An injectable, self-healing, electroconductive hydrogel loaded with neural stem cells and donepezil for enhancing local therapy effect of spinal cord injury.
An injectable, self-healing, electroconductive hydrogel loaded with neural stem cells and donepezil for enhancing local therapy effect of spinal cord injury.
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一种可注射的、自愈合的、负载有神经干细胞和多奈哌齐的水凝胶，用于增强脊髓损伤的局部治疗效果。
DOI：
10.1186/s13036-023-00368-2
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发表时间：
2023-07-24
影响因子：
5.6
通讯作者：
Yang, Xiaoyu
中科院分区：
文献类型：
--
作者：
Liu, Tiemei;Zhang, Qiang;Li, Hongru;Cui, Xiaoqian;Qi, Zhiping;Yang, Xiaoyu
脊髓损伤（SCI）是一种死亡率和致残率高的严重损伤，目前尚无有效的治疗方法。据报道，一些治疗方法，如药物干预和干细胞移植，对促进神经系统恢复有积极的作用。尽管这些治疗方法对神经再生是有效的，但许多缺点，如低干细胞存活率和全身用药引起的副作用，限制了它们的发展。近年来，可注射水凝胶材料因其良好的生物相容性、可生物降解性、可控性和低侵入性而在组织工程中得到广泛应用。可注射水凝胶联合干细胞或药物的治疗策略在脊髓损伤修复中取得了一定进展，显示出克服传统药物和干细胞治疗弊端的潜力。在这项研究中，基于透明质酸钠（SAO）和聚苯胺移植明胶（NH2-Gel-PANI）开发了一种新型可注射电活性水凝胶（NGP），作为装载神经干细胞（NSCs）和多奈哌齐（DPL）的材料，促进脊髓损伤后神经再生。为了评估所制备的NGP水凝胶在脊髓损伤修复中的应用潜力，我们分析了所制备的水凝胶的表面形貌、自修复性能、电导率和细胞相容性。同时，我们用脊髓损伤大鼠模型评估了装载DPL和NSCs的NGP水凝胶的神经修复能力。NGP水凝胶具有合适的孔径、良好的生物相容性、优异的导电性、可注射性和自修复性，其降解速率符合脊髓损伤的修复周期。DPL可以连续缓慢地从NGP水凝胶中释放出来；因此，NGP水凝胶可以作为药物和细胞的优良载体。体外细胞实验结果表明，NGP水凝胶具有良好的细胞相容性，可显著促进NSCs的神经元分化和轴突生长，而负载DPL可显著增强这一作用。更重要的是，负载DPL的NGP水凝胶在体外对NSCs的星形细胞分化有明显的抑制作用。动物实验表明，NGP水凝胶与DPL、NSCs联合使用对大鼠运动功能和神经传导功能恢复的治疗效果最好。装载NSCs和DPL的NGP水凝胶不仅显著增加髓鞘面积、新神经元数量和轴突面积，而且使囊腔和胶质瘢痕面积最小化，促进神经回路重建。本研究制备的负载DPL和nsc的电活性水凝胶是治疗外伤性脊髓损伤的理想生物材料。在线版本包含补充材料，可在10.1186/s13036-023-00368-2获得。
Spinal cord injury (SCI) is a serious injury with high mortality and disability rates, and there is no effective treatment at present. It has been reported that some treatments, such as drug intervention and stem cell transplantation have positive effects in promoting neurological recovery. Although those treatments are effective for nerve regeneration, many drawbacks, such as low stem cell survival rates and side effects caused by systemic medication, have limited their development. In recent years, injectable hydrogel materials have been widely used in tissue engineering due to their good biocompatibility, biodegradability, controllable properties, and low invasiveness. The treatment strategy of injectable hydrogels combined with stem cells or drugs has made some progress in SCI repair, showing the potential to overcome the drawbacks of traditional drugs and stem cell therapy. In this study, a novel injectable electroactive hydrogel (NGP) based on sodium hyaluronate oxide (SAO) and polyaniline-grafted gelatine (NH2-Gel-PANI) was developed as a material in which to load neural stem cells (NSCs) and donepezil (DPL) to facilitate nerve regeneration after SCI. To evaluate the potential of the prepared NGP hydrogel in SCI repair applications, the surface morphology, self-repairing properties, electrical conductivity and cytocompatibility of the resulting hydrogel were analysed. Meanwhile, we evaluated the neural repair ability of NGP hydrogels loaded with DPL and NSCs using a rat model of spinal cord injury. The NGP hydrogel has a suitable pore size, good biocompatibility, excellent conductivity, and injectable and self-repairing properties, and its degradation rate matches the repair cycle of spinal cord injury. In addition, DPL could be released continuously and slowly from the NGP hydrogel; thus, the NGP hydrogel could serve as an excellent carrier for drugs and cells. The results of in vitro cell experiments showed that the NGP hydrogel had good cytocompatibility and could significantly promote the neuronal differentiation and axon growth of NSCs, and loading the hydrogel with DPL could significantly enhance this effect. More importantly, the NGP hydrogel loaded with DPL showed a significant inhibitory effect on astrocytic differentiation of NSCs in vitro. Animal experiments showed that the combination of NGP hydrogel, DPL, and NSCs had the best therapeutic effect on the recovery of motor function and nerve conduction function in rats. NGP hydrogel loaded with NSCs and DPL not only significantly increased the myelin sheath area, number of new neurons and axon area but also minimized the area of the cystic cavity and glial scar and promoted neural circuit reconstruction. The DPL- and NSC-laden electroactive hydrogel developed in this study is an ideal biomaterial for the treatment of traumatic spinal cord injury. The online version contains supplementary material available at 10.1186/s13036-023-00368-2.
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