Superior oxygen and glucose supply in perfusion cell cultures compared to static cell cultures demonstrated by simulations using the finite element method

Abstract

Oxygen and glucose supply is one of the important factors for the growth and viability of the cells in cultivation of tissues, e.g., spheroid, multilayered cells, and three-dimensional tissue construct. In this study, we used finite element methods to simulate the flow profile as well as oxygen and glucose supply to the multilayered cells in a microwell array chip for static and perfusion cultures. The simulation results indicated that oxygen supply is more crucial than glucose supply in both static and perfusion cultures, and that the oxygen supply through the wall of the perfusion culture chip is important in perfusion cultures. Glucose concentrations decline with time in static cultures, whereas they can be maintained at a constant level over time in perfusion cultures. The simulation of perfusion cultures indicated that the important parameters for glucose supply are the flow rate of the perfusion medium and the length of the cell culture chamber. In a perfusion culture chip made of oxygen-permeable materials, e.g., polydimethylsiloxane, oxygen is hardly supplied via the perfusion medium, but mainly supplied through the walls of the perfusion culture chip. The simulation of perfusion cultures indicated that the important parameters for oxygen supply are the thickness of the flow channel and the oxygen permeability of the walls of the channel, i.e., the type of material and the thickness of the wall.

Detachably assembled microfluidic device for perfusion culture and post‐culture analysis of a spheroid array

“…Interestingly, no significant difference was observed between the high‐flow‐rate and low‐flow‐rate perfusion conditions. These results indicate that oxygen was supplied mainly through the gas‐permeable PDMS surface of the microfluidic chamber chip, which agrees with our previous study [16]. The distance from the bottom surface of the microwell to the upper layer of the medium was approximately 2.0 mm in the static culture but only 0.8 mm in the PDMS microfluidic chamber array chip.…”

“…As is typical for cell culture, nutrients and oxygen must be supplied to spheroid cultures [15, 16]. The removal of waste metabolites is also important [17, 18].…”

Cultivation of agarose-based microfluidic hydrogel promotes the development of large, full-thickness, tissue-engineered articular cartilage constructs

“…The effects of the former of these approaches are short‐lived, as cell proliferation and matrix deposition quickly fill the void space in the nanoporous hydrogels, and the latter approach requires large pressure heads, due to the low permeability of the constructs. Embedded microfluidic channels offer the potential to maximize the perfusion capacity, create spatial complexity and allow control over the spatial and temporal presentation of hydrodynamic and chemical cues within the developing construct (Bettinger and Borenstein, ; Bettinger et al ., ; Borenstein et al ., ; Choi et al ., ; Golden and Tien, ; Huang et al ., ; Johann and Renaud, ; Khademhosseini et al ., ; Ling et al ., ; Song et al ., ; Sugiura et al ., ). Methods for the production of the microfluidic channels include moulding (Borenstein et al ., ; Choi et al ., ; Ling et al ., ), bioprinting (Boland et al ., ; Lee et al ., ), photopatterning (Cuchiara et al ., ; Lee et al ., ) and use of sacrificial elements (Golden and Tien, ).…”

Hydrogel-based microfluidic incubator for microorganism cultivation and analyses

“…[10][11][12][19][20][21][22][23][24][25][26][27][28][29] Some of them report on partial 3D cell culture patterning by arrays of posts, [10][11][12] requiring delicate injection pressure control 10 and, therefore, preventing wide spread application. At the same time, PDMS has several other disadvantages.…”