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Development of Peptide-Based Wound Dressings for Prevention and Management of Infected Wounds
Reported here is the development of peptide-based wound dressings, a polyurethane foam dressing and a collagen dressing substrate both containing host defense peptides (HDPs)1-2 as active antimicrobial payload.
Discussed here is the optimization of the polyurethane foams to maximize the release of the active peptide payload from the dressings, coupled with the anti-biofilm efficacy assessment in a series of in vitro and in vivo studies.
The in vitro studies revolved around the use of Human Skin Equivalent (HSE) model3, a 3D tissue model formed on the cell culture inserts containing a porous membrane, and luminescent strains of Staphylococcus aureus or Pseudomonas aeruginosa.
The 24 h old biofilms were treated with polyurethane dressings containing active payload. Luminescence was used for visualization of the surviving bacteria both on the dressing and the skin surface. The survival was further evaluated through recovery and enumeration. The data shows that the dressings can significantly reduce microbial load both on the skin and within the dressing, i.e., > 4 log reduction. Moreover, this model served as a useful tool to identify synergistic effects of combination treatments, i.e., peptide + traditional antibiotic.
The polyurethane foam dressings containing antimicrobial treatment were further evaluated in mouse abscess model4 and porcine dermal biofilm5-6 model and showed the same trends of efficacy as in the HSE model indicating the usefulness of the HSE model in down-selection of candidate treatments. Finally, the most promising treatments – peptide and peptide+antibiotic combination, were loaded onto collagen dressings with the goal of further increasing the delivery of the antimicrobial agents to the wound site. The use of collagen dressings resulted in enhancement of anti-biofilm efficacy and > 3.5 log reduction of P. aeruginosa biofilms in the porcine dermal biofilm model. As comparison, silver sulfadiazine treatment, a positive control in these studies, reduced P. aeruginosa biofilm load by < 1 log.
This data indicates potentially important clinical implications of the use of peptide-based antimicrobial dressings.Acknowledgement: This study was supported by DOD Grant (W81XWH-18-2-0028) awarded to iFyber, LLC. iFyber would like to thank our collaborators at the University of Miami (Prof. Davis’s group).
References
1. Hancock, R.E.W., Alford, M.A. & Haney, E.F Antibiofilm activity of host defence peptides: complexity provides opportunities. Nature Rev. Microbiol 2021; 19: 786-797.
2. Hancock, R.E.W., Haney, E.F., Gill, E.E. The immunology of host defence peptides: beyond antimicrobial activity. Nat Rev Immunol, 2016; 16(5): 321-34.
3. Wu, B., Haney, E.F., Akhoundsadegh, N., Pletzer, D., Trimble, M.J., Adriaans, A.E., Nibbering, P.H., Hancock R.E.W., Human organoid biofilm model for assessing antibiofilm activity of novel agents. NPJ Biofilms and Microbiomes. 2021; 7: art 8.
4. Pletzer D., Mansour S.C., Wuerth K, Rahanjam N., Hancock R.E.W. New Mouse Model for Chronic Infections by Gram-Negative Bacteria Enabling the Study of Anti-Infective Efficacy and Host-Microbe Interactions. mBio 2017; 8 (1).
5. Davis, S.C., Gil, J., Solis, M., Higa, A., Mills, A., Simms, C., Valencia-Pena, P., Li, J., Raut, V. Antimicrobial Effectiveness of Wound Matrices containing Native Extra Cellular Matrix (ECM) with Polyhexamethylene Biguanide (PHMB), Int Wound J. 2021; 1-14.
6. Davis SC, Gil J, Li J, Simms C, Valdes J, Solis M, Higa A. Effect of Mechanical Debridement, and Irrigation with Hypochlorous Acid Wound Management Solution on Methicillin-resistant Staphylococcus aureus Contamination and Healing Deep Dermal Wounds in a Porcine Model. Wound Management Prevention. 2021; 67(8): 24-31.
