Injectable microspheres filled with copper-containing bioactive glass improve articular cartilage healing by regulating inflammation and recruiting stem cells

Abstract Osteoarthritis (OA) is a frequent chronic illness in orthopaedics that poses a major hazard to patient health. In situ cell therapy is emerging as a therapeutic option, but its efficacy is influenced by both the inflammatory milieu and the amount of stem cells, limiting its use. In this study, we designed a novel injectable porous microsphere (PM) based on microfluidic technology that can support in situ mesenchymal stem cells (MSCs) therapy by combining polylactic-glycolic acid copolymer, kartogenin, polydopamine, stromal cell-derived factor-1, and copper-doped bioactive glass (CuBG). The ex vivo tests demonstrated that PMs@CuBG microspheres were biocompatible and facilitated the transformation of synovial macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes by releasing CuBG to reduce joint inflammation. At the same time, the microspheres are able recruit MSCs into the joint cavity and encourage their differentiation into chondrocytes, thereby treating articular cartilage injury. The in vivo rat experimental results show that intra-articular injection of PMs@CuBG in rats with OA improves OARSI scores, Aggrecan content, and the ratio of Col-2α positive cells, indicating a reparative effect on damaged cartilage within the joint. As a result, PMs@CuBG microspheres are predicted to provide a novel and successful approach to in situ cell therapy for OA.