Angiogenesis. 2026 Feb 12;29(2):17. doi: 10.1007/s10456-026-10030-2.
ABSTRACT
Cardiovascular disease (CVD) is the leading cause of death worldwide, with arteries being the most common site of CVDs. Diseases caused by abnormal arterial morphology and dysfunction (e.g., atherosclerosis, arterial thrombosis) often have a grim prognosis when they progress. Conventional animal models and two-dimensional (2D) cell cultures fall short in replicating the complex geometry, cellular heterogeneity, and dynamic mechanical microenvironment of human arteries, which may bias the clinical evaluation of drug efficacy. Artery-on-a-Chip (AoC), an emerging organ-on-a-chip (OoC) platform, integrates microfluidics, tissue engineering, and biomaterials to recreate physiologically and pathologically relevant arterial structures under controlled biochemical and biomechanical cues. This review systematically summarizes the materials, fabrication strategies, and structural configurations of AoCs, with an emphasis on disease modeling for thrombosis, atherosclerosis, pulmonary hypertension, and aneurysms. We highlight key design parameters, including extracellular matrix composition, cellular origin, shear stress, cyclic stretch, and matrix stiffness, that determine model fidelity. Finally, we identify current challenges in long-term culture stability, standardization, and multi-factor coupling, and propose future directions toward clinically predictive, personalized AoC systems. By bridging the gap between basic research and clinical translation, this review provides a theoretical framework for developing next-generation highly realistic and translatable vascular models for application in pathophysiological research and therapeutic development.
PMID:41677980 | DOI:10.1007/s10456-026-10030-2