Associate Professor University of Florida Gainesville, Florida, United States
Introduction: The brain has an extensive specialized vascular network comprised of arteries, veins and capillaries. However, most in vitro studies of the brain vasculature utilize 2D or simple 3D models which fail to recreate the complexity of the vasculature tree. Tissue engineering offers the potential to create microfluidic models which feature perfusable 3D branched vessels that mimic the in vivo architecture and structural arrangement of the cells of the brain parenchyma.
Materials and
Methods: Vascular casting and microCT imaging was used to generate a computer aided design file of the mouse brain vasculature, specifically the middle cerebral artery. Scaffolds were then printed using the LumenX 3D bioprinter (CellInk). Scaffolds were perfused with dye to verify the formation of lumens that recapitulated the vascular architecture. To further advance this technology for the application to human health, we utilized 3D rotational angiograms to generate scaffolds of patient specific vascular networks. Scaffolds of branching lumens were endothelialized with pericytes to generate brain microvessels. Astrocytes were also embedded during the printing process to demonstrate the ability to form a blood-brain barrier.
Results, Conclusions, and Discussions: We show the potential of this technology to model mouse and patient specific complex vascular architectures. Future challenges include the incorporation of neurons and formation of neural circuits. Overall, these 3D bioprinted vasculatures can be used to model the brain vasculature, mimic vascular abnormalities and test the delivery of therapeutics.
