Organs-on-chips are broadly defined as microfabricated surfaces or devices designed to engineer cells into microscale tissues with native-like features and then extract physiologically relevant readouts at scale. Because they are generally compatible with patient-derived cells, these technologies can address many of the human relevance limitations of animal models. As a result, organs-on-chips have emerged as a promising new paradigm for patient-specific disease modeling and drug development. Because neuromuscular diseases span a broad range of rare conditions with diverse etiology and complex pathophysiology, they have been especially challenging to model in animals and thus are well suited for organ-on-chip approaches. In this Review, we first briefly summarize the challenges in neuromuscular disease modeling with animal models. Next, we describe a variety of existing organ-on-chip approaches for neuromuscular tissues, including a survey of cell sources for both muscle and nerve, and two- and three-dimensional neuromuscular tissue-engineering techniques. Although researchers have made tremendous advances in modeling neuromuscular diseases on a chip, the remaining challenges in cell sourcing, cell maturity, tissue assembly and readout capabilities limit their integration into the drug development pipeline today. However, as the field advances, models of healthy and diseased neuromuscular tissues on a chip, coupled with animal models, have vast potential as complementary tools for modeling multiple aspects of neuromuscular diseases and identifying new therapeutic strategies.? 2020. Published by The Company of Biologists Ltd.
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