Boosting MRSA Infectious Osteoporosis Treatment: Mg-Doped Nanofilm on Vacancy-Enriched TiO₂ Coating for Providing In Situ Sonodynamic Bacteria-Killing and Osteogenic Alkaline Microenvironment

To effectively combat infectious osteoporosis, Ti-based implants with enhanced antibacterial and osseointegrative properties are urgently required. Herein, a one-step method involving Mg thermal-reduction is employed to modify a hydroxyapatite (HA) array on Ti, which comprises an inner TiO2 layer and an outer nanorod-like HA layer. This process introduces oxygen vacancies (OVs) into the TiO2 layer and deposits a Mg & horbar;O-contained amorphous nanolayer on each HA nanorod. The introduced OVs enhance reactive oxygen species (ROS) yield by the array during ultrasound treatment via narrowing TiO2 bandgap and improving H2O molecules absorption. The produced ROS, combined with a weak alkaline microenvironment created by the degraded Mg & horbar;O nanolayer, endows the array with potent bacterial-killing and biofilm-eradicating efficacies within a 5 min ultrasound treatment via the combination of proton-consumption and cell envelop-detriment effects. Moreover, due to the alkaline microenvironment and the released Mg2+, the array hinders osteoclastogenesis by activating the inflammation-related FAK-PI3K-AKT signaling pathway in macrophages, as revealed by transcriptomic analysis, resulting in robust osseointegration in rat femoral shaft with concurrent bacterial-infection and osteoporosis. This work paves a new way for simultaneously endowing a sonosensitive coating on Ti with sonodynamic treatment-derived high antibacterial ability and alkaline microenvironment-mediated strong osseointegration for infectious osteoporosis treatment.