Advances in 3D printed blood-brain barrier models.

Abstract

Blood-brain barrier (BBB) integrity is critical for central nervous system (CNS) homeostasis and represents a key challenge for drug delivery. Three-dimensional (3D) bioprinting offers unprecedented control over architecture and cellular organisation in neurovascular models. This review presents recent advances in bioprinting methodologies, including extrusion-based coaxial nozzle printing for multilayered capillaries, droplet-based drop-on-demand deposition, digital light processing and two-photon polymerization for high-resolution vascular features, and hybrid systems integrating electrospun scaffolds. We detail composite bioink formulations combining natural and synthetic hydrogels that promote endothelial cell viability, tight junction protein expression and shear-responsive barrier function. Main outcomes reveal that 3D printed constructs achieve selective molecular permeability, sustained barrier integrity under perfusion and improved repeatability compared to conventional static cultures. We also discuss emerging strategies such as incorporation of astrocytes and pericytes to replicate the full neurovascular unit, integration of biosensors forin situmonitoring and scalable manufacturing approaches. Addressing current limitations in capillary-scale resolution, mechanical robustness and long-term culture stability will be essential to translate 3D bioprinted BBB models into standardized platforms for CNS drug screening and mechanistic investigations.