NERVE REPAIR BY SYNTHETIC AND BIOLOGICAL POLYMERS

描述（申请人提供）：目前，对于机械性割裂损伤的神经，还没有有效的治疗方法来恢复其功能。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体外切断的豚鼠脊髓和周围神经的复合动作电位（CAP）传导。然而，由于神经干的机械不稳定性，该技术在体内的类似损伤中并不成功。研究者正试图通过使用外科粘接剂粘合神经结缔组织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，在分离的坐骨神经横断模型中对细胞膜进行peg融合后，用于吻合切断的神经干。他们在动物（豚鼠）结缔组织上的初步实验表明，这些粘接剂能够在体内为新的融合神经干提供所需的机械稳定性。研究中使用的商业粘合剂（纤维蛋白和氰基丙烯酸酯）已用于普通外科手术，免疫反应可控。实验粘合剂（贻贝粘附蛋白）已在发表的文献中显示，引起最小的免疫反应。这些粘接剂的强粘合性能和合理的生物相容性使研究人员相信这些外科粘接剂是使用聚乙二醇进行神经融合研究的理想候选者。他们的研究将为随后的豚鼠体内研究奠定基础。手术粘接剂的使用将使聚乙二醇在体内修复横断的神经，从而提高神经创伤患者损伤后的生活质量。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，将手术粘接剂与PEG联合应用于分离的、完全切断的坐骨神经，确定PEG/手术粘接剂神经融合的最佳条件。每个手术粘接剂系统将使用CFTL值作为比较标准进行评估。此外，还将使用既定程序确定每种粘合剂的比较免疫性能。经常咨询神经外科医生，他是研究小组的成员，将为指导研究和实验提供必要的输入，以临床相关的解决神经横断损伤的方法。

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.