Publication Grant Recipient Maksym Pogorielov’s Article Published in MDPI Biomedicines

Complementary Effect of Non-Persistent Silver Nano-Architectures and Chlorhexidine on Infected Wound Healing

Surgical site infection (SSI) substantially contributes each year to patients' morbidity and mortality, accounting for about 15% of all nosocomial infections. SSI drastically increases the rehab stint and expenses while jeopardizing health outcomes. Besides prevention, the treatment regime relies on an adequate antibiotic therapy. On the other hand, resistant bacteria strains have actually reached up to 34.3% of the total infections and grow annually, reducing the efficacy of the common treatment schemes. Thus, new antibacterial strategies are urgently demanded.  In particular, some nanoparticles exhibit multiple mechanisms of action that affect the microbial wall, organelles and biochemical pathways. For this purpose, metal-containing nanoparticles have been extensively investigated for the development of antimicrobial drugs and silver nanoparticles have been one of the more promising. Even if already employed more than 100 years ago, silver nanoparticles are only recently being touted as the last-line of defense to both reduce the bacterial burden and the inflammatory response. Indeed, silver nanoparticles can penetrate the bacterial cell wall and disrupt the signaling cascades essential for bacterial survival and colony expansion. Although effective, noble metal-based treatments are precluded from clinics for the concern of metal persistence. Indeed, noble metal nanoparticles are not (bio)degradable and their size usually leads to severe clearance issues with accumulation and persistence in excretory organs. In this regard, silver nano-architectures (AgNAs) are biodegradable nanoplatforms that may bring again inorganic nanomaterials to the forefront of clinical applications. AgNAs are intrinsically sterile nanocapsules composed of 100 nm hollow silica nanospheres embedding ultrasmall silver nanoparticles in a polymeric functional matrix. The silica shell both protects the material in the inner cavity from the environment and provides an easily modifiable/functionalizable surface. Closely packed silver nanoparticles confer the chemo-physical behavior needed for therapeutic applications, while the polymer can be functionalized with active molecules of interest, among which drugs and peptides.

Here, we demonstrate in rats the effectiveness of non-persistent silver nano-architectures (AgNAs) in infected wound healing together with their synergistic action in combination with chlorhexidine. Besides the in vivo efficacy evaluation, we performed analysis of the bacteriological profile of purulent wound, histological evaluations and macrophages polarization quantifications to further validate our findings and elucidate the possible mechanisms of AgNAs action on wound healing. These findings open the way for the composition of robust multifunctional nanoplatforms for the translation of safe and efficient topical treatments of SSI.

This research was made in collaboration between Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia (Italy) and Biomedical Research Centre (Sumy, Ukraine)