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Am J Physiol Heart Circ Physiol 288: H1278-H1289, 2005. First published November 11, 2004; doi:10.1152/ajpheart.00787.2004
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Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers

Milica Radisic,1 William Deen,1 Robert Langer,1,2 and Gordana Vunjak-Novakovic2

1Department of Chemical Engineering and 2Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts

Submitted 3 August 2004 ; accepted in final form 6 November 2004

A steady-state model of oxygen distribution in a cardiac tissue construct with a parallel channel array was developed and solved for a set of parameters using the finite element method and commercial software (FEMLAB). The effects of an oxygen carrier [Oxygent; 32% volume perfluorocarbon (PFC) emulsion] were evaluated. The parallel channel array mimics the in vivo capillary tissue bed, and the PFC emulsion has a similar role as the natural oxygen carrier hemoglobin in increasing total oxygen content. The construct was divided into an array of cylindrical domains with a channel in the center and tissue space surrounding the channel. In the channel, the main modes of mass transfer were axial convection and radial diffusion. In the tissue region, mass transfer was by axial and radial diffusion, and the consumption of oxygen was by Michaelis-Menten kinetics. Neumann boundary conditions were imposed at the channel centerline and the half distance between the domains. Supplementation of culture medium by PFC emulsion improved mass transport by increasing convective term and effective diffusivity of culture medium. The model was first implemented for the following set of experimentally obtained parameters: construct thickness of 0.2 cm, channel diameter of 330 µm, channel center-to-center spacingof 700 µm, and average linear velocity per channel of 0.049 cm/s, in conjunction with PFC supplemented and unsupplemented culture medium. Subsequently, the model was used to define favorable scaffold geometry and flow conditions necessary to cultivate cardiac constructs of high cell density (108 cells/ml) and clinically relevant thickness (0.5 cm). In future work, the model can be utilized as a tool for optimization of scaffold geometry and flow conditions.

tissue engineering; cardiac myocyte; scaffold mass transport; perfluorocarbons



Address for reprint requests and other correspondence: G. Vunjak-Novakovic, Massachusetts Institute of Technology, Harvard-MIT Division of Health Science and Technology, 77 Massachusetts Ave., E25-330, Cambridge, MA 02139 (E-mail: Gordana{at}mit.edu)




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