Lin Daoyi, Peng Jun, Zhang Yichong, Wang Xiaoping, Xu Xiaodong, Jia Jing
Department of Trauma and Orthopedic, China-Japan Friendship Hospital, Beijing, China.
Department of Anesthesia, China-Japan Friendship Hospital, Beijing, China.
Front Neurol. 2025 May 13;16:1561177. doi: 10.3389/fneur.2025.1561177. eCollection 2025.
Previous research has highlighted the pivotal role of angiogenesis in facilitating nerve function repair following nerve injury. In this study, we employed polydopamine (PDA) to modify polycaprolactone (PCL) and subsequently loaded it with roxadustat (ROX), thereby constructing a vascularized nerve conduit for the repair of a 10 mm sciatic nerve defect in rats. At 2 weeks post-surgery, new blood vessels were evaluated by immunofluorescence staining. Twelve weeks post-surgery, a comprehensive suite of assessments was conducted to evaluate the efficacy of the conduit, including gait analysis, determination of gastrocnemius muscle wet weight recovery, electrophysiological examination of gastrocnemius compound action potential (CMAP), Masson staining to evaluate gastrocnemius muscle fiber cross-sectional area, toluidine blue staining to assess the total number of regenerated myelinated nerve fibers, and electron microscopic observation of myelin sheath thickness. Our findings revealed that ROX@PDA@PCL could promote the proliferation of vascular endothelial cells and significantly enhance angiogenesis in regenerated nerves ( < 0.05). Regarding the recovery of neurological function, compared to the PDA@PCL and PCL groups, the ROX@PDA@PCL group exhibited significantly superior outcomes in the sciatic functional index (SFI), CMAP, gastrocnemius muscle wet weight ratio, muscle fiber cross-sectional area, total number of regenerated myelinated nerve fibers, and myelin sheath thickness. These indices approached those of the autologous group, but were still lower than in the autograft group ( < 0.05). The study underscores the potential of the vascularized nerve graft (ROX@PDA@PCL), constructed through PDA-mediated loading of ROX onto PCL, to enhance functional nerve recovery. Our findings present a promising new therapeutic approach for the clinical repair of peripheral nerve defects.
先前的研究强调了血管生成在促进神经损伤后神经功能修复中的关键作用。在本研究中,我们使用聚多巴胺(PDA)修饰聚己内酯(PCL),随后将罗沙司他(ROX)负载于其上,从而构建一种血管化神经导管,用于修复大鼠10毫米的坐骨神经缺损。术后2周,通过免疫荧光染色评估新生血管。术后12周,进行了一系列综合评估以评价导管的疗效,包括步态分析、腓肠肌湿重恢复测定、腓肠肌复合动作电位(CMAP)的电生理检查、用于评估腓肠肌肌纤维横截面积的Masson染色、用于评估再生有髓神经纤维总数的甲苯胺蓝染色以及髓鞘厚度的电子显微镜观察。我们的研究结果显示,ROX@PDA@PCL可促进血管内皮细胞增殖,并显著增强再生神经中的血管生成(<0.05)。关于神经功能恢复,与PDA@PCL组和PCL组相比,ROX@PDA@PCL组在坐骨神经功能指数(SFI)、CMAP、腓肠肌湿重比、肌纤维横截面积、再生有髓神经纤维总数以及髓鞘厚度方面表现出明显更优的结果。这些指标接近自体组,但仍低于自体移植组(<0.05)。该研究强调了通过PDA介导将ROX负载于PCL构建的血管化神经移植物(ROX@PDA@PCL)在增强功能性神经恢复方面的潜力。我们的研究结果为临床修复周围神经缺损提供了一种有前景的新治疗方法。