title: Circumferentially aligned fibers guided functional neoartery regeneration in vivo.
abstract: An ideal vascular graft should have the ability to guide the regeneration of neovessels with structure and function similar to those of the native blood vessels. Regeneration of vascular smooth muscle cells (VSMCs) with circumferential orientation within the grafts is crucial for functional vascular reconstruction in vivo. To date, designing and fabricating a vascular graft with well-defined geometric cues to facilitate simultaneously VSMCs infiltration and their circumferential alignment remains a great challenge and scarcely reported in vivo. Thus, we have designed a bi-layered vascular graft, of which the internal layer is composed of circumferentially aligned microfibers prepared by wet-spinning and an external layer composed of random nanofibers prepared by electrospinning. While the internal circumferentially aligned microfibers provide topographic guidance for in vivo regeneration of circumferentially aligned VSMCs, the external random nanofibers can offer enhanced mechanical property and prevent bleeding during and after graft implantation. VSMCs infiltration and alignment within the scaffold was then evaluated in vitro and in vivo. Our results demonstrated that the circumferentially oriented VSMCs and longitudinally aligned ECs were successfully regenerated in vivo after the bi-layered vascular grafts were implanted in rat abdominal aorta. No formation of thrombosis or intimal hyperplasia was observed up to 3 month post implantation. Further, the regenerated neoartery exhibited contraction and relaxation property in response to vasoactive agents. This new strategy may bring cell-free small diameter vascular grafts closer to clinical application.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Meifeng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Jingrui
authors.initials: J
authors.lastname: Chen
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Guanwei
authors.initials: G
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Shenglu
authors.initials: S
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China; State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China. Electronic address: kongdeling@nankai.edu.cn.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China. Electronic address: wly@nankai.edu.cn.
authors.forename: Lianyong
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology / Q000254:growth & development*; D001807:Blood Vessel Prosthesis; D004867:Equipment Design; D019544:Equipment Failure Analysis; D048091:Guided Tissue Regeneration / Q000295:instrumentation*; D008422:Materials Testing; D008968:Molecular Conformation; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000254:growth & development*; D057139:Nanofibers / Q000737:chemistry / Q000648:ultrastructure*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D054457:Tissue Scaffolds
keywords: Aligned microfiber; Poly(ε-caprolactone); Vascular grafts; Vascular smooth muscle cells; Wet-spinning