Abstract
Scaffold-free three-dimensional (3D) cellular spheroid cultures better replicate the in vivo cellular microenvironments of complex tissues than traditional two-dimensional (2D) cell cultures, as they promote more intricate cell-cell and cell-extracellular matrix (ECM) interactions. In the context of cardiovascular research, 3D spheroids have emerged as valuable models for studying angiogenesis, modeling the cardiac microenvironment, and advancing drug development and cardiac tissue repair. Given that cardiovascular disease remains the leading cause of morbidity worldwide, exploring 3D spheroids as in vitro models in cardiovascular research holds potential for advancing the field. Despite their promise, the experimental potential of 3D spheroids in cardiovascular disease and biology has yet to be realized. Therefore, this review discusses the advantages and limitations of 3D spheroid models for studying angiogenesis and cardiovascular pathobiology, their applications in cardiac drug development and tissue repair, and how these models can advance cardiovascular research.