Advancing tissue engineering through vascularized cell spheroids: building blocks of the future

Vascularization is a crucial aspect of biofabrication, as the development of vascular networks is essential for tissue survival and the optimization of cellular functions. Spheroids have emerged as versatile units for vascularization, demonstrating significant potential in angiogenesis and prevascularization for tissue engineering and regenerative medicine. However, a major challenge in creating customized vascularized spheroids is the construction of a biomimetic extracellular matrix (ECM) microenvironment. This process requires careful regulation of environmental factors, including the modulation of growth factors, the selection of culture media, and the co-culture of diverse cell types. Recent advancements in biofabrication have expanded the potential applications of vascularized spheroids. The integration of microfluidic technology with bioprinting offers promising solutions to existing challenges in regenerative medicine. Spheroids have been widely studied for their ability to promote vascularization in in vitro models. This review highlights the latest developments in vascularized biofabrication, and systematically explores strategies for constructing vascularized spheroids. We provide a comprehensive analysis of spheroid applications in specific tissues, including skin, liver, bone, cardiac, and tumor models. Finally, the review addresses the major challenges and future directions in the field.