Antibacterial Agent-Loaded Hydrogels for Implant-Associated Osteomyelitis: A Review

Implant-associated osteomyelitis (IAO) is a major clinical challenge due to persistent biofilms, antibiotic resistance, and impaired osteogenesis. Hydrogels, with tunable physicochemical properties, biocompatibility, and localized drug delivery capabilities, offer advanced solutions to these problems. This review systematically examines advanced hydrogel-based strategies for IAO treatment, categorized into two primary approaches. Antibiotic-loaded hydrogels leverage nanomaterial integration and hybrid composites to achieve precise, spatiotemporal drug release, thereby minimizing toxicity and resistance. Non-antibiotic approaches, including nanomaterial-based agents such as metals and photothermal nanohybrids, as well as peptides, plant polyphenols, and phage therapy, provide alternative options to circumvent antibiotic resistance. Crucially, we highlight key optimization strategies that encompass controlled cross-linking, stimuli-responsive systems (e.g., pH and temperature), anti-biofilm mechanisms, and biomimicry, synergistically enhancing both antibacterial and osteogenic functions in these platforms. Collectively, these advances signify a shift from passive drug carriers to multifunctional, bioactive platforms that both eradicate resistant bacteria and support bone regeneration. This transformative shift, however, reveals persistent challenges while suggesting promising research avenues for advancing hydrogel-based therapies against IAO.