Oxygen is known to be a critical factor that influences insulin secretion by islets. The diffusional limitations imposed by a biocapsule construct can potentially make it a hy-poxic environment for the cells. In the attempt to partially overcome this constraint, cells were seeded in various extracellular matrix materials within the biocapsule. Their behavior was compared with free cells, which form aggregates. We showed that the addition of a matrix, particularly alginate or collagen, within the micromachined biocapsule proved to augment the functionality islets in microfabricated biocapsules  (Figure 10.10). Supporting our studies, Tatarkiewicz et al. also demonstrated that the use of alginate three-dimensional matrix allowed cell clusters to be cultured at least two times higher density compared with culture in suspension. The clusters immobilized in a matrix resulted with 3-fold increase in insulin content and 9-fold increase in insulin/DNA ratio . This suggests the importance of optimizing cell density in within a matrix in the encapsulation device.
It is important to remember that that inclusion of matrix materials does promote a more homogeneous distribution of cells, but can also limit the density of cells that can be attained in the device. The importance of cell density in a practical encapsulation device is increasingly being recognized. It has been noted that we must better understand of the role of packing density on cell function and then incorporate those considerations into our devices. King et al. suggested that for planar devices, the goal should be a device less than 3 times the volume of the tissue inside and with the center of every islet less than 250 microns from the outer surface of the capsule. Due to the micron thickness of our membrane and an
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