title: Low oxygen concentrations impair tissue development in tissue-engineered cardiovascular constructs.
abstract: Cardiovascular tissue engineering has shown considerable progress, but in vitro tissue conditioning to stimulate the development of a functional extracellular matrix still needs improvement. We investigated the environmental factor oxygen concentration for its potential to increase the amount of collagen and collagen cross-links, and therefore improve tissue quality. Cardiovascular tissue engineered (TE) constructs, made of rapidly degrading PGA/P4HB scaffold seeded with human vascular-derived cells, were cultured at 7%, 4%, 2%, 0.5% O(2) for 4 weeks and compared to control cultures at 21% O(2). Tissue properties were evaluated by measuring the extracellular matrix production and mechanical behavior. The culture environment was monitored closely and the oxygen gradient throughout the constructs was simulated with a theoretical model. TE constructs cultured at 21%, 7% and 4% O(2) showed dense and homogeneous tissue formation with comparable strength, stiffness, collagen and collagen cross-link content. At 2% O(2), collagen content and stiffness decreased, whereas at 0.5% O(2), hardly any tissue was formed. Overall, tissue properties deteriorated at the lowest oxygen concentrations, opposing our hypothesis that was based on previous culture at low oxygen concentrations. Further research will focus on establishing the balance between applied oxygen conditions (concentration and exposure time) and optimal tissue outcome.
authors: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. m.a.a.v.vlimmeren@tue.nl
authors: Marijke A A
authors: MA
authors: van Vlimmeren
authors: Anita
authors: A
authors: Driessen-Mol
authors: Cees W J
authors: CW
authors: Oomens
authors: Marloes
authors: M
authors: van den Broek
authors: Reinout
authors: R
authors: Stoop
authors: Carlijn V C
authors: CV
authors: Bouten
authors: Frank P T
authors: FP
authors: Baaijens
mesh_terms: D001696:Biomechanical Phenomena / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000378:metabolism; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D007773:Lactates; C479138:PLOD2 protein, human; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D005947:Glucose; D010100:Oxygen