Perfusion systems that minimize vascular volume fraction in engineered tissues

This study determines the optimal vascular designs for perfusing engineered tissues. Here, “optimal” describes a geometry that minimizes vascular volume fraction (the fractional volume of a tissue that is occupied by vessels) while maintaining oxygen concentration above a set threshold throughout the tissue. Computational modeling showed that optimal geometries depended on parameters that affected vascular fluid transport and oxygen consumption. Approximate analytical expressions predicted optima that agreed well with the results of modeling. Our results suggest one basis for comparing the effectiveness of designs for microvascular tissue engineering

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Modulation of Invasive Phenotype by Interstitial Pressure-Driven Convection in Aggregates of Human Breast Cancer Cells

<div><p>This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.</p> </div

Suppression of invasion by elevated <i>P_base</i> relative to <i>P_tip</i>.

<p>(A–C) Invasion frequency (A), number of nuclei per invasive protrusion (“invasion”) (B), and length per invasion (C) for the three pressure conditions. In (A), <i>n</i> = 57, 56, and 51 for <i>P_base</i> ≈ <i>P_tip</i>, <i>P_base</i>><i>P_tip</i>, and <i>P_base</i><<i>P_tip</i>, respectively. (D) Distribution of invasive protrusions as a function of distance from the aggregate tip. (E) Frequency of new invasion or extension of pre-existing invasive protrusion for aggregates that were switched from <i>P_base</i>><i>P_tip</i> to <i>P_base</i> ≈ <i>P_tip</i> (<i>n</i> = 65) or left unchanged (<i>n</i> = 42), or from <i>P_base</i><i>P_tip</i> to <i>P_base</i>><i>P_tip</i> (<i>n</i> = 45) or left unchanged (<i>n</i> = 38). (F) Invasion frequency as a function of <i>P_base</i> − <i>P_tip</i> (<i>n</i> = 13, 27, 16, 14, 22, and 15 for <i>P_base</i> − <i>P_tip</i> of 1.2 to 1.6 cm H₂O, 0.8 to 1.1 cm H₂O, 0.4 to 0.7 cm H₂O, −0.4 to −0.7 cm H₂O, −0.8 to −1.1 cm H₂O, and −1.2 to −1.6 cm H₂O, respectively).</p

Modulation of invasion via pressure-induced changes in the local chemical microenvironment.

<p>(A) Schematic diagram of the formation of opposing aggregates. (B) Invasion frequencies in the presence of an opposing aggregate (<i>n</i> = 14) or cavity (<i>n</i> = 21) with <i>P_left</i> ♦ <i>P_right</i>. (C) Invasion frequencies in the presence of an opposing aggregate (<i>n</i> = 19) or cavity (<i>n</i> = 18) with <i>P_left</i>><i>P_right</i>. (D) Invasion frequencies in single aggregates that were fed with conditioned media and its variants and with <i>P_base</i><i>P_tip</i> (<i>n</i> = 51, 53, 43, 34, 48, 47, and 32 for control media, conditioned media, conditioned media with 10% FBS, dialyzed conditioned media, low-glucose media, low-glucose media that was supplemented with glucose, and low-glucose media that was supplemented with lactic acid, respectively). (E) Formation of aggregates in a T-shaped gel. (F) <i>Top</i>, invasion frequencies at the upstream and downstream halves at the aggregates (<i>n</i> = 45). <i>n.s.</i>, not significant. <i>Bottom</i>, representative images of invasions (arrows). Flow is from top to bottom, perpendicular to the aggregate axes.</p

Formation of 3D micropatterned aggregates of MDA-MB-231 cells.

<p>(A) Schematic diagram of the completed experimental setup (<i>left</i>) and the procedure used to form single aggregates (<i>right</i>). Each aggregate consisted of a “base” that ended in a “tip” in a type I collagen gel. (B) Representative phase-contrast and fluorescence (<i>insets</i>) images of Hoechst-stained tips for <i>P_base</i> equal to or greater than <i>P_tip</i>, seven days after establishing the pressure set-points.</p