Injectable Thermosensitive Hydrogel Encapsulating Mesenchymal Stem Cell Membrane-Based Biomimetic Liposomes for Local Rheumatoid Arthritis Treatment.

In rheumatoid arthritis (RA), the immune system mistakenly attacks joints by releasing harmful inflammatory substances that cause swelling and gradual joint damage. As inflammation progresses, patients experience severe pain and reduced mobility. Therefore, localized anti-inflammatory and analgesic therapeutic interventions may offer a viable strategy for the clinical management of RA. To effectively regulate joint inflammation, it is essential to prolong the retention time of therapeutic agents within the joint cavity and enhance the target delivery capability. To achieve this, we loaded mesenchymal stem cell membrane biomimetic liposomes (MSCsome) into the injectable thermosensitive hydrogel for RA therapy in this study. Specifically, the thermosensitive hydrogels injected into the joint cavity enabled the sustained and localized release of dexamethasone (Dex)-encapsulated MSCsome due to the slow degradation rate, and subsequently, Dex-MSCsome can be internalized by activated macrophages due to the intrinsic targeting capability. This composite biomimetic formulation effectively alleviated joint inflammation and pain, while significantly promoting articular cartilage repair. In conclusion, this study presents a novel strategy using cell membrane-based biomimetic carriers combined with thermosensitive hydrogels, offering a promising platform for targeted and sustained anti-inflammatory therapy.