Copper tannic acid coordination nanosheet as a potent in-situ antibiotic sustained-release carrier for chronic osteomyelitis

Chronic osteomyelitis remains a major challenge in orthopedic therapy. Developing a biodegradable, non-toxic material capable of providing sustained antibiotic release has emerged as a promising approach for localized antibiotic delivery in managing this condition. In this study, copper-tannic acid (CuTA) nanosheets were synthesized and employed as a coating material for vancomycin, resulting in the formation of vancomycin@CuTA (Van@CuTA) nanocomposites. The morphological and structural characterization of CuTA and Van@CuTA was performed using various techniques. The sustained release behavior of vancomycin, and in vitro effects of Van@CuTA on methicillin-resistant Staphylococcus aureus (MRSA) growth, bone marrow mesenchymal stem cells (BMSCs) viability, osteogenesis, and human umbilical vein endothelial cells (HUVECs) angiogenesis were systematically investigated. A rabbit model of chronic osteomyelitis was established to assess the therapeutic effect of Van@CuTA, in combination with fibrin gel, in controlling infection, preventing bone destruction, and inhibiting the progression of chronic osteomyelitis. The characterization results confirmed the formation of Van@CuTA nanocomposites. In vitro experiments revealed that Van@CuTA enabled gradual vancomycin release, effectively suppressed MRSA growth, and demonstrated no toxicity to BMSCs. Furthermore, Van@CuTA significantly promoted osteogenic differentiation of BMSCs and improved angiogenesis in HUVEC. The in vivo studies demonstrated that Van@CuTA coated with fibrin gel ameliorated the appearance of local infection, reduced bone structural damage, and diminished inflammatory infiltration within the bone marrow in the rabbit model of chronic osteomyelitis. Current findings indicated that CuTA nanosheets served as a promising in-situ antibiotic carrier for sustained release in chronic osteomyelitis treatment. Van@CuTA demonstrated improved antibacterial properties, enabled sustained vancomycin release, and promoted both osteogenesis and angiogenesis, leading to its preliminary therapeutic efficacy in rabbit models of chronic osteomyelitis and strong potential for clinical application in osteomyelitis treatment.