Integrated Implantation of an Ultrasound‐Actuated BiFeO 3 Piezoelectric Film and Bone Marrow Mesenchymal Stem Cell Sheet for Spatially and Stage‐Programmed Osteoarthritis Repair

ABSTRACT Osteoarthritis (OA) therapy remains constrained by the coexistence of irreversible cartilage loss and a persistently hostile joint microenvironment characterized by oxidative stress, synovial inflammation, and impaired tissue‐regenerative signaling. Conventional stem‐cell injection often suffers from poor intra‐articular retention, whereas ex vivo cell‐sheet harvesting may compromise cellular viability and sheet integrity. Here, we developed an integrated implantable platform composed of an ultrasound‐actuated bismuth ferrite (BiFeO 3 and BFO) piezoelectric film and an in situ‐enriched bone marrow mesenchymal stem cell (BMSC) sheet for spatially and stage‐programmed OA repair. BMSCs were cultured directly on the BFO film to form a contiguous cell sheet, enabling the construct to be implanted as a unified therapeutic interface. Upon external ultrasound stimulation, mechanical stress triggered piezoelectric polarization within BFO and promoted controllable interfacial dissociation, allowing noninvasive deposition of the BMSC sheet onto cartilage‐defect regions. In severely damaged regions, the released BMSC sheet served as a living regenerative template to support chondrogenic differentiation and cartilage‐like matrix reconstruction. In partially injured but viable cartilage regions, ultrasound‐activated BFO attenuated excessive reactive oxygen species and restored redox homeostasis, thereby preserving chondrocyte function. Furthermore, the platform remodeled the inflammatory synovial microenvironment by shifting macrophages from a proinflammatory M1‐like phenotype toward a proresolving M2‐like state. This ultrasound‐responsive BFO–BMSC‐sheet system integrates structural defect filling, redox regulation, and immunomodulation, providing a programmable strategy for heterogeneous OA repair.