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Updated: Feb 1, 2026

Murine Model of Wound Healing
Published on: May 28, 2013
Bacteriophage and Nitric Oxide Combined Release from a Dual Hydrogel Matrix for Wound Healing Applications
Sarah N Wilson1, Adam B Goodman1, Aasma Sapkota1
1School of Chemical, Materials, and Biological Engineering, College of Engineering, University of Georgia, Athens, Georgia, USA.
Abstract:
Infection sites and open wounds provide a prime environment for the growth of opportunistic pathogens, leading to persistent infections caused by bacteria that contain antimicrobial-resistant phenotypes. Mistreatment of these wound infections often increases antimicrobial resistance (AMR), thereby decreasing the effectiveness of antibiotics. With the increase in AMR, new antimicrobial therapeutics that target these hard-to-kill pathogens are needed. Herein, naturally harvested bacteriophages (ECΦ) were combined with another established antimicrobial molecule, nitric oxide (NO). This combination has rarely been explored in biomedical devices but shows excellent potential for developing broad-spectrum, antibacterial materials. Bacteriophages were encapsulated in alginate microbeads and suspended in a NO-releasing thermoresponsive hydrogel. The phages were shown to have a delayed release from the alginate beads when incorporated into the gel, compared to the release observed within 24 h in aqueous medium. This delayed release enabled tunable phage delivery by adjusting the viscosity of the bulk gel base. Additionally, we used alginate as the base for microbeads, resulting in a physiologically safe material due to its proven biocompatibility. The final ECΦ and NO-releasing bead-gel matrix demonstrated 5-10 times larger zones of bacterial killing while maintaining low cytotoxicity, enabling further development in various clinical applications, including wound healing.
Insights
This study combines bacteriophages (ECΦ) and nitric oxide (NO) in a hydrogel for wound healing. The novel material shows enhanced bacterial killing and tunable delivery, offering a promising new antimicrobial therapeutic.
Area of Science:
- Biomaterials Science
- Microbiology
- Drug Delivery
Background:
- Opportunistic pathogens in wounds can develop antimicrobial resistance (AMR).
- Existing treatments for resistant wound infections are limited, necessitating novel therapeutics.
- Combining bacteriophages (ECΦ) and nitric oxide (NO) offers a potential broad-spectrum antibacterial strategy.
Purpose of the Study:
- To develop and evaluate a novel antimicrobial material combining bacteriophages (ECΦ) and nitric oxide (NO) for wound healing.
- To investigate the controlled release of bacteriophages from an alginate hydrogel matrix.
- To assess the antibacterial efficacy and cytotoxicity of the combined ECΦ and NO-releasing hydrogel.
Main Methods:
- Bacteriophages (ECΦ) were encapsulated in alginate microbeads.
- The microbeads were suspended in a nitric oxide (NO)-releasing thermoresponsive hydrogel.
- Phage release kinetics, antibacterial activity, and cytotoxicity were evaluated.
Main Results:
- A delayed release of bacteriophages from the alginate beads within the hydrogel was observed, enabling tunable delivery.
- The ECΦ and NO-releasing hydrogel demonstrated significantly larger zones of bacterial killing (5-10 times) compared to controls.
- The developed material exhibited low cytotoxicity, indicating good biocompatibility.
Conclusions:
- The combination of bacteriophages and nitric oxide in a tunable hydrogel matrix presents a promising approach for combating antimicrobial resistance in wound infections.
- Alginate microbeads facilitate controlled phage delivery, enhancing the material's therapeutic potential.
- This novel biomaterial warrants further development for clinical applications in wound healing and infection control.
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