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In this study we investigated whether the presence of phage itself could help repair delayed\u2010healing wounds in diabetic mice. Three strains of phage that target\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    ,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , and\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage\u2010cocktail) was encapsulated in a porous hydrogel dressing made with three\u2010dimensional printing. The phage\u2010cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full\u2010thickness skin wound in diabetic mice. The phage\u2010cocktail dressing released 1.7%\u20135.7% of the phages embedded in 24\u2009h, and reduced between 37%\u201379% of the surface bacteria compared with the blank dressing (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;.05). The phage\u2010cocktail dressing exhibited no sign of cytotoxicity after 3\u2009days (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;.05). In vivo studies showed that 14\u2009days after incision, the full\u2010thickness wound treated with a phage\u2010cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;.01). Histological analysis showed that the structure of the skin layers in the group treated with phage\u2010cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage\u2010cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re\u2010epithelialization (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;.05). The slow\u2010released phage has demonstrated positive effects in repairing diabetic skin wounds.\n                  <\/jats:p>","DOI":"10.1002\/jbm.a.37728","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T03:45:19Z","timestamp":1714967119000},"page":"1846-1859","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Bacteriophage\u2010cocktail hydrogel dressing to prevent multiple bacterial infections and heal diabetic ulcers in mice"],"prefix":"10.1002","volume":"112","author":[{"given":"Sheng\u2010Jie","family":"Shiue","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital Taipei Medical University  Taipei Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Shun","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital Taipei Medical University  Taipei Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Hsien","family":"Chiang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Chemical Engineering National Taipei University of Technology  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1401-1603","authenticated-orcid":false,"given":"Hsin\u2010Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Chemical Engineering National Taipei University of Technology  Taipei Taiwan"},{"name":"Graduate Institute of Biochemical and Biomedical Engineering National Taipei University of Technology  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1615439"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina57101072"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.37757\/MR2021.V23.N3.8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-020-01818-x"},{"issue":"10","key":"e_1_2_8_6_1","first-page":"20","article-title":"Antibiotics and the rise of superbugs","volume":"18","author":"Casey G","year":"2012","journal-title":"Nursing"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-020-01820-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.114727"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjm-2017-0030"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2018.00561","article-title":"Liposome entrapment of bacteriophages improves wound healing in a diabetic mouse MRSA infection","volume":"9","author":"Chhibber S","year":"2018","journal-title":"Front Microbiol"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2016.25.7.S27"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12056"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2017.03.029"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2018.12.004"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100656"},{"key":"e_1_2_8_16_1","article-title":"Bacteriophage interactions with epithelial cells: therapeutic implications","volume":"11","author":"G\u00f3rski A","year":"2020","journal-title":"Front. 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