Responsive bone regeneration membranes targeting Macrophages: A novel strategy for promoting bone defect repair and regeneration

• Proposes a materials-centered framework for macrophage-targeted bone regeneration membranes. • Elucidates how responsive materials regulate macrophage behavior and the healing microenvironment. • Shows that multifunctional membranes enhance bone regeneration via immunomodulation and controlled bioactivity. • Identifies challenges in material design and multifunctional integration for clinically translatable bone repair. Background. Bone defects caused by trauma, infection, tumors, and metabolic disorders remain difficult to treat due to hostile microenvironments and the limited functionality of conventional materials. With the rapid development of materials science, bone regeneration strategies have shifted from passive barrier membranes to multifunctional responsive systems capable of actively regulating the repair process. Among these, macrophage-mediated immunomodulation has emerged as a critical mechanism for coordinating inflammation, angiogenesis, and osteogenesis; however, a material-centered synthesis of this field remains lacking. Methods: This study systematically reviews macrophage-targeted responsive bone regeneration membranes, with a focus on material design strategies, microenvironment-responsive mechanisms, and immunoregulatory functions. Results: Advanced membrane systems integrate responsive elements (e.g., pH, ROS, and enzyme sensitivity), controlled drug delivery, and physicochemical surface functionalization to precisely modulate macrophage polarization, activate osteogenic signaling pathways, and enhance bone regeneration performance. Conclusions: Responsive membrane design represents a promising materials-driven strategy for precise bone repair. Nevertheless, challenges remain in structural optimization, multifunctional integration, scalable fabrication, and clinical translation, highlighting the need for further innovation toward high-performance and application-oriented biomaterials.