Piezoelectric Nanomotors for Active Cartilage Regeneration of Osteoarthritis via Ultrasonic Vibration and Water Splitting

Osteoarthritis (OA) is a multifactorial joint disorder characterized by articular cartilage degradation and progressive synovial inflammation. The dense and avascular nature of cartilage hinders the delivery efficiency of nanocarriers to their target cells, resulting in limited therapeutic efficacy in clinical trials. Here, we report the design of a Piezo-MnO 2 motor for in situ reestablishment of the articular microenvironment by effectively degrading the local excess hydrogen peroxide in the OA microenvironment into oxygen. The generated oxygen ameliorates hypoxic conditions and acts as a propellant for nanomotor actuation, thereby enabling the motor to penetrate deeply into cartilage and synovium. Under mechanical stress induced by ultrasonic vibration, Piezo-MnO 2 motors efficiently produced electrical signals via piezoelectric effect. This initiates an influx of extracellular calcium ions, which further upregulates the expression of transforming growth factors and drives cartilage repair. Recognized for its anti-inflammatory and antioxidant properties, the hydrogen produced by ultrasonic piezoelectric effect of the motors significantly diminishes the level of pro-inflammatory cytokines. The developed strategy facilitates rapid in situ cartilage regeneration and articular microenvironment modulation, offering a transformative alternative to conventional OA interventions.