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Int. J. Mol. Sci. 2014, 15(10), 18593-18609; doi:10.3390/ijms151018593

Use of Natural Neural Scaffolds Consisting of Engineered Vascular Endothelial Growth Factor Immobilized on Ordered Collagen Fibers Filled in a Collagen Tube for Peripheral Nerve Regeneration in Rats

1
Fudan University Huashan Hospital, Department of Neurosurgery, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College-Fudan University, 12 Wulumuqi Zhong Rd., Shanghai 200040, China
2
The Affiliated Bayi Brain Hospital, the Military General Hospital of Beijing People's Liberation Army, No. 5 Nanmen Cang, Dongcheng District, Beijing 100700, China
3
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing 100190, China
*
Authors to whom correspondence should be addressed.
Received: 23 July 2014 / Revised: 15 September 2014 / Accepted: 29 September 2014 / Published: 15 October 2014
(This article belongs to the Special Issue Artificial Organs)
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Abstract

The search for effective strategies for peripheral nerve regeneration has attracted much attention in recent years. In this study, ordered collagen fibers were used as intraluminal fibers after nerve injury in rats. Vascular endothelial growth factor (VEGF) plays an important role in nerve regeneration, but its very fast initial burst of activity within a short time has largely limited its clinical use. For the stable binding of VEGF to ordered collagen fibers, we fused a collagen-binding domain (CBD) to VEGF through recombinant DNA technology. Then, we filled the ordered collagen fibers-CBD-VEGF targeting delivery system in a collagen tube to construct natural neural scaffolds, which were then used to bridge transected nerve stumps in a rat sciatic nerve transection model. After transplantation, the natural neural scaffolds showed minimal foreign body reactions and good integration into the host tissue. Oriented collagen fibers in the collagen tube could guide regenerating axons in an oriented manner to the distal, degenerating nerve segment, maximizing the chance of target reinnervation. Functional and histological analyses indicated that the recovery of nerve function in the natural neural scaffolds-treated group was superior to the other grafted groups. The guiding of oriented axonal regeneration and effective delivery systems surmounting the otherwise rapid and short-lived diffusion of growth factors in body fluids are two important strategies in promoting peripheral nerve regeneration. The natural neural scaffolds described take advantage of these two aspects and may produce synergistic effects. These properties qualified the artificial nerve conduits as a putative candidate system for the fabrication of peripheral nerve reconstruction devices. View Full-Text
Keywords: engineered vascular endothelial growth factor (VEGF); natural neural scaffolds; biodebradable materials; peripheral nerve regeneration engineered vascular endothelial growth factor (VEGF); natural neural scaffolds; biodebradable materials; peripheral nerve regeneration
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Ma, F.; Xiao, Z.; Meng, D.; Hou, X.; Zhu, J.; Dai, J.; Xu, R. Use of Natural Neural Scaffolds Consisting of Engineered Vascular Endothelial Growth Factor Immobilized on Ordered Collagen Fibers Filled in a Collagen Tube for Peripheral Nerve Regeneration in Rats. Int. J. Mol. Sci. 2014, 15, 18593-18609.

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