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However, the potential to program synthetic cells into self\u2010organized 3D collectives to replicate the structure and function of tissues has remained largely untapped. Here, self\u2010assembly properties are engineered into synthetic cells to form millimeter\u2010sized 3D lymphatic bottom\u2010up tissues (lymphBUTs) with mechanical adaptability, metabolic activity, and hierarchical microstructural organization. It is demonstrated that primary human immune cells spontaneously infiltrate and functionally integrate into these synthetic lymph nodes to form living tissue hybrids. Applying lymphBUTs, it is shown that structured 3D organization and mechanical support drives T cell activation and the application of lymphBUTs for ex vivo expansion of regulatory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells is demonstrated. The study highlights the functional integration of living and non\u2010living matter, advancing synthetic cell engineering toward 3D tissue structures.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202503498","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T07:34:38Z","timestamp":1761204878000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthetic Cell\u2010Based Tissues for Bottom\u2010Up Assembly of Artificial Lymphatic Organs"],"prefix":"10.1002","volume":"15","author":[{"given":"Anna","family":"Burgstaller","sequence":"first","affiliation":[{"name":"INM \u2013 Leibniz Institute for New Materials  Campus D2 2 66123 Saarbr\u00fccken Germany"},{"name":"Helmholtz Institute for Pharmaceutical Research Saarland Helmholtz Center for Infection Research  Campus E8 1 66123 Saarbr\u00fccken Germany"},{"name":"Center for Biophysics Saarland University  Campus Saarland 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Nink","sequence":"additional","affiliation":[{"name":"INM \u2013 Leibniz Institute for New Materials  Campus D2 2 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Walter","sequence":"additional","affiliation":[{"name":"INM \u2013 Leibniz Institute for New Materials  Campus D2 2 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick Angel Lopez","family":"Lopez","sequence":"additional","affiliation":[{"name":"INM \u2013 Leibniz Institute for New Materials  Campus D2 2 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin\u2010Fang","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Integrative Physiology and Molecular Medicine (CIPMM) Saarland University  66421 Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8015-3132","authenticated-orcid":false,"given":"Oskar","family":"Staufer","sequence":"additional","affiliation":[{"name":"INM \u2013 Leibniz Institute for New Materials  Campus D2 2 66123 Saarbr\u00fccken Germany"},{"name":"Helmholtz Institute for Pharmaceutical Research Saarland Helmholtz Center for Infection Research  Campus E8 1 66123 Saarbr\u00fccken Germany"},{"name":"Center for Biophysics Saarland University  Campus Saarland 66123 Saarbr\u00fccken Germany"},{"name":"Max Planck Bristol Centre for Minimal Biology Cantock's Close  Bristol BS8 1TS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1042\/ETLS20190120"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00686-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28422"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202303334"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-018-0174-9"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2017.11.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2020.08.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01440-5"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb4920"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121522"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","DOI":"10.1177\/15330338231204198","volume":"22","author":"Zhao D.","year":"2023","journal-title":"Technol. 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