Biodegradable Polymer Implants for Spinal Cord Repair
用于脊髓修复的可生物降解聚合物植入物
基本信息
- 批准号:7090637
- 负责人:
- 金额:$ 33.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-09-30 至 2007-07-31
- 项目状态:已结题
- 来源:
- 关键词:Schwann cellsaxonbiodegradable productbiomaterial compatibilitycomputed axial tomographycomputer graphics /printingdrug delivery systemsenzyme activityimplantlaboratory ratmedical implant sciencemicrocapsulemolecular weightmorphometrynervous system regenerationnuclear magnetic resonance spectroscopypolymerizationpolymersspinal cord injurythree dimensional imaging /topography
项目摘要
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.
描述(由申请人提供):脊髓轴突具有损伤后再生的能力。然而,患者和实验动物模型中脊髓损伤(SCI)后的功能改善一直难以捉摸。我们聚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方面的专业知识。我们开发了一系列新型可生物降解聚合物植入物,用于治疗 SCI。在大鼠横断脊髓模型中对植入物的初步研究表明,该植入物具有促进轴突再生的潜力。植入物在脊髓中具有良好的耐受性,并且装载有存活下来的雪旺细胞。植入后三个月内,轴突在整个移植物长度上生长。我们假设植入物可以作为支持轴突跨间隙生长的支架、作为支持细胞的来源以及作为促进再生的药物的受控局部递送的载体。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。第一个目标是研究两种聚合物的降解特性和生物相容性;聚乳酸-乙醇酸 (PLGA) 和聚己内酯富马酸酯 (PCLF)。我们将使用计算机辅助设计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)是否能产生最佳结构。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(原代施万细胞和施万细胞系;SpL201)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,我们将研究可生物降解聚合物作为治疗剂递送载体的作用。软骨素酶-ABC 将用作模型蛋白质。它是一种增强脊髓轴突再生的酶。将比较封装在微球或移植物中后活性酶的递送,并评估酶递送在再生脐带中的效果。 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程度。
项目成果
期刊论文数量(15)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Implantation of cauda equina nerve roots through a biodegradable scaffold at the conus medullaris in rat.
- DOI:10.1016/j.spinee.2014.01.059
- 发表时间:2014-09-01
- 期刊:
- 影响因子:0
- 作者:Grahn PJ;Vaishya S;Knight AM;Chen BK;Schmeichel AM;Currier BL;Spinner RJ;Yaszemski MJ;Windebank AJ
- 通讯作者:Windebank AJ
Importance of the vasculature in cyst formation after spinal cord injury.
脉管系统在脊髓损伤后囊肿形成中的重要性。
- DOI:10.3171/2009.4.spine08784
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:Rooney,GemmaE;Endo,Toshiki;Ameenuddin,Syed;Chen,Bingkun;Vaishya,Sandeep;Gross,Louann;Schiefer,TerryK;Currier,BradfordL;Spinner,RobertJ;Yaszemski,MichaelJ;Windebank,AnthonyJ
- 通讯作者:Windebank,AnthonyJ
Optimizing conditions and avoiding pitfalls for prolonged axonal tracing with carbocyanine dyes in fixed rat spinal cords.
优化固定大鼠脊髓中使用碳青染料进行长时间轴突追踪的条件并避免陷阱。
- DOI:10.1016/j.jneumeth.2005.12.025
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Chen,BingkunK;Miller,StevenM;Mantilla,CarlosB;Gross,Louann;Yaszemski,MichaelJ;Windebank,AnthonyJ
- 通讯作者:Windebank,AnthonyJ
Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord.
- DOI:10.1016/j.actbio.2009.03.021
- 发表时间:2009-09
- 期刊:
- 影响因子:9.7
- 作者:Krych, Aaron J.;Rooney, Gemma E.;Chen, Bingkun;Schermerhorn, Thomas C.;Ameenuddin, Syed;Gross, LouAnn;Moore, Michael J.;Currier, Bradford L.;Spinner, Robert J.;Friedman, Jonathan A.;Yaszemski, Michael J.;Windebank, Anthony J.
- 通讯作者:Windebank, Anthony J.
Axon regeneration through scaffold into distal spinal cord after transection.
横断后,通过支架再生到脊髓远端的轴突再生。
- DOI:10.1089/neu.2008-0610
- 发表时间:2009-10
- 期刊:
- 影响因子:4.2
- 作者:Chen BK;Knight AM;de Ruiter GC;Spinner RJ;Yaszemski MJ;Currier BL;Windebank AJ
- 通讯作者:Windebank AJ
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ANTHONY John WINDEBANK其他文献
ANTHONY John WINDEBANK的其他文献
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{{ truncateString('ANTHONY John WINDEBANK', 18)}}的其他基金
A non-secreted form of IGF-1 is a protective factor for neural stem cells
非分泌形式的 IGF-1 是神经干细胞的保护因子
- 批准号:
8307841 - 财政年份:2008
- 资助金额:
$ 33.11万 - 项目类别:
Biodegradable Polymer Implants for Spinal Cord Repair
用于脊髓修复的可生物降解聚合物植入物
- 批准号:
6932084 - 财政年份:2003
- 资助金额:
$ 33.11万 - 项目类别:
Biodegradable Polymer Implants for Spinal Cord Repair
用于脊髓修复的可生物降解聚合物植入物
- 批准号:
6726002 - 财政年份:2003
- 资助金额:
$ 33.11万 - 项目类别:
Biodegradable Polymer Implants for Spinal Cord Repair
用于脊髓修复的可生物降解聚合物植入物
- 批准号:
6803495 - 财政年份:2003
- 资助金额:
$ 33.11万 - 项目类别:
MECHANISMS OF NEURONAL DEATH AND NEUROPROTECTION
神经元死亡和神经保护的机制
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6193094 - 财政年份:2000
- 资助金额:
$ 33.11万 - 项目类别:
Mechanisms of Neuronal Death and Neuroprotection
神经元死亡和神经保护机制
- 批准号:
7743995 - 财政年份:2000
- 资助金额:
$ 33.11万 - 项目类别:
MECHANISMS OF NEURONAL DEATH AND NEUROPROTECTION
神经元死亡和神经保护的机制
- 批准号:
6540324 - 财政年份:2000
- 资助金额:
$ 33.11万 - 项目类别:
MECHANISMS OF NEURONAL DEATH AND NEUROPROTECTION
神经元死亡和神经保护的机制
- 批准号:
6394512 - 财政年份:2000
- 资助金额:
$ 33.11万 - 项目类别:
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