Abstract Summary Bacteriophages—viruses that kill bacteria—are a powerful weapon against anti-microbial resistant (AMR) pathogens, including skin, bladder, and ear infections caused by the bacterium Pseudomonas aeruginosa (Pa). Phages require sustained exposure to kill bacteria effectively but unfortunately are rapidly cleared from circulation, making intravenous delivery impractical. We need better ways to deliver topical phage therapy. The overall goal of this work is to develop a translatable hydrogel platform technology for delivering topical phage therapy in a local and sustained manner. The concept is to use dynamic covalent crosslinks to weakly connect hydrogel polymers to peptides naturally presented on the phage capsid, thereby allowing the phage to slowly diffuse out of the gel. This approach does not require any modification of the phages. In our preliminary studies, we have developed hydrogels that exhibit sustained release of high dose phage as well as delivery of multiple phage types. Delivery via dynamic covalently crosslinked hydrogels represents an innovative, groundbreaking approach to phage therapy with applications across many tissue sites and infections. To facilitate these studies, we have developed a novel pre-clinical model of phage therapy. This model incorporates immunologically intact animals, bacterial isolates from human wound infection cases, and biofilm infections to recapitulate chronic wounds. In preliminary studies, we find that repeated but not one-time treatment eradicates infections in this model, indicating a requirement for sustained phage delivery. We have also developed innovative radionuclide imaging techniques to facilitate the assessment of phage pharmacokinetics and biodistribution within the body. In these studies, we have administered phages radiolabeled with technetium-99m (99mTc), a widely used SPECT imaging radio-isotope, in conjunction with scintillation well counting of 99mTc activity in cells and tissues. In t