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Disease and injury in the nervous system have tremendous impacts on quality of life, and there is a need for experimental models to study pathologies and advance therapeutic strategies. In the peripheral nervous system, nerve injuries often result in significant disability and neuropathic pain. Better nerve repair treatments are needed, as recovery in patients with current treatments is often unsatisfactory and complications arise at secondary surgical sites. For the central nervous system, there is a high demand for in vitro models to study neurological disorders, injuries, toxicity, and drug efficacy. Three-dimensional in vitro models can bridge the gap between traditional two-dimensional culture and animal models as they present an in vivo-like microenvironment in a tailorable experimental platform. To address the complex biomedical questions in the nervous system, the Hoffman-Kim research group has utilized biomaterial and tissue engineering technologies to develop in vitro models that replicate its key components and functions.