In situ Antibiotic-Loaded Copper Tannic Acid Coordination Nanospheres Targeting Biofilms for the Treatment of Chronic Osteomyelitis

Purpose The formation of biofilms hinders direct contact between antibiotics and bacteria, reducing the efficacy of antibiotic therapy and presenting a substantial obstacle to the treatment of chronic osteomyelitis. To address this problem, we successfully constructed a chemically and structurally robust vancomycin-copper-tannic acid (Van@CuTA) antibiotic sustained-release system via a simple synthetic method, to target bacteria and inhibit biofilm formation.Methods Tannic acid (TA), copper ions (Cu2+), and vancomycin hydrochloride (Van) were mixed and stirred at a low temperature to afford Van@CuTA nanospheres. Their antibacterial activity was evaluated against methicillin-resistant S. aureus (MRSA) using the Oxford cup method and live/dead bacterial staining. Their anti-biofilm activity was assessed via FE-SEM observations. Cell viability was assessed via MTT assay and osteogenic activity was detected via Western blotting (WB) and alkaline phosphatase (ALP) staining after co-culture with MG-63 cells. In vivo tibia-induced osteomyelitis model in rabbits was conducted to further validate the efficacy of Van@CuTA in treating osteomyelitis.Results The developed nanospheres exhibited drug release properties, with TA being released from the carrier and inhibiting the formation of bacterial biofilms. In vivo experiments demonstrated inhibition of MRSA biofilm formation through the encapsulation of TA within fibrin and its sustained release, followed by the sequential release of Van and Cu2⁺ to directly eradicate MRSA. Moreover, Van@CuTA effectively promoted cell proliferation and bone formation. Van@CuTA is a multifunctional system that integrates biofilm targeting, drug release, antimicrobial activity, and cuproptosis-like bacterial death.Conclusion This study offers a novel and promising strategy for the development of antimicrobial agents to combat MRSA-induced chronic osteomyelitis.