Antimicrobial materials
1. Background and state-of-the-art
Infections continue to be among the leading threaten to human life.1 In the same time, designing effective and long-lasting antimicrobial therapies is one of the most difficult tasks of modern pharmacy.2 When the delicate balance of bacterial ecosystem in the human organism is disrupted, pathogens become dominant and induce infections.3-5 Particularly complicated situation starts when planktonic pathogens start to colonize surfaces leading to biofilms- forms highly resistant to antibiotics.2 Prevailing antimicrobial therapies are based on biochemical stimuli (antibiotics, antimicrobial nanoparticles, antimicrobial ions, antimicrobial peptides etc.) with mechanisms that give a lot of possibility for bacteria to develop resistance.1,6 In contrast to them physical stimuli (thermal,7 mechanical,8 magnetic9 or electrical10) affect bacterial life in different way. Numerous studies have shown that defects in the bacterial membrane induced by the physical stimuli increase the susceptibility to biochemical stimuli.5 Therefore, the synergy between the physical and the biochemical stimuli could be particularly effective in targeting not only planktonic but also bacteria in biofilms and eliminating their chances to develop resistant forms. This opens interesting novel standpoints for designing innovative antimicrobial (nano)technologies.
Figure 1: Stimuli affecting bacterial life: a pathway of developing a problem of antimicrobial resistance (AMR) in the past and combining physical stimuli with antimicrobials as new options for the future.
2. Objectives, originality and impact on new research approaches
The main objective of the proposed study is beyond state-of-the-art research in designing novel generation of antimicrobials based on combination of physical and biochemical stimuli. Our intention is to prove that combination of physical stimuli (that mechanically destroy membrane) and biochemical stimuli (that affect different phases of bacterial life) will leave bacteria without any possibility to develop resistance. For that purpose, we plan to design new antimicrobials with alternative methods of action against bacteria, including:
- CONTACT-BASED ANTIMICROBIALS: High density of cationic surface charge that disrupt negative potential of bacterial cell wall (hierarchically structured cationic, amino acid functionalized AuNPs)
- PIEZOELECTRIC ANTIMICROBIALS: Piezostimulation for disintegration of bacterial cells using medical ultrasound (organic piezoelectrics based on piezoelectric PLLA surfaces and their composites)
- PHOTOTHERMAL ANTIMICROBIALS: Near-infrared (NIR) light activated local heating and exploring its effect on viability of bacterial cells (core-shell structures of AuNPs)
Figure 2: Antimicrobials developed in our lab - illustration of the design of antimicrobials which use physical stimuli (electrical charge or heat) as mechanism of action against bacteria.
So far we have designed different innovative antimicrobial technologies which use physical or biochemical stimuli against bacteria. Some of them are pioneered by our team. We are holding a patent on contact-based antimicrobials which will be the bases for further studies containing cationic AuNPs.11 Using hierarchically structured functionalized AuNPs we managed to tailor antimicrobial spectrum of nisin towards Gram negative bacteria, including antibiotic-resistant strains, and to decrease the effective concentrations of this antibiotic for several orders.12 We effectively designed texture and defects on material surface to optimize antimicrobial effect.13 and combined antimicrobial effects of nano-Ga and functionalized nano-gold into very effective antimicrobial technology.14 In one of important recent research we have confirmed that destroying the membrane is the main mechanism of piezostimulation against bacteria.15 We already integrated nanoparticles inside PLLA structures16 and in perspective we plan to combine antimicrobial properties provided by nanoparticles with antimicrobial action of piezoelectric structures in order to explore potential synergies.
REFERENCES:
1 N. F. Kamaruzzaman, Br J Pharmacol., 174(14), 2225, 2017.
2 Y. F. Dufrêne, A. Persat, Nat Rev Microbiol, 2020.
3 R. Sender et al., PLoS Biol., 14(8), 2016.
4 J. Libertucci & V. B. Young, Nature Microbiol. 4, 35–45, 2019.
5 M. M. Fernandes et al. Frontiers Bioeng. Biotechnol., 7, 277, 2019.
6 M. Lomazzi et al., BMC Public Health, 19, 858, 2019.
7 J.-W. Xu et al., Nanoscale, 11, 8680, 2019.
8 T. F. C. Mah and G. A. O’Toole, Trends Microbiol., 9, 34–39, 2001.
9 D. L. Worcester, D. L. Proc. Natl. Acad. Sci. U.S.A., 75, 5475–5477, 1978.
10 D. Miklavcic, et al. Bioelectrochemistry, 63, 311–315, 2004.
11 M. Vukomanovic, S. Skapin, D. Suvorov, EP2863751A1, P-201200204
12 M. Vukomanović et al. Sci. Rep., 7, 4324, 2017. doi.org/10.1038/s41598-017-04670-0
13 M. Vukomanović et al. Small, 1800205, 2018. doi.org/10.1002/smll.201800205
14 M. Kurtjak, M. Vukomanovic, D. Suvorov, Mater. Lett., 193, 126, 2017. doi.org/10.1016/j.matlet.2017.01.092
15 L. Gazvoda, M. Perisic-Nanut, M. Spreitzer, M. Vukomanovic, Biomater. Sci., 10, 4933-4948, 2022. https://doi.org/10.1039/D2BM00644H
16 M. Kurtjak. M. Macek Krzmanc, M. Spreitzer, M. Vukomanovic, Pharmaceutics, 16(2), 228, 2024. https://www.mdpi.com/1999-4923/16/2/228
Biomaterials team
Team Leader: Dr. Marija Vukomanović
Researchers: Dr. Lea Gazvoda
Young Researchers: Martina Žabčić
