{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:59:56Z","timestamp":1790747996276,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"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":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic inflammation drives tissue dysfunction and aging, yet the dynamic interplay between persistent inflammatory signaling and structural deterioration remains difficult to study in human\u2010relevant systems. Here, an advanced long\u2010term human skin platform is presented that preserves native tissue architecture and epidermal, stromal, and immune\u2010associated molecular programs for up to 4 weeks. Time\u2010course RNA sequencing of 199 tissue samples from 20 donors revealed an early culture adaptation phase followed by stabilization of tissue\u2010associated transcriptional programs. Using this system, sustained IL\u201017\/IL\u201022 stimulation over 3 weeks induced chronic inflammatory transcriptional programs, progressive histopathological changes, and persistent secretion of IL\u20108, MCP\u20101, S100A8\/A9, and MMP\u20101, which was broadly suppressed by the Janus kinase inhibitor tofacitinib. In aged donor tissue, prolonged senolytic\u2010associated treatment attenuated inflammatory and remodeling pathways and reduced senescence\u2010associated secretory factors, including IL\u20106 and MMP\u20101, with significant treatment\u2010associated effects evident at Week 3 but not Week 1. Finally, ultraviolet B exposure triggered coordinated stress and inflammatory responses that were mitigated using topical sunscreen, demonstrating compatibility with environmental stress modeling and topical intervention. Together, these findings establish a versatile human skin platform for modeling chronic inflammation, aging\u2010associated tissue remodeling, and environmental stress, providing a translational framework for investigating skin tissue dysfunction and evaluating therapeutic interventions.<\/jats:p>","DOI":"10.1002\/advs.78035","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:32:16Z","timestamp":1790746336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010Term Human Skin Platform for Modeling Chronic Inflammation, Environmental Stress, and Therapeutic Intervention"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8216-8709","authenticated-orcid":false,"given":"Purnendu Kumar","family":"Sharma","sequence":"first","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"Schaafsma","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elysia","family":"Anderson","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Chiari","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Thompson","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9221-6659","authenticated-orcid":false,"given":"Erin","family":"Galt","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8574-3998","authenticated-orcid":false,"given":"Sunghoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7748-4312","authenticated-orcid":false,"given":"Jason","family":"Holsapple","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Hein","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey L.","family":"Coates","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade","family":"Michaud","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6142-7065","authenticated-orcid":false,"given":"Sabrina","family":"Zuccaro","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Kent","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Hinojosa","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-1703","authenticated-orcid":false,"given":"Kyung\u2010Jin","family":"Jang","sequence":"additional","affiliation":[{"name":"Outer Biosciences, Inc.  Malden Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.280"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2807"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3646"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010032713\u2010120225"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2000.tb06651.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu057"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010019\u20100675\u20100"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathol\u2010121808\u2010102144"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2010.10.005"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000599"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.005"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1704203"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a015370"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000371708"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.138.11.1462"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00759"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2016.09.015"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11030794"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2024.04.032"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201078292\u20104"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.4514"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2025.12.022"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2025.12.011"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2026.7074"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700701"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00028.2011"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11060959"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700865"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.040403.103635"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010026\u201002552\u20108"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05659"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a004911"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12783"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2125"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.12.007"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3712"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.006"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.12.1318"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.184"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155382"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102133.2008.08769.x"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.03.014"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12320"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2019.12.003"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867323666160418114600"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555\u20103298"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7897263"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12344"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.12.052"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.08.069"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104481"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpblue.2026.100004"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010025\u201001568\u2010y"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2017.12.023"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523\u20101747.ep12284412"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18527"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22083974"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2010.1054"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2026.117898"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.5402\/2012\/352135"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.70538"},{"key":"e_1_2_10_63_1","volume-title":"nf\u2010core\/rnaseq: Nf\u2010core\/Rnaseq v3.19.0 \u2013 Tungsten Turtle","author":"Patel H.","year":"2025"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010020\u20100439\u2010x"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3820"},{"key":"e_1_2_10_66_1","volume-title":"nf\u2010core\/Differentialabundance: V1.4.0\u20102023\u201011\u201027","author":"Wacker O.","year":"2023"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100550\u20108"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1101\/060012"},{"key":"e_1_2_10_70_1","article-title":"MSigDB Gene Sets for Multiple Organisms in a Tidy Data Format","volume":"1","author":"Dolgalev I.","year":"2026","journal-title":"R package version 26"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac757"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.78035","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.78035","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.78035","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:32:18Z","timestamp":1790746338000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.78035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":71,"alternative-id":["10.1002\/advs.78035"],"URL":"https:\/\/doi.org\/10.1002\/advs.78035","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2026-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e78035"}}