title: Design and efficacy of a single-use bioreactor for heart valve tissue engineering.
abstract: Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system for nondestructive valve seeding and mechanical conditioning. Here we report the design for manufacture and the production of full scale, functional prototypes of such a system. To evaluate the efficacy of this bioreactor as a tool for seeding, ovine aortic valves were decellularized and subjected to seeding with human mesenchymal stem cells (hMSC). The effects of pulsatile conditioning using cyclic waveforms tuned to various negative and positive chamber pressures were evaluated, with respect to the seeding of cells on the decellularized leaflet and the infiltration of seeded cells into the interstitium of the leaflet. Infiltration of hMSCs into the aortic valve leaflet was observed following 72 h of conditioning under negative chamber pressure. Additional conditioning under positive pressure improved cellular infiltration, while retaining gene expression within the MSC-valve interstitial cell phenotype lineage. This protocol resulted in a subsurface pilot population of cells, not full tissue recellularization. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 249-259, 2017.
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, Kansas City, Missouri, 64108.
authors.forename: Gabriel L
authors.initials: GL
authors.lastname: Converse
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, Kansas City, Missouri, 64108.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Buse
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, Kansas City, Missouri, 64108.
authors.forename: Kari R
authors.initials: KR
authors.lastname: Neill
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, Kansas City, Missouri, 64108.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McFall
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, Kansas City, Missouri, 64108.
authors.forename: Holley N
authors.initials: HN
authors.lastname: Lewis
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, Kansas City, Missouri, 64108.
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: VeDepo
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, Kansas City, Missouri, 64108.
authors.forename: Rachael W
authors.initials: RW
authors.lastname: Quinn
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children's Mercy Kansas City, Kansas City, Missouri, 64108.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hopkins
mesh_terms: D000818:Animals; D001021:Aortic Valve; D001705:Bioprosthesis; D019149:Bioreactors; D006350:Heart Valve Prosthesis; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D012756:Sheep; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods
keywords: bioreactor; heart valve; mesenchymal stem cells; regenerative medicine; tissue engineering