Regulating macrophage activation precisely is crucial in treating chronic inflammation in osteoarthritis (OA). However, the stable pro-inflammatory state and deep distribution of macrophages in vivo pose a great challenge to treatment. In this study, inspired by the innate immune, immune cell mobilized hydrogel microspheres were constructed by microfluidic methods and load chemokines, macrophage antibodies and engineered cell membrane vesicles (sEVs) via covalent and non-covalent junctions. The immune cell mobilized hydrogel microspheres, based on a mixture of streptavidin grafted hyaluronic acid methacrylate (HAMA-SA) and Chondroitin sulfate methacrylate (ChSMA) microspheres (HCM), can recruit, capture and reprogram proinflammatory macrophages in the joint cavity to improve the joint inflammatory microenvironment. In vitro experiments demonstrated that immune cell mobilized hydrogel microspheres had excellent macrophage recruitment, capture, and reprogramming abilities. Pro-inflammatory macrophages can be transformed into anti-inflammatory macrophages with an efficiency of 88.5 %. Animal experiments also revealed significant reduction in synovial inflammation and cartilage matrix degradation of OA. Therefore, the immune cell mobilized hydrogel microspheres may be an effective treatment of OA inflammation for the future.

精确调节巨噬细胞活化对于治疗骨关节炎 (OA) 慢性炎症至关重要。然而，体内巨噬细胞稳定的促炎状态和深层分布给治疗带来了巨大的挑战。在本研究中，受先天免疫的启发，通过微流控方法构建了免疫细胞动员水凝胶微球，并通过共价和非共价连接负载趋化因子、巨噬细胞抗体和工程化细胞膜囊泡（sEV）。免疫细胞动员水凝胶微球基于链霉亲和素接枝透明质酸甲基丙烯酸酯（HAMA-SA）和硫酸软骨素甲基丙烯酸酯（ChSMA）微球（HCM）的混合物，可以招募、捕获和重新编程关节腔中的促炎巨噬细胞，以改善关节炎症微环境。体外实验表明，免疫细胞动员水凝胶微球具有优异的巨噬细胞招募、捕获和重编程能力。促炎巨噬细胞可以转化为抗炎巨噬细胞，效率高达88.5%。动物实验还显示，OA 的滑膜炎症和软骨基质降解显着减少。因此，免疫细胞动员水凝胶微球可能是未来治疗骨关节炎炎症的有效方法。