, the lack of regeneration promoting substrates in the injured spinal cord limits the efficacy of growth factor delivery and cell transplantation approaches. We hypothesize that controlled release of growth factors over a prolonged period of time (weeks) from a fibrin-based biomaterial scaffold alone or in combination with embryonic stem cell-derived neural lineage cells (ESNLCs) is needed to achieve significant regeneration following spinal cord injury. This hypothesis will be tested systematically by addressing the following specific aims, all of which are necessary to achieve the goal of spinal cord regeneration. The aims of this proposal are: (1) To test the hypothesis that a fibrin-based biomaterial scaffold enables sufficient controlled release of growth factor (neurotrophin-3) to enable enhanced short and long-term regeneration compared to uncontrolled growth factor release in a rat spinal cord injury model. (2) To test the hypothesis that growth factor delivery from a fibrin-based biomaterial scaffold will enable survival and differentiation of embryonic stem cell-derived neural lineage cells (ESNLCs) into neurons in an in vitro setting comparable to or better than that observed with traditional differentiation protocols. (3) To test the hypothesis that growth factor delivery from a fibrin-based biomaterial scaffold will enable enhance survival and differentiation of embryonic stem cell-derived neural lineage cells (ESNLCs) into neurons compared with ESNLCs alone (no scaffold) in vivo in the setting of spinal cord injury.