Synergistic Antibacterial and Osteogenic Activities of Cu/Sr-Empowered 13-93 Bioglass in PMMA Composites for Sequential Promotion of Infectious Osseointegration.

Poly(methyl methacrylate) (PMMA) is among the most prevalent antibiotic delivery systems for the prevention and treatment of bone infections. Nevertheless, its restricted antibiotic release efficacy generally does not eradicate pathogens at localized infection sites, potentially resulting in bacterial resistance, and it has inadequate capacity to facilitate osseointegration. This study involved the synthesis of a copper (Cu)/strontium (Sr)-doped 13-93 bioactive glass, which was subsequently combined with a PMMA matrix to produce a 13-93 Cu/Sr-doped cement (13-93CuSr/PC). The Cu and Sr in 13-93CuSr/PC feature a time-sequenced, dual-point release mechanism. In the initial phase (0-7 days), the infiltration of high-concentration Cu ions (Cu2+) effectively eliminates the bacteria. In vitro, 13-93CuSr/PC demonstrates sustained antibacterial activity by interrupting biofilm formation, enhancing cell membrane permeability, inducing oxidative stress, and impeding energy consumption. Subsequent to the maximum release of Cu2+, the concurrent release of low-concentration Cu2+ and Sr ions modifies the postclearance environment, establishing an immunological microenvironment conducive to osteogenesis, thereby promoting the osteogenic differentiation of mesenchymal stem cells by aiding the polarization of M1 macrophages into the M2 phenotype. This offers a promising solution for simultaneously tackling infection management and bone regeneration challenges through sequential ion release and integrated biofunctions.