Crampton, Alexandra2021-10-132021-10-132019-08https://hdl.handle.net/11299/225026University of Minnesota Ph.D. dissertation. August 2019. Major: Biomedical Engineering. Advisor: David Wood. 1 computer file (PDF); viii, 134 pages.There is an urgent need for predictive drug screening and biological discovery tools, as the current standard systems either lack physiological relevance or are logistically incompatible with large-scale screens. Here, we present a solution to this problem – a novel droplet-based workflow to fabricate, culture, and assess cell-matrix interactions on short (<7days) and long (>28 days) timescales. With this technology, we can assess 3D cell-ECM interactions in a high-throughput and high-content manner, opening new avenues for assessing cell performance in response to therapies in a 3D microenvironment. The specific applications of this platform are broad, and we demonstrated the applicability for this technology to improve collagen contraction assays, endothelial barrier function measurements, and human liver model systems for toxicity studies. We also show that microtissue constructs can be cryopreserved, which allows this technology to be disseminated more broadly, as only standard cell culture equipment is needed to culture microtissues after fabrication. Because of the low reagent volumes and small cell numbers required for our system, this platform could become a logistically feasible answer to 3D functional screening of samples (e.g. tumor biopsies) on a patient-by-patient basis. We are eager to continue to refine and expand the capabilities of our technology, as well as amplify the in vitro biological systems we can generate with this platform.enThesis or Dissertation