Peer-reviewedCC BY-NC-NDNature communications
Dosing and delivery of bacteriophage therapy in a murine wound infection model.
11 affiliations
- 1Department of Chemical Engineering, Stanford University, Stanford, CA, USA
- 2Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA
- 3Institute of Medical Microbiology, University Hospital of Muenster, Muenster, Germany
- 4Department of Orthopaedic Surgery, Stanford Hospital and Clinics, Redwood City, CA, USA
- 5Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA
- 6Institute for Molecules and Materials, Radboud University, Nijmegen, Netherlands
- 7Department of Biomedical Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ, USA
- 8Department of Biology, Stanford University, Stanford, CA, USA
- 9Division of Pediatric Radiology and Nuclear Medicine, Department of Radiology, Lucile Packard Children's Hospital, Stanford, CA, USA
- 10Department of Mechanical Engineering, Stanford University, Stanford, CA, USA. [email protected]
- 11Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA. [email protected]
Abstract
Lytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistant Pseudomonas aeruginosa. However, dosing and delivery strategies for phage therapy remain underdeveloped. In a mouse wound infection model specifically designed to evaluate the treatment of established infections-a critical gap in existing preclinical models-we investigated the impact of administration route, dose, and frequency on phage therapy efficacy. In this model, topical, but not systemic, delivery reduced wound bacterial burden. In vitro and in vivo data revealed rapid emergence of phage resistance and suggested potential benefit of using high and repeated doses. Building on these insights, we developed HydroPhage, a phage-containing hyaluronan-based hydrogel formed with dynamic covalent crosslinks that delivers high-titer phages over one week. Here, we show that sustained hydrogel-based delivery is a practical and effective approach for topical phage application.
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BibTeX
@article{lin2026dosing,
title = {{Dosing and delivery of bacteriophage therapy in a murine wound infection model.}},
author = {Yung‐Hao Lin and Tejas Dharmaraj and Qingquan Chen and Arne Echterhof and Robert Manasherob and Lucy J. Zhang and Zhiwei Li and Cas de Leeuw and Nana Ansuah Peterson and Tony Hong Wei Chang and Whitney Stannard and Maryam Hajfathalian and Aviv Hargil and Hunter A. Martinez and Julie D. Pourtois and Maya Abhyankar and Francis G. Blankenberg and Derek F. Amanatullah and Ovijit Chaudhuri and Paul L. Bollyky},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77992-1},
url = {https://europepmc.org/article/MED/42901960},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Dosing and delivery of bacteriophage therapy in a murine wound infection model.
AU - Yung‐Hao Lin
AU - Tejas Dharmaraj
AU - Qingquan Chen
AU - Arne Echterhof
AU - Robert Manasherob
AU - Lucy J. Zhang
AU - Zhiwei Li
AU - Cas de Leeuw
AU - Nana Ansuah Peterson
AU - Tony Hong Wei Chang
AU - Whitney Stannard
AU - Maryam Hajfathalian
AU - Aviv Hargil
AU - Hunter A. Martinez
AU - Julie D. Pourtois
AU - Maya Abhyankar
AU - Francis G. Blankenberg
AU - Derek F. Amanatullah
AU - Ovijit Chaudhuri
AU - Paul L. Bollyky
PY - 2026
DA - 2026/09/19
JO - Nature communications
DO - 10.1038/s41467-026-77992-1
UR - https://europepmc.org/article/MED/42901960
AB - Lytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistant Pseudomonas aeruginosa. However, dosing and delivery strategies for phage therapy remain underdeveloped. In a mouse wound infection model specifically designed to evaluate the treatment of established infections-a critical gap in existing preclinical models-we investigated the impact of administration route, dose, and frequency on phage therapy efficacy. In this model, topical, but not systemic, delivery reduced wound bacterial burden. In vitro and in vivo data revealed rapid emergence of phage resistance and suggested potential benefit of using high and repeated doses. Building on these insights, we developed HydroPhage, a phage-containing hyaluronan-based hydrogel formed with dynamic covalent crosslinks that delivers high-titer phages over one week. Here, we show that sustained hydrogel-based delivery is a practical and effective approach for topical phage application.
SN - 2041-1723
ER -