A mechanically compliant SrTiO₃ nanofilm interface promotes diabetic osseointegration by modulating Piezo1-associated...

As a widely applied material for bone repair in clinical practice, titanium alloy showed multiple excellent characteristics including mechanical properties and biocompatibility. However, under the state of diabetes mellitus (DM), insufficient osseointegration and impaired bone repair occurred driven by the tendency of macrophage pro-inflammatory polarization. To alleviate diabetes-associated macrophage inflammation, we fabricated a SrTiO₃ nanofilm-engineered titanium surface (RTS) with a mechanically compliant film-stiff substrate interface and sustained Sr ion release. Under diabetic-mimicking conditions, RTS provided an integrated osteoimmune interface and suppressed pro-inflammatory macrophage polarization and osteoclast-like differentiation tendency, combined with reduced Piezo1-associated Ca²⁺ signaling and CaMKII activation. Macrophages regulated by RTS further created a favorable immune microenvironment for osteogenic differentiation of MC3T3-e1 cells, followed by the superior osteogenic differentiation, as verified in vitro and in vivo. Notably, in diabetic rats, collagen formation and osteopontin (OPN) expression surrounding the RTS implants combined with superior osseointegration were observed, indicating improved peri-implant bone formation. Yoda1 partially reversed the protective effect of RTS, supporting the involvement of Piezo1-associated mechanotransduction in RTS-mediated osteoimmunomodulation. These findings suggest that RTS may serve as a promising candidate for improving osseointegration under diabetic conditions.