Macrophagenex Based on Multifunctional Ta@Sr2+ Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization

Osteoarthritis (OA) is a progressive joint disease that involves damage to the cartilage, inflammation in the synovium, and injury to the subchondral bone, which highlights the need for the creation of novel treatment options. Nevertheless, finding an effective method that combines anti-inflammatory properties with the ability to regenerate cartilage remains a significant challenge. TA@Sr²⁺ is a bioactive coordination complex formed through chelation between tannic acid (TA) and strontium ions (Sr²⁺), exhibiting a hierarchically structured metal-phenolic network. This research presents an innovative strategy utilizing a Macrophage_nex developed from multifunctional TA@Sr²⁺, which promotes chondrogenesis and exhibits strong anti-inflammatory effects. The Macrophage_nex based on TA@Sr²⁺ is constructed by self-assembling a single-cell layer using varying concentrations of TA and Sr²⁺ on RAW264.7 cell surfaces. This Macrophage_nex demonstrates robust biological activity, enhancing chondrocyte proliferation, differentiation, and migration, alongside the upregulation of anabolic genes such as aggrecan (ACAN) and collagen II, while simultaneously inhibiting the expression of catabolic genes like MMP13 in a dose-dependent manner under LPS-induced inflammation. In addition, TA@Sr²⁺ reduces the expression of proinflammatory cytokines (TNF-α and IL-6) in macrophages and promotes their polarization to the anti-inflammatory M2 phenotype. These results suggest that TA@Sr²⁺ has significant promise for treating OA by regulating both chondrogenesis and macrophage polarization simultaneously.