Biomaterial-guided macrophage modulation: Therapeutic engineering of immune microenvironments

Macrophages are central regulators of immunity, tissue homeostasis, and repair, whose plasticity enables them to integrate cues from their local microenvironment. Dysregulated macrophages contribute to chronic inflammation, fibrosis, impaired wound healing, and tumor progression. Biomaterials enable the modulation of macrophages through localized delivery of immunomodulatory signals and by creating instructive microenvironments. In this review, we examine macrophage-biomaterial interactions, emphasizing how surface chemistry, topography, mechanics, porosity, and degradation profiles shape macrophage recruitment and phenotype. We discuss emerging strategies for macrophage modulation, including programmable systems that provide spatiotemporal control over immune signaling. We further highlight how these applications can improve disease outcomes. Finally, we discuss design considerations, characterization, and translational challenges that must be overcome to advance macrophage-targeted biomaterials toward clinical implementation.