title: Effect of sustained heparin release from PCL/chitosan hybrid small-diameter vascular grafts on anti-thrombogenic property and endothelialization.
abstract: Thrombus formation and subsequent occlusion are the main reasons for the failure of small-diameter vascular grafts. In this study, a hybrid small-diameter vascular graft was developed from synthetic polymer poly(ε-caprolactone) (PCL) and natural polymer chitosan (CS) by the co-electrospinning technique. Heparin was immobilized on the grafts through ionic bonding between heparin and CS fibers. The immobilization was relatively stable, and heparin could continuously release from the grafts for more than 1month. Heparin functionalization evidently improved the hemocompatibility of the PCL/CS vascular grafts, which was illustrated by the reduced platelet adhesion and prolonged coagulation time (activated partial thromboplastin time, prothrombin time and thromboplastin time) as shown in the human plasma assay, and was further confirmed by the ex vivo arteriovenous shunt experiment. In vitro cell proliferation assay showed that heparin can promote the growth of human umbilical vein endothelial cells, while moderately inhibiting the proliferation of vascular smooth muscle cells, a main factor for neointimal hyperplasia. Implantation in rat abdominal aorta was performed for 1month. Results indicate that sustained release of heparin provided optimal anti-thrombogenic effect by reducing thrombus formation and maintaining the patency. Furthermore, heparin functionalization also enhanced in situ endothelialization, thereby preventing the occurrence of restenosis. In conclusion, it provides a facile and useful technique for the development of heparinized medical devices, including vascular grafts.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China; Center for Advanced Materials and Biotechnology, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300192, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300192, People's Republic of China.
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300192, People's Republic of China.
authors.forename: Yuejie
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China. Electronic address: qiangzhao@nankai.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China; Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300192, People's Republic of China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
mesh_terms: D001807:Blood Vessel Prosthesis; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D011091:Polyesters / Q000737:chemistry*; D013927:Thrombosis / Q000517:prevention & control*; D054457:Tissue Scaffolds
chemical_list: D011091:Polyesters; C016240:polycaprolactone; D006493:Heparin; D048271:Chitosan
keywords: Anti-thrombogenic property; Endothelialization; Heparin; Vascular grafts