title: Arterial graft with elastic layer structure grown from cells.
abstract: Shortage of autologous blood vessel sources and disadvantages of synthetic grafts have increased interest in the development of tissue-engineered vascular grafts. However, tunica media, which comprises layered elastic laminae, largely determines arterial elasticity, and is difficult to synthesize. Here, we describe a method for fabrication of arterial grafts with elastic layer structure from cultured human vascular SMCs by periodic exposure to extremely high hydrostatic pressure (HP) during repeated cell seeding. Repeated slow cycles (0.002 Hz) between 110 and 180 kPa increased stress-fiber polymerization and fibronectin fibrillogenesis on SMCs, which is required for elastic fiber formation. To fabricate arterial grafts, seeding of rat vascular SMCs and exposure to the periodic HP were repeated alternatively ten times. The obtained medial grafts were highly elastic and tensile rupture strength was 1451 ± 159 mmHg, in which elastic fibers were abundantly formed. The patch medial grafts were sutured at the rat aorta and found to be completely patent and endothelialized after 2.5 months, although tubular medial constructs implanted in rats as interpositional aortic grafts withstood arterial blood pressure only in early acute phase. This novel organized self-assembly method would enable mass production of scaffold-free arterial grafts in vitro and have potential therapeutic applications for cardiovascular diseases.
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan. utako@yokohama-cu.ac.jp.
authors.forename: Utako
authors.identifier: 0000-0003-1803-0155
authors.initials: U
authors.lastname: Yokoyama
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tonooka
authors.affiliation: Department of Mechanical Engineering, Osaka University, Osaka, Japan.
authors.forename: Ryoma
authors.initials: R
authors.lastname: Koretake
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan.|Department of Neurosurgery, Yokohama City University, Yokohama, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Gonda
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Saito
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Micro-Nano Systems Engineering, Nagoya University, Nagoya, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sakuma
authors.affiliation: Department of Micro-Nano Systems Engineering, Nagoya University, Nagoya, Japan.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Arai
authors.affiliation: Department of Mechanical Engineering, Osaka University, Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan. yishikaw@med.yokohama-cu.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000379:methods; D002478:Cells, Cultured; D004548:Elasticity; D006801:Humans; D006874:Hydrostatic Pressure; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D051381:Rats; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*