{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:00:14Z","timestamp":1790503214758,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Anastomotic leakage continues to be a severe and prevalent complication in colorectal surgery, leading to elevated morbidity and mortality rates despite modern advancements in surgical and perioperative care. To address this persistent clinical challenge, the aim of the present study was to engineer a biocompatible poly(lactic\u2010co\u2010glycolic acid) (PLGA) matrix designed for the sustained release of melatonin, subsequently evaluating its therapeutic efficacy in promoting colon anastomotic repair. Seventy\u2010two male Wistar albino rats were randomly assigned to three experimental groups: anastomosis (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a024); anastomosis + matrix (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a024); and anastomosis + melatonin\u2010loaded matrix (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a024). Anastomotic segments were harvested on postoperative days 3 and 7, and colonic bursting pressure was measured as a functional indicator of anastomotic integrity. The melatonin\u2010loaded matrix significantly enhanced anastomotic healing on postoperative day 7. Melatonin delivery: (1) markedly reduced the gene expression of pro\u2010inflammatory cytokines; (2) modulated\n                    <jats:italic>iNOS<\/jats:italic>\n                    ,\n                    <jats:italic>COX\u20102<\/jats:italic>\n                    and\n                    <jats:italic>MPO<\/jats:italic>\n                    expression on both days 3 and 7; (3) decreased\n                    <jats:italic>HO\u20101<\/jats:italic>\n                    and catalase expression on day 7; (4) promoted collagen synthesis; (5) enhanced collagen deposition through upregulation of\n                    <jats:italic>Arg\u20101<\/jats:italic>\n                    ; and (6) regulated\n                    <jats:italic>ADAM10<\/jats:italic>\n                    and\n                    <jats:italic>ADAM17<\/jats:italic>\n                    gene expression. These results are correlated with the histological analysis findings. Collectively, controlled release of melatonin via a PLGA\u2010based biomaterial matrix promotes colon anastomosis healing. This strategy represents a promising translational approach for reducing postoperative anastomotic complications.\n                  <\/jats:p>","DOI":"10.1113\/ep093987","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:55:48Z","timestamp":1790502948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing colonic anastomotic healing with a novel melatonin\u2010loaded PLGA matrix"],"prefix":"10.1113","author":[{"given":"Ufuk","family":"Demir","sequence":"first","affiliation":[{"name":"Department of Physiology Faculty of Medicine, \u00c7anakkale Onsekiz Mart University  \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zekiye G\u00fclfem","family":"Yurtgezen","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology Faculty of Medicine, \u00c7anakkale Onsekiz Mart University  \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1127-9380","authenticated-orcid":false,"given":"G\u00fclfem","family":"Erbil","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine, \u00c7anakkale Onsekiz Mart University  \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oru\u00e7 Numan","family":"G\u00f6k\u00e7e","sequence":"additional","affiliation":[{"name":"Department of General Surgery Faculty of Medicine, \u00c7anakkale Onsekiz Mart University  \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayhan","family":"Oral","sequence":"additional","affiliation":[{"name":"Department of Physico\u2010Chemistry Faculty of Science, \u00c7anakkale Onsekiz Mart University  \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1406-5473","authenticated-orcid":false,"given":"Metehan","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine, \u00c7anakkale Onsekiz Mart University  \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"issue":"8","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.3390\/ijms21082678","article-title":"Matrix Metalloproteinases: How Much Can They Do?","volume":"21","author":"\u00c5gren M. 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