Blood vessel remodeling in late stage of vascular network reconstruction is essential for peripheral nerve regeneration.
Blood vessel remodeling in late stage of vascular network reconstruction is essential for peripheral nerve regeneration.
复制标题
血管网络重建后期的血管重塑对于周围神经再生至关重要
DOI：
10.1002/btm2.10361
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发表时间：
2022-09
影响因子：
7.4
通讯作者：
Wang, Hongkui
中科院分区：
文献类型：
--
作者：
Wang, Gang;Lu, Panjian;Qiao, Pingping;Zhang, Ping;Cai, Xiaodong;Tang, Leili;Qian, Tianmei;Wang, Hongkui
关键词：
组织工程在再生医学领域的深入研究的瓶颈之一是快速、功能性血管化。为了更深入地理解血管化，使用Micro-CT扫描对周围神经再生过程中灌注的血管网重建进行了详尽的、动态的和三维的描绘。用自体神经或组织工程化神经桥接大鼠坐骨神经10 mm缺损。神经残端与自体神经的血管吻合在术后4天至1周完成，为成熟血管网重建奠定了充分的基础。与组织工程神经相比，自体神经具有更强的出芽、血管生成和血管重塑能力。然而，周围神经再生中血管化的共同阶段被描绘为：缺氧起始、萌芽血管生成、重塑和成熟。进一步分析了神经挤压伤后较少关注的血管重塑对神经再生的影响。血管内皮生长因子阻断晚期血管重塑，可明显抑制轴突和髓鞘再生，减弱神经冲动传导。结果表明，神经再生微环境中大量未成熟血管的存在，而非必要的血管重塑，导致局部炎症水平升高。这些数据启发我们从更广的维度理解血管化与周围神经再生之间的密切联系，从而在临床上实现更好的组织工程神经的构建、调控和修复效果。
One of the bottlenecks of advanced study on tissue engineering in regenerative medicine is rapid and functional vascularization. For a deeper comprehension of vascularization, the exhaustive, dynamic, and three‐dimensional depiction of perfused vascular network reconstruction during peripheral nerve regeneration was performed using Micro‐CT scanning. The 10 mm defect of sciatic nerve in rat was bridged by the autologous or tissue engineered nerve. The blood vessel anastomosis between nerve stumps and autologous nerve accomplished at 4 days to 1 week after surgery, which was a sufficient basis for the mature vascular network re‐establishment. The stronger ability for sprouting angiogenesis and vascular remodeling of autologous nerve compared with tissue engineered nerve was revealed. However, common phases of vascularization in peripheral nerve regeneration were painted: hypoxic initiation, sprouting angiogenesis, and remodeling and maturation. The effect of less‐concerned vascular remodeling on nerve regeneration was further analyzed after nerve crush injury. The blockage of vascular remodeling in late stage by VEGF injection significantly inhibited axons and myelin sheaths regeneration, which attenuated the impulse conduction toward reinnervated muscles. It was illustrated that a large amount of immature blood vessels rather than necessary vascular remodeling elevated local inflammation level in nerve regeneration microenvironment. The figures inspired us to understand the close connections between vascularization and peripheral nerve regeneration from a broader dimension to achieve better constructions, regulations and repair effects of tissue engineered nerves in clinic.
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