Dong Xianhao, Yang Yueyue, Bao Zheheng, Midgley Adam C, Li Feiyi, Dai Shuxin, Yang Zhuangzhuang, Wang Jin, Liu Lihua, Li Wenlei, Zheng Yayuan, Liu Siyang, Liu Yang, Yu Weijian, Liu Jun, Fan Meng, Zhu Meifeng, Shen Zhongyang, Xiaosong Gu, Kong Deling
State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, China.
Department of Orthopaedics, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
Bioact Mater. 2023 Jul 27;30:98-115. doi: 10.1016/j.bioactmat.2023.06.015. eCollection 2023 Dec.
Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair. Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominent donor-site complications. Instead, imitating the native neural microarchitecture using synthetic conduits is expected to offer an alternative strategy for improving nerve regeneration. Here, we designed nerve conduits composed of high-resolution anisotropic microfiber grid-cordes with randomly organized nanofiber sheaths to interrogate the positive effects of these biomimetic structures on peripheral nerve regeneration. Anisotropic microfiber-grids demonstrated the capacity to directionally guide Schwann cells and neurites. Nanofiber sheaths conveyed adequate elasticity and permeability, whilst exhibiting a barrier function against the infiltration of fibroblasts. We then used the composite nerve conduits bridge 30-mm long sciatic nerve defects in canine models. At 12 months post-implant, the morphometric and histological recovery, gait recovery, electrophysiological function, and degree of muscle atrophy were assessed. The newly regenerated nerve tissue that formed within the composite nerve conduits showed restored neurological functions that were superior compared to sheaths-only scaffolds and Neurolac nerve conduit controls. Our findings demonstrate the feasibility of using synthetic biophysical cues to effectively bridge long-gap peripheral nerve injuries and indicates the promising clinical application prospects of biomimetic composite nerve conduits.
周围神经损伤可能导致严重的长段神经中断，修复起来具有挑战性。自体移植是修复长段神经损伤的金标准手术方法，但可能会导致明显的供体部位并发症。相反，利用合成导管模仿天然神经微结构有望为改善神经再生提供一种替代策略。在此，我们设计了由高分辨率各向异性微纤维网格索和随机排列的纳米纤维鞘组成的神经导管，以探究这些仿生结构对周围神经再生的积极作用。各向异性微纤维网格显示出定向引导雪旺细胞和神经突的能力。纳米纤维鞘具有足够的弹性和渗透性，同时对成纤维细胞的浸润表现出屏障功能。然后，我们使用复合神经导管桥接犬模型中30毫米长的坐骨神经缺损。在植入后12个月，评估形态计量学和组织学恢复情况、步态恢复情况、电生理功能以及肌肉萎缩程度。复合神经导管内形成的新再生神经组织显示出恢复的神经功能，与仅使用鞘的支架和Neurolac神经导管对照相比更优。我们的研究结果证明了利用合成生物物理线索有效桥接长段周围神经损伤的可行性，并表明仿生复合神经导管具有广阔的临床应用前景。
