Ultrasound-Driven Selenium Nanoparticles Realize Bone Defect Repair through Activating Selenoproteins to Regulate PI3K/AKT Signaling Pathway

Excessive and variable inflammation in bone defects is a key factor that impedes effective bone repair. Herein, an ultrasound-controlled composite hydrogel (LNT-SeNPs@Gel) integrating gelatin-methacryloyl and lentinan-decorated selenium nanoparticles (LNT-SeNPs) is developed, exhibiting strong antioxidant and anti-inflammatory properties to remodel the inflammatory microenvironment of bone defects. This hydrogel serves as a platform for integrating bifunctional ultrasound (ultrasound modulation, USc and ultrasound for repairing, USr), facilitating cascade treatment and reducing the overall treatment period. During the inflammatory phase of bone repair, USc remotely modulates the LNT-SeNPs@Gel hydrogel, regulating the release of LNT-SeNPs to inhibit the overproduction of reactive oxygen species (ROS) and inflammatory factors, ultimately remodeling the inflammatory microenvironment. Subsequently, USr could activate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway regulated by selenoproteins to enhance the osteogenesis of MC3T3-E1 cells, thereby accelerating the bone repair process. Consequently, the combination of bifunctional ultrasound and LNT-SeNPs@Gel significantly improves bone repair outcomes and reduces the treatment period in rats. In conclusion, this study implies that the coordinated integration of the dual effects of ultrasound is a promising strategy for handling the complex and lengthy bone defects repair.