Osteomyelitis is difficult to treat because infective bone is poorly accessible for intravenously administering antibiotics and biofilm formation increases bacterial resistance. In this study, microspheres prepared using poly(lactide-co-glycolide) (PLGA) and embedded with moxifloxacin (MOX-PLGA microspheres) and rifampicin/moxifloxacin (RIF/MOX-PLGA microspheres) using the water-in-oil-inwater double emulsion solvent evaporation technique were used for local delivery. Shape of MOX-PLGA microspheres and RIF/MOX-PLGA microspheres were spherical, mean particle size of them were 20.52 lm and 16.62 lm, respectively. Encapsulation efficiency of the MOX-PLGA microspheres was 17.35% ± 2.42%. However, the encapsulation efficiency for MOX and RIF in RIF/MOX-PLGA microspheres was 33.25% ± 7.51% and 49.0% ± 11.25%, respectively. Moxifloxacin and rifampicin were released slowly from microspheres. Both microspheres can efficiently release antibiotics in vitro. Antibacterial and bacterial biofilm-inhibition properties of the released solution were investigated from RIF/MOX-PLGA, MOX-PLGA, and blank PLGA microspheres at varying time points in vitro. RIF/ MOX-PLGA microspheres demonstrated the strongest antibacterial activity and bacterial biofilm-inhibition property than the other two microspheres (p < .05). This study suggests that the novel RIF/ MOX-PLGA microspheres can be used as a promising carrier for osteomyelitis treatment.

Osteoarthritis (OA) is a serious disease of the articular cartilage characterized by excessive inflammation. Lately, mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) have been proposed as a novel strategy for the treatment of OA. We aimed to investigate the effects of EV-encapsulated miR-3960 derived from MSCs on chondrocyte injury in OA. The cartilage tissues from OA patients were collected to experimentally determine expression patterns of miR-3960, PHLDA2, SDC1, and β-catenin. Next, luciferase assay was implemented to testify the binding affinity among miR-3960 and PHLDA2. EVs were isolated from MSCs and cocultured with IL-1β-induced OA chondrocytes. Afterwards, cellular biological behaviors and levels of extracellular matrix- (ECM-) related protein anabolic markers (collagen II and aggrecan), catabolic markers (MMP13 and ADAMTS5), and inflammatory factors (IL-6 and TNF-α) in chondrocytes were assayed upon miR-3960 and/or PHLDA2 gain- or loss-of-function. Finally, the effects of miR-3960 contained in MSC-derived EVs in OA mouse models were also explored. MSCs-EVs could reduce IL-1β-induced inflammatory response and extracellular matrix (ECM) degradation in chondrocytes. miR-3960 expression was downregulated in cartilage tissues of OA patients but enriched in MSC-derived EVs. miR-3960 could target and inhibit PHLDA2, which was positively correlated with SDC1 and Wnt/β-catenin pathway activation. miR-3960 shuttled by MSC-derived EVs protected against apoptosis and ECM degradation in chondrocytes. In vivo experiment also confirmed that miR-3960 alleviated chondrocyte injury in OA. Collectively, MSC-derived EV-loaded miR-3960 downregulated PHLDA2 to inhibit chondrocyte injury via SDC1/Wnt/β-catenin.