{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:35:23Z","timestamp":1793878523283,"version":"4.7.0"},"reference-count":71,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2025,6,22]],"date-time":"2025-06-22T00:00:00Z","timestamp":1750550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,22]],"date-time":"2025-06-22T00:00:00Z","timestamp":1750550400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Bone healing is a multifaceted scenario with tightly orchestrated sequences that decide upon successful bone fracture healing or nonunion. In this context, the immune system, particularly the impact of macrophages on mesenchymal stromal cell (MSC) recruitment and differentiation, cannot be overemphasized. Further adding to the complexity, fracture healing is not only governed by chemical signals but strongly depends on mechanical stimulation. Here, an in\u2010house built bioreactor is used to culture THP\u20101 macrophages, stimulated with lipopolysaccharide and interferon\u2010gamma (M(LPS)) or interleukin 4 (M(IL\u20104)) in fibrin hydrogels under compression and shear. Subsequently, MSC\u2010pellets are cultured in conditioned media, derived from macrophages, and analyzed for chondrogenic or osteogenic gene expression after 9 days. In M(IL\u20104) conditions under mechanical load, expression of\n                    <jats:italic>IL1B, IL6, TNF, IL10, CCL18, CD163<\/jats:italic>\n                    , and\n                    <jats:italic>CD206<\/jats:italic>\n                    is increased compared to the static condition. In MSCs, osteogenic genes\n                    <jats:italic>RUNX2<\/jats:italic>\n                    and\n                    <jats:italic>ALPL<\/jats:italic>\n                    as well as chondrogenic genes\n                    <jats:italic>ACAN<\/jats:italic>\n                    and\n                    <jats:italic>COL2A1<\/jats:italic>\n                    are increased in conditions treated with a medium derived from mechanically stimulated macrophages. The results suggest that culture in fibrin and under loading induces a complex macrophage polarization phenotype which affects processes during endochondral ossification in human MSC.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202500706","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T02:54:00Z","timestamp":1750647240000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Conditioned Media from Mechanically Stimulated Macrophages Upregulate Osteogenic Genes in Human Mesenchymal Stromal Cells"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9374-0275","authenticated-orcid":false,"given":"Anne G\u00e9raldine","family":"Guex","sequence":"first","affiliation":[{"name":"AO Research Institute Davos  Davos 7270 Switzerland"},{"name":"Department Research University Center for Dental Medicine Basel UZB University of Basel  Basel 4058 Switzerland"},{"name":"Department of Biomedicine University of Basel  Basel 4031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7921-1166","authenticated-orcid":false,"given":"Ursula","family":"Menzel","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos  Davos 7270 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7446-4188","authenticated-orcid":false,"given":"Yann","family":"Ladner","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos  Davos 7270 Switzerland"},{"name":"Institute for Biomechanics ETH Zurich  Zurich 8008 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3285-0419","authenticated-orcid":false,"given":"Angela R.","family":"Armiento","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos  Davos 7270 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9538-1517","authenticated-orcid":false,"given":"Martin J.","family":"Stoddart","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos  Davos 7270 Switzerland"},{"name":"Department of Orthopedics and Trauma Surgery Medical Center\u2010Albert\u2010Ludwigs\u2010University of Freiburg Faculty of Medicine  79110 Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,22]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.081003"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2011.03.031"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.08.017"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2422"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-024-00869-z"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.535"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-018-0458-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-19-7540-0_50"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-019-02302-4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41526-023-00293-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41526-018-0057-9"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/os.14026"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/os.12885"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1040638716679861"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01501-9"},{"key":"e_1_2_8_16_1","volume":"11","author":"Jia Y.","year":"2023","journal-title":"Front. Bioengineer. Biotechnol."},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/20417314231172573"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2025.111786"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20230"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-019-0092-2"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202400581"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.2c00330"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.2210"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2009.00780.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.03.002"},{"key":"e_1_2_8_26_1","volume":"11","author":"Wang B.","year":"2020","journal-title":"Front. Immunol."},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00383"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-71031-5_5"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107092"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2009.0262"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018501108"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.05.001"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102884"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201801106"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.11.011"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000491742"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2011.03.055"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152324099"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108881"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2019.112721"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.09.030"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.05.027"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150835"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.09.024"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.5.2887"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2022.100303"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/6871269"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1TB00898F"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114566"},{"key":"e_1_2_8_50_1","volume":"10","author":"Lee M.","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-024-03616-8"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.767319"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319569111"},{"key":"e_1_2_8_54_1","first-page":"198","author":"Liu H.","year":"2024","journal-title":"J. Bone Miner. Res."},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20220147"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201488856"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2014.0096"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094785"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1354479"},{"key":"e_1_2_8_60_1","volume":"9","author":"Lu D.","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202001502"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202303814"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12907"},{"key":"e_1_2_8_64_1","first-page":"65","volume":"46","author":"Gong L.","year":"2016","journal-title":"Ann. Clin. Lab. Sci."},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-017-2598-8"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-023-00918-9"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijos.2012.33"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.06.013"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-1578-1"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2839-3_6"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2839-3_9"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202500706","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202500706","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202500706","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:19:33Z","timestamp":1793877573000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202500706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,22]]},"references-count":71,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/adhm.202500706"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202500706","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,22]]},"assertion":[{"value":"2025-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2500706"}}