{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:05:22Z","timestamp":1791821122564,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Novel antimicrobial wound dressings impregnated with copper oxide micro-particles have been cleared for treatment of acute and chronic wounds. Our objective is to provide preliminary data regarding the potential benefit of using these novel wound dressings including in non-infected wounds. Methods involved the treatment of wounds that responded partially or poorly to conventional wound healing treatments with copper oxide impregnated wound dressings in patients with a range of etiologies. Ten cases of patients with etiologies such as diabetes mellitus, sickle cell disease, renal failure, and necrotizing fasciitis, in which the application of copper oxide impregnated wound dressings in infected and non-infected wounds, which resulted in significant enhanced wound healing, are presented. This was exemplified by clearing of the wound infections, reduction of the fibrous and\/or necrotic tissue and by intense granulation, epithelialization, and wound closure. The described 10 case reports support our hypothesis that the copper oxide-containing wound dressing not only confers protection to the wound and the dressing from microbial contamination, and in some cases may help clear the wound infections, but in addition and more importantly, stimulate skin regeneration and wound healing. Our findings are in line with previous animal and in vitro studies showing that copper plays a key role in angiogenesis and skin regeneration. These case reports support the notion that the use of copper oxide impregnated wound dressings may be an important intervention in the arsenal of wound treatment modalities, especially in hard to heal wounds.<\/jats:p>","DOI":"10.3390\/medicina57030296","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T11:13:26Z","timestamp":1616411606000},"page":"296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Healing of Chronic Wounds by Copper Oxide-Impregnated Wound Dressings\u2014Case Series"],"prefix":"10.3390","volume":"57","author":[{"given":"Eyal","family":"Melamed","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Rambam Medical Center, Haifa 31096, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Kiambi","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Kenyatta National Hospital, Nairobi 00202, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dancan","family":"Okoth","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Kenyatta National Hospital, Nairobi 00202, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Honigber","sequence":"additional","affiliation":[{"name":"Foot and Ankle Unit, Yitzhak Shamir Medical Center, Tzrifin 7073001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eran","family":"Tamir","sequence":"additional","affiliation":[{"name":"Foot and Ankle Unit, Yitzhak Shamir Medical Center, Tzrifin 7073001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6170-5344","authenticated-orcid":false,"given":"Gadi","family":"Borkow","sequence":"additional","affiliation":[{"name":"MedCu Technologies Ltd., Herzliya 4672837, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.mehy.2007.06.006","article-title":"Could chronic wounds not heal due to too low local copper levels?","volume":"70","author":"Borkow","year":"2008","journal-title":"Med. Hypotheses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jinorgbio.2016.02.012","article-title":"The neglected role of copper ions in wound healing","volume":"161","author":"Kornblatt","year":"2016","journal-title":"J. Inorg. Biochem."},{"key":"ref_3","first-page":"173","article-title":"Characterization and quantification of copper sulfate-induced vascularization of the rabbit cornea","volume":"130","author":"Parke","year":"1988","journal-title":"Am. J. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1524-475X.2010.00573.x","article-title":"Molecular mechanisms of enhanced wound healing by copper oxide-impregnated dressings","volume":"18","author":"Borkow","year":"2010","journal-title":"Wound Repair Regen."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"H1821","DOI":"10.1152\/ajpheart.01015.2001","article-title":"Copper-induced vascular endothelial growth factor expression and wound healing","volume":"282","author":"Sen","year":"2002","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33783","DOI":"10.1038\/srep33783","article-title":"Endothelial Antioxidant-1: A Key Mediator of Copper-dependent Wound Healing in vivo","volume":"6","author":"Das","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1046\/j.1365-2133.1999.02603.x","article-title":"In vitro modulation of keratinocyte wound healing integrins by zinc, copper and manganese","volume":"140","author":"Tenaud","year":"1999","journal-title":"Br. J. Dermatol."},{"key":"ref_8","first-page":"163","article-title":"Copper and the synthesis of elastin and collagen","volume":"79","author":"Harris","year":"1980","journal-title":"Ciba Found. Symp."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3109\/03008207.2012.665970","article-title":"Beneficial regulation of fibrillar collagens, heat shock protein-47, elastin fiber components, transforming growth factor-beta1, vascular endothelial growth factor and oxidative stress effects by copper in dermal fibroblasts","volume":"53","author":"Philips","year":"2012","journal-title":"Connect. Tissue Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0142-9612(98)00015-5","article-title":"Stabilization of fibronectin mats with micromolar concentrations of copper","volume":"20","author":"Ahmed","year":"1999","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0142-9612(03)00596-9","article-title":"Stabilisation of cables of fibronectin with micromolar concentrations of copper: In vitro cell substrate properties","volume":"25","author":"Ahmed","year":"2004","journal-title":"Biomaterials"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1046\/j.1524-475X.2002.20101.x","article-title":"Metallothioneins: Potential therapeutic aids for wound healing in the skin","volume":"10","author":"Lansdown","year":"2002","journal-title":"Wound Repair Regen."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"996S","DOI":"10.1093\/ajcn\/67.5.996S","article-title":"Copper, lysyl oxidase, and extracellular matrix protein cross-linking","volume":"67","author":"Rucker","year":"1998","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1046\/j.1523-1747.2000.00166.x","article-title":"Expression of glycosaminoglycans and small proteoglycans in wounds: Modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+)","volume":"115","author":"Simeon","year":"2000","journal-title":"J. Investig. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1016\/S0024-3205(00)00803-1","article-title":"The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures","volume":"67","author":"Simeon","year":"2000","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111859","DOI":"10.1016\/j.yexcr.2020.111859","article-title":"Copper promotes migration of adipose-derived stem cells by enhancing vimentin-Ser39 phosphorylation","volume":"388","author":"Chen","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.bbrc.2019.07.110","article-title":"Copper nanoparticles promote rapid wound healing in acute full thickness defect via acceleration of skin cell migration, proliferation, and neovascularization","volume":"517","author":"Alizadeh","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.2174\/0929867054637617","article-title":"Copper as a biocidal tool","volume":"12","author":"Borkow","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2174\/187231312801254723","article-title":"Using copper to fight microorganisms","volume":"6","author":"Borkow","year":"2012","journal-title":"Curr. Chem. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1515\/REVEH.2003.18.3.153","article-title":"Copper hypersensitivity: Dermatologic aspects\u2014An overview","volume":"18","author":"Hostynek","year":"2003","journal-title":"Rev. Environ. Health"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/01.mjt.0000127148.83065.e5","article-title":"Examination of the cutaneous absorption of copper after the use of copper-containing ointments","volume":"11","author":"Gorter","year":"2004","journal-title":"Am. J. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1053\/beog.2002.0267","article-title":"Intrauterine devices","volume":"16","author":"Bilian","year":"2002","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"952S","DOI":"10.1093\/ajcn\/67.5.952S","article-title":"Essentiality of copper in humans","volume":"67","author":"Uauy","year":"1998","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_24","first-page":"86","article-title":"Safety of using copper oxide in medical devices and consumer products","volume":"6","author":"Borkow","year":"2012","journal-title":"Curr. Chem. Biol."},{"key":"ref_25","first-page":"54","article-title":"Safety of using diapers containing copper oxide in chronic care elderly patients","volume":"6","author":"Weinberg","year":"2013","journal-title":"Open Biol. J."},{"key":"ref_26","first-page":"310","article-title":"Copper oxide impregnated wound dressings: Biocidal and safety studies","volume":"22","author":"Borkow","year":"2010","journal-title":"Wounds"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1590\/S1807-59322006000600014","article-title":"Complex wounds","volume":"61","author":"Ferreira","year":"2006","journal-title":"Clinics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1080\/07853890.2016.1231932","article-title":"Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis (dagger)","volume":"49","author":"Zhang","year":"2017","journal-title":"Ann. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Reiber, G.E. (2002). Epidemiology and health care costs of diabetic foot problems. The Diabetic Foot, Humana Press.","DOI":"10.1385\/1-59259-168-X:035"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/wrr.12391","article-title":"WHS guidelines update: Diabetic foot ulcer treatment guidelines","volume":"24","author":"Lavery","year":"2016","journal-title":"Wound Repair Regen."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejphar.2014.02.033","article-title":"Chitosan-based copper nanocomposite accelerates healing in excision wound model in rats","volume":"731","author":"Gopal","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"045008","DOI":"10.1088\/1748-6041\/9\/4\/045008","article-title":"Novel copper (II) alginate hydrogels and their potential for use as anti-bacterial wound dressings","volume":"9","author":"Klinkajon","year":"2014","journal-title":"Biomed. Mater."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2147\/IJN.S266692","article-title":"Antimicrobial Double-Layer Wound Dressing Based on Chitosan\/Polyvinyl Alcohol\/Copper: In vitro and in vivo Assessment","volume":"16","author":"Ghasemian","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.ijbiomac.2019.10.029","article-title":"Fabrication of Chitosan\/PVA\/GO\/CuO patch for potential wound healing application","volume":"143","author":"Venkataprasanna","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Abdollahi, Z., Zare, E.N., Salimi, F., Goudarzi, I., Tay, F.R., and Makvandi, P. (2021). Bioactive Carboxymethyl Starch-Based Hydrogels Decorated with CuO Nanoparticles: Antioxidant and Antimicrobial Properties and Accelerated Wound Healing In Vivo. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052531"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1096\/fj.04-2029fje","article-title":"Putting copper into action: Copper-impregnated products with potent biocidal activities","volume":"18","author":"Borkow","year":"2004","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1177\/1528083706060785","article-title":"Copper oxide impregnated textiles with potent biocidal activities","volume":"35","author":"Gabbay","year":"2006","journal-title":"J. Ind. Text."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1006\/abio.1995.1194","article-title":"A quantitative test for copper using bicinchoninic acid","volume":"226","author":"Brenner","year":"1995","journal-title":"Anal. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/j.1742-481X.2006.00265.x","article-title":"Silver dressings: Their role in wound management","volume":"3","author":"Leaper","year":"2006","journal-title":"Int. Wound J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.burns.2006.06.010","article-title":"Effect of silver on burn wound infection control and healing: Review of the literature","volume":"33","author":"Atiyeh","year":"2007","journal-title":"Burns"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1524-475X.2007.00201.x","article-title":"Silver treatments for leg ulcers: A systematic review","volume":"15","author":"Chambers","year":"2007","journal-title":"Wound Repair Regen."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6679","DOI":"10.2147\/IJN.S109695","article-title":"Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: Insight into the cytotoxicity and antiangiogenesis","volume":"11","author":"Yang","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1039\/C8MT00280K","article-title":"Copper affects the binding of HIF-1alpha to the critical motifs of its target genes","volume":"11","author":"Wu","year":"2019","journal-title":"Metallomics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"637","DOI":"10.14348\/molcells.2014.0150","article-title":"Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1","volume":"37","author":"Ruthenborg","year":"2014","journal-title":"Mol. Cells"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/57\/3\/296\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:39:02Z","timestamp":1760161142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/57\/3\/296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["medicina57030296"],"URL":"https:\/\/doi.org\/10.3390\/medicina57030296","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]}}}