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To investigate the synergistic effect of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) on cavernous nerve regeneration, two different aligned scaffolds consisting of coaxial electrospun silk fibers were prepared by switching the position of the two factors in either core or shell domain. The order and release rate of the dual factors delivery were relatively different because of the distinct location of two factors in coaxial fibers. An in vitro assay showed that the inner-VEGF/outer-BDNF scaffolds could more obviously accelerate Schwann cells growth, proliferation and spreading owing to the rapid release of BDNF. However, in vivo scaffold implantation demonstrated that the inner-BDNF/outer-VEGF scaffolds significantly facilitated more angiogenesis, and promoted more nerve regeneration based on great benefit of angiogenesis. Results showed that the reasonable dual-delivery order of VEGF and BDNF from scaffolds could enhance synergistic effect of the factors and promote cavernous nerve regeneration.

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