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Here we demonstrate the utility of developing a model of endothelial dysfunction that utilizes induced pluripotent stem cell-derived endothelial progenitors encapsulated in collagen hydrogels to study the effects of COVID-19 on the endothelium. We found that treating these cell-laden hydrogels with SARS-CoV-2 spike protein resulted in a significant decrease in the number of vessel-forming cells as well as vessel network connectivity. Following treatment with the anti-inflammatory drug dexamethasone, we were able to prevent SARS-CoV-2 spike protein-induced endothelial dysfunction. In addition, we confirmed release of inflammatory cytokines associated with the COVID-19 cytokine storm. In conclusion, we have demonstrated that even in the absence of immune cells, we are able to use this 3D\n                  <jats:italic>in vitro<\/jats:italic>\n                  model for angiogenesis to reproduce COVID-19 induced endothelial dysfunction seen in clinical settings.\n                <\/jats:p>","DOI":"10.1101\/2022.10.01.510442","type":"posted-content","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T18:35:10Z","timestamp":1664822110000},"source":"Crossref","is-referenced-by-count":1,"title":["SARS-CoV-2 spike protein induces endothelial dysfunction in 3D engineered vascular networks"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4336-6072","authenticated-orcid":false,"given":"Brett","family":"Stern","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-1421","authenticated-orcid":false,"given":"Peter","family":"Monteleone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7089-7683","authenticated-orcid":false,"given":"Janet","family":"Zoldan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2022100513050558000_2022.10.01.510442v1.1","unstructured":"World Health Organization. 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