title: Tropoelastin inhibits intimal hyperplasia of mouse bioresorbable arterial vascular grafts.
abstract: Neointimal hyperplasia, which results from the activation, proliferation and migration of vascular smooth muscle cells (SMCs), is a detrimental condition for vascular stents or vascular grafts that leads to stenosis. Preventing neointimal hyperplasia of vascular grafts is critically important for the success of arterial vascular grafts. We hypothesized that tropoelastin seeding onto the luminal surface of the graft would prevent neointimal hyperplasia through suppressing neointimal smooth muscle cell proliferation. In this study, we investigated the efficacy of tropoelastin seeding in preventing neointimal hyperplasia of bioresorbable arterial vascular grafts. Poly (glycolic acid) (PGA) fiber mesh coated with poly (l-lactic-co-ε-caprolactone) (PLCL) scaffolds reinforced by poly (l-lactic acid) (PLA) nano-fibers were prepared as bioresorbable arterial grafts. Tropoelastin was then seeded onto the luminal surface of the grafts. Tropoelastin significantly reduced the thickness of the intimal layer. This effect was mainly due to a substantial reduction the number of cells that stained positive for SMC (α-SMA) and PCNA in the vessel walls. Mature elastin and collagen type I and III were unchanged with tropoelastin treatment. This study demonstrates that tropoelastin seeding is beneficial in preventing SMC proliferation and neointimal hyperplasia in bioresorbable arterial vascular grafts.
  
  
  
  Small resorbable vascular grafts can block due to the over-proliferation of smooth muscle cells in neointimal hyperplasia. We show here that the proliferation of these cells is restricted in this type of graft. This is achieved with a simple dip, non-covalent coating of tropoelastin. It is in principle amendable to other grafts and is therefore an attractive process. This study is particularly significant because: (1) it shows that smooth muscle cell proliferation can be reduced while still accommodating the growth of endothelial cells, (2) small vascular grafts with an internal diameter of less than 1mm are amenable to this process, and (3) this process works for resorbable grafts.
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Tadahisa
authors.initials: T
authors.lastname: Sugiura
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Riddhima
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tara
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Tai
authors.initials: T
authors.lastname: Yi
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Yong-Ung
authors.initials: YU
authors.lastname: Lee
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Breuer
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia; Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Weiss
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA; Department of Cardiothoracic Surgery, The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA. Electronic address: toshiharu.shinoka@nationwidechildrens.org.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shinoka
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001807:Blood Vessel Prosthesis; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D005260:Female; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000473:pathology*; D014333:Tropoelastin / Q000737:chemistry*; D017539:Tunica Intima / Q000254:growth & development / Q000473:pathology*; D058017:Vascular Grafting / Q000295:instrumentation*
chemical_list: D020099:Coated Materials, Biocompatible; D014333:Tropoelastin
keywords: Bioresorbable vascular grafts; Intimal hyperplasia; Small diameter arterial grafts; Smooth muscle cells; Tropoelastin