Hydrogel delivery of DNase I and liposomal vancomycin to eradicate fracture-related methicillin-resistant staphylococcus aureus infection and support osteoporotic fracture healing

Li, Jie; Leung, Shui Yee Sharon; Chung, Yik Lok; Chow, Simon Kwoon‐Ho; Alt, Volker; Rupp, Markus; Brochausen, Christoph; Chui, Ernest; Ip, Margaret; Cheung, Wing-Hoi; Wong, Ronald Man Yeung

doi:10.1016/j.actbio.2023.03.044

Cited by 16 publications

(4 citation statements)

References 64 publications

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“…DNase may be a potential therapeutic for other disease models. Potential avenues include the administration of DNase in combination with antibiotic therapy ( Li et al., 2023 ) as well as DNase pre-treatment of medical implants ( Aktan et al., 2022 ).…”

Section: Edna and Biofilm Eradicationmentioning

confidence: 99%

Beyond the double helix: the multifaceted landscape of extracellular DNA in Staphylococcus aureus biofilms

Bowden,

Finlinson,

Jones

et al. 2024

Front. Cell. Infect. Microbiol.

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Staphylococcus aureus forms biofilms consisting of cells embedded in a matrix made of proteins, polysaccharides, lipids, and extracellular DNA (eDNA). Biofilm-associated infections are difficult to treat and can promote antibiotic resistance, resulting in negative healthcare outcomes. eDNA within the matrix contributes to the stability, growth, and immune-evasive properties of S. aureus biofilms. eDNA is released by autolysis, which is mediated by murein hydrolases that access the cell wall via membrane pores formed by holin-like proteins. The eDNA content of S. aureus biofilms varies among individual strains and is influenced by environmental conditions, including the presence of antibiotics. eDNA plays an important role in biofilm development and structure by acting as an electrostatic net that facilitates protein-cell and cell-cell interactions. Because of eDNA’s structural importance in biofilms and its ubiquitous presence among S. aureus isolates, it is a potential target for therapeutics. Treatment of biofilms with DNase can eradicate or drastically reduce them in size. Additionally, antibodies that target DNABII proteins, which bind to and stabilize eDNA, can also disperse biofilms. This review discusses the recent literature on the release, structure, and function of eDNA in S. aureus biofilms, in addition to a discussion of potential avenues for targeting eDNA for biofilm eradication.

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Section: Edna and Biofilm Eradicationmentioning

confidence: 99%

Beyond the double helix: the multifaceted landscape of extracellular DNA in Staphylococcus aureus biofilms

Bowden,

Finlinson,

Jones

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Some patients may even require extensive debridement surgeries, which can induce more trauma. [ 5 , 6 ] Thus, minimally invasive treatment has become a popular approach in the clinic, offering potential solutions to the limitations of traditional, ineffective osteomyelitis treatments. [ 7 , 8 ]…”

Section: Introductionmentioning

confidence: 99%

Injectable Nano‐Micro Composites with Anti‐bacterial and Osteogenic Capabilities for Minimally Invasive Treatment of Osteomyelitis

Lu,

Zhao,

Wang

et al. 2024

Advanced Science

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The effective management of osteomyelitis remains extremely challenging due to the difficulty associated with treating bone defects, the high probability of recurrence, the requirement of secondary surgery or multiple surgeries, and the difficulty in eradicating infections caused by methicillin‐resistant Staphylococcus aureus (MRSA). Hence, smart biodegradable biomaterials that provide effective and precise local anti‐infection effects and can promote the repair of bone defects are actively being developed. Here, a novel nano‐micro composite is fabricated by combining calcium phosphate (CaP) nanosheets with drug‐loaded GelMA microspheres via microfluidic technology. The microspheres are covalently linked with vancomycin (Van) through an oligonucleotide (oligo) linker using an EDC/NHS carboxyl activator. Accordingly, a smart nano‐micro composite called “CaP@MS‐Oligo‐Van” is synthesized. The porous CaP@MS‐Oligo‐Van composites can target and capture bacteria. They can also release Van in response to the presence of bacterial micrococcal nuclease and Ca2+, exerting additional antibacterial effects and inhibiting the inflammatory response. Finally, the released CaP nanosheets can promote bone tissue repair. Overall, the findings show that a rapid, targeted drug release system based on CaP@MS‐Oligo‐Van can effectively target bone tissue infections. Hence, this agent holds potential in the clinical treatment of osteomyelitis caused by MRSA.

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“…Hydrogel can also be a vehicle for administering medications to wounds given its high purity, ability to retain moisture, protect the body from impurities, and enable gas exchange, and its high biocompatibility [21,[27][28][29]. The incorporation of vancomycin (VAN) in hydrogel is a relevant alternative to enhance the antibacterial and antibiofilm action of biomaterials [30,31]. VAN is a glycopeptide that inhibits the polymerization of peptidoglycans in the bacterial cell wall, causing extravasation of intracellular components.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial and Antibiofilm Potential of Bacterial Cellulose Hydrogel Containing Vancomycin against Multidrug-Resistant Staphylococcus aureus and Staphylococcus epidermidis

Correia,

de Almeida Campos,

de Queiroz Macêdo

et al. 2024

Biology

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The present study aimed to evaluate the in vitro antibacterial and antibiofilm activity of bacterial cellulose hydrogel produced by Zoogloea sp. (HYDROGEL) containing vancomycin (VAN) against bacterial strains that cause wound infections, such as multidrug-resistant (MDR) Staphylococcus aureus and Staphylococcus epidermidis. Initially, HYDROGEL was obtained from sugar cane molasses, and scanning electron microscopy (SEM) was performed to determine morphological characteristics. Then, VAN was incorporated into HYDROGEL (VAN-HYDROGEL). The antibacterial activity of VAN, HYDROGEL, and VAN-HYDROGEL was assessed using the broth microdilution method to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against methicillin-sensitive S. aureus (MSSA) ATCC 25923, methicillin-resistant S. aureus (MRSA) ATCC 33591, S. epidermidis INCQS 00016 (ATCC 12228), five clinical isolates of MRSA, and nine clinical isolates of methicillin-resistant S. epidermidis, following the Clinical and Laboratory Standards Institute (CLSI) guidelines. Additionally, the antibacterial activity of VAN, HYDROGEL, and VAN-HYDROGEL was studied using the time-kill assay. Subsequently, the antibiofilm activity of VAN, HYDROGEL, and VAN-HYDROGEL was evaluated using crystal violet and Congo red methods, as well as SEM analysis. VAN and VAN-HYDROGEL showed bacteriostatic and bactericidal activity against MRSA and methicillin-resistant S. epidermidis strains. HYDROGEL did not show any antibacterial activity. Analysis of the time-kill assay indicated that HYDROGEL maintained the antibacterial efficacy of VAN, highlighting its efficiency as a promising carrier. Regarding antibiofilm activity, VAN and HYDROGEL inhibited biofilm formation but did not demonstrate biofilm eradication activity against methicillin-resistant S. aureus and S. epidermidis strains. However, it was observed that the biofilm eradication potential of VAN was enhanced after incorporation into HYDROGEL, a result also proven through images obtained by SEM. From the methods carried out in this study, it was possible to observe that HYDROGEL preserved the antibacterial activity of vancomycin, aside from exhibiting antibiofilm activity and enhancing the antibiofilm effect of VAN. In conclusion, this study demonstrated the potential of HYDROGEL as a candidate and/or vehicle for antibiotics against MDR bacteria that cause wound infections.

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Hydrogel delivery of DNase I and liposomal vancomycin to eradicate fracture-related methicillin-resistant staphylococcus aureus infection and support osteoporotic fracture healing

Cited by 16 publications

References 64 publications

Beyond the double helix: the multifaceted landscape of extracellular DNA in Staphylococcus aureus biofilms

Beyond the double helix: the multifaceted landscape of extracellular DNA in Staphylococcus aureus biofilms

Injectable Nano‐Micro Composites with Anti‐bacterial and Osteogenic Capabilities for Minimally Invasive Treatment of Osteomyelitis

Antibacterial and Antibiofilm Potential of Bacterial Cellulose Hydrogel Containing Vancomycin against Multidrug-Resistant Staphylococcus aureus and Staphylococcus epidermidis

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