Tissue engineering in spinal cord regeneration

组织工程在脊髓再生中的应用

基本信息

批准号：
7259709
负责人：
XUEJUN WEN
金额：
$ 33.1万
依托单位：
CLEMSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7259709
关键词：
Adhesives Adult Affect Anabolism Architecture Arginine Astrocytes Axon Biocompatible Materials Biological Caliber Cells Cerebellar cortex structure Chemicals Chondroitin ABC Lyase Chondroitin Sulfates Cicatrix Controlled Environment Cues Daily Deposition Development Devices Disease Disruption Distal Electron Microscopy Engineering Environment Evaluation Extracellular Matrix Failure Fascicle Fiber Filament Glycine Goals Hindlimb Histology Immunohistochemistry In Vitro Individual Infusion Pumps Infusion procedures Injury Inorganic Sulfates Ion Channel Isoleucine Laminin Lead Length Lesion Literature Membrane Modeling Molecular Natural regeneration Neocortex Nerve Nerve Regeneration Neural tube Neuraxis Neurites Neurons Numbers Pathologic Processes Pattern Peptides Performance Principal Investigator Property Proteoglycan Radial Range Rate Rattus Recovery of Function Regenerative Medicine Research Personnel Role Route Schwann Cells Serine Signal Transduction Site Spinal Cord Spinal Ganglia Spinal cord injury Staining method Stains Supporting Cell Synapses Testing Therapeutic Agents Therapeutic Intervention Thin Filament Time Tissue Engineering Tissues Tyrosine Unspecified or Sulfate Ion Sulfates Variant Walking Work arginyl-glycyl-aspartyl-serine axon growth axon regeneration axonal guidance axonal pathfinding base behavior measurement career central nervous system injury central pattern generator controlled release density design and construction disability falls human tissue implantation in vivo in vivo Model injured migration myelination nervous system disorder neural circuit organ regeneration programs reinnervation relating to nervous system repaired resilience response scaffold size spinal cord regeneration success tyrosyl-isoleucyl-glycyl-seryl-arginine

项目摘要

DESCRIPTION (provided by applicant): A damaging or pathological process that disrupts the continuity of axons in the adult mammalian central nervous system (CMS) often results in permanent disability due to the failure of injured axons to regenerate. Current therapeutic interventions are short of eliciting a robust regenerative response that leads to a decent degree of functional recovery. Recently, the emergence of neuronal bridging devices based upon tissue engineering principles offers new hope for the treatment and manipulation of CMS injuries and diseases. By engineering a controlled environment at the lesion site, neural bridging devices awaken the intrinsic ability of CMS axons to regenerate across and beyond the site of injury to reach their appropriate targets. The combined use of material scaffolds containing guidance cues with adhesive molecules and cells of selective properties further confers vitality and resilience to the devices. Our long-term goal is to develop a clinically applicable tissue-engineered neuronal bridging device to repair damaged CNS nerve tracts. The proposed project aims to construct and evaluate a tissue-engineered bridging device based upon a multi-filament entubulation approach in which bundles of ultra-thin filaments are entubulated into a semi- permeable biodegradable hollow fiber membrane sleeve. Our hypothesis is that such a bridging device will convey strong unidirectional guidance cues and define a well-controlled environment for regenerating axons, and therefore promote and guide axonal regeneration following spinal cord injury, leading to a greater degree of functional recovery compared to conventional neuronal bridging strategies. Aim #1 is to evaluate the effect of the packing density of the filament bundles within the HFM entubulation sleeve on the directional outgrowth length and directionality of axons in vitro. Aim #2 is to examine the efficiency of multifilament bridging device in promoting axonal outgrowth using a spinal cord hemisection model in vivo. Aim #3 is to determine whether a combined strategy aimed at 1) enhancing directional regeneration across the lesion gap, and 2) inhibiting glial scar formation at the device-host interface will further promote axonal growth to the lumbar central pattern generator (CPG; an intact neural circuit located within the L1-2 segment that responsible for hindlimb locomotor function), resulting in both anatomical reconnection and functional recovery.

描述（由申请人提供）：一种破坏或病理过程，破坏成人哺乳动物中枢神经系统（CMS）中轴突的连续性，通常由于受伤的轴突无法再生而导致永久性残疾。当前的治疗干预措施缺乏引起强大的再生反应，从而导致功能恢复程度。最近，基于组织工程原理的神经元桥接设备的出现为治疗和操纵CMS损伤和疾病提供了新的希望。通过在病变部位进行控制环境，神经桥接设备唤醒了CMS轴突在跨伤害部位再生以达到其适当目标的内在能力。含有粘合剂分子和选择性特性细胞的指导线索的材料支架的联合使用进一步赋予了对设备的活力和弹性。我们的长期目标是开发一种临床适用的组织工程神经元桥接装置来修复受损的中枢神经系统神经区。拟议的项目旨在基于多丝诱因方法来构建和评估组织设计的桥接装置，其中将一束超薄细丝捆绑成半渗透的可生物降解的空心纤维纤维膜袖。我们的假设是，这种桥接装置将传达强大的单向引导线索，并为脊髓损伤后促进和指导轴突再生，定义了一个良好控制的环境，从而促进和指导轴突再生，从而导致与常规神经元桥梁策略相比，功能恢复更大程度。目的＃1是评估HFM诱因套筒内细丝束的填料密度对轴突在体外的定向产物长度和方向性上的影响。 AIM＃2是检查使用体内脊髓半分配模型促进轴突生长的多腔桥接装置的效率。目的＃3是确定针对1）增强病变间隙的方向再生的组合策略是否会进一步促进腰部中央模式生成器（CPG; CPG; CPG; CPG; CPG;一个完整的神经电路的轴突生长）在L1-2段中的轴突增长，该范围位于L1-2段中，负责Hindlimb locomotor函数的L1- 2段，均可恢复。