The formation of new blood vessels is a critical process in several physiological and pathological contexts. The complexity of the angiogenic process is not completely reproducible using standard two-dimensional (2D) culture models. Three-dimensional (3D) models have emerged as effective tools for deciphering molecular mechanisms controlling endothelial cell sprouting and vascular morphogenesis. These models allow dynamic and detailed analysis of the distinct angiogenic steps, as well as molecular manipulation. The “state-of-the-art” in 3D culture models developed for the study of angiogenesis has been review. The potential for 3D cell and tissue culture models to fill the gap between 2D models and clinical application has been assessed. Advances in combining engineering, materials science, and cell biology to highlight the most promising device and microfluidic systems for 3D angiogenesis have also been reported.
