Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Int J Pharm. 2024 Apr 25;655:123978. doi: 10.1016/j.ijpharm.2024.123978. Epub 2024 Mar 7.
Peripheral nerve injury is a critical condition that can disrupt nerve functions. Despite the progress in engineering artificial nerve guidance conduits (NGCs), nerve regeneration remains challenging. Here, we developed new nanofibrous NGCs using polycaprolactone (PCL) and chitosan (CH) containing piracetam (PIR)/vitamin B12(VITB12) with an electrospinning method. The lumen of NGCs was coated by hyaluronic acid (HA) to promote regeneration in sciatic nerve injury. The NGCs were characterized via Scanning Electron Microscopy (SEM), Fourier transform infrared (FTIR), tensile, swelling, contact angle, degradation, and drug release tests. Neuronal precursor cell line (PCL12 cell) and rat mesenchymal stem cells derived from bone marrow (MSCs) were seeded on the nanofibrous conduits. After that, the biocompatibility of the NGCs was evaluated by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, and SEM images. The SEM demonstrated that PCL/CH/PIR/VITB12 NGCs had nonaligned, interconnected, smooth fibers. The mechanical properties of these NGCs were similar to rat sciatic nerve. These conduits had an appropriate swelling and degradation rate. The In Vitro studies exhibited favorable biocompatibility of the PCL/CH/PIR/VITB12 NGCs towards PC12 cells and MSCs. The in vitro studies exhibited favorable biocompatibility of the PCL/CH/PIR/VIT B12 NGCs towards MSCs and PC12 cells. To analyze functional efficacy, NGCs were implanted into a 10 mm Wistar rat sciatic nerve gap and bridged the proximal and distal stump of the defect. After three months, the results of sciatic functional index (55.3 ± 1.8), hot plate latency test (5.6 ± 0.5 s), gastrocnemius muscle wet weight-loss (38.57 ± 1.6 %) and histopathological examination using hematoxylin-eosin (H&E) /toluidine blue/ Anti-Neurofilament (NF200) staining demonstrated that the produced conduit recovered motor and sensory functions and had comparable nerve regeneration compared to the autograft that can be as the gold standard to bridge the nerve gaps.
周围神经损伤是一种严重的疾病，会破坏神经功能。尽管在工程人工神经引导导管（NGC）方面取得了进展，但神经再生仍然具有挑战性。在这里，我们使用聚己内酯（PCL）和壳聚糖（CH）制备了含有吡拉西坦（PIR）/维生素 B12（VITB12）的新型纳米纤维 NGC，采用静电纺丝法。用透明质酸（HA）涂覆 NGC 的管腔，以促进坐骨神经损伤后的再生。通过扫描电子显微镜（SEM）、傅里叶变换红外（FTIR）、拉伸、溶胀、接触角、降解和药物释放试验对 NGC 进行了表征。将神经元前体细胞系（PCL12 细胞）和骨髓来源的大鼠间充质干细胞（MSCs）接种在纳米纤维导管上。之后，通过 2,5-二苯基-2H-四唑溴盐（MTT）测定、4',6-二脒基-2-苯基吲哚（DAPI）染色和 SEM 图像评估 NGC 的生物相容性。SEM 显示 PCL/CH/PIR/VITB12 NGC 具有非对齐、相互连接、光滑的纤维。这些 NGC 的机械性能与大鼠坐骨神经相似。这些导管具有适当的溶胀和降解速率。体外研究表明，PCL/CH/PIR/VITB12 NGC 对 PC12 细胞和 MSCs 具有良好的生物相容性。体外研究表明，PCL/CH/PIR/VITB12 NGC 对 MSCs 和 PC12 细胞具有良好的生物相容性。为了分析功能效果，将 NGC 植入 10mm Wistar 大鼠坐骨神经间隙中，桥接缺陷的近端和远端残端。三个月后，坐骨神经功能指数（55.3±1.8）、热板潜伏期试验（5.6±0.5s）、腓肠肌湿重损失（38.57±1.6%）和苏木精-伊红（H&E）/甲苯胺蓝/抗神经丝（NF200）染色的组织病理学检查结果表明，所制备的导管恢复了运动和感觉功能，与可作为桥接神经间隙的金标准的自体移植物相比，具有相当的神经再生能力。
