Advances in engineering organ-on-a-chip models of angiogenesis

Angiogenesis plays a central role in embryonic development, tissue repair, tumor progression and cardiovascular remodeling. Because vascular growth involves a series of closely coordinated dynamic events, it is difficult for traditional in vitro and in vivo models to resolve the underlying mechanisms. Angiogenesis-on-a-chip (AoC) platforms provide microphysiological systems that can recapitulate key aspects of vascular growth in vitro, while enabling precise spatiotemporal control of the local microenvironment. These platforms combine microfluidic structures, three-dimensional hydrogels and relevant cell populations, so that biochemical gradients, mechanical cues and multicellular interactions can be regulated independently or in combination. When the relevant conditions are properly reproduced, endothelial sprouting, lumen formation and barrier function can be directly monitored and quantified. This review summarizes the recent progress of AoC design and discusses how these platforms can be used to study pathophysiological mechanisms, evaluate candidate therapeutic drugs and engineer vascularized tissues. The article also discusses persistent challenges, including platform standardization, characterization of the immune microenvironment, model validation and quantitative phenotypic analysis. By integrating engineering design with biological applications and an assessment of current limitations, this review provides a practical framework for advancing the application of AoC systems in vascular biology, therapeutic development and regenerative medicine.