NERVE REPAIR BY SYNTHETIC AND BIOLOGICAL POLYMERS

描述(申请人提供)：目前，还没有有效的治疗方法来恢复机械劈裂损伤的神经功能。通过应用生物相容的合成聚合物聚乙二醇组分，研究人员成功地在体外恢复了豚鼠脊髓和周围神经复合动作电位的传导。然而，由于神经干的机械不稳定，这项技术在体内类似的损伤中不会成功。研究人员试图通过使用外科粘合剂将神经结缔组织粘合在一起，实现机械上稳定的神经融合。具体地说，他们将使用两种商业上可用的外科粘合剂和一种实验性粘合剂，在一个孤立的坐骨神经横断模型中，在细胞膜聚乙二醇化融合后，将切断的神经主干吻合。他们对动物(豚鼠)结缔组织的初步实验表明，这些粘合剂将能够为体内新的融合神经主干提供所需的机械稳定性。研究中使用的商用粘合剂(纤维蛋白和氰基丙烯酸酯)已用于免疫反应可控的普通外科手术。已发表的文献表明，这种实验性粘附剂(贻贝粘附性蛋白)可引起最低限度的免疫反应。这些粘合剂强大的粘接性能和合理的生物相容性迫使研究人员相信，这些外科粘合剂是使用聚乙二醇神经融合研究的理想候选者。他们的研究将为后续的豚鼠活体研究奠定基础。手术粘合剂的使用将使体内横断神经的聚乙二醇化修复成为可能，这反过来将改善神经创伤患者的损伤后生活质量。作为研究的一部分，将对未损伤的豚鼠坐骨神经进行机械、电生理和组织学测试，以确定神经的临界功能拉伸负荷(CFTL)。在实验中，将手术粘合剂与聚乙二醇联用在分离的和完全切断的坐骨神经上，并确定聚乙二醇/手术粘连神经融合的最佳条件。将使用CFTL值作为比较的标准来评估每种手术粘接系统。此外，还将使用既定程序确定每种粘合剂的比较免疫性能。作为研究团队的一员，经常咨询神经外科医生将提供必要的意见，以指导研究和实验针对神经横断损伤的临床相关解决方案。

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.