Zhu Yaqiong, Peng Nan, Wang Jing, Jin Zhuang, Zhu Lianhua, Wang Yu, Chen Siming, Hu Yongqiang, Zhang Tieyuan, Song Qing, Xie Fang, Yan Lin, Li Yingying, Xiao Jing, Li Xinyang, Jiang Bo, Peng Jiang, Wang Yuexiang, Luo Yukun
Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China.
Beijing Key Lab of Regenerative Medicine in Orthopedics, Chinese PLA General Hospital, Beijing, China.
Biomater Res. 2022 Jun 11;26(1):24. doi: 10.1186/s40824-022-00264-8.
Developing biocompatible nerve conduits that accelerate peripheral nerve regeneration, lengthening and functional recovery remains a challenge. The combined application of nerve microtissues and platelet-rich plasma (PRP) provides abundant Schwann cells (SCs) and various natural growth factors and can compensate for the deficiency of SCs in the nerve bridge, as well as the limitations of applying a single type of growth factor. Multimodal ultrasound evaluation can provide additional information on the stiffness and microvascular flow perfusion of the tissue. This study was designed to investigate the effectiveness of a novel tissue-engineered nerve graft composed of an autogenous vein, nerve microtissues and PRP in reconstructing a 12-mm tibial nerve defect and to explore the value of multimodal ultrasound techniques in evaluating the prognosis of nerve repair.
In vitro, nerve microtissue activity was first investigated, and the effects on SC proliferation, migration, factor secretion, and axonal regeneration of dorsal root ganglia (DRG) were evaluated by coculture with nerve microtissues and PRP. In vivo, seventy-five rabbits were equally and randomly divided into Hollow, PRP, Micro-T (Microtissues), Micro-T + PRP and Autograft groups. By analysing the neurological function, electrophysiological recovery, and the comparative results of multimodal ultrasound and histological evaluation, we investigated the effect of these new nerve grafts in repairing tibial nerve defects.
Our results showed that the combined application of nerve microtissues and PRP could significantly promote the proliferation, secretion and migration of SCs and the regeneration of axons in the early stage. The Micro-T + PRP group and Autograft groups exhibited the best nerve repair 12 weeks postoperatively. In addition, the changes in target tissue stiffness and microvascular perfusion on multimodal ultrasound (shear wave elastography; contrast-enhanced ultrasonography; Angio PlaneWave UltrasenSitive, AngioPLUS) were significantly correlated with the histological results, such as collagen area percentage and VEGF expression, respectively.
Our novel tissue-engineered nerve graft shows excellent efficacy in repairing 12-mm defects of the tibial nerve in rabbits. Moreover, multimodal ultrasound may provide a clinical reference for prognosis by quantitatively evaluating the stiffness and microvescular flow of nerve grafts and targeted muscles.
开发能够加速周围神经再生、延长和功能恢复的生物相容性神经导管仍然是一项挑战。神经微组织与富血小板血浆（PRP）的联合应用可提供丰富的雪旺细胞（SCs）和多种天然生长因子，能够弥补神经桥中雪旺细胞的不足，以及单一类型生长因子应用的局限性。多模态超声评估可为组织的硬度和微血管血流灌注提供额外信息。本研究旨在探讨一种由自体静脉、神经微组织和PRP组成的新型组织工程神经移植物在修复12毫米胫神经缺损中的有效性，并探索多模态超声技术在评估神经修复预后中的价值。
在体外，首先研究神经微组织活性，并通过与神经微组织和PRP共培养评估其对雪旺细胞增殖、迁移、因子分泌以及背根神经节（DRG）轴突再生的影响。在体内，将75只兔子平均随机分为空心组、PRP组、微组织组（Microtissues）、微组织+PRP组和自体移植组。通过分析神经功能、电生理恢复情况，以及多模态超声和组织学评估的对比结果，我们研究了这些新型神经移植物在修复胫神经缺损中的效果。
我们的结果表明，神经微组织与PRP的联合应用可在早期显著促进雪旺细胞的增殖、分泌和迁移以及轴突再生。微组织+PRP组和自体移植组在术后12周表现出最佳的神经修复效果。此外，多模态超声（剪切波弹性成像；超声造影；血管平面波超声敏感成像，AngioPLUS）上目标组织硬度和微血管灌注的变化分别与组织学结果（如胶原面积百分比和VEGF表达）显著相关。
我们的新型组织工程神经移植物在修复兔12毫米胫神经缺损方面显示出优异的疗效。此外，多模态超声可通过定量评估神经移植物和目标肌肉的硬度和微血管血流为预后提供临床参考。
