Cytotoxicity in Wound Care: Is Silver Safe?

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The incorporation of silver into wound dressings has been a breakthrough to combat the effects of antibiotic resistance, despite silver safety concerns. Regardless of its recent popularity, silver is not a new tool in health care.

Brief History of Silver Use in Health Care

Silver has a demonstrated, far-reaching history of health benefits—from water purification to precursors of modern-day wound dressings. Medicinal use has been documented as early as 1850 BCE Egypt, where silver was applied directly to wounds.1

The beginning of silver in wound care occurred in 1520 CE. Silver nitrate was used to chemically cauterize wounds and is a method still used today. By the 1800s, silver nitrate treatments were the standard of care for skin ulcers and festering wounds. Silver-based wound care has evolved since the nineteenth century, however, because silver nitrate is known to have a higher potential for toxicity than silver nanoparticles.2

In 1891, B.C. Crede started using colloidal silver for wound hygiene. Colloidal silver was used to disinfect hospital equipment, as well as to control infections through wound application,3 eye drops, nose drops, and intravenous injection.4 Then in the early 1900s, colloidal silver was also ingested by or injected into tens of thousands of patients. Through this widespread use of silver, the phenomenon of argyria was discovered, where silver deposits develop in the skin and other tissues.

The long-term effects of argyria in humans are still unknown, but animal studies have shown no serious side effects. The silver deposits into the liver, kidneys, spleen, and testis, but no significant effects have been seen at the levels of silver that deposit into the tissue.2 Regardless, silver is still more commonly used topically or in wound dressings today, to prevent argyria caused by ingestion.

Silver lost its popularity when penicillin was discovered in 1928 but has recently resurged as a practical antimicrobial to treat antibiotic-resistant infections and to reduce the development of these infections.1

How much do you know about managing the use of silver in wound care? Take our 10-question quiz to find out! Click here.

Concerns About Silver Use in Wound Care

Despite the many benefits of silver, the literature highlights areas for concern as silver becomes more prevalent in wound care. Compared with past uses of silver, clinicians often choose not to prescribe ingested silver in colloidal or nanoparticle form. At high doses over a long period of time, ingested silver may cause damage to the kidney and liver as well as seizures. However, this effect has not been seen with the topical use of silver and is more common with colloidal silver ingestion.5

Even topically, however, silver may have local cytotoxic effects that could impair wound healing if it is used inappropriately. At a high enough concentration, silver nanoparticles have been shown to reduce the mitochondrial function of fibroblasts, epithelial cells, melanoma cells, and hepatoma cells.6 Fibroblasts specifically are essential to the wound healing process, and their inhibition could delay healing.7 Clinicians should therefore be conservative in their use of silver wound dressings in the long term and consider alternatives if the wound is not responding to the current treatment plan while taking into consideration healing time, the presence of infection, and the patient’s pain level.

Current safety studies of silver also have not separated the effects of silver on different microorganisms.8 There is currently no decision guide or protocol to determine whether the silver will be effective after a wound is cultured and the nature of infection has been determined to be bacterial, fungal, or viral. In consensus with experts, it is recommended to use silver dressings for 2 weeks at the first occurrence of infection. Clinicians should then reassess the wound every 2 weeks until it is healed and should change the treatment plan as appropriate according to the patient’s response to the silver dressing.9

Silver Resistance

Although rare, silver resistance is possible and therefore is a public health concern. Care must be taken not to overuse silver, to decrease the risk of bacteria developing silver resistance.10 As with antibiotics, bacteria can develop resistance to silver as an antimicrobial agent.11,12 Silver resistance is not as common as antibiotic resistance, given the multifaceted approach silver takes to combat bacteria.13 Silver interrupts multiple pathways within the bacteria cell as well as the biofilm formed between bacterial cells. Nevertheless, silver should be used conservatively and for a sufficient length of time to reduce the risk of resistance development.

Conclusion

When used appropriately, silver is a safe alternative to topical antibiotics. Topical use of silver nanoparticles in particular can improve wound care outcomes with few to no side effects for the patient. Further studies are needed to determine the toxicity of long-term and ingested silver use. However, in wound care, silver dressing use is a safe way to address wound infections topically.

January is Silver Safety Month

References

  1. Paladini F, Pollini, M. Antimicrobial silver nanoparticles for wound healing application: progress and future trends. Materials. 2019;12(16):2540. doi:http://dx.doi.org/10.3390/ma12162540
  2. Qin G, Tang S, Li S, et al. Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure. Environ Toxicol. 2017;32(2):609-618. doi:http://dx.doi.org/10.1002/tox.22263
  3. Alexander JW. History of the medical use of silver. Surg infect. 2009;10(3):289-292.
  4. Medici S, Peana M, Nurchi VM, Zoroddu MA. Medical uses of silver: history, myths, and scientific evidence. J Med Chem. 2019;62(13):5923-5943.
  5. Drake PL, Hazelwood KJ. Exposure-related health effects of silver and silver compounds: a review. Ann Occup Hyg. 2005;49(7):575-585. https://www.proquest.com/scholarly-journals/exposure-related-health-effe...
  6. Dakal TC, Kumar A, Majumdar RS, Yadav V. Mechanistic basis of antimicrobial actions of silver nanoparticles. Front Microbiol. 2016;71831. doi:10.3389/fmicb.2016.01831
  7. Radko L, Stypuła-Trębas S, Posyniak A, Żyro D, Ochocki J. Silver(I) complexes of the pharmaceutical agents metronidazole and 4-hydroxymethylpyridine: comparison of cytotoxic profile for potential clinical application. Molecules. 2019;24(10):1949. doi:http://dx.doi.org/10.3390/molecules24101949
  8. Kowalczyk P, Szymczak M, Maciejewska M, et al. All That glitters is not silver-a new look at microbiological and medical applications of silver nanoparticles. Int J Mol Sci. 2021;22(2):854. doi:10.3390/ijms22020854
  9. Leaper D. Appropriate use of silver dressings in wounds: international consensus document. Int Wound J. 2012;9(5):461-464. doi:10.1111/j.1742-481X.2012.01091.x
  10. Mariana BM, Klumpp J, Widmer M, et al. Chromosomal Sil system contributes to silver resistance in E. coli ATCC 8739. Biometals. 2018;31(6):1101-1114. doi:http://dx.doi.org/10.1007/s10534-018-0143-1
  11. Mijnendonckx K, Leys N, Mahillon J, Silver S, Van Houdt R. Antimicrobial silver: uses, toxicity and potential for resistance. Biometals. 2013;26(4):609-621. doi:http://dx.doi.org/10.1007/s10534-013-9645-z
  12. Finley PJ, Norton R, Austin C, Mitchell A, Zank S, Durham P. Unprecedented silver resistance in clinically isolated Enterobacteriaceae: major implications for burn and wound management. Antimicrob Agents Chemother. 2015;59(8):4734-4741. doi:10.1128/AAC.00026-15
  13. Wang H, Wang M, Xiaohan X, et al. Multi-target mode of action of silver against Staphylococcus aureus endows it with capability to combat antibiotic resistance. Nat Commun. 2021;12(1):3331. doi:http://dx.doi.org/10.1038/s41467-021-23659-y

The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, HMP Global, its affiliates, or subsidiary companies.

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