Multifunctional MXene-modified GelMA Hydrogel Loaded with Hypoxia-Induced Mesenchymal Stem Cells Derived Extracellular Vesicles Alleviates Allergic Rhinitis in Mice

Allergic rhinitis (AR) has gained an increasing prevalence over the years, a more effective and safe treatment strategy need to be carried out. Hypoxia induced Mesenchymal stem cell derived extracellular vesicles (hEVs) have shown great therapeutic potential for AR, however, their low bioavailability through systemic administration decreased efficacy in clinical application. In the current study, an MXene-modified GelMA hydrogel was developed as a sustained release platform for hEVs. The hEVs-loaded MXene-modified GelMA hydrogel (hEVs@M-GelMA hydrogel) we prepared had rich porous structure, good hydrophilicity, biocompatibility and antibacterial properties, and showed significant inhibitory effect on the generation of reactive oxygen species in vitro. By using AR mice model, we verified that hEVs@M-GelMA hydrogel significantly alleviated AR symptoms, reduced local eosinophil infiltration, inhibited the intensity of nasal oxidative stress response, suppressed the production of OVA-sIgE in blood, decreased IL-4 secretion and promoted IL-10 and IFN-γ expression. This study provides a novel delivery platform for MSC-EVs-based AR therapy.