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.
Immunotherapy has played an important role in the treatment of malignant tumors. Efforts in this area are focused on exploiting a facile scaffold-based cancer vaccine with admirable efficacy and favorable property for tumor immunotherapy. Herein, an implantable sponge-nanofiber Janus scaffold with lyophilization-inactivated cancer cells, immune adjuvant imiquimod, and 5-fluorouracil (5-FU) spatially loading has been developed for tumor postoperative immuno-chemotherapy. The inactivated cancer cells and imiquimod encapsulated macroporous sponge of the scaffold can act as an immune niche to initiate a potent immune response. While the 5-FU loaded nanofibers can not only enhance the mechanical property of the scaffold, but also increase the anti-tumor immunity of the scaffold by directly killing cancer cells and depleting myeloid-derived suppressor cells to remodel the tumor immunosuppression microenvironment. Based on these features, the excellent anti-recurrence and anti-metastasis efficiency of the composited Janus scaffold have been demonstrated in the mouse breast tumor model. Thus, it is convinced that the proposed Janus scaffold spatially encapsulated with lyophilization-inactivated cancer cell vaccines and chemotherapeutic agents will provide novel sights for combination therapy after tumor surgery.