Janus Piezoelectric Fibrous Scaffolds with Ultrasound-Triggered Electroresponsive Drug Release for Dual-Lineage Induction and Immune Microenvironment Remodeling in Tendon-Bone Interface Regeneration

A rotator cuff tear (RCT) is a common sports injury. Current surgical interventions frequently result in suboptimal healing and fail to regenerate the complex, heterogeneous tendon–bone interface. Piezoelectric materials, which convert ultrasound-derived micromechanical energy into electrical signals, offer a potential means to overcome the limitations of conventional electrical stimulation therapies for musculoskeletal tissue repair. Moreover, active and controlled drug release has become increasingly essential in modern regenerative strategies. We developed a Janus bilayered fibrous scaffold (KZP@PS/PSPM) with dual-phase induction and immunomodulatory capabilities using electrospinning and oxidative polymerization. Under ultrasonic exposure, the underlying PSPM fibrous membrane transduces mechanical energy into electrical signals that stimulate osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). Concurrently, the upper KZP@PS layer converts mechanical energy into electrical signals, activating the electrochemical reduction of polyaniline (PANI) and inducing a stress-responsive release of KZF, which secretes zinc ions (Zn 2 ⁺) and kartogenin (KGN) to promote immunomodulation and chondrogenesis. This process further enhances osteogenic and chondrogenic differentiation through upregulation of the ERK1 and PI3K–Akt signaling pathways. In a rotator cuff injury model, the KZP@PS/PSPM composite scaffold significantly reduced early inflammatory markers and markedly improved tendon-to-bone healing. By synergizing “ultrasound–electricity” with “electricity–drug release,” this Janus bilayer scaffold enables biphasic induction and immunomodulation, offering a novel strategy for addressing the complex challenges of tendon–bone interface regeneration.