Biodegradable Polymer Implants for Spinal Cord Repair

描述（由申请人提供）：脊髓轴突有能力在损伤后再生。然而，在患者和实验动物模型中，脊髓损伤（SCI）后的功能改善一直是难以捉摸的。我们汇集了一个新的研究小组，结合了基于聚合物的组织工程，细胞和分子神经生物学，脊柱外科，神经外科和脊髓损伤的专业知识。我们已经开发了一系列新的可生物降解的聚合物植入物用于治疗SCI。在大鼠横断脊髓模型中的植入物的初步研究证明了促进轴突再生的潜力。植入物在脊髓中耐受性良好，并装载有存活的许旺细胞。在植入后的三个月内，整个移植物的长度有轴突生长。我们假设，植入物可以作为一个支架，以支持轴突生长的差距，作为支持细胞的来源，并作为一个载体，促进再生剂的控制局部交付。我们现在建议系统地操纵再生脊髓的结构、细胞和分子环境。在第一个目标中，我们将研究两种聚合物的降解特性和生物相容性;聚（乳酸-共乙醇酸）（PLGA）和聚（富马酸己内酯）（PCLF）。我们将使用计算机辅助设计来生成支架的三维结构，然后确定真空成型或自由成型制造（微印刷）是否产生最佳架构。在第二个目标中，我们将通过测试具有不同直径通道的PLGA和PCLF支架来检查支架几何形状对再生的影响。将测量通过支架再生的轴突的数量和方向。在第三个目标中，我们将比较两种细胞类型（原代许旺细胞和许旺细胞系; SpL 201）支持再生和作为促进再生的生物分子来源的能力。在第四个目标中，我们将研究生物可降解聚合物作为治疗剂的递送载体的作用。软骨素酶-ABC将被用作模型蛋白。它是一种增强脊髓轴突再生的酶。将比较包封在微球或移植物中后活性酶的递送，并评估再生脊髓中酶递送的效果。Micro-CT和MR显微镜成像将与组织学和功能评估相结合，以衡量促进再生的成功率。

DESCRIPTION (provided by applicant): Spinal cord axons have the capacity to regenerate following injury. However, functional improvement following spinal cord injury (SCI) in patients and in experimental animal models has been elusive. We have brought together a new research group combining expertise in polymer-based tissue engineering, cellular and molecular neurobiology, spine surgery, neurosurgery, and spinal cord injury. We have developed a series of novel biodegradable polymer implants for use in the treatment of SCI. Pilot studies of the implant in the rat transected spinal cord model demonstrated the potential for promoting axon regeneration. Implants were well-tolerated in the spinal cord and were loaded with Schwann cells that survive. During three months after implantation, there was axon growth throughout the length of the graft. We hypothesize that the implant can serve as a scaffold to support axon growth across a gap, as a source of supporting cells, and as a vehicle for controlled local delivery of agents that promote regeneration. We now propose to systematically manipulate the structural, cellular and molecular environment of the regenerating cord. In the first aim, we will study the degradation characteristics and biocompatibility of two polymers; poly (lactic-coglycolic)acid (PLGA) and poly(caprolactone fumarate) (PCLF). We will use computer-aided design to generate the three-dimensional structure of the scaffold and then determine whether vacuum molding or free-form fabrication (micro-printing) produces the best architecture. In the second aim we will examine the effect of scaffold geometry on regeneration by testing PLGA and PCLF scaffolds with varying diameter channels. The number and direction of axons regenerating through the scaffolds will be measured. In the third aim we will compare the ability of two cell types (primary Schwann cells and a Schwann cell line;SpL201) to support regeneration and to act as a source of biomolecules that promote regeneration. In the fourth aim we will examine the role of the biodegradable polymer as a delivery vehicle for therapeutic agents. Chondritinase-ABC will be used as a model protein. It is an enzyme that enhances axonal regeneration in the cord. Delivery of active enzyme after encapsulation in microspheres or in the graft will be compared and the effect of enzyme delivery in the regenerating cord will be assessed. Imaging with Micro-CT and MR microscopy will be combined with histological and functional assessments to measure success in promoting regeneration.