Application of custom anatomy-based nerve conduits on rabbit sciatic nerve defects: in vitro and in vivo evaluations
摘要
Abstract
The intermingling of regenerated nerve fibers inside nerve grafts is the main reason for mismatched nerve fibers. This is one of the key factors affecting limb function recovery after nerve injury. Previous research has shown that the accuracy of axon regeneration can be im-proved by a bionic structural implant. To this aim, iodine and freeze-drying high-resolution micro-computed tomography was performed to visualize the 3D topography of the New Zealand rabbit sciatic nerve (25 mm). A series of 1-, 2-, 3-, and 4-custom anatomy-based nerve conduits (CANCs) were fabricated based on the anatomical structure of the nerve fascicle. The match index, luminal surface, and mechanical properties of CANCs were evaluated before implanting in a 10-mm gap of the sciatic nerve. Recovery was evaluated by histo-morphometric analyses, electrophysiological study, gastrocnemius muscle weight recovery ratio, and behavioral assessments at 12 and 24 weeks postoperatively. The accuracy of nerve regeneration was determined by changes in fluorescence-labeled profile number during simultaneous retrograde tracing. Our results showed that the optimal preprocessing condition for high-resolution micro-computed to-mography visualization was treatment of the sciatic nerve with 40% Lugol’s solution for 3 days followed by lyophilization for 2 days. In vitro experiments demonstrated that the match index was highest in the 3-CANC group, followed by the 2-, 1-, and 4-CANC groups. The lumi-nal surface was lowest in the 1-CANC group. Mechanical properties (transverse compressive and bending properties) were higher in the 3-and 4-CANC groups than in the 1-CANC group. In vivo experiments demonstrated that the recovery (morphology of regenerated fibers, compound muscle action potential, gastrocnemius muscle weight recovery ratio, pain-related autotomy behaviors, and range of motion) in the 3-CANC group was superior to the other CANC groups, and achieved the same therapeutic effect as the autograft. The simultaneous retrograde tracing results showed that the percentages of double-labeled profiles of the 2-, 3-, and 4-CANC groups were comparatively lower than that of the 1-CANC group, which indicates that regenerated nerve fascicles were less intermingled in the 2-, 3-, and 4-CANC groups. These findings demonstrate that the visualization of the rabbit sciatic nerve can be achieved by iodine and freeze-drying high-res-olution micro-computed tomography, and that this method can be used to design CANCs with different channels that are based on the anatomical structure of the nerve. Compared with the 1-CANC, 3-CANC had a higher match index and luminal surface, and improved the accuracy of nerve regeneration by limiting the intermingling of the regenerated fascicles. All procedures were approved by the Animal Care and Use Committee, Xinjiang Medical University, China on April 4, 2017 (ethics approval No. IACUC20170315-02).关键词
nerve regeneration/nerve conduits/mismatch/iodine and freeze-drying/high-resolution/micro-computed tomography/bio-mimic/custom/rabbit sciatic nerve/in vitro/in vivo/neural regenerationKey words
nerve regeneration/nerve conduits/mismatch/iodine and freeze-drying/high-resolution/micro-computed tomography/bio-mimic/custom/rabbit sciatic nerve/in vitro/in vivo/neural regeneration引用本文复制引用
Yamuhanmode·Alike,Maimaiaili·Yushan,Ajimu·Keremu,Alimujiang·Abulaiti,ZhenHui Liu,Wei Fu,LiWei Yan,Aihemaitijiang·Yusufu,QingTang Zhu..Application of custom anatomy-based nerve conduits on rabbit sciatic nerve defects: in vitro and in vivo evaluations[J].中国神经再生研究（英文版）,2019,14(12):2173-2182,10.基金项目
This study was supported by the National Natural Science Foundation of China, No. 81360270, 81560357 (both to AY), and 31670986 (to QTZ) （both to AY）
the Key Laboratory of Hand Reconstruction, Ministry of Health, China （）
the Shanghai Key Laboratory of Peripheral Nerve and Microsurgery of China, No. 17DZ2270500 (to AY) （to AY）
the Science and Technology Project of Guangdong Province of China, No. 2014B020227001, 2017A050501017 (both to QTZ). Financial support: This study was supported by the National Natural Science Foundation of China, No. 81360270, 81560357 (both to Aihemai-tijiang·Yusufu), and 31670986 (to QTZ) （both to QTZ）
the Key Laboratory of Hand Re-construction, Ministry of Health, China （）
the Shanghai Key Laboratory of Peripheral Nerve and Microsurgery of China, No. 17DZ2270500 (to AY) （to AY）
the Science and Technology Project of Guangdong Province of China, No. 2014B020227001, 2017A050501017 (both to QTZ). The funding sources had no role in study design, conception, analysis or interpretation of data, writing and deciding to submit this paper for publication. （both to QTZ）
