周围神经缺损断端桥接修复的PTB方法与作用研究

The treatment of peripheral nerve defect is still an unresolved clinical problem. In previous study, we used the collagen-chitosan nerve scaffolds which simulation-based designed by ourselves to successfully repair a short-segment sciatic nerve defect in rats model. However, facing with long-segment nerve defect in the clinical setting, longer regeneration time and scar tissues formation often lead repair to fail, which are regards as a development bottleneck in the field of nerve tissue engineering. In our preliminary study, we found that autologous nerve graft combined with the human amniotic membrane (HAM) wrap improved functional and histologic recovery using microsurgical nerve suture in rats model, and obviously prevented scar tissues formation compared with the autologous nerve graft without HAM. The study demonstrated that the application of HAM was feasible to prevent scar tissues formation. Based on this result, our research group intend to utilize photochemical tissue bonding (PTB) technique to realize the sutureless seal between the improved nerve scaffold and two repair sites, and in combination with the HAM wrap to prevent trauma of foreign body reaction and scar tissues formation. According to PTB's mechanism of action, using green laser irradiation can lead electron transfer between excited photosensitizer and collagen molecules to form covalent bonds. Therefore, in order to repair long-segment peripheral nerve defect by PTB, we're going to structure bridging sleeves at the nerve scaffold's both ends and enhance the controllability on the degradation rate of HAM, and use a series of assessment methods to evaluate the efficacy of PTB in the recovery of nerve function and prevention of scar tissues formation. In conclusion, this study will help us to research the microenvironment of nerve regeneration, and obtain experimental data for the repair of long-segment nerve defect.

周围神经缺损的治疗是仍未解决的临床难题，我们前期应用自行研制的仿真神经支架成功修复大鼠"短节段"神经缺损。然而，由于"长节段"神经缺损修复时间较长、吻合口处缝线所致瘢痕及再生神经与周围组织粘连的形成，常导致修复失败，是制约组织工程神经材料发展的瓶颈。我们研究发现，以人胎羊膜包裹自体神经周围，结合显微缝合修复大鼠坐骨神经缺损，神经成功再生并有效减少周围组织粘连。在此基础上，本课题组拟应用光化学组织粘合技术(PTB)，利用绿激光照射，使激发态的光敏剂与胶原分子间发生电子转移并形成共价键交联，实现支架材料与神经断端间、羊膜自身间的免缝合黏合；通过在神经支架两端构建桥接管、控制羊膜降解速率，实现"长节段"神经缺损的修复。利用相关检测，进一步明确PTB技术在神经功能恢复、瘢痕及粘连预防上的有效性及可行性。本课题有助于我们对神经再生微环境的研究，为"长节段"神经缺损的修复提供实验数据和理论支持。

周围神经缺损的治疗是仍未解决的临床难题，我们前期应用自行研制的仿真神经支架成功修复大鼠“短节段”神经缺损。然而，由于“长节段”神经缺损修复时间较长、吻合口处缝线所致瘢痕及再生神经与周围组织粘连的形成，常导致修复失败，是制约组织工程神经材料发展的瓶颈。前期研究发现，以人胎羊膜包裹自体神经周围，结合显微缝合修复大鼠坐骨神经缺损，神经成功再生并有效减少周围组织粘连。本课题组成功应用光化学组织粘合技术(PTB)，利用绿激光照射，使激发态的光敏剂与胶原分子间发生电子转移并形成共价键交联，实现支架材料与神经断端间、羊膜自身间的免缝合黏合；通过在神经支架两端构建桥接管、控制羊膜降解速率，实现神经缺损的修复。通过检测进一步证实PTB技术在神经功能恢复、瘢痕及粘连预防上的有效性及可行性。