{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:19:18Z","timestamp":1789708758081,"version":"4.0.1"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"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":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The foreign body response (FBR) to biomaterials is primarily driven by macrophages. At implant sites, macrophages often fuse into destructive foreign body giant cells (FBGCs), yet FBGC\u2010targeted treatments for FBR remain elusive. To fill this knowledge gap, a novel microscale core\u2013shell hydrogel 3D model is developed using heterogeneous alginate\u2010collagen microcapsules with varying matrix stiffness to culture macrophages. This 3D model more closely replicates in vivo conditions. This model is further used to investigate the effects of stiffness and TRPV4 (transient receptor potential vanilloid 4) on FBGC formation. Stiffer 3D hydrogel robustly enhances FBGC formation and F\u2010actin production in wild\u2010type macrophages compared to softer hydrogel, with IL4 and GMCSF priming amplifying these effects. Crucially, TRPV4\u2010null macrophages exhibit reduced FBGC formation and F\u2010actin production, underscoring TRPV4's role in mechanosensing. Further, the N\u2010terminal residues 1\u2013130 of TRPV4 are identified as critical for FBGC formation and F\u2010actin generation. RNA\u2010seq data reveal that TRPV4 modulates inflammatory, fibrotic, and mechanosensitive gene expression in macrophages in 3D environments, offering insights into how TRPV4 governs FBR. Overall, the data establish this 3D model as a powerful tool for biomaterials research and highlight TRPV4 as a key player in macrophage mechanosensing and FBGC formation in 3D condition.<\/jats:p>","DOI":"10.1002\/adhm.202501614","type":"journal-article","created":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T07:08:34Z","timestamp":1758352114000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Novel Core\u2013Shell Hydrogel 3D Model for Studying Macrophage Mechanosensing and Foreign Body Giant Cell Formation"],"prefix":"10.1002","volume":"15","author":[{"given":"Manisha","family":"Mahanty","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Science University of Maryland  College Park MD 20742 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenquan","family":"Ou","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering University of Maryland  College Park MD 20742 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Maryland  College Park MD 20742 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S","family":"Bromberg","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine  Baltimore MD 21201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"He","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering University of Maryland  College Park MD 20742 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6481-392X","authenticated-orcid":false,"given":"Shaik O.","family":"Rahaman","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science University of Maryland  College Park MD 20742 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,20]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005568"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbw006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0000000000001193"},{"key":"e_1_2_9_4_1","first-page":"82","volume":"16","author":"Velnar T.","year":"2016","journal-title":"Bosn J. Basic Med. Sci."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2007.11.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1715626"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.1320"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4290"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scirobotics.aax7043"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abd4077"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.04.016"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-18603-0_7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2015.00067"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.02.034"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.014597"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.570195"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.07.020"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002761"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2015.11.083"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2807"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201439246"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.01.038"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2007.11.004"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb8471"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.09.024"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.34104"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4094"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3904"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2019.08.010"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.8b00444"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122855"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-54215-2_12"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2009.10.002"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1418.012"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235619100"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319569111"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI75331"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0ib00034e"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00187.2016"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004276"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00221.2007"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005333107"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.08.002"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.10.045"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13306"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202102219"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.7b00834"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201503047"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3lc50678a"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw419"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2486-6"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt285"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1039\/C2TB00058J"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.7b00824"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104799"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw419"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63265-8"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.8.823"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220231110"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-6149-9"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.41075"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1490315"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00777-1"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14040266"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23482-5"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.00369.x"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202501614","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202501614","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202501614","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:25:00Z","timestamp":1768897500000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202501614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,20]]},"references-count":67,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/adhm.202501614"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202501614","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,20]]},"assertion":[{"value":"2025-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01614"}}