Department of Otolaryngology, Head and Neck Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, P.R. China.
Department of Orthopedics, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai 201499, P.R. China.
Sci Rep. 2016 Aug 25;6:32292. doi: 10.1038/srep32292.
Recurrent laryngeal nerve (RLN) injury remains a challenge due to the lack of effective treatments. In this study, we established a new drug delivery system consisting of a tube of Heal-All Oral Cavity Repair Membrane loaded with laminin and neurotrophic factors and tested its ability to promote functional recovery following RLN injury. We created recombinant fusion proteins consisting of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) fused to laminin-binding domains (LBDs) in order to prevent neurotrophin diffusion. LBD-BDNF, LBD-GDNF, and laminin were injected into a collagen tube that was fitted to the ends of the transected RLN in rats. Functional recovery was assessed 4, 8, and 12 weeks after injury. Although vocal fold movement was not restored until 12 weeks after injury, animals treated with the collagen tube loaded with laminin, LBD-BDNF and LBD-GDNF showed improved recovery in vocalisation, arytenoid cartilage angles, compound muscle action potentials and regenerated fibre area compared to animals treated by autologous nerve grafting (p < 0.05). These results demonstrate the drug delivery system induced nerve regeneration following RLN transection that was superior to that induced by autologus nerve grafting. It may have potential applications in nerve regeneration of RLN transection injury.
喉返神经(RLN)损伤仍然是一个挑战,因为缺乏有效的治疗方法。在这项研究中,我们建立了一个新的药物输送系统,由一个装有层粘连蛋白和神经营养因子的 Heal-All 口腔修复膜管组成,并测试了它在 RLN 损伤后促进功能恢复的能力。我们创建了由脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)与层粘连蛋白结合域(LBD)融合而成的重组融合蛋白,以防止神经营养因子扩散。LBD-BDNF、LBD-GDNF 和层粘连蛋白被注射到胶原管中,该胶原管安装在大鼠切断的 RLN 的两端。在损伤后 4、8 和 12 周评估功能恢复情况。尽管直到损伤后 12 周才恢复声带运动,但与自体神经移植治疗的动物相比,用载有层粘连蛋白、LBD-BDNF 和 LBD-GDNF 的胶原管治疗的动物在发声、杓状软骨角度、复合肌肉动作电位和再生纤维面积方面的恢复情况更好(p<0.05)。这些结果表明,药物输送系统在 RLN 横断后诱导的神经再生优于自体神经移植诱导的神经再生。它可能在 RLN 横断损伤的神经再生中有潜在的应用。