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, US_c and ultrasound for repairing, US_r), facilitating cascade treatment and reducing the overall treatment period. During the inflammatory phase of bone repair, US_c 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, US_r 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.