Macrophage Polarization-Targeted Hydrogels for Bone Regeneration

Bone regeneration is a multifaceted process involving inflammation and tissue remodeling, which are tightly regulated by the immune response. Macrophages, central players in bone regeneration, exhibit remarkable functional plasticity, transitioning between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. The regulation of macrophage polarization, specifically guiding the shift from the M1 to M2 phenotype, has emerged as a critical therapeutic target to enhance bone regeneration. This review explores the emerging field of macrophage-targeted hydrogels, a novel class of biomaterials designed to modulate macrophage polarization for enhanced bone regeneration. These hydrogels integrate bioactive agents such as growth factors, exosomes, peptides, and nanozymes to influence macrophage behavior, thereby creating a favorable microenvironment for tissue healing. By incorporating specific bioactive molecules that engage macrophage receptors, these hydrogels promote a shift toward the reparative M2 phenotype, facilitating osteogenesis, angiogenesis, and tissue remodeling. Despite their potential, challenges remain, including optimizing the precise control over macrophage polarization, improving targeted delivery, and ensuring the long-term safety and stability of these materials. This review provides a comprehensive overview of the mechanisms, applications, and therapeutic potential of macrophage-targeted hydrogels, highlighting their promise as an innovative strategy for bone regeneration.