{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:53:01Z","timestamp":1792162381567,"version":"4.4.0"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM162195"],"award-info":[{"award-number":["R35GM162195"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM007863"],"award-info":[{"award-number":["GM007863"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The foreign body response (FBR) is an immune reaction from the host to any foreign material that makes it beyond barrier tissues, resulting in the recruitment of immune cells and fibroblasts. The FBR to medical implants can lead to degradation and encapsulation, affecting their efficacy, lifespan, and safety. A key protein involved in myriad inflammatory responses is S100A9, inducing inflammatory cytokine secretion and leukocyte chemotaxis. Inspired by recent studies indicating that inhibiting systemic\u00a0S100A9 in mice results in a diminished FBR, we have identified S100A9 as a potential locally\u2010targetable molecule to reduce FBR. Paquinimod is a potential candidate for local drug delivery, as it is an experimentally available S100A9 inhibitor that has been investigated in autoimmunity and fibrotic disease. We first investigated paquinimod's effects on neutrophil and macrophage cell lines in\u00a0vitro and found reduced inflammatory cytokine expression. To leverage these effects of paquinimod and assess its ability to mitigate the FBR, we created wet\u2010spun PCL fibrous scaffolds loaded with varied doses of paquinimod. With these scaffolds, we demonstrate successful loading and release of paquinimod, with higher loading leading to decreased cell invasion and reduced deposition of collagen. These findings suggest paquinimod\u2010mediated inhibition of S100A9 activity can modulate inflammation in the FBR through decreased cytokine release and cell recruitment and identify S100A9 as a promising target to locally mediate the FBR to medical implants.<\/jats:p>","DOI":"10.1002\/jbm.a.70168","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:36:17Z","timestamp":1791005777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of Paquinimod\u2010Loaded Implants to Modulate the Foreign Body Response"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6931-7386","authenticated-orcid":false,"given":"Cole","family":"Weber","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Vanderzee","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Danon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor Michigan USA"},{"name":"Cellular and Molecular Biology Program University of Michigan Medical School  Ann Arbor Michigan USA"},{"name":"Medical Scientist Training Program University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7465-2797","authenticated-orcid":false,"given":"Shivanie","family":"Kodikalla","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4680-2493","authenticated-orcid":false,"given":"Aaron H.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor Michigan USA"},{"name":"Cellular and Molecular Biology Program University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44385-025-00053-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2007.11.004"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1533\/9780857090843.2.207"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0098578"},{"key":"e_1_2_11_6_1","unstructured":"\u201cDefinition of Neutrophil\u2014NCI Dictionary of Cancer Terms\u2014NCI \u201d(2011) https:\/\/www.cancer.gov\/publications\/dictionaries\/cancer\u2010terms\/def\/neutrophil."},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37983"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ma8095269"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181bf7f26"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmod.2018.04.002"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/193229681100500505"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S522469"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.05.051"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(01)00291-5"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.10.019"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201700370"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.31088"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13122077"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-025-00156-1"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2115857119"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/193229680800200504"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aec7053"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123110"},{"key":"e_1_2_11_24_1","first-page":"205","article-title":"Implantable Drug Delivery Systems and Foreign Body Reaction: Traversing the Current Clinical Landscape","volume":"8","author":"Fayzullin A.","year":"2021","journal-title":"Bioengineering. Multidisciplinary Digital Publishing Institute"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2019.08.010"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.659033"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines5040034"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52023-z"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.01.032"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0203228"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2016.04.006"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33493"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113971"},{"key":"e_1_2_11_34_1","unstructured":"\u201cPCL Polymers for Long\u2010Acting Drug Delivery Solutions\u2014BOC Sciences \u201d(2026) https:\/\/www.bocsci.com\/research\u2010area\/pcl\u2010polycaprolactone\u2010for\u2010long\u2010term\u2010drug\u2010release\u2010and\u2010tissue\u2010engineering\u2010applications.html."},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.03.049"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mex.2023.102416"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-8-27"},{"key":"e_1_2_11_38_1","article-title":"Samples in Many Cell\u2010Based Experiments Are Matched\/Paired but Taking This Into Account Does Not Always Increase Power of Statistical Tests for Differences in Means","volume":"35","author":"Zweifach A.","year":"2023","journal-title":"Molecular Biology of the Cell"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198943"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-54090-0_7"},{"key":"e_1_2_11_41_1","unstructured":"\u201cLy6g Lymphocyte Antigen 6 Family Member G [Mus musculus(House Mouse)]\u2014Gene\u2014NCBI [Internet] \u201d(2026) https:\/\/www.ncbi.nlm.nih.gov\/gene\/546644."},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2010.08.019"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2006.10.013"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-019-0377-5"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1225578"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.11.029"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2022.113405"},{"key":"e_1_2_11_48_1","first-page":"603","article-title":"Stimulation and Priming of Human Neutrophils by IL\u20101 Alpha and IL\u20101 Beta: Complete Inhibition by IL\u20101 Receptor Antagonist and no Interaction With Other Cytokines","volume":"23","author":"Yagisawa M.","year":"1995","journal-title":"Experimental Hematology"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309897"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01259"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63265-8"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)00013-3"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06640-7"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-025-03765-3"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082155"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12167"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016295"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.022"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukarGeneExpr.v20.i2.10"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2020.06.005"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.12703\/P6-97"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.01.006"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.11.044"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2017.05.001"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22102"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17629-z"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2409852122"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.0c00515"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31359-9"}],"container-title":["Journal of Biomedical Materials Research Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.70168","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbm.a.70168","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.70168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:39:28Z","timestamp":1792161568000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.a.70168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":68,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/jbm.a.70168"],"URL":"https:\/\/doi.org\/10.1002\/jbm.a.70168","archive":["Portico"],"relation":{},"ISSN":["1549-3296","1552-4965"],"issn-type":[{"value":"1549-3296","type":"print"},{"value":"1552-4965","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70168"}}