A multifunctional GaMOF–Cu2O-integrated GelMA hydrogel for synergistic antibacterial activity and tissue regeneration

Abstract

The rising threat of multidrug-resistant (MDR) bacterial infections and resilient biofilms in bone and soft tissue, exacerbated by antibiotic misuse, demands the development of novel non-antibiotic therapeutics that combine effective bactericidal activity with tissue-regenerative functions. To address this challenge, we developed a multifunctional gelatin methacryloyl (GelMA) hydrogel platform loaded with a gallium-based metal–organic framework and copper(I) oxide nanocomposite (GaMOF–Cu₂O). This system leverages a synergistic antibacterial mechanism: Ga³⁺ ions disrupt critical iron metabolism by mimicking Fe³⁺, while Cu⁺ ions catalyze the generation of reactive oxygen species (ROS) to inflict oxidative damage. Together, this dual action potently eradicates bacteria and inhibits biofilm formation. Simultaneously, the GelMA hydrogel matrix ensures localized and sustained release of the therapeutic agents and provides a bioactive, three-dimensional scaffold that facilitates cell migration and angiogenesis, thereby supporting tissue repair. Our findings demonstrate that the GaMOF–Cu₂O/GelMA hydrogel is a highly promising and integrative strategy for combating refractory MDR and biofilm-associated infections while promoting tissue regeneration, offering a potent alternative to conventional antibiotic therapies.