Zhao Yuanyuan, Liu Yang, Lu Cheng, Sun Daokuan, Kang Shiqi, Wang Xin, Lu Laijin
Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
School of Materials Science and Engineering, Jilin University, Changchun, Jilin, People's Republic of China.
Int J Nanomedicine. 2024 Mar 7;19:2341-2357. doi: 10.2147/IJN.S449160. eCollection 2024.
The treatment of long-gap peripheral nerve injury (PNI) is still a substantial clinical problem. Graphene-based scaffolds possess extracellular matrix (ECM) characteristic and can conduct electrical signals, therefore have been investigated for repairing PNI. Combined with electrical stimulation (ES), a well performance should be expected. We aimed to determine the effects of reduced graphene oxide fibers (rGOFs) combined with ES on PNI repair in vivo.
rGOFs were prepared by one-step dimensionally confined hydrothermal strategy (DCH). Surface characteristics, chemical compositions, electrical and mechanical properties of the samples were characterized. The biocompatibility of the rGOFs were systematically explored both in vitro and in vivo. Total of 54 Sprague-Dawley (SD) rats were randomized into 6 experimental groups: a silicone conduit (S), S+ES, S+rGOFs-filled conduit (SGC), SGC+ES, nerve autograft, and sham groups for a 10-mm sciatic defect. Functional and histological recovery of the regenerated sciatic nerve at 12 weeks after surgery in each group of SD rats were evaluated.
rGOFs exhibited aligned micro- and nano-channels with excellent mechanical and electrical properties. They are biocompatible in vitro and in vivo. All 6 groups exhibited PNI repair outcomes in view of neurological and morphological recovery. The SGC+ES group achieved similar therapeutic effects as nerve autograft group ( > 0.05), significantly outperformed other treatment groups. Immunohistochemical analysis showed that the expression of proteins related to axonal regeneration and angiogenesis were relatively higher in the SGC+ES.
The rGOFs had good biocompatibility combined with excellent electrical and mechanical properties. Combined with ES, the rGOFs provided superior motor nerve recovery for a 10-mm nerve gap in a murine acute transection injury model, indicating its excellent repairing ability. That the similar therapeutic effects as autologous nerve transplantation make us believe this method is a promising way to treat peripheral nerve defects, which is expected to guide clinical practice in the future.
长节段周围神经损伤（PNI）的治疗仍是一个重大的临床问题。基于石墨烯的支架具有细胞外基质（ECM）特性且能传导电信号，因此已被研究用于修复PNI。结合电刺激（ES），有望获得良好的效果。我们旨在确定还原氧化石墨烯纤维（rGOFs）联合ES对体内PNI修复的影响。
通过一步法尺寸受限水热策略（DCH）制备rGOFs。对样品的表面特性、化学成分、电学和力学性能进行表征。系统地研究了rGOFs在体外和体内的生物相容性。将54只Sprague-Dawley（SD）大鼠随机分为6个实验组：硅胶导管（S）组、S+ES组、填充rGOFs的导管（SGC）组、SGC+ES组、神经自体移植组和假手术组，用于修复10毫米的坐骨神经缺损。评估每组SD大鼠术后12周再生坐骨神经的功能和组织学恢复情况。
rGOFs呈现出排列整齐的微纳通道，具有优异的力学和电学性能。它们在体外和体内均具有生物相容性。从神经学和形态学恢复来看，所有6组均表现出PNI修复结果。SGC+ES组获得了与神经自体移植组相似的治疗效果（>0.05），显著优于其他治疗组。免疫组织化学分析表明，SGC+ES组中与轴突再生和血管生成相关的蛋白质表达相对较高。
rGOFs具有良好的生物相容性，同时具备优异的电学和力学性能。在小鼠急性横断损伤模型中，rGOFs联合ES为10毫米的神经缺损提供了 superior 运动神经恢复，表明其具有出色的修复能力。其与自体神经移植相似的治疗效果使我们相信这种方法是治疗周围神经缺损的一种有前景的途径，有望在未来指导临床实践。
