In vitro methods for screening small molecules for pharmacological potency or toxicity would benefit from the addition of key physiological features on the global and microscale. In particular, capturing the following rudimentary features of individual organs would improve the accuracy of these models: 1) liquid-volume to tissue-volume ratios, 2) volumes of distribution, 3) mass transfer rates, and 4) spatial distributions of key metabolites. In this talk, we will present the development and characterization of a three-dimensional (3-D) hepatocyte bioreactor that addresses some of these limitations by embedding microfluidic channels directly within the cell-seeded scaffold to act as vascular structures for the tissue volume. We will present the fabrication and characterization of pharmacokinetic parameters in this new bioreactor format. We will then discuss the roles of 3-D culture, oxygen tensions and gradients on hepatocyte function as measured by glucose consumption, albumin production, and cytochrome P4501 (CYP1) activity. We will conclude with comments on the design considerations for this reactor format and on opportunities for the incorporation of this type of model organ into more complex in vitro models of pharmacokinetics.

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