The disruption and reconstruction of the TREM2⁺ tissue resident macrophage (TRM) barrier on the surface of synovial lining play a key role in the activation and "remission" of rheumatoid arthritis (RA), which engender the prediction of this immunologic barrier as a potential driver for the achievement of "cure" in RA. However, strategies to promote the reconstruction of this barrier have not been reported, and the effect of patching this barrier remains unidentified. On the other hand, appropriate piezoelectric stimulation can reprogram macrophages, which has never been exerted on this barrier TRM yet. Herein, we design piezoelectric tetragonal BaTiO₃ (BTO) ultrasound-driven nanorobots (USNRs) by the solvothermal synthesis method, which demonstrates satisfactory electro-mechanical conversion effects, paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity. It is demonstrated that the immunologic barrier could be patched by this USNR effectively, thereby eliminating the hyperplasia of vessels and nerves (HVN) and synovitis. Additionally, TREM2 deficiency serum-transfected arthritis (STA) mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR. In all, our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases, providing a new idea and direction for the biomedical application of piezoelectric ceramics.

There has been great progress in the last decade in the synthesis of nanopowders with highly controlled size and size distribution. Meanwhile, the development of an unconventional pressureless two-step sintering strategy enabling densification without grain growth provides a novel technology suitable for commercial production of nanograin ceramics. The particular interest concerning bulk dense nanograin ceramics is the manifestation of ferroelectricity, which remains a fundamental issue to be understood and exploited. Combining the best powder synthesis and optimized two-step sintering, high-density barium titanate (BT) and related nanograin ceramics have been fabricated to allow for a detailed determination of the size effect on nanometer-scale ferroelectricity and piezoelectricity of fundamental and industrial interest. These include dense ceramics of undoped BT with an average grain size down to 5 nm, and of (1−x)BiScO₃−xPbTiO₃ (BSPT) solid solutions with an average grain size down to 10 nm. Here we review the fabrication methods of high-density BT and BSPT nanoceramics and the major findings of the size effect on their microstructure, phase transition and electrical properties. Robust ferroelectricity is demonstrated for the first time in 5 nm BT nanoceramics, while strong local piezoelectricity is present in 10 nm BSPT nanoceramics.