Osteoarthritis (OA) is a prevalent degenerative joint disease and current therapies are insufficient to halt its progression. Mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) offer promising therapeutic potential for OA treatment, and their efficacy can be enhanced through strategic engineering approaches. Inspired by the immune memory of the adaptive immune system, we developed an engineered strategy to impart OA-specific immune memory to MSCs-EVs. Using Luminex technology, inflammatory factors (IFN-γ, IL-6, and TNF-α), which mimic the OA inflammatory microenvironment, were identified and used to prime MSCs, generating immune memory-bearing MSCs-EVs (iEVs). Proteomic analysis and complementary experiments were conducted to evaluate iEVs’ effects on macrophage phenotypic reprogramming. iEVs, particularly IL-6-EV, exhibited potent immunoregulatory functions along with the ability to modulate mitochondrial metabolism. Both in vitro and in vivo, IL-6-EV significantly reprogrammed macrophages towards the M2 subtype, effectively suppressing articular inflammation and OA progression. Mechanistic studies revealed that IL-6-EV facilitated M2 polarization by regulating mitochondrial oxidative phosphorylation via the mt-ND3/NADH-CoQ axis. This study introduces a strategy to enhance MSCs-EVs’ therapeutic efficacy in OA. Multi-omics analysis and biological validation demonstrate its potential, providing new insights for MSCs-EVs’ future application in OA and other clinical conditions.

Magnesium alloys, noted for their substantial mechanical strength and exceptional biocompatibility, are increasingly being considered for use in biodegradable implants. However, their rapid degradation and significant hydrogen release have limited their applications in orthopaedics. In this study, a novel Mg-RE-Sr alloy was created by friction stir processing to modify its microstructure and enhance its degradation performance. Through microstructural characterization, the friction stir processing effectively refined the grains, accelerated the re-dissolution of precipitates, and ensured a uniform distribution of these phases. The processed alloy demonstrated improved comprehensive properties, with an in vitro corrosion rate of approximately 0.4 mm/y and increases in ultimate tensile strength and elongation by 37 % and 166 %, respectively. Notably, in vivo experiments involving a rat subcutaneous implantation model revealed a slower degradation rate of 0.09 mm/y and a uniform degradation process, basically achieving the requirements for ideal performance in orthopaedic applications. The superior degradation characteristics were attributed to the synergistic effect of attenuated galvanic corrosion and the formation of a dense Y(OH)₃/Y₂O₃ film induced by an exceptional microstructure with a highly solid-soluted matrix and uniformly refined precipitates. Meanwhile, the alloys exhibited excellent biocompatibility and did not cause undesirable inflammation or produce toxic degradation products. These improvements in biocompatibility and degradation characteristics indicate great promise for the use of this friction stir processed alloy in osteosynthesis systems in the clinical setting.

Self-assembled peptide scaffolds based on D-RADA16 are an important matrix for controlled drug release and three-dimensional cell culture. In this work, D-RADA16 peptide hydrogels were coated on artificial bone composed of nano-hydroxyapatite/polyamide 66 (nHA/PA66) to obtain a porous drug-releasing structure for treating bone defects. The developed materials were characterized via transmission electron microscopy and scanning electron microscopy. The proliferation and adhesion of bone mesenchymal stem cells (BMSCs) were examined by confocal laser microscopy and CCK-8 experiments. The osteogenic ability of the porous materials towards bone BMSCs was examined in vitro by staining with Alizarin Red S and alkaline phosphatase, and bioactivity was evaluated in vivo . The results revealed that nHA/PA66/D-RADA16/bFGF reduces the degradation rate of D-RADA16 hydrogels and prolongs sustained release of bFGF, which would promote BMSCs proliferation, adhesion and osteogenesis in vitro and bone repair in vivo . Thus, it deserves more attention and is worthy of further research.