Biomaterial-driven innovations in phage therapy: Current strategies and future perspectives

The escalating threat of antimicrobial resistance underscores the urgent need for innovative therapeutic strategies. Phage therapy has experienced a resurgence over the past five years following a prolonged period of neglect during the antibiotic era. Despite its therapeutic promise, critical barriers impede clinical translation, including susceptibility to interference from the host's complex physiological environment, a narrow host range, and the inability to lyse intracellular bacteria. To address these limitations and optimize the efficacy of phage-mediated treatment, recent research has increasingly focused on biomaterial-assisted approaches aimed at enhancing therapeutic efficacy. In this review, we concentrate on recent progress in biomaterial-assisted phage-based treatment strategies, including phage physical encapsulation strategies and phage surface chemical coupling strategies. Physical encapsulation employs liposomes, hydrogels, pH-sensitive polymers and etc. for controlled phage delivery, while surface chemical coupling modifies phage capsids with photosensitizers, nanozymes, or metal nanoparticles to enable multifunctional bactericidal mechanisms. In addition, accessibility for phage therapy of intracellular bacteria is discussed. We also conclude key biomaterial selection criteria-prioritizing biosafety, biodegradability, and microenvironment adaptability, and offer novel perspectives for advancing therapeutic precision as well as multidimensional innovation in combating antimicrobial resistance.