Injectable biomimetic microcarriers harness synergistic effects of paracrine factors and cellular membranes to alleviate osteoarthritis
Abstract
Osteoarthritis (OA), characterized by cartilage degeneration and functional impairment, remains a significant unmet medical need with limited therapeutic options available. While stem cell therapies, particularly those derived from bone marrow mesenchymal stem cells (BMSCs), hold great promise, they are hampered by challenges including cell instability and safety concerns. This study develops and investigates the potential of biomimetic microcarriers (BMSCs-CF@M-PLGA), synthetic cells that encapsulate BMSC paracrine factors within PLGA microspheres and are coated with BMSC membranes. These cells aim to overcome the limitations of conventional stem cell therapies while maintaining their therapeutic efficacy. In vitro experiments demonstrated that BMSCs-CF@M-PLGA significantly enhance chondrocyte proliferation, migration, and extracellular matrix synthesis, attributed to the synergistic action of paracrine factors and the protective properties of the cell membranes. In vivo studies confirmed the therapeutic efficacy of BMSCs-CF@M-PLGA in OA rat models, resulting in improved joint morphology and cartilage structure. Transcriptomic analysis revealed the regulation of extracellular matrix synthesis, cell survival, and inflammation pathways, with a shift towards reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. This study highlights the encouraging therapeutic potential of BMSCs-CF@M-PLGA, offering enhanced stability, safety, and convenience for OA treatment.