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However, in patients that experience recurrence despite treatment, the irradiated breast tissue may create a pre-metastatic niche that promotes tumor cell infiltration. Because current models of metastasis lack key physiological and microenvironmental cues, we developed a mammary vasculature-on-chip (MVoC) to model how the vasculature responds to RT and impacts immune and tumor cell behavior in mammary tissue. Murine and human MVoCs incorporated endothelial cells (ECs) cultured under physiologic shear stress and mammary-specific fibroblasts to mimic the vascular-fibrous stroma interface. MVoCs exhibited a transient, acute response to RT that led to a persistent phenotypic shift. Neutrophils, which play key roles in pre-metastatic niche formation, adhered more to irradiated ECs and induced persistent damage to the endothelial barrier, preventing recovery. Neutrophils also significantly increased tumor cell adhesion to the endothelium in MVoCs. These findings demonstrate that MVoCs can be used to study RT-induced pre-metastatic niche formation and suggest a positive feedback loop between damaged ECs and immune cell activation that may facilitate tumor cell colonization. MVoCs provide a biologically relevant approach to probe molecular and cellular interactions, improving translation toward developing novel therapies that improve patient outcomes.<\/jats:p>","DOI":"10.64898\/2026.09.03.749257","type":"posted-content","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:35:17Z","timestamp":1788816917000},"source":"Crossref","is-referenced-by-count":1,"title":["A mammary-specific microfluidic device for studying post-radiotherapy vascular-immune cell interactions"],"prefix":"10.64898","author":[{"given":"Shannon E.","family":"Martello","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia N.","family":"Luna","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"Derr","sequence":"additional","affiliation":[{"name":"Interdisciplinary Materials Science Program, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gladys","family":"Martinez Franco","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering, California State Polytechnic University Pomona, Pomona, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Susquehanna University, Susquehanna, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mc Veigh","sequence":"additional","affiliation":[{"name":"Interdisciplinary Materials Science Program, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon M.","family":"Bellan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA"},{"name":"Interdisciplinary Materials Science Program, Vanderbilt University, Nashville, TN, USA"},{"name":"Department of Mechanical Engineering, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Rafat","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA"},{"name":"Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA"},{"name":"Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA"},{"name":"Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091014450573000_2026.09.03.749257v1.1","first-page":"S216","volume":"75","year":"2009","journal-title":"Int. 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