{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:38:14Z","timestamp":1791229094231,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030E_202429"],"award-info":[{"award-number":["310030E_202429"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["205321_204318"],"award-info":[{"award-number":["205321_204318"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["IZJFZ3_202474"],"award-info":[{"award-number":["IZJFZ3_202474"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lymphatic vessels play an important role in pathologies, such as cardiovascular diseases or metastasizing cancers. However, mechanisms involved in cancer metastasis through lymphatic vessels remain largely unknown. In this study, we engineer 3D lymphatic microvessels by co\u2010culturing human lymphatic endothelial cells (hLECs) with human bone marrow\u2010derived mesenchymal stromal cells (hBM\u2010MSCs) in synthetic and fully defined enzymatically crosslinked poly(ethylene glycol) (TG\u2010PEG) hydrogels. By tuning the stiffness of the TG\u2010PEG scaffolds, varying seeding densities of hLECs and hBM\u2010MSCs, and stimulation with lymphangiogenic factors, we identify suitable culture conditions for lymphatic network formation. Immunocytochemistry\u2010based evaluations reveal the formation of lymphatic structures consisting of hLECs that are ensheathed with basement membrane extracellular matrix components and hBM\u2010MSCs, which express perivascular\u2010specific markers. Finally, the addition of non\u2010invasive MCF\u20107 and invasive MDA\u2010MB\u2010231 breast cancer cells to the forming lymphatic structures shows a clear negative influence of cancer cells on the length of lymphatic networks. Moreover, we observe a closer association of invasive than of non\u2010invasive cancer cells with the lymphatic networks, which can be inhibited by blocking of CCL21. Our findings present a promising approach to investigate the cancer microenvironment, as our model can serve as a tool to study physiological lymphangiogenesis and pathological phenomena in vitro.<\/jats:p>","DOI":"10.1002\/adhm.202503325","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T07:12:56Z","timestamp":1769065976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bioengineered Lymphatic Vessels in Synthetic Matrices to Study Breast Cancer Cell Functions"],"prefix":"10.1002","volume":"15","author":[{"given":"Rodi","family":"Odabasi","sequence":"first","affiliation":[{"name":"Department of Obstetrics, University Hospital Zurich University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Krattiger","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, University Hospital Zurich University of Zurich  Zurich Switzerland"},{"name":"Department Research University Center for Dental Medicine Basel UZB University of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalini","family":"Kanari","sequence":"additional","affiliation":[{"name":"University Children's Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira A.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, University Hospital Zurich University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas O.","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, University Hospital Zurich University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Tibbitt","sequence":"additional","affiliation":[{"name":"Macromolecular Engineering Laboratory Department of Mechanical and Process Engineering ETH Zurich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Halin","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences Department of Chemistry and Applied Biosciences ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ehrbar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, University Hospital Zurich University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"World Health Organisation.The top 10 causes of death(2020) https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/the\u2010top\u201010\u2010causes\u2010of\u2010death."},{"key":"e_1_2_9_3_1","unstructured":"C.Junker \u201cDeath and Its Main Causes in Switzerland \u201d Bundesamt f\u00fcr Statistik (BFS): Neuch\u00e2tel 8 (2018)."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1098"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2011"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21496"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201044133\u2010x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2018.08.001"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04480"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.36"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838140"},{"key":"e_1_2_9_12_1","first-page":"12","article-title":"Buttons and Zippers: Endothelial Junctions in Lymphatic Vessels","volume":"12","author":"Baluk P.","year":"2022","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(01)00150-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1235812"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2015.3486"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.846936"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13036\u2010018\u20100122\u20107"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2021.08.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010018\u20102939\u20100"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12793"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006894"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2101931118"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202000195"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.11.027"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.025"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12730"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12195\u2010023\u201000780\u20100"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2017.0760"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm070228f"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.11.082"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121483"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010024\u201006935\u20107"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201845964"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202301142"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201500795"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201067289\u20108"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201910282"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1013"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206036109"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1689"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.153033"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010025\u201008724\u20106"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00039.2021"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201010\u20100896"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/84643"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101321108"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.3.1230"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e19215"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010015\u20100306\u20104"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21855"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057110392995"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102359"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202209476"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab091"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202503325","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202503325","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202503325","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T08:58:05Z","timestamp":1775638685000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202503325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":53,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/adhm.202503325"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202503325","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"2025-07-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03325"}}