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NERVE REPAIR BY SYNTHETIC AND BIOLOGICAL POLYMERS

通过合成和生物聚合物修复神经

基本信息

批准号：
6603395
负责人：
RIYI SHI
金额：
$ 7.34万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-07-01 至 2005-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Presently, there are no effective therapies to restore function of nerves traumatized by mechanical cleavage. By applying a biocompatible and synthetic polymer, polyethylene glycol (PEG), the investigators have successfully restored the conduction of compound action potentials (CAP) in severed guinea pig spinal cord and peripheral nerves in vitro. However, the technique would not be successful for similar injuries in vivo due to the mechanical instability of the nerve trunk. The investigators are attempting to achieve mechanically stable nerve fusion by adhesively bonding the nerve connective tissue using surgical adhesives . Specifically, they will use two commercially available surgical adhesives and one experimental adhesive for anastomosing the severed nerve trunks after PEG-fusion of the cell membranes in an isolated sciatic nerve transection model. Their preliminary experiments with animal (guinea pig) connective tissue indicate that these adhesives would be able to provide the required mechanical stability to a new fused nerve trunk in vivo. The commercial adhesives used in the study (fibrin and cyanoacrylate) have been used in general surgery with manageable immune response. The experimental adhesive (Mussel Adhesive Protein) has been shown in published literature to elicit minimal immune response. The strong adhesive performance and reasonable biocompatibility of these adhesives compel the investigators to believe that these surgical adhesives are ideal candidates for nerve fusion studies using PEG. Their study will lay the groundwork for subsequent in vivo studies with guinea pigs. Use of surgical adhesives will enable PEG repair of transected nerves in vivo, which in turn will improve the post-injury quality of life of nerve-trauma victims. As part of the investigation, mechanical, electrophysiological and histological tests will be performed on uninjured guinea pig sciatic nerves to determine the critical functional tensile load (CFTL) of the nerve. ln the experiments, surgical adhesives will be used in conjunction with PEG on isolated and completely severed sciatic nerves, and the optimal conditions for PEG/surgical adhesive nerve fusion will be determined. Each surgical adhesive system will be evaluated using CFTL values as a standard for comparison. In addition, comparative immunological performance of each adhesive will also be determined using established procedures. Frequent consultation with a neurosurgeon, who is a member of the research team, will provide necessary input to direct the study and experiments towards clinically relevant solutions for transection nerve injuries.

描述（由申请人提供）：目前，没有有效的治疗方法来恢复因机械切割而受创伤的神经的功能。通过应用生物相容性和合成聚合物聚乙二醇（PEG），研究人员成功地恢复了离体豚鼠脊髓和周围神经复合动作电位（CAP）的传导。然而，由于神经干的机械不稳定性，该技术在体内类似损伤中不会成功。研究者试图通过使用外科粘合剂将神经结缔组织粘合在一起来实现机械稳定的神经融合。具体来说，他们将使用两种市售的外科粘合剂和一种实验粘合剂，在隔离的坐骨神经横断模型中，在细胞膜的PEG融合后，将切断的神经干重新闭合。他们对动物（豚鼠）结缔组织的初步实验表明，这些粘合剂能够为体内新融合的神经干提供所需的机械稳定性。研究中使用的市售粘合剂（纤维蛋白和氰基丙烯酸酯）已用于普外科，免疫反应可控。实验粘合剂（贻贝粘附蛋白）已在已发表的文献中显示可引起最小的免疫应答。这些粘合剂的强粘合性能和合理的生物相容性迫使研究者相信这些外科粘合剂是使用PEG进行神经融合研究的理想候选物。他们的研究将为随后的豚鼠体内研究奠定基础。使用外科粘合剂将使PEG修复体内横断的神经，这反过来将改善神经创伤受害者的损伤后生活质量。作为研究的一部分，将对未受伤的豚鼠坐骨神经进行机械、电生理和组织学试验，以确定神经的临界功能拉伸负荷（CFTL）。在实验中，将外科粘合剂与PEG结合用于分离的和完全切断的坐骨神经，并确定PEG/外科粘合剂神经融合的最佳条件。将使用CFTL值作为比较标准，对每种外科粘合剂系统进行评价。此外，还将使用既定程序确定每种粘合剂的比较免疫学性能。经常咨询神经外科医生，谁是研究小组的成员，将提供必要的输入，以指导研究和实验对横断神经损伤的临床相关解决方案。