A Blood-Brain Barrier Model Based on Flexible Tubes to Tailor the Biophysical and Chemical Environment for Drug Delivery Testing

The development of physiologically relevant in vitro models of the blood-brain barrier (BBB) is critical for reliable assessment of drug permeability and neurotherapeutic transport. Current platforms often fail to reproduce the three-dimensional geometry and mechanical compliance of cerebral microvessels, limiting their translational relevance. Here, we report the fabrication of soft, flexible and self-supporting tubular membranes via polyelectrolyte complexation of alginate and ε-poly-L-lysine, yielding cylindrical constructs that closely mimic the architecture and flexibility of small brain vessels. The resulting biomaterials support robust endothelial cell adhesion and the formation of a functional barrier, exhibiting controlled permeability consistent with selective molecular transport. Importantly, the compliant tubular constructs enable the application of external mechanical compression, allowing controlled modulation of vessel deformation and barrier integrity in a manner relevant to pathological conditions such as tumor-induced vascular compression. By integrating physiologically relevant cylindrical geometry with a mechanically compliant and deformable microenvironment, this platform provides a tunable and reproducible basis for endothelial barrier formation and mechanical perturbation, enabling the development of a more biomimetic in vitro BBB model.