Wound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation of this cytotoxicity to clinical settings is unclear. We applied dressings with various forms of silver on porcine skin ex vivo and investigated silver penetration and DNA damage. We assessed antimicrobial efficacy, cytotoxicity to skin cells, and immune response induced by the dressings. All dressings elevated the DNA damage marker γ-H2AX and the expression of stress-related genes in explanted skin relative to control. This corresponded with the amount of silver in the skin. The dressings reduced viability, induced oxidative stress and DNA damage in skin cells, and induced the production of pro-inflammatory IL-6 by monocytes. The oxidative burst and viability of activated neutrophils decreased. The amount of silver released into the culture medium varied among the dressings and correlated with in vitro toxicity. However, antimicrobial efficiencies did not correlate strongly with the amount of silver released from the dressings. Antimicrobial efficiency and toxicity are driven by the form of silver and the construction of dressings and not only by the silver concentration. The damaging effects of silver dressings in ex vivo skin highlight the importance of thorough in vivo investigation of silver dressing toxicity.

• MeSH
• buněčné linie MeSH
• infekce v ráně MeSH
• kůže chemie   cytologie   účinky léků   MeSH
• lidé MeSH
• obvazy škodlivé účinky   MeSH
• poškození DNA * MeSH
• prasata MeSH
• stříbro toxicita   MeSH
• techniky tkáňových kultur MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• stříbro MeSH

OBJECTIVES: The majority of human chronic wounds contain bacterial biofilms, which produce proteases and retard the resolution of inflammation. This in turn leads to elevated patient protease activity. Chronic wounds progressing towards closure show a reduction in proteolytic degradation. Therefore, the modulation of protease activity may lead to the faster healing of chronic wounds. Antimicrobials are used to control biofilm-based infection; however, some of them also exhibit the inhibition of matrix metalloproteinases and bacterial proteases. We investigated the antimicrobial agents used in wound healing for their potential to inhibit bacterial and host proteases relevant to chronic wounds. METHODS: Using in vitro zymography, we tested the ability of povidone-iodine, silver lactate, chlorhexidine digluconate, and octenidine hydrochloride to inhibit selected human proteases and proteases from Pseudomonas aeruginosa, Staphylococcus aureus, Serratia marcescens, and Serratia liquefaciens. We investigated penetration and skin protease inhibition by means of in situ zymography. RESULTS: All the tested antimicrobials inhibited both eukaryotic and prokaryotic proteases in a dose-dependent manner in vitro. The tested compounds were also able to penetrate into skin ex vivo and inhibit the resident proteases. Silver lactate and chlorhexidine digluconate showed an inhibitory effect ex vivo even in partial contact with skin in Franz diffusion cells. CONCLUSIONS: Our in vitro and ex vivo results suggest that wound healing devices which contain iodine, silver, chlorhexidine, and octenidine may add value to the antibacterial effect and also aid in chronic wound healing. Antiprotease effects should be considered in the design of future antimicrobial wound healing devices.

• MeSH
• antiinfekční látky farmakologie   MeSH
• Bacteria růst a vývoj   MeSH
• bakteriální nemoci kůže * farmakoterapie   enzymologie   mikrobiologie   MeSH
• chlorhexidin farmakologie   MeSH
• hojení ran účinky léků   MeSH
• iminy MeSH
• infekce v ráně * farmakoterapie   enzymologie   mikrobiologie   MeSH
• inhibitory proteas farmakologie   MeSH
• jod farmakologie   MeSH
• lidé MeSH
• prasata MeSH
• pyridiny farmakologie   MeSH
• stříbro farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiinfekční látky MeSH
• chlorhexidin MeSH
• iminy MeSH
• inhibitory proteas MeSH
• jod MeSH
• octenidine MeSH Prohlížeč
• pyridiny MeSH
• stříbro MeSH