title: Development of small diameter nanofiber tissue engineered arterial grafts.
abstract: The surgical repair of heart and vascular disease often requires implanting synthetic grafts. While synthetic grafts have been successfully used for medium-to-large sized arteries, applications for small diameter arteries (<6 mm) is limited due to high rates of occlusion by thrombosis. Our objective was to develop a tissue engineered vascular graft (TEVG) for small diameter arteries. TEVGs composed of polylactic acid nanofibers with inner luminal diameter between 0.5 and 0.6 mm were surgically implanted as infra-renal aortic interposition conduits in 25 female C17SCID/bg mice. Twelve mice were given sham operations. Survival of mice with TEVG grafts was 91.6% at 12 months post-implantation (sham group: 83.3%). No instances of graft stenosis or aneurysmal dilatation were observed over 12 months post-implantation, assessed by Doppler ultrasound and microCT. Histologic analysis of explanted TEVG grafts showed presence of CD31-positive endothelial monolayer and F4/80-positive macrophages after 4, 8, and 12 months in vivo. Cells positive for α-smooth muscle actin were observed within TEVG, demonstrating presence of smooth muscle cells (SMCs). Neo-extracellular matrix consisting mostly of collagen types I and III were observed at 12 months post-implantation. PCR analysis supports histological observations. TEVG group showed significant increases in expressions of SMC marker, collagen-I and III, matrix metalloproteinases-2 and 9, and itgam (a macrophage marker), when compared to sham group. Overall, patency rates were excellent at 12 months after implantation, as structural integrity of these TEVG. Tissue analysis also demonstrated vessel remodeling by autologous cell.
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kurobe
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Maxfield
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tara
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Rocco
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Bagi
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Tai
authors.initials: T
authors.lastname: Yi
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Brooks
authors.initials: B
authors.lastname: Udelsman
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Zhen W
authors.initials: ZW
authors.lastname: Zhuang
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Muriel
authors.initials: M
authors.lastname: Cleary
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Iwakiri
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Breuer
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shinoka
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001807:Blood Vessel Prosthesis / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D019344:Lactic Acid / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D057139:Nanofibers / Q000009:adverse effects / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011091:Polyesters; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D016019:Survival Analysis; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)
references.citation: Rejuvenation Res. 2010 Aug;13(4):411-4
references.pmid: 20426626
references.citation: Proc Natl Acad Sci U S A. 2011 May 31;108(22):9214-9
references.pmid: 21571635
references.citation: J Mater Sci Mater Med. 2010 Dec;21(12):3207-15
references.pmid: 20890639
references.citation: J Biomed Mater Res A. 2009 Jul;90(1):205-16
references.pmid: 18491396
references.citation: J Vasc Surg. 2007 Jan;45 Suppl S:S5-67
references.pmid: 17223489
references.citation: Circulation. 2009 Nov 24;120(21):2053-61
references.pmid: 19901192
references.citation: Biomaterials. 1996 Jan;17(2):93-102
references.pmid: 8624401
references.citation: Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6448-53
references.pmid: 8692835
references.citation: Adv Drug Deliv Rev. 2011 Apr 30;63(4-5):312-23
references.pmid: 21421015
references.citation: Tissue Eng Part B Rev. 2014 Dec;20(6):628-40
references.pmid: 24786567
references.citation: J Vasc Surg. 2015 Sep;62(3):734-43
references.pmid: 24745941
references.citation: FASEB J. 2011 Dec;25(12):4253-63
references.pmid: 21865316
references.citation: Gen Thorac Cardiovasc Surg. 2012 Oct;60(10):680-708
references.pmid: 22956281
references.citation: J Exp Med. 2010 Aug 30;207(9):1951-66
references.pmid: 20733031
references.citation: Cells Tissues Organs. 2012;195(1-2):60-72
references.pmid: 21996715
references.citation: Arch Ophthalmol. 1990 Mar;108(3):421-9
references.pmid: 2310346
references.citation: J Thorac Cardiovasc Surg. 2010 Feb;139(2):431-6, 436.e1-2
references.pmid: 20106404
references.citation: Cold Spring Harb Perspect Biol. 2011 Feb 01;3(2):
references.pmid: 21421915
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19777-82
references.pmid: 17170139
references.citation: FASEB J. 2000 Apr;14(5):740-51
references.pmid: 10744630
references.citation: Science. 1994 Mar 25;263(5154):1715-20
references.pmid: 8134835
references.citation: Basic Clin Pharmacol Toxicol. 2012 Jan;110(1):5-11
references.pmid: 21989114
references.citation: FASEB J. 2011 Aug;25(8):2731-9
references.pmid: 21566209
references.citation: J Biomed Mater Res A. 2007 Dec 15;83(4):999-1008
references.pmid: 17584890
references.citation: J Thorac Cardiovasc Surg. 2005 Jun;129(6):1330-8
references.pmid: 15942574
references.citation: J Clin Invest. 2003 Mar;111(6):897-906
references.pmid: 12639996
references.citation: Nat Med. 2012 Jul;18(7):1148-53
references.pmid: 22729285
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4669-74
references.pmid: 20207947
references.citation: N Engl J Med. 2001 Feb 15;344(7):532-3
references.pmid: 11221621
references.citation: Circulation. 2012 Mar 27;125(12):1551-62
references.pmid: 22451605
references.citation: Circ Res. 2002 Jun 14;90(11):1189-96
references.pmid: 12065322
references.citation: J Biomed Mater Res A. 2009 Mar 15;88(4):923-34
references.pmid: 18384169
references.citation: Cells Tissues Organs. 2012;195(1-2):144-58
references.pmid: 21996786
references.citation: Scand Cardiovasc J. 2012 Feb;46(1):57-62
references.pmid: 22029845