title: Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds.
abstract: We report that the functional assembly of engineered cardiac muscle can be enhanced by oxygen supply provided by mechanisms resembling those in normal vascularized tissues. To mimic the capillary network, cardiomyocytes and fibroblasts isolated from the neonatal rat hearts were cultured on a highly porous elastomer with a parallel array of channels that were perfused with culture medium. To mimic oxygen supply by hemoglobin, culture medium was supplemented with a perfluorocarbon (PFC) emulsion; constructs perfused with unsupplemented culture medium served as controls. In PFC-supplemented medium, the decrease in the partial pressure of oxygen in the aqueous phase was only 50% of that in control medium (28 mmHg vs. 45 mmHg between the construct inlet and outlet at a flow rate of 0.1 mL/min). Consistently, constructs cultivated in the presence of PFC contained higher amounts of DNA and cardiac markers (troponin I, connexin-43) and had significantly better contractile properties as compared to control constructs. In both groups, electron microscopy revealed open channels and the presence of cells at the channel surfaces as well as within constructs. Improved properties of cardiac constructs could be correlated with the enhanced supply of oxygen to the cells, by a combined use of channeled scaffolds and PFC.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Milica
authors.initials: M
authors.lastname: Radisic
authors.forename: Hyoungshin
authors.initials: H
authors.lastname: Park
authors.forename: Fen
authors.initials: F
authors.lastname: Chen
authors.forename: Johanna E
authors.initials: JE
authors.lastname: Salazar-Lazzaro
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Dennis
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Freed
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D040761:Biomimetic Materials; D002478:Cells, Cultured; D005240:Feasibility Studies; D005466:Fluorocarbons / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005466:Fluorocarbons; D010100:Oxygen