<p>Treatment of wound infections has been a matter of concern due to the emergence of antimicrobial resistance (AMR) in <i>Pseudomonas aeruginosa</i> (PA). As an alternative to antibiotics, phage therapy has proven to be an effective strategy to combat AMR. The present study aimed to fabricate PA phage (PAΦ)-gentamicin (GeN)-loaded dressing made from chitosan and alginate, to thwart wound infections associated with PA. Various chitosan-alginate (CA) scaffolds (1&#xa0;C:1&#xa0;A/1&#xa0;C:3&#xa0;A/3&#xa0;C:1&#xa0;A) were prepared by physical crosslinking and subjected to parametric analysis for screening, followed by functionalizing using PAΦ-GeN combination. The findings revealed that 1&#xa0;C:1&#xa0;A dressing exhibited high swelling index (1887%), protein adsorption ability (845.8&#xa0;µg.cm<sup>− 2</sup>), and in vitro biodegradability within 7 days. FTIR spectroscopy and thermogravimetric analysis supported biophysical characterization and electron microscopy revealed microporous structure of the dressing. Functionalized CA dressings demonstrated broad-range antibacterial potential against standard strains of <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, <i>Acinetobacter baumannii</i>, <i>Klebsiella pneumoniae</i>, and clinical strains of PA, while displaying a biocompatible/non-allergenic nature. The therapeutic potential of functionalized CA dressing was further validated in vivo using a thermal injury murine model infected with PA. Topical application of PAΦ-GeN-loaded CA dressing significantly lowered bacterial burden on day 3 post-infection (p.i.) and completely eradicated pseudomonal infection by day 21 p.i. Furthermore, the functionalized CA dressing significantly enhanced skin re-epithelialization and resulted in complete wound closure in BALB/c mice on day 21 p.i. Overall, the present study reinforces the application of functionalized wound dressings as promising alternative to traditional wound care products for management of skin infections.</p> Graphical Abstract <p></p>

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Synergistic Phage-Antibiotic Functionalized Chitosan-Alginate Advanced Wound Dressing for Combating Pseudomonas Aeruginosa Infection

  • Lavanya Khullar,
  • Jatin Chadha,
  • Kusum Harjai,
  • Vasundhara Singh,
  • Sanjay Chhibber

摘要

Treatment of wound infections has been a matter of concern due to the emergence of antimicrobial resistance (AMR) in Pseudomonas aeruginosa (PA). As an alternative to antibiotics, phage therapy has proven to be an effective strategy to combat AMR. The present study aimed to fabricate PA phage (PAΦ)-gentamicin (GeN)-loaded dressing made from chitosan and alginate, to thwart wound infections associated with PA. Various chitosan-alginate (CA) scaffolds (1 C:1 A/1 C:3 A/3 C:1 A) were prepared by physical crosslinking and subjected to parametric analysis for screening, followed by functionalizing using PAΦ-GeN combination. The findings revealed that 1 C:1 A dressing exhibited high swelling index (1887%), protein adsorption ability (845.8 µg.cm− 2), and in vitro biodegradability within 7 days. FTIR spectroscopy and thermogravimetric analysis supported biophysical characterization and electron microscopy revealed microporous structure of the dressing. Functionalized CA dressings demonstrated broad-range antibacterial potential against standard strains of Escherichia coli, Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae, and clinical strains of PA, while displaying a biocompatible/non-allergenic nature. The therapeutic potential of functionalized CA dressing was further validated in vivo using a thermal injury murine model infected with PA. Topical application of PAΦ-GeN-loaded CA dressing significantly lowered bacterial burden on day 3 post-infection (p.i.) and completely eradicated pseudomonal infection by day 21 p.i. Furthermore, the functionalized CA dressing significantly enhanced skin re-epithelialization and resulted in complete wound closure in BALB/c mice on day 21 p.i. Overall, the present study reinforces the application of functionalized wound dressings as promising alternative to traditional wound care products for management of skin infections.

Graphical Abstract