Artificial M2 macrophages for disease-modifying osteoarthritis therapeutics

Osteoarthritis (OA) is one of the most common joint diseases worldwide and the focus is shifting to disease prevention and the pharmaceutical and surgical treatment of early OA. However, at present few have proven ability to block or delay the progression of OA. Nevertheless, M2 macrophages present an anti-inflammatory function and promote cartilage repair, thereby alleviating OA in mice. However, it is a significant challenge to regulate the helpful secretion of M2 macrophages on demand toward disease-modifying osteoarthritis therapeutics. Here, artificial M2 macrophage (AM2M) with yolk-shell structure was proposed and fabricated to enhance the therapeutic efficacy of M2 macrophages in the treatment of OA. AM2M was composed of macrophage membrane as "shell" and inflammation-responsive nanogel as "yolk". The nanogel was prepared via physical interaction of gelatin and chondroitin sulfate (ChS) through ionic bond and hydrogen bond, achieving burst release to down-regulate inflammation during acute flares and sustainable release to repair cartilage during low inflammatory activity. Furthermore, AM2M exhibited the targeting and long-term residence in the inflamed area and blocked the immune stimulation of macrophages by ChS. Therefore, our fabrication provided a new insight that artificial M2 macrophages are expected to break a vicious and self-perpetuating cycle of OA.