title: Long-Term Functional Efficacy of a Novel Electrospun Poly(Glycerol Sebacate)-Based Arterial Graft in Mice.
abstract: Many surgical interventions for cardiovascular disease are limited by the availability of autologous vessels or suboptimal performance of prosthetic materials. Tissue engineered vascular grafts show significant promise, but have yet to achieve clinical efficacy in small caliber (<5 mm) arterial applications. We previously designed cell-free elastomeric grafts containing solvent casted, particulate leached poly(glycerol sebacate) (PGS) that degraded rapidly and promoted neoartery development in a rat model over 3 months. Building on this success but motivated by the need to improve fabrication scale-up potential, we developed a novel method for electrospinning smaller grafts composed of a PGS microfibrous core enveloped by a thin poly(ε-caprolactone) (PCL) outer sheath. Electrospun PGS-PCL composites were implanted as infrarenal aortic interposition grafts in mice and remained patent up to the 12 month endpoint without thrombosis or stenosis. Many grafts experienced a progressive luminal enlargement up to 6 months, however, due largely to degradation of PGS without interstitial replacement by neotissue. Lack of rupture over 12 months confirmed sufficient long-term strength, due primarily to the persistent PCL sheath. Immunohistochemistry further revealed organized contractile smooth muscle cells and neotissue in the inner region of the graft, but a macrophage-driven inflammatory response to the residual polymer in the outer region of the graft that persisted up to 12 months. Overall, the improved surgical handling, long-term functional efficacy, and strength of this new graft strategy are promising, and straightforward modifications of the PGS core should hasten cellular infiltration and associated neotissue development and thereby lead to improved small vessel replacements.
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, New Haven, CT, 06511, USA. ramak.khosravi@yale.edu.
authors.forename: Ramak
authors.initials: R
authors.lastname: Khosravi
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, 575 Children's Crossroads, Research III - WB4151, Columbus, OH, 43215, USA.
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Best
authors.affiliation: Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Allen
authors.affiliation: Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA.
authors.forename: Chelsea E T
authors.initials: CET
authors.lastname: Stowell
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, 575 Children's Crossroads, Research III - WB4151, Columbus, OH, 43215, USA.
authors.forename: Ekene
authors.initials: E
authors.lastname: Onwuka
authors.affiliation: Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Zhuang
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, 575 Children's Crossroads, Research III - WB4151, Columbus, OH, 43215, USA.
authors.forename: Yong-Ung
authors.initials: YU
authors.lastname: Lee
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, 575 Children's Crossroads, Research III - WB4151, Columbus, OH, 43215, USA.
authors.forename: Tai
authors.initials: T
authors.lastname: Yi
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, New Haven, CT, 06511, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Bersi
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, 575 Children's Crossroads, Research III - WB4151, Columbus, OH, 43215, USA.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shinoka
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, New Haven, CT, 06511, USA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Humphrey
authors.affiliation: Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, 575 Children's Crossroads, Research III - WB4151, Columbus, OH, 43215, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Breuer
mesh_terms: D000818:Animals; D001011:Aorta; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D003651:Decanoates; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D051379:Mice; D011108:Polymers
chemical_list: D003651:Decanoates; D011108:Polymers; C469892:poly(glycerol-sebacate); D005990:Glycerol
keywords: Cell-free polymeric scaffold; Elastomer; Electrospinning; Murine model; Neoartery development