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Use of bioactive glass and antiseptics to treat MRSA-infected skin wounds

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Multidrug resistant skin infection bacteria is currently considered as a major public health problem (Michael, Dominey-Howes et al. 2014, Ventola and therapeutics 2015). We urgently need treatments that can be used in addition to conventional antimicrobials. One such option can be bioactive glass (BAG) - a synthetic silica-based material, which releases ions from the granules’ surfaces when it comes in contact with biological fluids. The released ions increase the osmotic pressure and pH, and make the surrounding environment unsuitable for microbial growth (Coraca-Huber, Fille et al. 2014, van Gestel, Geurts et al. 2015, Drago, Toscano et al. 2018). There are several types of BAG with different types of antibacterial activity. BAG S53P4 (BonAlive Biomaterials, Turku Finland) is widely investigated (Baino, Hamzehlou et al. 2018 , Drago, Toscano et al. 2018). In clinical practice, bioactive glass has been routinely used in the treatment of osteomyelitis in orthopedic surgery (Lindfors, Hyvönen et al. 2010), chronic frontal sinusitis surgery (Peltola, Aitasalo et al. 2006), and in mastoid obliteration surgery for chronic otitis media (Sarin, Grenman et al. 2012, Silvola 2012).
Also antiseptics may play an important role in fighting multidrug resistant skin bacteria (Grønseth, Vestby et al. 2017). Antiseptics have many advantages over antibiotics, acting on different microorganisms and demonstrating less risk of resistance (Traoré, Fayard et al. 1996). Antiseptics inhibit different groups of bacteria, fungi, viruses, and protozoa (McDonnell and Russell 1999). However, the use of antibiotics has reduced the scientific attention to antiseptics.
Lugol´s solution and crystal violet (Gentian violet 1%) have been used as antiseptics in medical practice since the 19th century. They may have a potential to be used as inexpensive antimicrobial agents to treat skin infections (Maley and Arbiser 2013).
The antimicrobials will be applied on mouse skin to treat multidrug resistant S. aureus.
In principle, using these antimicrobials will reduce the amount of antibiotics in hospitals and decrease the spread of antibiotic resistant bacteria.
Since immune response to bacteria varies greatly between individual animals, we will use a well established inbred mouse strain - BALB/c female mice between 6 and 10 weeks. To assess the efficacy of treatment of S. aureus we will use luminescent-tagged bacteria, allowing non-invasive visualization of infection during the treatment, thus obtaining better and safer data from each animal and using fewer animals per experiment.
During the experiment mice may experience short-term localized skin pain and less likely systemic symptoms including fever, flu-like aches. Thus during all experiments mice will be regularly injected with painkillers (Temgesic, 0.1 mg/kg/8 h). We strive to maintain a stable environment with constant temperature, humidity and light conditions. Temperature and humidity are recorded on a daily basis by using sensors in relevant rack positions. We also minimize traffic in the animal room to reduce stress to the animals. Each cage has a running wheel and house to increase their activity levels and wellbeing. We underline the importance of avoiding stress in the lab and housing room by e.g. high frequency sounds or non-gentle handling of animals.