title: Pushing the envelope in tissue engineering: ex vivo production of thick vascularized cardiac extracellular matrix constructs.
abstract: Functional vascularization is a prerequisite for cardiac tissue engineering of constructs with physiological thicknesses. We previously reported the successful preservation of main vascular conduits in isolated thick acellular porcine cardiac ventricular ECM (pcECM). We now unveil this scaffold's potential in supporting human cardiomyocytes and promoting new blood vessel development ex vivo, providing long-term cell support in the construct bulk. A custom-designed perfusion bioreactor was developed to remodel such vascularization ex vivo, demonstrating, for the first time, functional angiogenesis in vitro with various stages of vessel maturation supporting up to 1.7 mm thick constructs. A robust methodology was developed to assess the pcECM maximal cell capacity, which resembled the human heart cell density. Taken together these results demonstrate feasibility of producing physiological-like constructs such as the thick pcECM suggested here as a prospective treatment for end-stage heart failure. Methodologies reported herein may also benefit other tissues, offering a valuable in vitro setting for "thick-tissue" engineering strategies toward large animal in vivo studies.
authors.affiliation: 1 The Laboratory of Cancer Drug Delivery & Mammalian Cell Technology, Faculty of Biotechnology and Food Engineering, Technion-Israel Institute of Technology , Haifa, Israel .
authors.forename: Udi
authors.initials: U
authors.lastname: Sarig
authors.forename: Evelyne Bao-Vi
authors.initials: EB
authors.lastname: Nguyen
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Sherwin
authors.initials: S
authors.lastname: Ting
authors.forename: Tomer
authors.initials: T
authors.lastname: Bronshtein
authors.forename: Hadar
authors.initials: H
authors.lastname: Sarig
authors.forename: Nitsan
authors.initials: N
authors.lastname: Dahan
authors.forename: Maskit
authors.initials: M
authors.lastname: Gvirtz
authors.forename: Shaul
authors.initials: S
authors.lastname: Reuveny
authors.forename: Steve K W
authors.initials: SK
authors.lastname: Oh
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheper
authors.forename: Yin Chiang Freddy
authors.initials: YC
authors.lastname: Boey
authors.forename: Subbu S
authors.initials: SS
authors.lastname: Venkatraman
authors.forename: Marcelle
authors.initials: M
authors.lastname: Machluf
mesh_terms: D000818:Animals; D019149:Bioreactors; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000378:metabolism*; D005240:Feasibility Studies; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D034421:Sus scrofa; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*