Biomaterial-mediated macrophage polarization remodeling and sequential regulation: a potential strategy in bone infections treatment

Osteomyelitis remains a global challenge in the field of orthopedics. Even after standard debridement and antibiotic-assisted treatment, the long-term recurrence rate remains at 20%-30%. Given the dynamic changes in immune responses and defense mechanisms during bone infection, as well as the complex "race for the surface" involving bacterial adhesion and host cells (macrophages and tissue cells) on implant surfaces, biomaterials with immunomodulatory functions have attracted considerable attention. Macrophages, as crucial components of the immune system, participate in the inflammatory regulation and tissue remodeling of bone infections through highly plastic polarization mechanisms after bacterial invasion. The different microenvironmental characteristics and therapeutic needs at different stages of bone infection highlight the promising applications of biomaterials capable of macrophage polarization remodeling and sequential regulation. In this review, we provide a detailed discussion of the complex immune regulatory patterns in the bone infection microenvironment and the critical functions of macrophage polarization. We then explore how implant surface properties influence bacterial adhesion and macrophage function, highlighting the importance of achieving precise and dynamic regulation of macrophage polarization based on the Race for the Surface theory. Furthermore, we focus on recent advances, potential challenges, and opportunities in biomaterial-mediated macrophage polarization remodeling and sequential modulation strategies across different stages of osteomyelitis, aiming to offer insights that may accelerate the clinical translation of novel biomaterial-based macrophage immunotherapies.