Abstract:In this paper, we discuss the basic design requirements for the development of physiologically meaningful in vitro systems comprising cells, scaffolds and bioreactors, through a bottom up approach. Very simple micro-and milli-fluidic geometries are first used to illustrate the concepts, followed by a real device case-study. At each step, the fluidic and mass transport parameters in biological tissue design are considered, starting from basic questions such as the minimum number of cells and cell density required to represent a physiological system and the conditions necessary to ensure an adequate nutrient supply to tissues. At the next level, we consider the use of three-dimensional scaffolds, which are employed both for regenerative medicine applications and for the study of cells in environments which better recapitulate the physiological milieu. Here, the driving need is the rate of oxygen supply which must be maintained at an appropriate level to ensure cell viability throughout the thickness of a scaffold. Scaffold and bioreactor design are both critical in defining the oxygen profile in a cell construct and are considered together. We also discuss the oxygen-shear stress trade-off by considering the levels of mechanical stress required for hepatocytes, which are the limiting cell type in a multi-organ model. Similar considerations are also made for glucose consumption in cell constructs. Finally, the allometric approach for generating multi-tissue systemic models using bioreactors is described.

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Zirconia-supported tungsten oxide samples, prepared by the equilibrium adsorption method in the pH range 2−13 by using as a support either hydrous [ZrO2(383)] or thermally pretreated [ZrO2(T)] zirconium oxide, were studied by laser Raman and diffuse reflectance spectroscopies. The W uptake increased (from ∼1.0 to ∼2.8 atoms nm-2) as the pH decreased for the ZrO2(T) supports, whereas for hydrous zirconia support showed the opposite trend. Different tungsten species were revealed depending on the amount of the adsorbed tungsten but not on the pH of the contacting solution. The continuous frequency shift of the Raman bands with the tungsten content, from 930 to 975 cm-1, indicated the presence of monomeric species at low tungsten concentrations and of polymeric species at high loading. The uptake of the tungsten species depends on the morphology and the texture of the support.