Stabilizing and Programming Gallium in Hydrogels: From Iron-Mimetic Bioactivity to Localized Therapeutic Function

Abstract

Gallium (Ga) is an iron-mimetic metal with broad-spectrum antimicrobial activity and emerging potential in bone regeneration and localized cancer therapy. However, its biomedical translation is limited by unfavorable pharmacokinetics, systemic exposure, and hydrolytic instability of free Ga³⁺ under physiological conditions. Hydrogels offer a versatile strategy by stabilizing gallium species, enhancing local retention, regulating release, and providing tissue-compatible interfaces and microenvironmental modulation. This review focuses on how hydrogel design can stabilize different gallium species, control their local availability, and improve therapeutic performance across distinct pathological microenvironments. We summarize gallium bioactivity and speciation, classify gallium-containing hydrogels according to gallium incorporation and network interactions, and analyze how network architecture, coordination chemistry, degradation, and external stimuli govern retention and release. Emerging applications include infected wound and biofilm treatment, bone repair, localized cancer therapy, and other site-specific interventions. We further discuss iron competition, immune regulation, cytotoxicity, liquid-metal stability, and translational barriers, and outline directions for mechanism-guided and quantitatively standardized gallium-hydrogel design.