中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (8): 1652-1659.doi: 10.4103/1673-5374.303040

• 原著:退行性病与再生 • 上一篇    下一篇

神经基质膜包裹周围神经损伤的安全和有效性:一项随机单盲多中心临床试验

  

  • 出版日期:2021-08-15 发布日期:2021-01-14
  • 基金资助:
    吴阶平医学基金会项目(320.6750.17273)

Safety and efficacy of a nerve matrix membrane as a collagen nerve wrapping: a randomized, single-blind, multicenter clinical trial

Yong-Bin Gao1, Zhi-Gang Liu2, Guo-Dong Lin3, Yang Guo1, Lei Chen2, Bo-Tao Huang3, Yao-Bin Yin1, Chen Yang1, Li-Ying Sun1, Yan-Bo Rong1, Shanlin Chen1, *   

  1. 1Department of Hand Surgery, Beijing Jishuitan Hospital, Beijing, China; 2Department of Hand Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin Province, China; 3Department of Hand and Foot Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
  • Online:2021-08-15 Published:2021-01-14
  • Contact: Shan-Lin Chen, MD, PhD, chenshanlin@jst-hosp.com.cn or drcsl@qq.com.
  • Supported by:
    This study was supported by the Wu Jieping Medical Foundation of China, No. 320.6750.17273 (to YBG).

摘要:

由去细胞猪神经衍生出的一种新型神经基质膜由于保留主要的细胞外基质成分,含有多种生物活性成分,已被证实可在大鼠坐骨神经横断模型中有效防止神经吻合口与周围组织粘连,促进神经再生。此次前瞻性随机单盲平行对照的多中心临床试验旨在比较这种新型的神经基质膜与已经批准临床使用的牛肌腱来源的神经鞘管膜在修复周围神经损伤安全和有效性方面的差异。(1)试验于北京积水潭医院、吉林大学白求恩第一医院以及烟台毓璜顶医院招募了120例周围神经损伤患者,随机分为试验组(n=60,男52例,女8例,平均年龄41.34岁)和对照组(n=60,男42例,女18例,平均年龄40.17岁),分别采用新型的神经基质膜和肌腱来源的神经鞘管包裹端-端无张力神经吻合部位进行损伤神经的修复;(2)于术后14±530±790±10180±20d进行随访。安全性评价包括局部和全身反应,相关的实验室检查,以及不良反应等。有效性检查包括静态2点鉴别试验、移动2点鉴别试验和Semmes-Weinstein单丝检查。根据英国医学研究委员会量表和Semmes-Weinstein单丝检查对感觉神经功能恢复情况进行评价。以术后180±20d感觉神经恢复优良率为主要疗效指标;(3)结果显示,试验组和对照组的感觉神经恢复优良率接近,分别为98.00%94.44%。术后14和180d时血常规、肝肾功能、凝血功能、免疫球蛋白检测结果也无差异。表明在修复周围神经损伤方面,新型神经基质膜并不劣于牛肌腱来源的神经鞘管膜,可作为其替代材料;(4)试验于2016年10月8日经北京积水潭医院伦理委员会批准(批准号20160902),2016年12月14日经得吉林大学白求恩第一医院伦理委员会批准(批准号160518-088),2016年12月9日经烟台毓璜顶医院伦理委员会批准(批准号:2016-10-01)。此次前瞻性随机单盲平行多中心对照临床试验于2020年5月20日在中国临床注册中心注册(注册号ChiCTR2000033324)。

https://orcid.org/0000-0003-1027-338X (Shanlin Chen)

关键词:

神经吻合, 周围神经损伤, 神经基质, 神经导管, 神经修复, 细胞外基质, 感觉神经功能, 临床试验, 神经再生

Abstract: A new nerve matrix membrane derived from decellularized porcine nerves has been shown to retain the major extracellular matrix components, and to be effective in preventing adhesion between the nerve anastomosis sites and the surrounding tissues in a rat sciatic nerve transection model, thereby enhancing regeneration of the nerve. The effectiveness of the membrane may be attributed to its various bioactive components. In this prospective, randomized, single-blind, parallel-controlled multicenter clinical trial, we compared the safety and efficacy of the new nerve matrix membrane with a previously approved bovine tendon-derived type I collagen nerve wrapping. A total of 120 patients with peripheral nerve injury were recruited from Beijing Jishuitan Hospital, The First Bethune Hospital of Jilin University, and Yantai Yuhuangding Hospital, China. The patients were randomly assigned to undergo end-to-end and tension-free neurorrhaphy with nerve matrix membrane (n = 60, 52 male, 8 female, mean age 41.34 years, experimental group) or tendon-derived collagen nerve wrapping (n = 60, 42 male, 18 female, mean age 40.17 years, control group). Patients were followed-up at 14 ± 5, 30 ± 7, 90 ± 10 and 180 ± 20 days after the operation. Safety evaluation included analyses of local and systemic reactions, related laboratory tests, and adverse reactions. Efficacy evaluation included a static 2-point discrimination test, a moving 2-point discrimination test, and a Semmes–Weinstein monofilament examination. Sensory nerve function was evaluated with the British Medical Research Council Scale and Semmes–Weinstein monofilament examination. The ratio (percentage) of patients with excellent to good results in sensory nerve recovery 180 ± 20 days after the treatment was used as the primary effectiveness index. The percentages of patients with excellent to good results in the experimental and control groups were 98.00% and 94.44%, respectively, with no significant difference between the two groups. There were no significant differences in the results of routine blood tests, liver and renal function tests, coagulation function tests, or immunoglobulin tests at 14 and 180 days postoperatively between the two groups. These findings suggest that the novel nerve matrix membrane is similar in efficacy to the commercially-available bovine-derived collagen membrane in the repair of peripheral nerve injury, and it may therefore serve as an alternative in the clinical setting. The clinical trial was approved by the Institutional Ethics Committee of Beijing Jishuitan Hospital, China (approval No. 20160902) on October 8, 2016, the Institutional Ethics Committee of the First Bethune Hospital of Jilin University, China (approval No. 160518-088) on December 14, 2016, and the Institutional Ethics Committee of Yantai Yuhuangding Hospital, China (approval No. 2016-10-01) on December 9, 2016. The clinical trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2000033324) on May 28, 2020.

Key words: clinical trial, extracellular matrix, nerve conduit, nerve matrix, nerve repair, neural regeneration, neurorrhaphy, peripheral nerve injury, sensory nerve recovery