{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:04:17Z","timestamp":1788923057156,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010033","name":"Queen Margaret University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Wound Journal"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetic foot ulcers (DFUs) are a major cause of infection, hospitalisation, and amputation. Collagen\u2010based dressings\u2014especially collagen combined with oxidised regenerated cellulose (ORC)\u2014are proposed to improve healing by modulating matrix metalloproteinases (MMPs), stabilising the extracellular matrix (ECM), and tempering inflammation; some formulations also include antimicrobial or bioactive adjuncts. We conducted a systematic review of randomised controlled trials (RCTs) following Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses (PRISMA) guidance. Adults with DFUs were eligible. Interventions included collagen\u2010alone or collagen\u2010combination dressings (e.g., collagen\u2013oxidised regenerated cellulose [collagen\u2013ORC]\/silver, collagen\u2013chitosan) versus standard of care (SOC) or alternative dressings. To ensure comparable outcomes, the quantitative synthesis was pre\u2010specified and restricted to complete wound closure (yes\/no, intention\u2010to\u2010treat [ITT]) from collagen\u2010combination RCTs with aligned constructs; other outcomes were synthesised narratively. Meta\u2010analyses were performed in Microsoft Excel using Mantel\u2013Haenszel methods for risk ratios (RR) with a fixed\u2010effect primary model and DerSimonian\u2013Laird random\u2010effects sensitivity analysis; heterogeneity was summarised with Cochran's Q, between\u2010study variance (\n                    <jats:italic>\u03c4<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    ), and Higgins'\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    statistic (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    ), and a 95% prediction interval was reported for random\u2010effects. (Protocol not registered). Six studies (five randomized controlled trials and one single\u2010blinded non\u2010randomized comparative study; total\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009314) met inclusion. In a focused meta\u2010analysis of the two collagen\u2010combination RCTs, treatment was associated with a higher probability of complete wound closure versus control (RR 1.69, 95% confidence interval [CI] 1.05\u20132.72;\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090%). One assessor\u2010blinded RCT of collagen alone reported higher 12\u2010week closure versus a placebo dressing and was not pooled due to heterogeneity. Across studies, signals also favored collagen\u2010based care for earlier area reduction and, in one trial, fewer infection\u2010related withdrawals; mechanistic work showed reductions in MMP\u20109\/TIMP\u20102. However, most trials were small and single\u2010centre, comparators and adjuncts varied, follow\u2010up was short (~8 days\u201324 weeks, clinical endpoints typically 4\u201320 weeks), outcome definitions were non\u2010standardised, and key confounders (off\u2010loading, infection management, vascular status, glycaemic control) were inconsistently addressed. Collagen\u2010based dressings\u2014particularly collagen\u2010combination formulations\u2014appear to improve complete closure when added to the standard of care (SOC) for diabetic foot ulcers (DFUs), but the evidence is limited by study size, heterogeneity, and risk of bias. Larger, prospectively registered, multicentre RCTs with standardised outcomes and longer follow\u2010up are needed to define clinical and cost\u2010effectiveness and to identify which patients benefit most. Collagen\u2013ORC dressings show promise as an adjunctive treatment for DFUs by influencing the inflammatory microenvironment and supporting tissue repair. However, the certainty of the current evidence remains limited, highlighting the need for further high\u2010quality randomised studies.\n                  <\/jats:p>","DOI":"10.1111\/iwj.70782","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T04:41:26Z","timestamp":1763440886000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Collagen\u2013\n                    <scp>ORC<\/scp>\n                    Versus Standard Treatment in Diabetic Foot Ulcers: A Systematic Review and Meta\u2010Analysis of Randomised Trials"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1196-539X","authenticated-orcid":false,"given":"George","family":"Theodorakopoulos","sequence":"first","affiliation":[{"name":"Wound and Foot Specialist  Athens Greece"},{"name":"Technological Educational Institute of Patras  Patras Greece"},{"name":"Queen Margaret University  Edinburgh UK"},{"name":"University of West Attica  Aigaleo Greece"},{"name":"University of Thessaly  Larisa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Southwestern Academic Limb Salvage Alliance (SALSA)  Los Angeles California USA"},{"name":"Center to Stream Healthcare in Place (C2SHiP)  Alexandria Virginia USA"},{"name":"Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1615439"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13569"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc22\u20100621"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2020.1305"},{"key":"e_1_2_11_6_1","unstructured":"Podimetrics The True Cost of Diabetic Foot Complications 2022 accessed May 4 2025 https:\/\/podimetrics.com\/the\u2010true\u2010cost\u2010of\u2010diabetic\u2010foot\u2010complications\/."},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10198\u2010022\u201001465\u20106"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.13372"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semvascsurg.2019.02.001"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.13133"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1067\u20102516(07)60001\u20105"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v11.i8.1684"},{"key":"e_1_2_11_13_1","unstructured":"International Working Group on the Diabetic Foot (IWGDF) IWGDF Guidelines on the Prevention and Management of Diabetic Foot Disease 2019 accessed May 3 2025 https:\/\/iwgdfguidelines.org."},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2017.26.1.20"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2023.32.6.383"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2017.08.003"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3280"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.12414"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(05)67700\u20108"},{"key":"e_1_2_11_20_1","first-page":"3197","article-title":"The Metabolic Characteristics of Patients at Risk for DFU","volume":"16","author":"Li X.","year":"2023","journal-title":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy"},{"issue":"22","key":"e_1_2_11_21_1","first-page":"4267","article-title":"Structure and Function of Human Matrix Metalloproteinases","volume":"77","author":"Laronha H.","year":"2020","journal-title":"Cellular and Molecular Life Sciences"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464\u20105491.2008.02408.x"},{"issue":"5","key":"e_1_2_11_23_1","first-page":"361","article-title":"Expression of MMPs and Their Inhibitors in Wounds of Diabetic and Non\u2010Diabetic Patients","volume":"20","author":"Lobmann R.","year":"2006","journal-title":"Journal of Diabetes and Its Complications"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524\u2010475X.2009.00466.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9040174"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.13679"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.5195\/jmla.2018.345"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.21501"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.5.855"},{"key":"e_1_2_11_30_1","volume-title":"Randomised Controlled Trial Checklist","author":"Critical Appraisal Skills Programme (CASP)","year":"2023"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107861"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2020.29.Sup3.S13"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12020"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2007.03.006"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"}],"container-title":["International Wound Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iwj.70782","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:11:07Z","timestamp":1764029467000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iwj.70782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":34,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/iwj.70782"],"URL":"https:\/\/doi.org\/10.1111\/iwj.70782","archive":["Portico"],"relation":{},"ISSN":["1742-4801","1742-481X"],"issn-type":[{"value":"1742-4801","type":"print"},{"value":"1742-481X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70782"}}