Next-Gen Stroke Models: The Promise of Assembloids and Organ-on-a-Chip Systems

The complexity of stroke pathophysiology, involving intricate neurovascular interactions and dynamic cellular responses, has long challenged the development of effective preclinical models. Traditional 2D cultures and animal models often fail to fully recapitulate human-specific features, limiting translational success. Emerging 3D systems, particularly brain assembloids and organ-on-a-chip platforms, are offering new opportunities to create more physiologically relevant stroke models. Assembloids, which integrate multiple brain-region-specific organoids, enable the study of interregional connectivity and complex cellular responses under ischemic conditions. Organ-on-a-chip platforms, by mimicking key tissue interfaces such as the blood-brain barrier and incorporating controlled fluid dynamics, enable a dynamic and highly customizable microenvironment with real-time monitoring capabilities. This review introduces and characterizes these two cutting-edge platforms (assembloids and organ-on-chip technologies), exploring their potential in stroke research while also discussing current challenges that need to be addressed for their broader adoption in translational applications.