Work

Bioelectric signals promote diabetic bone regeneration through Piezo1-mediated activation of the efferocytic immune microenvironment

Year: 2026

Type: article

Abstract: Defective macrophage efferocytosis sustains inflammation and compromises bone repair in diabetic defects, yet strategies that restore efferocytic immune homeostasis remain limited. Here, we engineered an ultrasound-responsive piezoelectric hydrogel (Gel BC@ZnO) by incorporating zinc oxide (ZnO) nanoparticles into a bacterial cellulose (BC)-reinforced gelatin methacryloyl (GelMA) network to provide localized bioelectric cues. Gel BC@ZnO exhibited good cytocompatibility, structural stability, and robust ultrasound-triggered piezoelectric output. Under diabetic-mimicking conditions, ultrasound activation generated bioelectric signals that engaged Piezo1, induced Piezo1-dependent Ca 2+ influx, and rescued macrophage efferocytosis. This efferocytic reactivation attenuated ROS accumulation, shifted macrophages toward a pro-regenerative phenotype, enhanced osteogenic differentiation, and suppressed osteoclast genesis, thereby restoring bone-remodeling homeostasis. In a diabetic femoral condyle defect model, Gel BC@ZnO combined with ultrasound accelerated bone repair, increased local Piezo1 expression, promoted collagen deposition and osteogenic marker expression, and rebuilt a favorable immune microenvironment. These results define a bioelectric signal-Piezo1-Ca 2+ -efferocytosis axis for diabetic bone regeneration and establish a non-invasive, ultrasound-controllable immunomodulatory strategy for compromised bone repair.

Source: Bioactive Materials

DOI: 10.1016/j.bioactmat.2026.05.037