Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy
Grzegorz Fila1, Kamola Kasimova2, Yaxal Arenas3
1Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk Gdansk, Poland.
Abstract:
It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24-48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections.
Insights
Antimicrobial Photodynamic Therapy (APDT) shows promise for chronic wounds. A new mouse model allows real-time pathogen monitoring, aiding APDT development for wound infections.
Area of Science:
- Infectious Diseases
- Biomedical Engineering
- Photomedicine
Background:
- Antibiotic resistance necessitates alternative treatments for chronic wound infections.
- Antimicrobial Photodynamic Therapy (APDT) is approved for some conditions but not yet established for chronic wounds.
Purpose of the Study:
- To develop and validate an animal model for studying APDT in chronic wound infections.
- To evaluate the efficacy of four photosensitizers in a murine model of chronic wounds.
Main Methods:
- A full-thickness skin wound model in mice with an optically transparent cover was established.
- Two bioluminescent pathogens, MRSA and Pseudomonas aeruginosa, were used for real-time monitoring.
- Four photosensitizers (Rose Bengal, TMPyP, New Methylene Blue, TLD1411) were tested in vitro and in vivo.
Main Results:
- The model supported rapid pathogen growth for up to 8 days.
- In vitro, all photosensitizers showed good to excellent antimicrobial activity.
- In vivo, limited pathogen growth delay (24-48h) was observed for MRSA; P. aeruginosa showed longer suppression with TLD1411.
Conclusions:
- The developed murine model effectively mimics chronic wound hallmarks and pathogen dynamics.
- Further strategies are needed to enhance APDT efficacy for treating chronic wound infections.
- TLD1411 demonstrated potential for P. aeruginosa suppression in this model.
