Biomedical subjects

Robin N Coger

Publications and source records attributed to Robin N Coger.

7 recordsLinked to original sources

PubMed2006

Contribution of non-parenchymal cells to the performance of micropatterned hepatocytes.

Hepatocytes within current bioartificial liver designs are unable to maintain the wide range of differentiated functions observed for the liver in vivo. As recent studies suggest, the absence of controlled interactions between hepatocytes and non-parenchymal cell populations of the liver may contribute to this hepatocyte dedifferentiation. The current study investigates the effect of Kupffer cells, fibroblasts, and human umbilical vein endothelial cells on hepatocyte function. To effectively study the effect of these heterotypic cell-to-cell interactions, it is necessary to establish a culture environment that controls the interactions between multiple cell types. Micropatterning is such a technique and was used in the current study. In addition, to elucidate the influence of soluble factors on hepatocyte function, the micropatterned results were compared with those of the trans-well culture system. Specifically, we compared the morphological and functional changes of hepatocytes cultured with these cells at varying ratios. Our results suggest that direct heterotypic cell-to-cell contact between hepatocytes and fibroblasts, and soluble factor exchanges between hepatocytes and human umbilical vein endothelial cells, significantly enhanced hepatocyte performance.

Animals↗

PubMed2006

Hepatocyte and kupffer cells co-cultured on micropatterned surfaces to optimize hepatocyte function.

One strategy for temporarily extending the lives of patients with liver failure is the use of bioartificial liver (BAL) support devices. The functional components of BALs are the parenchymal liver cells known as hepatocytes. One design option for further improving current BAL performance levels is to include the non-parenchymal cells of the liver (e.g., Kupffer cells) in the design. In the current study, the effect of Kupffer cells on hepatocyte function was investigated using micropatterned co-cultures of these two liver cell populations. With traditional co-culture methods, the user is unable to control the relative proximity of one cell type to another. In this study, two different micropatterning techniques were used to engineer macro and fine micropatterned configurations for evaluating hepatocyte-Kupffer cell co-cultures. The ratio of one cell population to the other was also adjusted to evaluate the effects on hepatocyte function. The micropatterned co-cultures were maintained for ten days to evaluate for morphological and functional (e.g., albumin, urea) changes. The results illustrate that micropatterning hepatocytes, in the arrangements of this study, significantly improved hepatocyte function.

Albumins↗

PubMed2005

Engineering micropatterned surfaces for the coculture of hepatocytes and Kupffer cells.

Bioartificial liver (BAL) devices are used for applications ranging from pharmaceutical testing to temporary liver replacement. The capabilities of these devices can be improved by optimizing the range of hepatocyte functions that the BAL is able to perform. One means of achieving this is to design the BAL such that it establishes communication between hepatocytes and nonparenchymal cells. To understand how these heterotypic interactions can be favorably utilized in BAL design, it is first necessary to establish a culture environment that permits the controlled interactions of multiple cell types. This is the goal of the current study, which focuses on micropatterned cocultures of hepatocytes with Kupffer cells. The micropatterning technique relies on a polydimethylsiloxane (PDMS) membrane to achieve various two-dimensional configurations of the ECM prior to seeding the cell populations. The easy and inexpensive method of making the PDMS membranes differs from that reported in the literature and is detailed in the current study. To demonstrate the success of the method, surface characterization of the resultant micropatterns, as well as morphological and functional results are also presented.

Animals↗

PubMed2003

Modeling O2 transport within engineered hepatic devices.

Predicting and improving oxygen transport within bioartificial liver (BAL) devices continues to be an important engineering challenge since oxygen is one of the critical nutrients necessary for maintaining hepatocyte viability and function. Such a computational model would not only help predict outcomes but it would also allow system modifications to be analyzed prior to developing experimental protocols. This would help to facilitate future design improvements while reducing both experimental time and capital resource costs, and is the focus of the current study. Specifically, a computational model of O(2) transport through collagen and microporous collagen ECMs is analyzed for hollow fiber (HF), flat plate (FP), and spheroid BAL designs. By modifying the O(2) boundary conditions, hepatocyte O(2) consumption levels, O(2) permeability of the ECM, and ECM void fractions, O(2) transport predictions are determined for each system as a function of time and distance. Accuracy of the predictive model is confirmed by comparing computational vs. experimental results for the HF BAL system. The model's results indicate that O(2) transport within all three BAL designs can be improved significantly by incorporating the enhancement technique. This technique modifies a diffusion-dominant gel ECM into a porous matrix with diffusive and convective flows that mutually transport O(2) through the ECMs. Although tortuous pathways increase the porous ECM's overall effective length of O(2) travel, the decreased transport resistances of these pathways allow O(2) to permeate more effectively into the ECMs. Furthermore, because the HF design employs convective flow on both its inner and outer ECM surfaces, greater control of O(2) transport through its ECM is predicted, as compared with the single O(2) source inputs of the flat plate and spheroid systems. The importance of this control is evaluated by showing how modifying the O(2) concentration and/or transfer coefficients of the convective flows can affect O(2) transport.

Animals↗

PubMed2002

A new device for measuring the viscoelastic properties of hydrated matrix gels.

Determinations of the viscoelastic properties of extracellular matrices (ECMs) are becoming increasingly important for accurate predictive modeling of biological systems. Since the interactions of the cells with the ECM and surrounding fluid (e.g., blood, media) each affect cell behavior; it is advantageous to evaluate the ECM's material properties in the presence of the hydrating fluid. Conventional rheometry methods evaluate the bulk material properties of gel materials while displacing the hydrating liquid film. Such systems are therefore nonideal for testing materials such as ECMs, whose properties change with dehydration. The new patent pending, piezoelectrically actuated linear rheometer is designed to eliminate this problem. It uses a single cantilever to apply an oscillating load to the gel and to sense the gel's deflection. Composed of two thin film piezopolymer layers, the cantilever uses one layer as the actuator, and the second piezopolymer layer to measure the lateral movement of its attached probe. The viscoelastic nature of the ECM adds stiffness and damping to the system, resulting in the attenuation and phase shift of the sensor's output voltage. From these parameters, the ECM's shear storage and loss moduli are then determined. Initial tests on the BioMatrix I and type I collagen ECMs reveal that the first prototype of the piezoelectrically actuated linear rheometer is capable of accurately determining the trend and order of magnitude of an ECM's viscoelastic properties. In this paper, details of the rheometer's design and operating principles are described.

Animals↗

PubMedDate not supplied

Effects of enhanced O(2) transport on hepatocytes packed within a bioartificial liver device.

The functional performance of an extracorporeal bioartificial liver (BAL) device requires that suitable nutrient pathways exist to support the hepatocytes packed within it. Consequently the limited transport distance of the nutrient oxygen is a limiting factor in the scale-up of many BAL designs. In this study the porosity of a collagen extracellular matrix is increased to evaluate how enhanced O(2) transport alters the viability and functional performance of gel-entrapped hepatocytes packed within a BAL. Our results indicate that the porous collagen increases the number of viable hepatocytes that can be supported by a single O(2) source. Furthermore, the results illustrate that, compared with normal collagen, porous collagen extends the O(2) transport distance such that hepatocytes located at larger distances from the O(2) source of the BAL can be supported. Finally, the function results reveal that hepatocytes within the porous collagen experience significantly improved function over the control cultures. Hence our results demonstrate that enhancing O(2) transport through the extracellular matrix of densely packed BAL designs is one way to significantly improve the functionality of these devices.

Animals↗

PubMedDate not supplied

Heat and mass transfer during the cryopreservation of a bioartificial liver device: a computational model.

Bioartificial liver devices (BALs) have proven to be an effective bridge to transplantation for cases of acute liver failure. Enabling the long-term storage of these devices using a method such as cryopreservation will ensure their easy off the shelf availability. To date, cryopreservation of liver cells has been attempted for both single cells and sandwich cultures. This study presents the potential of using computational modeling to help develop a cryopreservation protocol for storing the three dimensional BAL: Hepatassist. The focus is upon determining the thermal and concentration profiles as the BAL is cooled from 37 degrees C-100 degrees C, and is completed in two steps: a cryoprotectant loading step and a phase change step. The results indicate that, for the loading step, mass transfer controls the duration of the protocol, whereas for the phase change step, when mass transfer is assumed negligible, the latent heat released during freezing is the control factor. The cryoprotocol that is ultimately proposed considers time, cooling rate, and the temperature gradients that the cellular space is exposed to during cooling. To our knowledge, this study is the first reported effort toward designing an effective protocol for the cryopreservation of a three-dimensional BAL device.

Computer Simulation↗