中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (9): 2064-2071.doi: 10.4103/1673-5374.335166

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

持续释放血管内皮生长因子的甲基丙烯酸酐化明胶水凝胶可加速挤压损伤周围神经的再生

  

  • 出版日期:2022-09-15 发布日期:2022-03-08

Sustained delivery of vascular endothelial growth factor mediated by bioactive methacrylic anhydride hydrogel accelerates peripheral nerve regeneration after crush injury

Wanlin Xu1, #, Yifan Wu1, #, Hao Lu1, Yun Zhu1, Jinhai Ye2, *, Wenjun Yang1, *   

  1. 1Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China; 2Jiangsu Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
  • Online:2022-09-15 Published:2022-03-08
  • Contact: Wenjun Yang, PhD, 450907991@qq.com; Jinhai Ye, PhD, jhyeedoctor@163.com.
  • Supported by:
    This work was supported by the Interdisciplinary Program of Shanghai Jiao Tong University, China, No. YG2021QN60 (both to WL); and Fundamental Research Program Funding of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China, No. JYZZ086B (both to WL).

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摘要：

目前治疗周围神经挤压伤仍以口服、静滴或肌肉注射神经营养因子等方法为主，但这些方法由于有效药物浓度较低，因而最终治疗效果不十分令人满意，所以亟需一种可提高损伤区局部有效药物浓度的治疗方式。实验首先将血管内皮生长因子负载至甲基丙烯酸酐化明胶中从而构建了一种持续释放血管内皮生长因子的水凝胶，且这种水凝胶具有良好的理化性能及生物相容性，能够支持RSC96细胞及人脐静脉内皮细胞的黏附及增殖。然后将这种水凝胶注射至大鼠挤压损伤的坐骨神经中，其可有效促进损伤神经的再生、功能恢复和血管化。上述结果表明，负载血管内皮生长因子的甲基丙烯酸酐化明胶可显著促进大鼠周围神经挤压伤的恢复。

https://orcid.org/0000-0002-3291-8153 (Wanlin Xu)

关键词: 神经再生, 周围神经, 挤压伤, 生物活性物质, 水凝胶, 控制性释放, 血管内皮生长因子, 血管化

Abstract: Neurotrophic factors, currently administered orally or by intravenous drip or intramuscular injection, are the main method for the treatment of peripheral nerve crush injury. However, the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes. Therefore, there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area. In this study, we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor. This modified gelatin exhibited good physical and chemical properties, biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells. When injected into the epineurium of crushed nerves, the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration, functional recovery and vascularization. The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves. 

Key words: bioactive material, controlled release, crush injury, hydrogel, muscle function, nerve regeneration, peripheral nerve, sciatic function index, vascular endothelial growth factor, vascularization