Traditionally, the interactions of drugs and toxicants with human tissue have been investigated in a reductionist way—for example, by focusing on specific molecular targets and using single-cell-type cultures before testing compounds in whole organisms. More recently, “systems biology” approaches attempt to enhance the predictive value of in vitro biological data by adopting a comprehensive description of biological systems and using computational tools that are sophisticated enough to handle the complexity of these systems. However, the utility of computational models resulting from these efforts completely relies on the quality of the data used to construct them. Here, we propose that recent advances in the development of bioengineered, three-dimensional, multicellular constructs provide in vitro data of sufficient complexity and physiological relevance to be used in predictive systems biology models of human responses. Such predictive models are essential to maximally leveraging these emerging bioengineering technologies to improve both therapeutic development and toxicity risk assessment. This brief outlines the opportunities presented by emerging technologies and approaches for the acceleration of drug development and toxicity testing, as well as the challenges lying ahead for the field.
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