title: The effect of thick fibers and large pores of electrospun poly(ε-caprolactone) vascular grafts on macrophage polarization and arterial regeneration.
abstract: The vascular grafts prepared by electrospinning often have relatively small pores, which limit cell infiltration into the grafts and hinder the regeneration and remodeling of the grafts into neoarteries. To overcome this problem, macroporous electrospun polycaprolactone (PCL) scaffolds with thicker fibers (5-6 μm) and larger pores (∼30 μm) were fabricated in the present study. In vitro cell culture indicated that macrophages cultured on thicker-fiber scaffolds tended to polarize into the immunomodulatory and tissue remodeling (M2) phenotype, while those cultured on thinner-fiber scaffolds expressed proinflammatory (M1) phenotype. In vivo implantation by replacing rat abdominal aorta was performed and followed up for 7, 14, 28 and 100 d. The results demonstrated that the macroporous grafts markedly enhanced cell infiltration and extracellular matrix (ECM) secretion. All grafts showed satisfactory patency for up to 100 days. At day 100, the endothelium coverage was complete, and the regenerated smooth muscle layer was correctly organized with abundant ECM similar to those in the native arteries. More importantly, the regenerated arteries demonstrated contractile response to adrenaline and acetylcholine-induced relaxation. Analysis of the cellularization process revealed that the thicker-fiber scaffolds induced a large number of M2 macrophages to infiltrate into the graft wall. These macrophages further promoted cellular infiltration and vascularization. In conclusion, the present study confirmed that the scaffold structure can regulate macrophage phenotype. Our thicker-fiber electrospun PCL vascular grafts could enhance the vascular regeneration and remodeling process by mediating macrophage polarization into M2 phenotype, suggesting that our constructs may be a promising cell-free vascular graft candidate and are worthy for further in vivo evaluation.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), 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, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors.forename: Jianing
authors.initials: J
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: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300192, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300192, China.
authors.forename: Yuejie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry & Molecular Biology, Libin Cardiovascular Institute of Alberta, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
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, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China; Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300192, China. Electronic address: kongdeling@hotmail.com.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China. Electronic address: qiangzhao@nankai.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology*; D001807:Blood Vessel Prosthesis; D016764:Cell Polarity; D002478:Cells, Cultured; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D011091:Polyesters / Q000737:chemistry*; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D058017:Vascular Grafting
chemical_list: D011091:Polyesters; C016240:polycaprolactone
keywords: Cellularization; Electrospinning; Macrophage polarization; PCL; Vascular grafts