Smart hydrogel bioinks integrated with two-dimensional nanomaterials for cardiovascular bioprinting and atherosclerosis modeling

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, and atherosclerosis underlies most ischemic cardiovascular events. However, conventional in vitro and in vivo models fail to fully reproduce the complex cellular interactions, extracellular matrix remodeling, oxidative stress, and hemodynamic microenvironment of human vascular lesions. This review summarizes recent advances in stimuli-responsive hydrogel bioinks for three-dimensional (3D) bioprinting of atherosclerosis models. We discuss how disease-responsive biomaterials can dynamically regulate the cellular microenvironment and improve the physiological relevance of engineered vascular tissues. Particular emphasis is placed on the integration of two-dimensional (2D) nanomaterials. Graphene-based materials provide electrical conductivity, mechanical reinforcement, and sensing capabilities; black phosphorus (BP) offers biodegradability, photothermal responsiveness, and reactive oxygen species (ROS)-sensitive behavior; while emerging Xene materials such as germanene present additional opportunities for multifunctional bioink design. Their respective advantages and limitations for cardiovascular bioprinting are comparatively evaluated. Finally, we discuss key translational challenges, including material standardization, long-term biosafety, biological validation, manufacturing scalability, and regulatory approval. We propose that multifunctional, disease-responsive bioinks combined with advanced biofabrication technologies will accelerate the development of physiologically relevant cardiovascular disease models and precision medicine platforms.