Ultrasound-triggered piezocatalytic nanotherapy for intervertebral disc regeneration: remodeling the inflammatory milieu and restoring matrix homeostasis

Intervertebral disc degeneration (IVDD) is the principal cause of chronic low back pain, characterized by extracellular matrix (ECM) catabolism and an exacerbated inflammatory milieu. Given the inherent difficulties in achieving biological restoration through conventional clinical modalities, we herein designed an ultrasound (US)-driven electroactive composite system aimed at non-invasively modulating the degenerative disc via exogenous bioelectric signaling. To overcome the charge carrier recombination drawback typical of single-phase piezoelectrics, a BaTiO₃/ZnO heterojunction (shortened as BTOZ) was engineered to amplify the piezocatalytic output via interfacial band alignment, followed by polydopamine (PDA) surface functionalization (denoted as BTOZP) to confer synergistic biocompatibility and antioxidant capacity. In vitro evaluations demonstrated that this system not only generates stable bioelectric currents under US stimulation but also efficiently scavenges reactive oxygen species (ROS), thereby remodeling a favorable cellular niche and reinitiating the anabolic activity of nucleus pulposus cells (NPCs) through integrated acousto-electric-biochemical cues. In vivo experiments further confirmed that the composite effectively decelerated IVDD progression, suppressed ECM degradation, and maintained the structural integrity of the disc. This study proposes a US-responsive electroactive strategy that synergizes physical stimulation with biochemical regulation, providing a novel and non-invasive therapeutic avenue for IVDD management.