Ultrasound-triggered injectable piezoelectric nanocomposite hyaluronic acid-based hydrogel for modulating inflammation and chondrogenesis in osteoarthritis treatment.

Osteoarthritis (OA), a common chronic joint disorder, is characterized by cartilage degeneration and inflammation. Electrical stimulation has shown promise as a treatment modality for OA, providing pain relief and fostering cartilage regeneration. However, its clinical application still remains limited. To overcome these issues, our study introduces a novel piezoelectric nanocomposite hyaluronic acid (HA)-based hydrogel (PBT-Gel) tailored for straightforward injection into affected joints. The PBT-Gel is crafted through the coordination of ions (Gallium, Ga3+) with the carboxyl groups of HA, and incorporates piezoelectric barium titanate (BaTiO3) nanoparticles modified with polydopamine (PDA). This unique composition allows the hydrogel to produce localized electrical signals when exposed to ultrasound (US), which helps manage inflammation and promote chondrogenesis to alleviate OA progression. In vitro assessments have confirmed that PBT-Gel offers excellent biocompatibility and antioxidant capabilities. Further experiments demonstrated that, when combined with US, its anti-inflammatory effects through the repolarization of macrophages and its ability to enhance chondrogenesis by activating the TGF-β/Smad signaling pathway in bone marrow mesenchymal stem cells (BMSCs). Subsequent in vivo studies in OA rat models confirmed that PBT-Gel with US effectively reduces cartilage degradation and synovitis. Together, these findings highlight the significant clinical potential of this US-triggered piezoelectric hydrogel as a novel therapeutic approach for managing OA.