Wang Xuanzhi, Xu Tao, Wang Fei
Department of Neurosurgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Department of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
J Biomed Mater Res A. 2025 Jul;113(7):e37943. doi: 10.1002/jbm.a.37943.
Currently, autologous nerve (AN) transplantation remains the gold standard for treating peripheral nerve injuries (PNIs). However, its inherent limitations, including donor site morbidity and immune rejection risks associated with allografts, have prompted the exploration of alternative therapeutic strategies. Among these, tissue engineering approaches have gained significant attention, with nerve conduit design emerging as a particularly promising research direction. Electrospinning technology has been widely adopted for its ability to fabricate nanofibrous scaffolds that closely mimic the native extracellular matrix. In this study, we engineered an aligned nanofiber conduit utilizing polylactic acid and gelatin through electrospinning, and integrated a sodium alginate hydrogel enriched with Schwann cells (SCs) and neural stem cells (NSCs) via coaxial bioprinting. The three-dimensional (3D) hydrogel microenvironment facilitated synergistic interactions between SCs and NSCs, augmenting the secretion of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). A dynamic perfusion culture system was further employed to optimize cell viability and functionality. In vivo studies revealed that the implantation of this conduit in a sciatic nerve defect model markedly enhanced motor function recovery, nerve regeneration, and muscle morphology. These improvements were substantiated by an increased sciatic functional index (SFI), heightened expression of S-100 and NF-200, and greater myelin thickness and axon diameter. Although the efficacy of the 3D-aligned nanofiber conduit cocultured with SCs and NSCs approximated that of AN transplantation, further research is imperative to identify more efficient seed cells and biocompatible 3D carriers to achieve optimal nerve regeneration. This study highlights the potential of tissue-engineered nerve conduits as a viable alternative for PNI repair, paving the way for future advancements in the field.
目前，自体神经（AN）移植仍是治疗周围神经损伤（PNI）的金标准。然而，其固有的局限性，包括供体部位的发病率以及与同种异体移植相关的免疫排斥风险，促使人们探索替代治疗策略。其中，组织工程方法受到了广泛关注，神经导管设计成为一个特别有前景的研究方向。静电纺丝技术因其能够制造出与天然细胞外基质极为相似的纳米纤维支架而被广泛应用。在本研究中，我们通过静电纺丝利用聚乳酸和明胶构建了一种排列整齐的纳米纤维导管，并通过同轴生物打印整合了富含雪旺细胞（SCs）和神经干细胞（NSCs）的海藻酸钠水凝胶。三维（3D）水凝胶微环境促进了SCs和NSCs之间的协同相互作用，增加了神经营养因子如脑源性神经营养因子（BDNF）和神经生长因子（NGF）的分泌。进一步采用动态灌注培养系统来优化细胞活力和功能。体内研究表明，将这种导管植入坐骨神经缺损模型中可显著增强运动功能恢复、神经再生和肌肉形态。坐骨神经功能指数（SFI）增加、S - 100和NF - 200表达升高以及髓鞘厚度和轴突直径增大证实了这些改善。尽管与SCs和NSCs共培养的3D排列纳米纤维导管的疗效接近AN移植，但仍需进一步研究以确定更有效的种子细胞和生物相容性3D载体，以实现最佳的神经再生。本研究突出了组织工程神经导管作为PNI修复可行替代方案的潜力，为该领域的未来发展铺平了道路。
