Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (5): 903-912.doi: 10.4103/1673-5374.249239

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Aligned fibers enhance nerve guide conduits when bridging peripheral nerve defects focused on early repair stage

Qi Quan 1 , Hao-Ye Meng 1, 3 , Biao Chang 2 , Guang-Bo Liu 1 , Xiao-Qing Cheng 1 , He Tang 1 , Yu Wang 1, 4 , Jiang Peng 1, 4 , Qing Zhao 4, 5 , Shi-Bi Lu 1   

  1. 1 Department of Orthopedic Surgery, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing Key Lab of Regenerative Medicine in Orthopedics, Chinese PLA General Hospital, Beijing, China
    2 Department of Laser Medicine, Chinese PLA General Hospital, Beijing, China
    3 School of Materials Science and Engineering, University of Science & Technology Beijing, Beijing, China
    4 Neural Regeneration Co-innovation Center of Jiangsu Province, Nantong, Jiangsu Province, China
    5 Department of Orthopedic Surgery, First Affiliated Hospital of PLA General Hospital, Beijing, China
  • Online:2019-05-15 Published:2019-05-15
  • Contact: Shi-Bi Lu, PhD, MD, lusb301@126.com; Qing Zhao, PhD, MD, zqmd301@126.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 31771052 (to YW); the National Basic Re¬search Program of China (973 Program), No. 2014CB542201 (to JP); the National Key Research and Development Program of China, No. 2016YFC1101601 (to QZ), 2017YFA0104702 (to YW); the PLA General Hospital Translational Medicine Project of China, No. 2016TM-030 (to QZ); the Beijing Municipal Natural Science Foundation of China, No. 7172202 (to YW); the PLA Youth Training Project for Medical Sci¬ence, China, No. 16QNP144 (to YW); the Beijing Municipal Science and Technology Project, China, No. Z161100005016059 (to YW).

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Abstract:

Nerve conduits enhance nerve regeneration in the repair of long-distance peripheral nerve defects. To help optimize the effective¬ness of nerve conduits for nerve repair, we developed a multi-step electrospinning process for constructing nerve guide conduits with aligned nanofibers. The alignment of the nerve guide conduits was characterized by scanning electron microscopy and fast Fourier trans¬form. The mechanical performance of the nerve guide conduits was assessed by testing for tensile strength and compression resistance. The biological performance of the aligned fibers was examined using Schwann cells, PC12 cells and dorsal root ganglia in vitro. Immunohisto¬chemistry was performed for the Schwann cell marker S100 and for the neurofilament protein NF200 in PC12 cells and dorsal root ganglia. In the in vivo experiment, a 1.5-cm defect model of the right sciatic nerve in adult female Sprague-Dawley rats was produced and bridged with an aligned nerve guide conduit. Hematoxylin-eosin staining and immunohistochemistry were used to observe the expression of ATF3 and cleaved caspase-3 in the regenerating matrix. The recovery of motor function was evaluated using the static sciatic nerve index. The number of my¬elinated fibers, axon diameter, fiber diameter, and myelin thickness in the distal nerve were observed by electron microscopy. Gastrocnemius muscle mass ratio was also determined. The analyses revealed that aligned nanofiber nerve guide conduits have good mechanical properties and can induce Schwann cells, PC12 cells and dorsal root ganglia to aggregate along the length of the nanofibers, and promote the growth of longer axons in the latter two (neuronal) cell types. The aligned fiber nerve conduits increased the expression of ATF3 and cleaved caspase-3 at the middle of the regenerative matrix and at the distal nerve segment, improved sciatic nerve function, increased muscle mass of the gastroc¬nemius muscle, and enhanced recovery of distal nerve ultrastructure. Collectively, the results show that highly aligned nanofibers improve the performance of the nerve conduit bridge, and enhance its effectiveness in repairing peripheral nerve defects.

Key words: nerve regeneration, nerve guide conduit, electrospinning, peripheral nerve injury, aligned fiber, sciatic nerve, structure, mechanical function, nerve scaffold, nanofiber, neural regeneration