Antibacterial polyphenols for osteomyelitis treatment: from antibacterial mechanisms to biomaterial-based delivery.

Osteomyelitis is a refractory infection caused by bacterial invasion of bone tissue. Biofilms, small-colony variants (SCVs), and intracellular persistence enable bacteria to evade immune clearance and antibiotic killing, while sequestra and implant surfaces may act as long-term infection reservoirs. Some pathogens can also invade the osteocyte lacuno-canalicular network, further hindering complete eradication. Meanwhile, persistent inflammation, oxidative stress, and impaired local blood supply aggravate bone destruction and inhibit tissue repair. Therefore, osteomyelitis treatment requires not only infection control, but also the reduction of inflammatory damage, promotion of angiogenesis, and enhancement of bone regeneration. Natural polyphenols exhibit multitarget antibacterial and antibiofilm activities by disrupting bacterial membranes and cell walls, interfering with key enzymes and energy metabolism, regulating metal homeostasis, and increasing bacterial susceptibility to antibiotics. They also possess anti-inflammatory and redox-regulatory properties and can modulate osteogenesis and bone resorption. Their abundant phenolic hydroxyl groups and coordination sites facilitate their integration with metal ions, polymers, and inorganic materials to construct local delivery systems. Nanoparticles, coatings, hydrogels, and bone scaffolds can improve the retention and release of polyphenols at infected sites and enable infection-responsive or stage-specific treatment. These biomaterial-based strategies may adapt to the acidic, hypoxic, and persistently inflamed osteomyelitis microenvironment, coordinating antibacterial activity, immune regulation, and bone regeneration. This mini-review summarizes the major classes and structural features of natural polyphenols, their antibacterial mechanisms, and biomaterial-based delivery strategies, with emphasis on microenvironmental adaptation and clinical translation in osteomyelitis treatment.