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This book explores the convergence of biomaterials science and systems immunology in addressing atherosclerosis. It highlights how stimuli-responsive scaffolds can dynamically regulate the cellular microenvironment, influencing macrophage polarization and functional plasticity within arterial lesions. By integrating single-cell transcriptomics, the book reveals molecular signatures that link scaffold-mediated cues with immune checkpoint pathways, providing new insights into immunometabolic reprogramming and vascular inflammation control. Emphasis is placed on translational potential, from mechanistic understanding to therapeutic design, positioning these technologies as promising strategies for precision medicine in cardiovascular disease.