PMMA bone cement with AgNP@CDs nanocomposite for infection control and inflammation mitigation

Bioinert poly(methyl methacrylate) (PMMA) is widely employed as a bone cement material in orthopedic and trauma surgery applications; however, its susceptibility to bacterial infection and bioinert nature limits its clinical applications. In this study, we developed a PMMA-based bone cement incorporating a silver nanoparticle-carbon dots (AgNP@CDs) nanocomposite (∼70 nm) at concentrations (2 wt%) with a Young's modulus (324.74 ± 7.08 MPa) to simultaneously combat bacterial infections, minimize cytotoxicity and support tissue regeneration. The CDs stabilize and functionalize AgNPs, improving their dispersion and bioavailability while enabling the controlled and sustained release of antimicrobial ions through incorporation with bone cement. The antibacterial efficacy of the composite was thoroughly evaluated, revealing its ability to disrupt bacterial cell membranes, generate reactive oxygen species and inhibit bacterial growth. These mechanisms collectively contribute to a significant reduction in bacterial growth of up to ∼90% in both in vitro and in vivo studies. The incorporation of AgNP@CDs ensures sustained antimicrobial activity, preventing bacterial colonization by controlling the leaching of Ag ions. Biocompatibility assessments showed that the PMMA composite (PMMA@2Ag-CDs) significantly improved cell proliferation, adhesion and migration compared with pure PMMA bone cement. Additionally, histological analysis revealed that the PMMA group showed a fibrous layer thickness of 699 ± 35.32 µm, indicative of inflammation, while the PMMA@2Ag-CDs group reduced this thickness from 301.18 ± 22.42 µm on day 7 to 198.07 ± 15.21 µm on day 14, significantly decreasing inflammation. The PMMA@2Ag-CDs composite demonstrated better tissue integration, with organized collagen deposition and enhanced angiogenesis, indicating more efficient tissue regeneration. The reduced inflammation and improved tissue remodeling suggest that this composite promotes a more favorable tissue regeneration environment and minimizes complications. This study demonstrates that the PMMA@2Ag-CDs composite offers a promising solution for the prevention of infections and mitigation of inflammatory responses. Functionalization of bone cement through the incorporation of Ag nanoparticle-carbon dot nanocomposites is a promising strategy with potential practical applications in orthopedic and trauma surgery.