Zhiwei Li

All Publications

• Hydrogels for Local and Sustained Delivery of Bacteriophages to Treat Multidrug-Resistant Wound Infections. bioRxiv : the preprint server for biology Lin, Y. H., Dharmaraj, T., Chen, Q., Echterhof, A., Manasherob, R., Zheng, L. J., de Leeuw, C., Peterson, N. A., Stannard, W., Li, Z., Hajfathalian, M., Hargil, A., Martinez, H. A., Chang, T. H., Blankenberg, F. B., Amanatullah, D., Chaudhuri, O., Bollyky, P. 2024

  Abstract

  Bacteriophages (phages), viruses that specifically target and kill bacteria, represent a promising strategy to combat multidrug-resistant (MDR) pathogens such as Pseudomonas aeruginosa (Pa). However, delivering sufficient concentrations of active phages directly to the infection site remains challenging, with current methods having variable success. Here we present "HydroPhage", an innovative hydrogel system for the sustained release of high-titer phages to effectively treat infections caused by MDR pathogens. Our injectable hydrogels, featuring dual-crosslinking of hyaluronic acid and PEG-based hydrogels through static covalent thioether bonds and dynamic covalent hemithioacetal crosslinks (DCC), encapsulate phages at concentration up to 1011 PFU/mL, and achieves controlled release of 109 PFU daily over a week, surpassing levels of current clinical dosages, with more than 60% total phage recovery. In a preclinical mouse model of extended wound infection, compared to intravenous treatment, we demonstrate enhanced bacterial clearance by localized, high-dose, and repeated phage dosing despite the emergence of bacterial resistance to phages. This work advances the development of clinically practical wound dressings tailored for resistant infections.

  View details for DOI 10.1101/2024.05.07.593005

  View details for PubMedID 38766200

  View details for PubMedCentralID PMC11100690