Treatment Strategies for Infected Wounds

Neguț, Irina; Grumezescu, Valentina; Grumezescu, Alexandru Mihai

doi:10.3390/molecules23092392

Cited by 550 publications

(424 citation statements)

References 168 publications

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“…According to the results of Table 1 and Figure 12, coated scaffolds (sample B) against E. coli appear to have superior antibacterial effects in comparison with S. aureus after 24h. This is in consistent with the findings of our previous study [36] as well as results reported in other studies [43][44][45]. It seems that the high hydrophilicity of Gram-negative bacteria in comparison with Gram-positive species renders them more susceptible to the membrane damage via chitosan cations.…”

Section: Discussionsupporting

confidence: 93%

Tailored PCL Scaffolds as Skin Substitutes Using Sacrificial PVP Fibers and Collagen/Chitosan Blends

Sadeghi-Avalshahr

Nokhasteh

Molavi

et al. 2020

IJMS

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Electrospinning is a versatile technique for fabrication of made-on-purpose biomimetic scaffolds. In this study, optimized electrospun fibrous membranes were produced by simultaneous electrospinning of polycaprolactone (PCL) and polyvinylpyrrolidone (PVP), followed by the selective removal of PVP from the PCL/PVP mesh. After aminolysis, a blend of collagen/chitosan was grafted on the surface. Physicochemical characterizations as well as in vitro evaluations were conducted using different methods. Successful cell infiltration into samples was observed. It seems that the positive trend of cell ingress originates from the proper pore size obtained after removal of pvp (from 4.46 μm before immersion in water to 33.55 μm after immersion in water for 24 h). Furthermore, grafting the surface with the collagen/chitosan blend rendered the scaffolds more biocompatible with improved attachment and spreading of keratinocyte cell lines (HaCaT). Viability evaluation through MTT assay for HDF cells did not reveal any cytotoxic effects. Antibacterial assay with Staphylococcus aureus as Gram-positive and Escherichia coli as Gram-negative species corroborated the bactericidal effects of chitosan utilized in the composition of the coated blend. The results of in vitro studies along with physicochemical characterizations reflect the great potentials of the produced samples as scaffolds for application in skin tissue engineering.

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Section: Discussionsupporting

confidence: 93%

Tailored PCL Scaffolds as Skin Substitutes Using Sacrificial PVP Fibers and Collagen/Chitosan Blends

Sadeghi-Avalshahr

Nokhasteh

Molavi

et al. 2020

IJMS

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“…S. aureus biofilms rarely resolve with antibiotic treatment alone and usually require surgical intervention (debridement, drainage, incision) 35 . Many antibiotics reduce bacterial burdens within biofilms but eradication represents an arduous challenge even in vitro 5,11 .…”

Section: Discussionmentioning

confidence: 99%

Harnessing Ultrasound-Stimulated Phase Change Contrast Agents to Improve Antibiotic Efficacy Against Methicillin-ResistantStaphylococcus aureusBiofilms

Durham

Sidders

Dayton

et al. 2020

Preprint

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17Bacterial biofilms, often associated with chronic infections, respond poorly to antibiotic 18 therapy and frequently require surgical intervention. Biofilms harbor persister cells, metabolically 19 indolent cells, which are tolerant to most conventional antibiotics. In addition, the biofilm matrix 20 can act as a physical barrier, impeding diffusion of antibiotics. Novel therapeutic approaches 21 frequently improve biofilm killing, but usually fail to achieve eradication. Failure to eradicate the 22 biofilm leads to chronic and relapsing infection, associated with major financial healthcare costs 23 and significant morbidity and mortality. We address this problem with a two-pronged strategy 24 using 1) antibiotics that target persister cells and 2) ultrasound-stimulated phase-change 25 contrast agents (US-PCCA) , which improve antibiotic penetration. 26We previously demonstrated that rhamnolipids, produced by Pseudomonas aeruginosa, 27 could induce aminoglycoside uptake in gram-positive organisms, leading to persister cell death. 28We have also shown that US-PCCA can transiently disrupt biological barriers to improve 29 penetration of therapeutic macromolecules. We hypothesized that combining antibiotics which 30 target persister cells with US-PCCA to improve drug penetration could eradicate methicillin 31 resistant S. aureus (MRSA) biofilms. Aminoglycosides alone or in combination with US-PCCA 32 displayed limited efficacy against MRSA biofilms. In contrast, the anti-persister combination of 33 rhamnolipids and aminoglycosides combined with US-PCCA dramatically reduced biofilm 34 viability, frequently culminating in complete eradication of the biofilm. These data demonstrate 35 that biofilm eradication can be achieved using a combined approach of improving drug 36 penetration of therapeutics that target persister cells.37 38 42 osteomyelitis, endocarditis and pneumonia 2,3. In addition to the high degree of mortality, chronic 43 and relapsing S. aureus infections are common and associated with significant morbidity. This is 44 2 due to frequent treatment failure of S. aureus infections. This is best illustrated by SSTIs, with 45 some studies suggesting treatment failure rates as high as 45% and a recurrence rate of 70% 4. 46Importantly the failure of antibiotic therapy cannot be adequately explained by antibiotic 47 resistance 1. Failure to clear the infection leads to a need for prolonged antibiotic therapies, 48 increased morbidity and mortality, increased likelihood of antibiotic resistance development as 49 well as an enormous financial healthcare burden. 50 S. aureus forms biofilms, bacterial cells embedded in a self-produced extracellular 51 matrix, which act as a protective barrier from the host immune response and other 52 environmental assaults. Biofilms expand up to 1200μm in thickness when attached to indwelling 53 devices such as catheters 5. Non-surface attached biofilms, in chronic wounds and chronic lung 54 infections, harbor smaller non-surface attached cell aggregates ranging from 2-200μm in 5...

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“…Modern dressings are capable of both maintaining this moist wound environment and providing a physical barrier between the wound and contamination from the external environment [4,29]. Therapeutic outcomes and wound response to drugs can also be improved when dressings are fully dissolvable, non-replaceable, or non-adherent and if they distribute treatments (e.g., components that can help in the removal of necrotic tissues, prevent/treat infections, or both) to the wound site in a precise manner [88]. Wound dressings are, today, functionalized to incorporate several classes of antibiotics (e.g., quinolones, tetracyclines, aminoglycosides, cephalosporins) or other substances with antibacterial properties (e.g., essential oils) delivered directly at the wound sites [88].…”

Section: Non-phage-based Wound Treatmentsmentioning

confidence: 99%

“…Therapeutic outcomes and wound response to drugs can also be improved when dressings are fully dissolvable, non-replaceable, or non-adherent and if they distribute treatments (e.g., components that can help in the removal of necrotic tissues, prevent/treat infections, or both) to the wound site in a precise manner [88]. Wound dressings are, today, functionalized to incorporate several classes of antibiotics (e.g., quinolones, tetracyclines, aminoglycosides, cephalosporins) or other substances with antibacterial properties (e.g., essential oils) delivered directly at the wound sites [88]. The recruitment of cells, stimulation of cell proliferation, and regulation of extracellular matrix deposition can all be achieved using growth factors [4].…”

Section: Non-phage-based Wound Treatmentsmentioning

confidence: 99%

Bacteriophages for Chronic Wound Treatment: From Traditional to Novel Delivery Systems

Pinto

Cerqueira

Bañobre-Lópes

et al. 2020

Viruses

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The treatment and management of chronic wounds presents a massive financial burden for global health care systems, with significant and disturbing consequences for the patients affected. These wounds remain challenging to treat, reduce the patients' life quality, and are responsible for a high percentage of limb amputations and many premature deaths. The presence of bacterial biofilms hampers chronic wound therapy due to the high tolerance of biofilm cells to many firstand second-line antibiotics. Due to the appearance of antibiotic-resistant and multidrug-resistant pathogens in these types of wounds, the research for alternative and complementary therapeutic approaches has increased. Bacteriophage (phage) therapy, discovered in the early 1900s, has been revived in the last few decades due to its antibacterial efficacy against antibiotic-resistant clinical isolates. Its use in the treatment of non-healing wounds has shown promising outcomes. In this review, we focus on the societal problems of chronic wounds, describe both the history and ongoing clinical trials of chronic wound-related treatments, and also outline experiments carried out for efficacy evaluation with different phage-host systems using in vitro, ex vivo, and in vivo animal models. We also describe the modern and most recent delivery systems developed for the incorporation of phages for species-targeted antibacterial control while protecting them upon exposure to harsh conditions, increasing the shelf life and facilitating storage of phage-based products. In this review, we also highlight the advances in phage therapy regulation.

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Treatment Strategies for Infected Wounds

Cited by 550 publications

References 168 publications

Tailored PCL Scaffolds as Skin Substitutes Using Sacrificial PVP Fibers and Collagen/Chitosan Blends

Tailored PCL Scaffolds as Skin Substitutes Using Sacrificial PVP Fibers and Collagen/Chitosan Blends

Harnessing Ultrasound-Stimulated Phase Change Contrast Agents to Improve Antibiotic Efficacy Against Methicillin-ResistantStaphylococcus aureusBiofilms

Bacteriophages for Chronic Wound Treatment: From Traditional to Novel Delivery Systems

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