Mesenchymal stem cells (MSCs) have been widely used for the treatment of autoimmune and inflammatory diseases due to their pluripotent differentiation potential and immunomodulatory function. Macrophage (Mφ) polarization also acts an essential and central role in regulating inflammation, basically the dynamic balance of pro-inflammatory M1-like (M1φ) and anti-inflammatory M2-like macrophages (M2φ), affecting the occurrence and progression of inflammatory diseases. Since a pivotal molecular crosstalk between MSCs and Mφ has been elucidated using in vitro and in vivo preclinical studies, we presume that the mesenchymal stem cell/macrophages axis (MSC/Mφ axis) acts an important role in pathophysiological mechanisms of inflammatory diseases and should be the potential therapeutic target. However, the crucial effects of EVs as intercellular communicators and therapeutic agents in the MSC/Mφ axis remains explorable. Therefore, this review elaborated on the mechanisms of EVs mediating the MSC/Mφ axis regulating inflammation in-depth, hoping to provide more references for related research in the future.

Metal alloys in arthroplasty face limitations including aseptic loosening, material failure, and allergic reactions. High-performance oxide ceramics (HPOCs) represent an alternative but are bioinert, restricting osseointegration and osteoconduction. The aim of this study was to convert bioinert HPOC surfaces into bioactive osteogenic microenvironments through stable peptide-biofunctionalization with cyclic-arginylglycylaspartic acid (cRGD) or modified-hepatocyte growth factor (mod-HGF). In a rabbit femoral defect model, cylindrical ATZ implants were press-fitted into 4.5 × 8 mm defects and examined after 18 weeks. Three groups were compared: uncoated ATZ, cRGD-coated, and mod-HGF-coated implants (n = 8 each). Histomorphometry (Movat Pentachrome, H&E, Alcian Blue), scanning electron microscopy, and energy-dispersive X-ray spectroscopy were performed. Both cRGD- and mod-HGF-coated implants significantly increased bone formation and bone–implant contact relative to controls. Reduced fibrotic encapsulation and enhanced vascularization were observed in both groups, with the strongest effects in the mod-HGF group. Microscopy and spectroscopy confirmed greater mineralization and continuous bone–implant interfaces in coated implants. These results demonstrate that biologically functionalizing ATZ with cRGD or mod-HGF effectively enhances bone formation and implant integration in vivo while reducing fibrotic responses. We proved through the in vivo experiments that bioinert HPOCs obtain osseointegrative behavior due to the hydrolytically stable organo-chemical surface functionalization.