Hydrogel-based microfluidic model of the blood-brain barrier: progress and future perspectives

The development of brain-targeted delivery systems is significantly hindered by the blood-brain barrier (BBB), which prevents drugs from effectively reaching therapeutic regions in the brain. To evaluate drug efficacy and study pathogenesis, BBB models are used to simulate the brain microenvironment and the action of the BBB. In vitro models, which overcome the cost and ethical issues associated with animal models and avoid species-specific differences, are particularly valuable. However, traditional in vitro models, such as two-dimensional cell cultures and transwell systems, lack three-dimensional structure and physiological and mechanical conditions, including shear stress, making it challenging for endothelial cells (ECs) to recapitulate BBB properties. Recent advancements have incorporated microfluidics and gel materials to support cell growth into BBB models, enabling near physiological replication of the BBB in vitro to mimic pathogenesis and critical physiological and pathological processes. This paper discusses recent advancements in in vitro BBB modeling, current design concepts for microfluidic BBB models, and key influencing factors. It also reviews different types of hydrogels used in microfluidic platforms for the BBB, highlighting their respective features. Furthermore, it explores potential biocompatible hydrogel structures for future applications in microfluidic BBB models, aiming to provide valuable data and a theoretical foundation for future BBB model optimization.