Engineering biomaterials to tailor the microenvironment for macrophage–endothelium interactions

Macrophages and endothelial cells (ECs) have essential roles in physiological and pathological conditions by regulating inflammation, vascularization and tissue remodelling. Although the interactions between macrophages and ECs in tissue homeostasis and disease progression have been extensively studied in the past few decades, the role of the extracellular matrix in this intercellular process is less known. Here, we review the current knowledge on how microenvironmental cues, biophysical and biochemical, dictate macrophage–endothelium crosstalk in the pathology of different diseases. We summarize studies using biomaterials as extracellular matrix with tenable properties to manipulate macrophage–EC fate to regulate innate and adaptive immunity, angiogenesis and regeneration. Finally, we discuss the potential and challenges of developing novel therapeutic strategies to tailor macrophage–EC niches to restore homeostasis in various diseases. The interactions between macrophages and endothelial cells are regulated by microenvironmental cues in the extracellular matrix. This Perspective highlights recent advances in using biomaterials as extracellular matrix to mimic macrophage–endothelium niches and to regulate cell fate in tissue homeostasis and disease progression.