Lubricated hydrogel with STING-inhibiting EXOs protect the osteoarthritis by suppressing the senescent microenvironment

Excessive friction and cellular senescence contribute to osteoarthritis (OA) development. However, synergistic treatments targeting these two causes of OA may have significant implications for OA. In this study, we propose a novel strategy for exosome delivery encapsulated an injectable and lubricated hydrogel to synchronously reduce the excessive friction and the accumulation of aged chondrocytes. A cartilage-targeting peptide HABP-PEG-COLBP was employed to achieve a stable and efficient lubrication. The zwitterions of phosphatidylcholine lipids secreted by the synovial membrane of the joint can adsorb water molecules, forming a hydrated layer around the charge. Moreover, the exosomes derived from bone marrow stem cell (BMSCs) were engineered with a chondrocyte affinity peptide (CAP) in the out membrane and si-STING in the exosome to reshape the senescence microenvironment. Furthemore, the in vivo data showed that the hydrogel/exosome delivery system successfully can alleviate the joint wear and rejuvenate chondrocytes to reverse the development of OA. The HD-T@CAP-Exos-siSTING gels can provide efficient lubrication and potentially alleviate friction-related diseases such as osteoarthritis. Teaser An injectable hydrogel delivering exosomes rejuvenates chondrocytes and reduces mechanical stress, presenting a potential osteoarthritis treatment strategy.