A practical guide to vascularized microphysiological systems

Microphysiological systems (MPS) are emerging as human-relevant models for pharmaceutical research, reducing reliance on animal testing. Despite progress in reproducing organ-specific features, integrating functional microvasculature remains challenging. Advances have expanded the number of available options, making it difficult to identify the most suitable one for a specific MPS. Here, we provide a guide to designing vascularized MPS by comparing current vascularization strategies according to key design drivers, including the microfluidic platform, organotypic vascular architecture, matrix properties, and coculture with perivascular cells. We highlight trade-offs between biological fidelity, engineering control, and translational needs, while considering approaches widely adopted in commercial MPS. Finally, we discuss how close the field is to delivering physiologically accurate vascularized MPS and how emerging omics technologies may redefine vascular identity and functionality.