Nike Walter, Christoph Brochhausen, Thaqif El Khassawna, Corina Vater, Aaron Teja Bolte, Mohammadali Khan Mirzaei, Ronald Man Yeung Wong, Wing-Hoi Cheung, Christian Heiss, Volker Alt, Anja Lode, Li Deng, Markus Rupp
Hydrogel-based local phage therapy is a feasible strategy for infection control No major adverse effects were reported in the included studies, although safety reporting was limited. Standardized in vivo comparisons and clinical trials are needed to optimize delivery and dosing.
BACKGROUND: Localized biofilm-associated infections such as chronic wounds, osteomyelitis, and implant infections remain difficult to treat with systemic antibiotics amid rising resistance. Hydrogel delivery may enhance bacteriophage (phage) therapy by protecting phages, prolonging residence, and enabling controlled release. This systematic review summarizes in vivo evidence for hydrogel-mediated phage delivery and its translational relevance.
METHODS: Following PRISMA 2020, PubMed, Web of Science were searched to 14 January 2026 using MeSH terms for bacteriophages, hydrogels/local delivery, and in vivo or clinical applications. Eligible studies reported original in vivo animal or human data; in vitro-only work was excluded.
RESULTS: Nineteen studies met criteria: three clinical and sixteen preclinical. Clinical use included fracture-related, burn wound, and prosthetic joint infections treated with commercially available phage preparations in hydrogels. In a single compassionate-use fracture-related infection case managed with concurrent surgical debridement and systemic antibiotics, infection control without recurrence and good bone healing were observed at one year; locally applied phages remained detectable for approximately 72 h, indicating in vivo release and surgical compatibility, although the independent contribution of the hydrogel-phage component could not be isolated. Preclinical studies tested 28 phages against six bacterial species via topical, injected, intraoperative, oral, or irrigation delivery. Consistent benefits occurred in burn (n = 6) and wound/soft-tissue models (n = 5) with lower bacterial load, improved healing, and increased survival in two burn studies. Bone/joint models (n = 4) showed partial reduction but inconsistent eradication. Other studies demonstrated ~2000-fold pathogen reduction in colitis and decreased bacterial and inflammatory markers in endodontic infection.
CONCLUSIONS: Hydrogel-based local phage therapy is a feasible strategy for infection control No major adverse effects were reported in the included studies, although safety reporting was limited. Standardized in vivo comparisons and clinical trials are needed to optimize delivery and dosing.