Department of Orthopedics, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
Department of Orthopedics, Yangxin People's Hospital, Huangshi, Hubei, China.
Cell Biol Int. 2021 Aug;45(8):1733-1742. doi: 10.1002/cbin.11613. Epub 2021 May 3.
The nerve conduits have been developed for nerve defect repair. However, no artificial conduits have obtained comparable results to autografts to bridge the large gaps. A possible reason for this poor performance may be a lack of sustainable neurotrophic support for axonal regrowth. Previous studies suggested nanocomposite conduits can be used as a carrier for valproic acid (VPA), a common drug that can produce effects similar to the neurotrophic factors. Here, we developed the novel bioabsorbable conduits based on hydroxyapatite/poly d-l-lactic acid (PDLLA)/poly{(lactic acid)-co-[(glycolic acid)-alt-(l-lysine)]} with sustained release of VPA. Firstly, the sustained release of VPA in this conduit was examined by high-performance liquid chromatography. Then Schwann cells were treated with the conduit extracts. The cell metabolic activity and proliferation were assayed by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide and bromodeoxyuridine staining. A 10-mm segment of rat sciatic nerve was resected and then repaired, respectively, using the VPA conduit (Group A), the PDLLA conduit (Group B), or the autografts (Group C). Nerve conduction velocities (NCVs), compound muscle action potentials (CMAPs), and histological staining were assayed following the surgery. The cell metabolic activity and proliferation were significantly increased (p < .05) by the extracts from VPA-conduit extract compared to others. NCVs and CMAPs were significantly higher in Groups A and C than Group B (p < .05). The nerve density of Groups A and C was higher than Group B. There was no significant difference between Groups A and C. Taken together, this study suggested the sustained-release VPA conduit promoted peripheral nerve regeneration that was comparable to the autografts. It holds potential for future use in nerve regeneration.
神经导管已被开发用于修复神经缺损。然而，没有任何人工导管能够获得与自体移植物相当的结果来桥接大的间隙。这种性能不佳的一个可能原因是缺乏对轴突再生的可持续神经营养支持。先前的研究表明，纳米复合导管可用作丙戊酸（VPA）的载体，VPA 是一种常见的药物，可产生类似神经营养因子的作用。在这里，我们开发了基于羟基磷灰石/聚 d-丙交酯（PDLLA）/聚{[丙交酯]-共-[(乙醇酸)-交替-（L-赖氨酸）]}的新型可生物吸收导管，可实现 VPA 的持续释放。首先，通过高效液相色谱法检查该导管中 VPA 的持续释放。然后用导管提取物处理施万细胞。通过 3-[4,5-二甲基-2-噻唑基]-2,5-二苯基-2-四氮唑溴盐和溴脱氧尿苷染色测定细胞代谢活性和增殖。切除大鼠坐骨神经 10mm 段，分别用 VPA 导管（A 组）、PDLLA 导管（B 组）或自体移植物（C 组）修复。手术后测定神经传导速度（NCVs）、复合肌肉动作电位（CMAPs）和组织学染色。与其他组相比，VPA 导管提取物显著增加了细胞代谢活性和增殖（p <.05）。A 组和 C 组的 NCVs 和 CMAPs 均明显高于 B 组（p <.05）。A 组和 C 组的神经密度均高于 B 组。A 组和 C 组之间无显著差异。综上所述，本研究表明，持续释放 VPA 的导管促进了周围神经再生，与自体移植物相当。它有可能用于未来的神经再生。
