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Biomaterials, including fibrinogen\u2010based collagen fleece (TachoSil) and fibrin glue, are ineffective for bile sealing. Synthetic sealants, including cyanoacrylate and polymer\u2010based materials, independent of coagulation, are inadequate for bile leakage management. Therefore, in the present study, a novel hydrogel\u2010based sealant (DCSN_100_25) is developed using 3 types of poly(ethylene glycol) (PEG) with a dual\u2010stage cross\u2010linking mechanism, termed the delayed cross\u2010linked single network (DCSN). This design facilitates rapid initial solidification followed by gradual network formation, ensuring immediate sealing and stable adhesion to the amputated liver tissue surface. Experiments using in vivo rat hepatectomy models demonstrated that DCSN_100_25 achieved hemostasis within 1 min, outperforming conventional sealants, such as SURGICEL and TachoSil, and effectively preventing both bleeding and bile leakage. Furthermore, in vivo safety assessments confirmed its safety profile, with PEG brushes remaining on the liver tissue and exhibiting minimal inflammation and no chronic liver damage. These findings suggest that DCSN_100_25 is a promising surgical sealant that effectively manages bile leakage and enhances hepatectomy safety.<\/jats:p>","DOI":"10.1002\/adhm.202503518","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T08:06:07Z","timestamp":1762157167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Novel Synthetic Hydrogel Sealant for Effective Prevention of Liver Resection\u2010Associated Bile Leakage"],"prefix":"10.1002","volume":"15","author":[{"given":"Kazuyoshi","family":"Matsubara","sequence":"first","affiliation":[{"name":"Division of Vascular Surgery, Department of Surgery, Graduate School of Medicine The University of Tokyo 7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20108655 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7442-9454","authenticated-orcid":false,"given":"Shohei","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biotechnology School of Engineering The University of Tokyo 7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20138656 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5933-8677","authenticated-orcid":false,"given":"Hiroyuki","family":"Kamata","sequence":"additional","affiliation":[{"name":"Department of Bioengineering School of Engineering The University of Tokyo 7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20108656 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Almog","family":"Gur","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biotechnology School of Engineering The University of Tokyo 7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20138656 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayano","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Bioengineering School of Engineering The University of Tokyo 7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20108656 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Pathology Yaizu City Hospital 1000 Dobara Yaizu\u2010shi Shizuoka 425\u20100055 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuyuki","family":"Hoshina","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Department of Surgery, Graduate School of Medicine The University of Tokyo 7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20108655 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takamasa","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biotechnology School of Engineering The University of Tokyo 7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20138656 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-003-2712-2"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000324042"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hpb.12322"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2015.10.006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000103661"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/0971-3026.95398"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1510\/icvts.2009.212175"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2010.09.017"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.3c00378"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.1053"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ma100176f"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.01.043"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2022.01.016"},{"key":"e_1_2_9_14_1","first-page":"3389","volume":"7","author":"Zhang Y.","year":"2019","journal-title":"Front Chem"},{"key":"e_1_2_9_15_1","volume-title":"Bioconjugate Techniques","author":"Hermanson G. 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