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Here, we developed a Matrigel\u2010agarose core\u2010shell bio\u2010casting platform that separates biochemical and structural cues by confining MCF10A cells or MCF10A organoids\u2010laden Matrigel within a hollow agarose shell. This defined architecture supported the formation of elongated mammary epithelial mini\u2010tissues and induced dynamic morphological remodeling, including longitudinal compaction, lateral tissue reorganization, and budding\u2010like protrusions. Compared to MCF10A cultured in Matrigel without the agarose shell, agarose core\u2010shell constructs showed enhanced epithelial and lumen\u2010like organization, as indicated by increased Ep\u2010CAM and MUC1 expression and enlarged lumen\u2010like regions. Strikingly, core\u2010shell filaments developed a transparent tube\u2010like phenotype with visible internal structures and retained epithelial marker expression. Gene\u2010expression analysis showed increased expression of selected mammary\u2010 and lipid\u2010associated markers, including Perilipin\u20102, fatty acid synthase, and casein, suggesting early mammary\u2010associated molecular expression. Together, these results established Matrigel\u2010agarose core\u2010shell bio\u2010casting as a modular culture strategy for guiding mammary epithelial tubulogenesis in\u00a0vitro.<\/jats:p>","DOI":"10.1002\/jbm.a.70173","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:23:13Z","timestamp":1792642993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Agarose\u2010Based Core\u2010Shell Scaffolds Facilitate Mammary Epithelial Tubulogenesis"],"prefix":"10.1002","volume":"114","author":[{"given":"Isabelle Inacay","family":"Crisostomo","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering UC Davis  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2665-1279","authenticated-orcid":false,"given":"Junjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7250-975X","authenticated-orcid":false,"given":"Jiandi","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering UC Davis  Davis California USA"},{"name":"Department of Chemical Engineering UC Davis  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010food\u2010063020\u2010123940"},{"key":"e_1_2_10_3_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Completes First Pre\u2010Market Consultation for Human Food Made Using Animal Cell Culture Technology \u201d2022 accessed June 21 2026 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