Biomimetic cellular sponges for neutralizing inflammatory cytokines in osteoarthritic joints

Osteoarthritis (OA) is a joint disease characterized by age-related cartilage degradation, synovial inflammation, and imbalanced macrophage polarization. Pro-inflammatory cytokines, such as IL-1β and TNF-α, play critical roles in the progression of OA. Current treatments provide symptomatic relief but fail to address the underlying pathophysiological mechanisms, necessitating innovative therapeutic strategies. In this study, engineered macrophage membrane-incorporated hyaluronic acid methacrylate hydrogel microspheres (EMM@HMs) were used to neutralize pro-inflammatory cytokines and promote cartilage repair in osteoarthritic joints. The EMM@HMs were prepared using microfluidic techniques and characterized using scanning electron microscopy (SEM), zeta potential analysis, and particle size analysis. Cartilage organoids were prepared as a three-dimensional model to simulate native cartilage. The anti-inflammatory and cartilage-protective effects of the EMM@HMs were evaluated in vitro and in rats with OA. Results demonstrated that EMM@HMs neutralized IL-1β and TNF-α, promoted M2 macrophage polarization, and reduced cartilage degradation in cartilage organoids and OA rats. The EMM@HMs upregulated extracellular matrix (ECM)-related genes (COL2A1 and SOX9) and suppressed catabolic markers (MMP13 and COL10A1), highlighting their role in regulating ECM remodeling and chondrocyte differentiation. These findings demonstrated the potential of EMM@HMs to target inflammatory and degenerative pathways, offering a promising strategy for OA treatment.