Osteoarthritis (OA) is a degenerative illness that greatly impacts the life quality of patients. Currently, the therapeutic approaches for OA are very limited in clinical. The extracellular vesicles (EVs) derived from different mesenchymal stem cells displayed a prominent therapeutic effect on OA. But most EVs have limited resources and the risks of host rejection, immunological response, and etc. Human umbilical cord mesenchymal stem cells (hUCMSCs) hold the advantages of easy availability, minimal immune rejection, and excellent immunomodulatory effects, although hUCMSCs-EVs have seldom been applied in OA. Herein, we investigated the potential immunomodulatory and anti-inflammatory effects of hUCMSCs-EVs on the treatment of OA. In our results, the treatment of hUCMSCs-EVs promoted the polarization of M2-type macrophages and the expression of anti-inflammation-related cytokines (IL-10). Notably, the supernate of M2 macrophages induced by hUCMSCs-EVs inhibited the level of inflammation-associated factors in OA chondrocytes caused by IL-1β. Further, injection of hUCMSCs-EVs in the articular lumen ameliorated progression of OA and exerted chondroprotective potential based on the OA joint model created by the surgical transection of the anterior cruciate ligament (ACLT). In addition, we found five highly enriched miRNAs in hUCMSCs-EVs, including has-miR-122-5p, has-miR-148a-3p, has-miR-486-5p, has-miR-let-7a-5p, and has-miR-100-5p by High-throughput sequencing of miRNAs, with targeted genes mainly enriched in the PI3K-Akt signaling pathway. Furthermore, we also detected the protein abundance of hUCMSCs-EVs using liquidation chromatography with tandem quadrupole mass spectrometry (LC–MS/MS) analysis. Thus, our study indicates that hUCMSCs-EVs can alleviate cartilage degradation during the OA progression, mechanically may through delivering key proteins and modulating the PI3K-Akt signaling pathway mediated by miRNAs to promote polarization of M2 macrophage, exhibiting potent immunomodulatory potential. The current findings suggest that hUCMSCs-EVs might serve as a new reagent for the therapy of OA. Graphical Abstract

The synergistic effect of antibacterial and anti-inflammatory is needed to overcome the problem of wound healing difficulties. Based on the favorable antibacterial and anti-inflammatory effect of zinc ions (Zn²⁺) and the physicochemical properties of metal organic frameworks (MOFs), we prepared nanosized zinc-based MOF: Zn-BTC with the ability to slowly release Zn²⁺. In cellular levels, Zn-BTC possessed lower toxicity to fibroblasts and enhanced capacity of cell proliferation and migration. It also had good bactericidal effect on multiple drug-resistant bacteria by reducing 41.4% MRSA and 47.2% Escherichia coli. In addition, Zn-BTC also displayed the ability of lowering the expression of antioxidant genes: superoxide dismutase 1, superoxide dismutase 2 and interleukin 6, and enhancing the expression of wound healing genes: transforming growth factors-β and type I collagen. Finally, it also demonstrated that Zn-BTC could effectively improve the skin wound healing of SD rats and had no toxicity on major organs. The favorable biocompatibility, antibacterial and anti-inflammatory properties of Zn-BTC gave a new insight of designing novel MOFs for promoting skin wound healing.