Department of Orthopedics and Trauma, Peking University People's Hospital, Beijing, China.
Department of Foot and Ankle Surgery, Center for Orthopaedic Surgery, the Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
CNS Neurosci Ther. 2022 Jan;28(1):145-157. doi: 10.1111/cns.13752. Epub 2021 Nov 2.
Peripheral nerve injury is a significant clinical problem with a substantial impact on quality of life, for which no optimal treatment has been found. This study aimed to analyze the effect and mechanism of Wnt5a-loaded fibrin hydrogel on a 10-mm rat sciatic nerve defect.
The Wnt5a-loaded fibrin hydrogel was synthesized by mixing a Wnt5a solution with thrombin and fibrinogen solutions. The loading capacity and release profile of Wnt5a-loaded fibrin hydrogel and the effect of Wnt5a on Schwann cells were evaluated in vitro. We also assessed the in vivo repair status via histological analysis of the regenerative nerve and gastrocnemius muscle, electrophysiological examination, gait analysis, and muscle wet weight.
We developed a nerve conduit filled with Wnt5a-loaded fibrin hydrogel (Fn) as a sustained-release system to repair a 10-mm rat sciatic nerve defect. In vitro, Wnt5a could promote SC proliferation and the gene expression of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and cholinergic neurotrophic factor (CNTF), as well as the protein secretion of VEGF and NGF. In vivo, the Wnt5a/Fn group was superior to the hollow, fibrin hydrogel, and Wnt5a groups in terms of axonal growth, myelination, electrophysiological recovery, target organ innervation, and motor function recovery 12 weeks after the operation.
The Wnt5a/Fn nerve conduit can promote peripheral nerve defect regeneration, with potential clinical applications. The mechanism for this may be the facilitation of multiple neurotrophin secretion, combining vascularization and neurotrophic growth cues.
周围神经损伤是一个严重的临床问题，对生活质量有重大影响，但目前尚未找到理想的治疗方法。本研究旨在分析载 Wnt5a 纤维蛋白水凝胶对 10mm 大鼠坐骨神经缺损的作用及机制。
通过将 Wnt5a 溶液与凝血酶和纤维蛋白原溶液混合，合成载 Wnt5a 纤维蛋白水凝胶。评估了载 Wnt5a 纤维蛋白水凝胶的载药量和释放曲线，以及 Wnt5a 对许旺细胞的作用。我们还通过再生神经和腓肠肌的组织学分析、电生理学检查、步态分析和肌肉湿重评估了体内修复情况。
我们开发了一种填充载 Wnt5a 纤维蛋白水凝胶（Fn）的神经导管作为一种缓释系统，以修复 10mm 大鼠坐骨神经缺损。体外实验中，Wnt5a 可促进 SC 增殖及血管内皮生长因子（VEGF）、神经生长因子（NGF）和胆碱能神经营养因子（CNTF）的基因表达，以及 VEGF 和 NGF 的蛋白分泌。体内实验中，与空心管、纤维蛋白水凝胶和 Wnt5a 组相比，Wnt5a/Fn 组在术后 12 周时轴突生长、髓鞘形成、电生理恢复、靶器官神经支配和运动功能恢复方面更具优势。
载 Wnt5a 纤维蛋白神经导管可促进周围神经缺损的再生，具有潜在的临床应用价值。其作用机制可能是促进多种神经营养因子的分泌，结合血管生成和神经营养生长信号。
