2023 Apr 11;16(4):573. doi: 10.3390/ph16040573. An ancient Egyptian medical text, known as the Smith Papyrus (circa 2400 B.C. In the normal wound healing process the inflammation phase usually lasts for 25days. Copper has two key properties that endow it as an excellent active ingredient to be used in products, which come in contact with the skin, aiming to improve the skins well-being. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Gabbay J, Mishal J, Magen E, et al. Burning of copper sulphate in houses and shops (as a good luck charm and for religious activities) is a common practice among Buddhists and Hindus. Lippincott Williams & Wilkins; 2001. At best, we could only discern a trend towards enhanced skin regeneration and angiogenesis in most of the studies, with significant improvement in those who had copper NP exposure. . Notwithstanding etiology, chronic wounds have high levels of ROS, proinflammatory cytokines, proteases and senescent cells, as well as the existence of stubborn infection and decreased levels of stem cells [44,45]. The excellent performance stems from the combined effects of hyperthermia, radical oxygen species and released copper ions produced during NIR irradiation of nanocomposite hydrogels (NP-hydrogels), where NP-hydrogel has been demonstrated to have the ability to kill bacteria while promoting healing of wounds. Could chronic wounds not heal due to too low local copper levels. In this phase, the recruited neutrophils begin the phagocytosis of infectious agents by releasing a large variety of highly active antimicrobial substances like reactive oxygen species (ROS), cationic peptides, eicosanoids, proteases and myeloperoxidase [16], which also lead to the debridement of devitalized tissue by secreting enzymes such as matrix metalloproteinases (MMPs). Unauthorized use of these marks is strictly prohibited. NPs nanoparticles, TGF transforming growth factor, VEGF vascular endothelial growth factor, PDGF platelet derived growth factor. This uptake is primarily mediated by the CTR1 copper importer [82,83]. These events, accelerate by inflammation and oxidative stress in photoaged skin [3, 17, 18], are controlled chiefly via the mitogen activated protein kinase (MApK) and NF-B/p65 signal transduction pathways [17, 19, 20]. 2004 May 29;359(1445):839-50. doi: 10.1098/rstb.2004.1475. These include alterations in the dermal extracellular matrix (ECM) made up mainly by collagen (which provides strength and structure) and elastin (which provides elasticity and resilience) fibres. Borkow G, Zhou SS, page T, Gabbay J. Some representative data and pictures are shown in (Fig. However, other studies have shown that copper concentrations at these levels cause no adverse reaction when applied to human skin [78]. Providing a moist environment to the wound bed is the currently accepted way of promoting wound healing [1, 2].In moist wounds, an environment that is rich in white blood cells, enzymes, cytokines and growth factors can be easily generated and maintained throughout the healing process [3-5].Much research has focused on the development of materials that provide a moist environment for a wound. Schultz GS, Chin GA, Moldawer L, Diegelmann RF. Fibroblasts were dosed with 2008;70(3):610-3. doi: 10.1016/j.mehy.2007.06.006. Stimulation of Fibroblast proliferation by Copper. Fandez G, Troncoso M, Navarrete P, Figueroa G. Perelshtein I, Applerot G, Perkas N, Wehrschuetz-Sigl E, Hasmann A, Guebitz G, et al. Also, in areas of the foot where no fungal infection was present, the skin looked healthier (unpublished observations). The transcription repression mechanism is not well defined, but the chromatin compaction could inhibit transcript elongation. Mace KA, Yu DH, paydar KZ, Boudreau N, Young DM. . Abicht HK, Gonskikh Y, Gerber SD, Solioz M. Non-enzymic copper reduction by menaquinone enhances copper toxicity in Lactococcus lactis IL1403. This article discusses the benefits of copper sulfate and the side effects that can come from copper sulfate exposure. Both gram positive and gram negative bacteria, including antibiotic resistant bacteria as well as hard to kill bacterial spores, fungi and viruses, when exposed to high copper concentrations, are killed [42, 43]. Controlling the growth of algae in farm ponds, waterways, water bodies, and reservoirs It is considered as the best algaecide, so it is generally used to kill the unwanted algae on the roofs and lawns also. Grass G, Rensing C, Solioz M. Metallic copper as an antimicrobial surface. These include direct contact killing and damage caused by exposure to released copper ions [42, 43, 62-64]. In this article, we review the physiology of wound healing and its relationship with epigenetics. FOIA Med Hypotheses. Feng C, Ouyang J, Tang Z, Kong N, Liu Y, Fu L, et al. Nevertheless, despite recent advances in the management of wounds, bacterial infections as Staphylococcus aureus, methicillin-resistant S. aureus and Pseudomonas aeruginosa are still diagnosed and considered as painful states in patients with infected wounds [50]. Publication types Case Reports MeSH terms Animals Safety of using diapers containing copper oxide in chronic care elderly patients. Kim JH, Cho H, Ryu SE, Choi MU. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). sharing sensitive information, make sure youre on a federal Copper hypersensitivity dermatologic aspects--an overview. . Hostynek JJ, Maibach HI. Improved wound healing. Looking older fi-broblast collapse and therapeutic implications. 3D Image Analysis GFM phaseshift Rapid in vivo Measurement of Skin (pRIMOS) system), photography, and by expert graders. These glycoproteins released from plateletalpha granules include fibrinogen, fibronectin, thrombospondin and von Willebrand factor. The remodeling phase starts at the end of the granulation tissue development, where mechanical tension and cytokines drive fibroblasts to differentiate into myofibroblasts, which express -smooth muscle actin and contract the wound [25]. Published by Oxford University Press. The positive effect of the socks on the skin, is not only due to the biocidal properties of the socks, but as determined in a double blind, placebo controlled study that was conducted with healthy volunteers by CuTest, a UK company that conducts dermatological clinical trials, the copper oxide containing socks improved significantly the elasticity of the skin [94] (Fig. All forms of copper may cause biotoxicity at high exposure concentrations [98]. Changes induced in the permeability barrier of the yeast plasma mem-brane by cupric ion. Pierpont YN, Dinh TP, Salas RE, Johnson EL, Wright TG, Robson MC, et al. Hostynek JJ, Dreher F, Maibach HI. the use of copper oxide containing socks. Fage SW, Faurschou A, Thyssen Jp. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises, Isolation of putative progenitor endothelial cells for angiogenesis, Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1, Adipose-derived stem cell-seeded hydrogels increase endogenous progenitor cell recruitment and neovascularization in wounds, Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells, Formation and function of the myofibroblast during tissue repair, Morphometric evaluation of wound healing in burns treated with Ulmo (, El Rol de la Miel en los Procesos Morfofisiolgicos de Reparacin de Heridas, Skin wound healing: an update on the current knowledge and concepts, The methylation pattern of p16INK4a gene promoter in psoriatic epidermis and its clinical significance, Epigenetic regulation of gene expression in keratinocytes, Wound healing and inflammation genes revealed by array analysis of 'macrophageless' PU.1 null mice, Polycomb group proteins are key regulators of keratinocyte function, Epigenetic reprogramming during wound healing: loss of polycomb-mediated silencing may enable upregulation of repair genes, Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains, Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing, Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells, Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation, Polycomb repression: from cellular memory to cellular proliferation and cancer, Polycomb, epigenomes, and control of cell identity, Challenges in the treatment of chronic wounds, Cellular senescence is a promising target for chronic wounds: a comprehensive review, Obesity and surgical wound healing: a current review, Diabetic foot disorders. http://creativecommons.org/licenses/by-nc/3.0/. Due to the loss of zinc during injury, zinc therapy has been used in wound care to enhance healing in zinc-deficient patients [32,167]. Wonder Dust product is a wound powder and blood coagulant for use on certain types of abrasions. Monk AB, Kanmukhla V, Trinder K, Borkow G. po-tent bactericidal efficacy of copper oxide impregnated non-porous solid surfaces. Moreover, NPs with a concentration of 200g/ml could significantly promote cell proliferation in in vitro and in vivo models [59]. Neutralizing viruses in suspensions by copper oxide based filters. Borkow G, Gabbay J. putting copper into action copper-impregnated products with potent biocidal ac-tivities. ), mentions using copper as a sterilization agent for drinking water and wounds. Antimicrobial activity of copper helps to reduce the microbial load at the site of wound and enhances the pace of healing. These trials were conducted by independent researchers and specialized labs. Borkow G, Lara HH, Covington CY, Nyamathi A, Gabbay J. Deactivation of human immunodeficiency virus type 1 in medium by copper oxide-containing filters. Also, it has been shown that relocalization of ATP7A from the TGN is triggered not just by increased cytoplasmic Cu but also by non-metal stimulants such as insulin, N-methyl-D-aspartic acid or N-methyl-D-aspartate, platelet-derived growth factor and hypoxia [84,91]. Chitosan-based copper nanocomposite accelerates healing in excision wound model in rats. An ancient remedy returning to fight microbial, fungal and viral infections. Copper is essential to wound healing, as it promotes angiogenesis and skin ECM formation and stabilization [37-41]. We hypothesized that the copper impregnated socks continuously release copper ions that are absorbed through the skin. Bastianelli C, Farris M, Benagiano G. Emergency contraception a review. Among many known growth factors, vascular endothelial growth factor (VEGF) is believed to be the most prevalent, efficacious, and long-term signal that is known to stimulate angiogenesis in wounds. For example, one day after wounding there was ~6 fold increase in integrins (proteins that bind extracellular matrix proteins and transduce signals crucial for cell processes in wound healing [95]) and 22 fold increase in placental growth factor (pLGF; an angiogenic factor known to be markedly reduced in diabetic wounds). of elastase and matrixmetalloproteinases and stimulation A better understanding of these interactions might suggest potential new targets for therapeutic intervention on scars or non-healing wounds. official website and that any information you provide is encrypted Stimulation of cell proliferation and expression of matrixmetalloproteinase-1 and interluekin-8 genes in dermal fibroblasts by copper, Differential production of metalloproteinases after instilling various urban air particle samples to rat lung, CuS nanodots with ultrahigh efficient renal clearance for positron emission tomography imaging and image-guided photothermal therapy, Hydrogel cross-linked with dynamic covalent bonding and micellization for promoting burn wound healing, Engineering pharmaceutical nanocarriers for photodynamic therapy on wound healing: review. Angiogenesis; Copper; Inflammation; Metal ion homeostasis; Nerve Growth Factor; Would healing. The NP-hydrogel is demonstrated to have the ability to kill bacteria while promoting healing of wounds. Therefore, when exposed to high concentrations of copper they are irreversibly damaged and killed. TO 1100 A.D.), who used copper (sulfate or sulfide) for topical treatment of skin and eye diseases and also for treatment of systemic infections by oral administration of copper; the Mayan, Aztec, and Inca cultures . Lazary A, Weinberg I, Vatine JJ, et al. TO 1100 A.D.), who used copper (sulfate or sulfide) for topical treatment of skin and eye diseases and also for treatment of systemic infections by oral administration of copper; the Mayan, Aztec, and Inca cultures (~600 B.C. The prepared PU and PU nanocomposites showed smooth fibers without any bead defects. Claimed benefits of colloidal copper include: treats wounds, infections, and burns. A clinical practice guideline (2006 revision), Wound microbiology and associated approaches to wound management, Skin and soft-tissue infections: a critical review and the role of telavancin in their treatment, Wound healing: biologics, skin substitutes, biomembranes and scaffolds, Fighting chronic wound infection-one model at a time, Systemic antibiotics for treating malignant wounds, Antibiotics: achieving the balance between access and excess, Chemical composition, antimicrobial and antibiotic potentiating activity of essential oils from 10 tropical medicinal plants from Mauritius, Essential Oils: Historical Significance, Chemical Composition and Medicinal Uses and Benefits, United States of America: Nova Science Publishers, Quantitative analysis of dermal scars in deep skin burns treated with Ulmo honey supplemented with ascorbic acid, Can regenerative medicine and nanotechnology combine to heal wounds? Reducing the risk of skin pathologies in diabetics by using copper im-pregnated socks. copper is involved in the synthesis and stabilization of extracellular matrix skin proteins and The site is secure. Fisher GJ, Varani J, Voorhees JJ. Using MeSH terms ("wound healing" AND "copper nanoparticles" AND "chronic wounds") and text words relating to the role of Cu NPs in wound healing for chronic wounds by the research question, several databases (MEDLINE, EMBASE, Scopus, and Web of Science) were examined from January 2012 to January 2022 for original articles in English. These events lead to chromatin compaction which subsequently leads to suppression of transcription. This activity outlines the indications, action, and contraindications for zinc as a valuable agent. Copper plays a key role in the synthesis and stabilization of skin proteins, and it also has potent biocidal properties. Uses Mode of Action Toxicity Classification Acute Toxicity Chronic Toxicity Endocrine Disruption Carcinogenicity Reproductive and Teratogenic Effects Fate in the Body Medical Tests and Monitoring Environmental Fate Ecotoxicity Studies Regulatory Guidelines Molecular Structure - Copper Sulfate Chemical Class and Type: However, microorganisms cannot deal with copper overload. 2.1.1. ), who used copper sulfide or copper sulfate for nonspecific medical purposes; the ancient Chinese culture (~3000 B.C. Diabetes hinders the capacity to deal with skin damage and infections. Copper compounds are widely used in anthroposophical medicine [77], via oral, subcutaneous injections, or topical applications, in order to stimulate the body to heal itself. Copper serves as a cofactor for enzymes such as superoxide dismutase and cytochrome oxidase [ 2 ]. Copper is an important micronutrient associated with vascular endothelial growth factor expression, causing angiogenesis and remodeling of the extracellular matrix. Mathieu D, Linke JC, Wattel F. Non-healing wounds. Linder MC, Wooten L, Cerveza p, et al. In the first step, solid alginate films were prepared using . supports cardiovascular health. HIF-1 has been recognized as a critical helper factor in wound healing [105] induced by copper. Ferracane JL. Skin Aging New Research ebook Nova Science. there is a) normal skin regeneration (histological analysis after 17 days of wounding) and b) upregulation of Skin photoprotection by nat-ural polyphenols anti-inflammatory, antioxidant and DNA repair mechanisms. Milanino R. Copper in medicine and personal care a historical overview. Olivares C, Solano F. New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins. peltonen L, Kuivaniemi H, palotie A, et al. In addition, often disguised as a comorbid condition, chronic wounds represent a silent epidemic that affects a large fraction of the world population [5], where the dramatic increase in the aging population will increase these numbers as wound closure is negatively associated with age [6,7]. It also augments the immunity by stimulating the production of interleukin-2 [ 3 ]. Watson RE, Griffiths CE, Craven NM, Shuttleworth CA, Kielty CM. Zatcoff RC, Smith MS, Borkow G. Treatment of tinea pedis with socks containing copper-oxide impregnated fibers. Switzerland:: Springer International publishing; 2014. Borkow G, Gabbay J. mRNA expression analysis of biopsies taken from the wound beds at several days following wounding, revealed significant upregulation of key proteins involved in wound healing in the mice treated with the copper oxide wound dressings as compared to the control mice (Fig. Topical zinc sulphate (ZnSO 4) application, usually at an optimal 3% concentration, has been widely used in wound healing for its antioxidant effect . . Socks, containing copper oxide, have been found to increase skin elasticity and eliminate athletes foot infections when used regularly. Nanoparticles such as silver, gold and copper combat infectious processes through the inhibition of protein synthesis, peroxidation of the cell membrane and destroying the nucleic acids of bacteria and viruses. More importantly, copper plays a key role in skin regeneration and angiogenesis [101,102] and has been described to accelerate the healing process in animal models through induction of VEGF and angiogenesis [103] by hypoxia-induced factor-1-alpha (HIF-1) action where copper enhances HIF-1 expression [8]. Data is taken from [94]. Copper oxide impregnated textiles with potent biocidal activities. . The skin is differentiated into the epidermis, dermis and subcutaneous layers. Borkow G. Safety of using copper oxide in medical devices and consumer products. Bleichert p, Espirito SC, Hanczaruk M, Meyer H, Grass G. Inactivation of bacterial and viral biothreat agents on metallic copper surfaces. It also helps to prevent loss of water and other endogenous substances, participates in thermoregulation of the body and serves as an excretory organ [1, 2]. [52, 83]. eCollection 2023 Jun 29. With age, the skin undergoes vast changes, becoming wrinkled and rigid, losing its firmness, elasticity, tone, texture, thickness, flexibility and moisture content [3]. 11); b) upregulates collagen (types I, II, and V) and elastin fiber components (elastin, fibrillins) production by fibroblasts [27] (Fig. Borkow G, Gabbay J. Endowing textiles with perma-nent potent biocidal properties by impregnating them with copper oxide. However, the lack of data linking wound infection and wound healing with Cu NPs remains a limitation of this study and needs to be addressed in future original studies. 22), seemingly through the induction of TGF- [27]; c) stimulates HSp-47, essential to collagen fibril formation [27]; d) serves as a cofactor of LOX needed for efficient ECM protein cross-linking [10]; e) stabilizes the skin ECM once formed, as increased crosslinking of collagen and elastin matrices occurs in a copper dose dependant manner [28, 29]; f) serves as a cofactor of superoxide dismutase, an antioxidant enzyme present in the skin, important for protection against free radicals [30, 31]; g) inhibits cellular oxidative effects such as membrane damage and lipid peroxidation [27]; and h) serves as a cofactor of tyrosinase, a melanin biosynthesis essential enzyme responsible for skin and hair pigmentation [32, 33]. The most common and inevitable impairment to wound healing is the installation of an infection, usually in the case of chronic wounds. The skin is the largest organ of the body that protects our internal tissues from chemical, physical, and microbial damage. Ahire JJ, Hattingh M, Neveling DP, Dicks LM. . The white dots are the copper Borkow G, Gabbay J, Dardik R, et al. philips N, Hwang H, Chauhan S, Leonardi D, Gonza-lez S. Stimulation of cell proliferation and expression of matrixmetalloproteinase-1 and interluekin-8 genes in dermal fibroblasts by copper. In addition, ATP7A is partly implicated in VEGF- or ischemia-induced angiogenesis in ECs [80,90]. In the skin, copper a) stimulates dermal fibroblasts proliferation [26] (Fig. Borkow G, Gabbay J, Lyakhovitsky A, Huszar M. Improvement of facial skin characteristics using cop-per oxide containing pillowcases a double-blind, pla-cebo-controlled, parallel, randomized study. Figure 1 illustrates the flow chart for the study selection process. General Fact Sheet What is copper sulfate? Even though many biological and biochemical mechanisms associated with the steps of physiological wound healing are known, there is still significant morbidity and mortality due to dysregulation of physiological mechanisms. Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. Topical treatments are the classic procedure for wound management. The combination of these two qualities makes copper an attractive material for the improvement of skin wellness. Indeed, such socks, designed specifically for diabetic patients, are sold in pharmacies (e.g. Similarly, in an additional trial with ~ 200 soldiers that used the socks continuously for one week under harsh field conditions, the number of soldiers reporting to the infirmary due to foot problems was significantly lower as compared to soldiers using regular socks without copper (unpublished data). Gadi Borkow 1 , Neta Okon-Levy, Jeffrey Gabbay Affiliation 1Cupron Scientific, Richomond, Virginia; Email:gadi@cupron.com. Rucker RB, Kosonen T, Clegg MS, et al. Then, the PRC1 complex binds to H3K27me3 through CBX protein of to anchor the PRC1 complex at this site, while the PRC1 Ring1B protein catalyzes ubiquitylation of histone H2A at lysine K119 [37,38].
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