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RESEARCH ARTICLE (Open Access)

Antibacterial hydrogel therapy for eradication of wound associated polymicrobial biofilms

Hanif Haidari A and Zlatko Kopecki A *
+ Author Affiliations
- Author Affiliations

A Future Industries Institute, University of South Australia, Mawson Lakes, SA 5095, Australia.




Dr Hanif Haidari is a Research Associate at University of South Australia. His research interests include inorganic nanoparticles synthesis and applications against antibacterial resistance using latest in vitro and in vivo models. He also has strong interest in the development of smart drug-delivery systems for prevention of antimicrobial resistance and wound infection development.



Dr Zlatko Kopecki is a Senior Research Fellow at the University of South Australia and a Channel 7 Children’s Research Foundation Mid‐Career Fellow for Childhood Wound Infections. Dr Kopecki’s research is focussed on developing novel therapeutics for wound repair and working on understanding the mechanisms involved in wound healing, scar formation and fragile skin syndromes. He is also interested in integration of different approaches and biomaterials for the development of novel wound dressings and therapeutic approaches to improve healing and combat wound infection.

* Correspondence to: zlatko.kopecki@unisa.edu.au

Microbiology Australia 44(2) 104-108 https://doi.org/10.1071/MA23029
Submitted: 25 March 2023  Accepted: 20 April 2023   Published: 19 May 2023

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of the ASM. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

The recalcitrance of bacterial biofilms to current antimicrobials has presented a major cause of clinical recurrence of wound infections. These biofilm-associated infections are often present in polymicrobial nature associated with the presence of Pseudomonas aeruginosa and Staphylococcus aureus creating a large heterogeneity that shares a common resistance to current antimicrobials making pathogen eradication extremely challenging. In this study, we overcome the intrinsic biofilm barriers by delivering ultrasmall-sized silver nanoparticles (AgNP) using a smart hydrogel system that allows slow and sustained release of silver ions mediating successful accumulation and penetration of bacterial biofilms. The antibiofilm efficacy of the AgNP hydrogel was assessed using ex vivo porcine wound polymicrobial biofilms. Treatment with AgNP hydrogel resulted in significant dispersion of early to mature biofilms, 2–5-log reduction of bacteria compared to untreated controls. This approach overcomes the enhanced tolerance and resistance of polymicrobial biofilms by using the combined benefits of smart delivery system and the antibiofilm properties of ultrasmall AgNPs to ensure biofilm complete destruction and elimination.

Keywords: antimicrobial resistance, biofilm, hydrogel drug delivery, polymicrobial infection, silver nanoparticles.


References

[1]  Donlan, RM and Costerton, JW (2002) Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 15, 167–193.
Biofilms: survival mechanisms of clinically relevant microorganisms.Crossref | GoogleScholarGoogle Scholar |

[2]  Haidari, H et al. (2021) Eradication of mature bacterial biofilms with concurrent improvement in chronic wound healing using silver nanoparticle hydrogel treatment. Biomedicines 9, 1182.
Eradication of mature bacterial biofilms with concurrent improvement in chronic wound healing using silver nanoparticle hydrogel treatment.Crossref | GoogleScholarGoogle Scholar |

[3]  Frieri, M et al. (2017) Antibiotic resistance. J Infect Public Health 10, 369–378.
Antibiotic resistance.Crossref | GoogleScholarGoogle Scholar |

[4]  Stacy, A et al. (2016) The biogeography of polymicrobial infection. Nat Rev Microbiol 14, 93–105.
The biogeography of polymicrobial infection.Crossref | GoogleScholarGoogle Scholar |

[5]  DeLeon, S et al. (2014) Synergistic interactions of Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro wound model. Infect Immun 82, 4718–4728.
Synergistic interactions of Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro wound model.Crossref | GoogleScholarGoogle Scholar |

[6]  Shaw, ZL et al. (2021) Broad-spectrum solvent-free layered black phosphorus as a rapid action antimicrobial. ACS Appl Mater Interfaces 13, 17340–17352.
Broad-spectrum solvent-free layered black phosphorus as a rapid action antimicrobial.Crossref | GoogleScholarGoogle Scholar |

[7]  Arafa, MG et al. (2018) Thermoresponsive gels containing gold nanoparticles as smart antibacterial and wound healing agents. Sci Rep 8, 13674.
Thermoresponsive gels containing gold nanoparticles as smart antibacterial and wound healing agents.Crossref | GoogleScholarGoogle Scholar |

[8]  Sirelkhatim, A et al. (2015) Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nanomicro Lett 7, 219–242.
Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism.Crossref | GoogleScholarGoogle Scholar |

[9]  Ravindran Girija, A et al. (2019) Ultrasmall gold nanocluster based antibacterial nanoaggregates for infectious wound healing. ChemNanoMat 5, 1176–1181.
Ultrasmall gold nanocluster based antibacterial nanoaggregates for infectious wound healing.Crossref | GoogleScholarGoogle Scholar |

[10]  Haidari, H et al. (2020) Silver-based wound dressings: current issues and future developments for treating bacterial infections. Wound Pract Res 28, 176–183.
Silver-based wound dressings: current issues and future developments for treating bacterial infections.Crossref | GoogleScholarGoogle Scholar |

[11]  Haidari, H et al. (2019) The interplay between size and valence state on the antibacterial activity of sub-10 nm silver nanoparticles. Nanoscale Adv 1, 2365–2371.
The interplay between size and valence state on the antibacterial activity of sub-10 nm silver nanoparticles.Crossref | GoogleScholarGoogle Scholar |

[12]  Haidari, H et al. (2020) Ultrasmall AgNP-impregnated biocompatible hydrogel with highly effective biofilm elimination properties. ACS Appl Mater Interfaces 12, 41011–41025.
Ultrasmall AgNP-impregnated biocompatible hydrogel with highly effective biofilm elimination properties.Crossref | GoogleScholarGoogle Scholar |

[13]  Haidari, H et al. (2021) Multifunctional ultrasmall AgNP hydrogel accelerates healing of S. aureus infected wounds. Acta Biomater 128, 420–434.
Multifunctional ultrasmall AgNP hydrogel accelerates healing of S. aureus infected wounds.Crossref | GoogleScholarGoogle Scholar |

[14]  Haidari, H et al. (2022) Polycationic silver nanoclusters comprising nanoreservoirs of Ag+ ions with high antimicrobial and antibiofilm activity. ACS Appl Mater Interfaces 14, 390–403.
Polycationic silver nanoclusters comprising nanoreservoirs of Ag+ ions with high antimicrobial and antibiofilm activity.Crossref | GoogleScholarGoogle Scholar |

[15]  Yang, Q et al. (2013) Development of a novel ex vivo porcine skin explant model for the assessment of mature bacterial biofilms. Wound Repair Regen 21, 704–714.
Development of a novel ex vivo porcine skin explant model for the assessment of mature bacterial biofilms.Crossref | GoogleScholarGoogle Scholar |

[16]  Haidari, H et al. (2017) Development of topical delivery systems for flightless neutralizing antibody. J Pharm Sci 106, 1795–1804.
Development of topical delivery systems for flightless neutralizing antibody.Crossref | GoogleScholarGoogle Scholar |

[17]  Haidari, H et al. (2022) Bacteria-activated dual pH- and temperature-responsive hydrogel for targeted elimination of infection and improved wound healing. ACS Appl Mater Interfaces 14, 51744–51762.
Bacteria-activated dual pH- and temperature-responsive hydrogel for targeted elimination of infection and improved wound healing.Crossref | GoogleScholarGoogle Scholar |

[18]  Nair, N et al. (2014) Impact of Staphylococcus aureus on pathogenesis in polymicrobial infections. Infect Immun 82, 2162–2169.
Impact of Staphylococcus aureus on pathogenesis in polymicrobial infections.Crossref | GoogleScholarGoogle Scholar |

[19]  Sanyasi, S et al. (2016) Polysaccharide-capped silver nanoparticles inhibit biofilm formation and eliminate multi-drug-resistant bacteria by disrupting bacterial cytoskeleton with reduced cytotoxicity towards mammalian cells. Sci Rep 6, 24929.
Polysaccharide-capped silver nanoparticles inhibit biofilm formation and eliminate multi-drug-resistant bacteria by disrupting bacterial cytoskeleton with reduced cytotoxicity towards mammalian cells.Crossref | GoogleScholarGoogle Scholar |

[20]  Wu, S et al. (2021) Biofilm-sensitive photodynamic nanoparticles for enhanced penetration and antibacterial efficiency. Adv Funct Mater 31, 2103591.
Biofilm-sensitive photodynamic nanoparticles for enhanced penetration and antibacterial efficiency.Crossref | GoogleScholarGoogle Scholar |

[21]  Uroro, EO et al. (2022) Biocompatible polycationic silver nanocluster-impregnated PLGA nanocomposites with potent antimicrobial activity. ChemNanoMat 8, e202200349.
Biocompatible polycationic silver nanocluster-impregnated PLGA nanocomposites with potent antimicrobial activity.Crossref | GoogleScholarGoogle Scholar |

[22]  Liu, J et al. (2019) Boosting antibacterial activity with mesoporous silica nanoparticles supported silver nanoclusters. J Colloid Interface Sci 555, 470–479.
Boosting antibacterial activity with mesoporous silica nanoparticles supported silver nanoclusters.Crossref | GoogleScholarGoogle Scholar |

[23]  Wu, J et al. (2019) Responsive assembly of silver nanoclusters with a biofilm locally amplified bactericidal effect to enhance treatments against multi-drug-resistant bacterial infections. ACS Cent Sci 5, 1366–1376.
Responsive assembly of silver nanoclusters with a biofilm locally amplified bactericidal effect to enhance treatments against multi-drug-resistant bacterial infections.Crossref | GoogleScholarGoogle Scholar |

[24]  Yuan, X et al. (2014) Ultrasmall Ag+-rich nanoclusters as highly efficient nanoreservoirs for bacterial killing. Nano Res 7, 301–307.
Ultrasmall Ag+-rich nanoclusters as highly efficient nanoreservoirs for bacterial killing.Crossref | GoogleScholarGoogle Scholar |

[25]  Uroro, EO et al. (2023) Enzyme-responsive polycationic silver nanocluster-loaded PCL nanocomposites for antibacterial applications. Mater Today Chem 28, 101376.
Enzyme-responsive polycationic silver nanocluster-loaded PCL nanocomposites for antibacterial applications.Crossref | GoogleScholarGoogle Scholar |

[26]  Bright, R et al. (2022) Surfaces containing sharp nanostructures enhance antibiotic efficacy. Nano Lett 22, 6724–6731.
Surfaces containing sharp nanostructures enhance antibiotic efficacy.Crossref | GoogleScholarGoogle Scholar |