<i>In vitro</i> liver model using microfabricated scaffolds in a modular bioreactor

Vinci, Bruna; Cavallone, Daniela; Vozzi, Giovanni; Mazzei, Daniele; Domenici, Claudio; Brunetto, Maurizia Rossana; Ahluwalia, Arti

doi:10.1002/biot.200900074

Cited by 39 publications

(52 citation statements)

References 38 publications

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“…These velocities are consistent with those typically reported for micro-fluidic cell culture devices [42]. For the MCmB model, the v in was set to 3.82 × 10 −3 m/s (corresponding to 180 μL/min inflow), on the basis of previous experiments with this bioreactor [31,[62][63][64][65][66]. Table 4.…”

Section: Model Implementationsupporting

confidence: 64%

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

2014

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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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Section: Model Implementationsupporting

confidence: 64%

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

2014

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“…Aft er equilibration the sensors were extremely stable in medium with a maximum of 4% deviation in |Z p | for up to 7 days. In the presence of cell culture media the impedance decreases with frequency up to 2MHz; this is rather diff erent than the results reported by Lo et al [57] and Huang et al [58] where between 50 kHz and 1MHz the measured impedance without cells is constant and very low in magnitude. It should be noted that the impedance measurement set up is slightly diff erent here because the conductive substrate completely covers the surface and there are no insulating islands to contribute to large capacitive eff ects.…”

Section: Membrane Impedance Measurementcontrasting

confidence: 78%

Smart Sensing Scaffolds

Maria

Whulanza

Vozzi

et al. 2014

Smart Membranes and Sensors

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There is great interest in measuring cell functions on three dimensional scaffolds without using invasive and destructive methods. Here we describe how scaffolds for tissue engineering can also be used as sensors for monitoring cellular activity such as adhesion and spreading. Carbon nanotube polyester-polymer composites were fabricated into membranes and scaffolds with electro-conductive properties. Several nanotube concentrations were introduced aiming at understanding their influence on mechanical properties, impedance features and electric percolation threshold of the polymer matrix. It was observed that a concentration of 0.3% was able to transform an insulating matrix into a conductive one. Experimental results were compared with theoretical models. Impedance techniques were used to measure the effects of media and cell cultures on composite membranes and the results were analysed using lumped parameter models. Impedance changes can be correlated with protein or cell adhesion, spreading and changes in cell density

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“…LB1 is a single flow transparent bioreactor with an internal hydrodynamic design which ensures a low wall shear stress for high fluid turnover rates. The bioreactor is an upgrade of the MCmB (multi-compartmental modular bioreactor), which has been successfully used with hepatocytes [21,22]. The geometry of LB1 differs slightly from the MCmB, to increase the optical transparency of the system and enable optical imaging during the experiment.…”

Section: The Livebox1 Bioreactormentioning

confidence: 99%

Environmental Control in Flow Bioreactors

et al. 2017

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Abstract:The realization of physiologically-relevant advanced in vitro models is not just related to the reproduction of a three-dimensional multicellular architecture, but also to the maintenance of a cell culture environment in which parameters, such as temperature, pH, and hydrostatic pressure are finely controlled. Tunable and reproducible culture conditions are crucial for the study of environment-sensitive cells, and can also be used for mimicking pathophysiological conditions related with alterations of temperature, pressure and pH. Here, we present the SUITE (Supervising Unit for In Vitro Testing) system, a platform able to monitor and adjust local environmental variables in dynamic cell culture experiments. The physical core of the control system is a mixing chamber, which can be connected to different bioreactors and acts as a media reservoir equipped with a pH meter and pressure sensors. The chamber is heated by external resistive elements and the temperature is controlled using a thermistor. A purpose-built electronic control unit gathers all data from the sensors and controls the pH and hydrostatic pressure by regulating air and CO 2 overpressure and flux. The system's modularity and the possibility of imposing different pressure conditions were used to implement a model of portal hypertension with both endothelial and hepatic cells. The results show that the SUITE platform is able to control and maintain cell culture parameters at fixed values that represent either physiological or pathological conditions. Thus, it represents a fundamental tool for the design of biomimetic in vitro models, with applications in disease modelling or toxicity testing.

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In vitro liver model using microfabricated scaffolds in a modular bioreactor

Cited by 39 publications

References 38 publications

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

Smart Sensing Scaffolds

Environmental Control in Flow Bioreactors

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