Nanomaterial-based strategies to modulate macrophage polarization in osteoarthritis: A systematic review

Osteoarthritis (OA) is a chronic degenerative joint disease characterised by progressive functional impairment due to erosion of the articular cartilage, remodelling of the subchondral bone and inflammation of the synovial tissue. In addition to mechanical and metabolic alterations, there is increasing evidence highlighting the pivotal role of macrophages in OA pathophysiology. The imbalance between pro-inflammatory M1 and anti-inflammatory M2 phenotypes drives joint inflammation, extracellular matrix degradation, chondrocyte apoptosis and impaired tissue repair. Therefore, modulating macrophage polarization appears to be an attractive therapeutic target for preventing OA progression. In recent years, nanomaterials have emerged as an innovative approach to tackling this challenge. Their tunable size, morphology, and surface properties enable both direct immunomodulation and the delivery of therapeutic agents. This systematic review examined preclinical studies published between 2021 and 2025 that investigated the potential of various developed nanomaterials to polarize macrophages towards the M2 phenotype, thereby reducing joint inflammation and promoting cartilage protection and repair. Consistent results from both in vitro and in vivo included studies demonstrated their ability to reduce pro-inflammatory mediators related to M1-type macrophages while enhancing the expression of anti-inflammatory ones linked to M2-type macrophages, despite their differences in physicochemical properties. This suggested that nanomaterials could reprogram macrophages to suppress the inflammatory microenvironment of OA and slow down disease progression by lowering synovitis and cartilage damage. By influencing macrophage polarization and fostering a regenerative environment, nanotechnology may pave the way for more effective, targeted strategies in OA management.