{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:57:54Z","timestamp":1782280674634,"version":"3.54.5"},"posted":{"date-parts":[[2025,8,21]]},"group-title":"Bioengineering","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21 EB030834"],"award-info":[{"award-number":["R21 EB030834"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 HL160540"],"award-info":[{"award-number":["R01 HL160540"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["GRFP DGE1840340"],"award-info":[{"award-number":["GRFP DGE1840340"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent gastrointestinal inflammation that requires long-term therapeutic intervention. While anti-TNF-\u03b1 monoclonal antibodies (mAbs) are effective in maintaining remission in IBD, systemic delivery is associated with immunosuppression, poor targeting efficiency, and high cost. To address these limitations, we developed a synthetic mucin-based hydrogel for localized delivery of TNF-\u03b1-targeting mAbs. Mucins are heavily glycosylated biopolymers that naturally bind antimicrobial and anti-inflammatory proteins, making them well-suited for local biologic drug delivery at mucosal sites. Synthetic mucin-based hydrogels were formed by crosslinking mucin harvested from porcine small intestine with a 4-arm PEG-thiol and loaded with mAbs to evaluate biocompatibility, antibody release kinetics, and therapeutic efficacy.\n                  <jats:italic>In vitro<\/jats:italic>\n                  studies confirmed cytocompatibility of mucin-based hydrogels and demonstrated sustained release of full-length IgG antibodies, with enhanced release under proteolytic conditions simulating the gastrointestinal environment. Moreover, mucin-based hydrogels alone were found to modulate macrophage activation and dampen inflammation in LPS-stimulated macrophages. Treatment of LPS-stimulated macrophages with mAb-loaded hydrogels reduced pro-inflammatory cytokine production and macrophage activation, confirming retention of mAb bioactivity. Compared to antibodies administered in solution,\n                  <jats:italic>in vivo<\/jats:italic>\n                  biodistribution studies revealed greater absorption of antibodies when loaded in mucin-based hydrogels and administered via enema in TNBS-induced colitis mice likely due to enhanced adhesion to mucosal epithelium and slowed intestinal clearance. This study demonstrates the potential of mucin-based hydrogels as a platform for local mAb delivery in IBD, enabling targeted immunosuppression while minimizing systemic exposure.\n                <\/jats:p>","DOI":"10.1101\/2025.08.15.670558","type":"posted-content","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T21:10:17Z","timestamp":1755810617000},"source":"Crossref","is-referenced-by-count":0,"title":["Synthetic Mucus Biomaterials Enable Localized Therapeutic Antibody Delivery in Inflammatory Bowel Disease"],"prefix":"10.64898","author":[{"given":"Taj","family":"Yeruva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Kaluzienski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Louisthelmy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadin","family":"Doski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Maisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg A.","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025082307450917000_2025.08.15.670558v1.1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30587"},{"key":"2025082307450917000_2025.08.15.670558v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-006-1995-7"},{"key":"2025082307450917000_2025.08.15.670558v1.3","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200565160-00002"},{"key":"2025082307450917000_2025.08.15.670558v1.4","doi-asserted-by":"publisher","DOI":"10.5009\/gnl16308"},{"key":"2025082307450917000_2025.08.15.670558v1.5","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007301623"},{"key":"2025082307450917000_2025.08.15.670558v1.6","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.02.070"},{"key":"2025082307450917000_2025.08.15.670558v1.7","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e328354567f"},{"key":"2025082307450917000_2025.08.15.670558v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.138"},{"key":"2025082307450917000_2025.08.15.670558v1.9","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.3c00050"},{"key":"2025082307450917000_2025.08.15.670558v1.10","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa5657"},{"key":"2025082307450917000_2025.08.15.670558v1.11","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202200281"},{"key":"2025082307450917000_2025.08.15.670558v1.12","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303207"},{"key":"2025082307450917000_2025.08.15.670558v1.13","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.058453"},{"key":"2025082307450917000_2025.08.15.670558v1.14","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000117"},{"key":"2025082307450917000_2025.08.15.670558v1.15","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ado8222"},{"key":"2025082307450917000_2025.08.15.670558v1.16","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2021.1939605"},{"key":"2025082307450917000_2025.08.15.670558v1.17","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.1c19250"},{"key":"2025082307450917000_2025.08.15.670558v1.18","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.0c03645"},{"key":"2025082307450917000_2025.08.15.670558v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37559"},{"key":"2025082307450917000_2025.08.15.670558v1.20","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.202400359"},{"key":"2025082307450917000_2025.08.15.670558v1.21","doi-asserted-by":"publisher","DOI":"10.1039\/c9sm01715a"},{"key":"2025082307450917000_2025.08.15.670558v1.22","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1752-5_18"},{"key":"2025082307450917000_2025.08.15.670558v1.23","unstructured":"Dash, S. 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