Vascularized Organoids for Modeling Cardiovascular Diseases: Advances and Challenges

Organoid technology has emerged as a highly promising tool in biomedical research, with extensive applications in drug discovery, disease modeling, and mechanistic investigation. However, conventional organoid models generally lack a functional vascular network, which compromises the diffusion of oxygen and nutrients, predisposes to central necrosis, and limits long-term culture, thereby severely impeding their clinical translation. To address this critical bottleneck, research on vascularized organoids has gained considerable momentum. This review provides a systematic overview of recent advances in the field of vascularized organoids, with a core focus on vascularized cardiac organoids and cardiovascular disease modeling. We first discuss the molecular mechanisms of angiogenesis and discuss their essential contribution to the establishment of a functional organoid microenvironment. Subsequently, we critically evaluate current mainstream and emerging vascularization strategies. Next, we dissect mainstream and emerging strategies to achieve organoid vascularization, and further distinguish two major cardiac model categories: self-organizing vascular cardiac organoids and engineered vascularized cardiac tissue constructs. Finally, we explore the translational potential of vascularized organoids, with particular emphasis on their application in cardiovascular disease modeling and regenerative repair. This review aims to offer a systematic technological roadmap for addressing the intrinsic limitations of conventional organoids, and to provide a novel theoretical foundation for accelerating their transition from basic research to clinical applications.