Embedded 3D‐Coaxial Bioprinting of Stenotic Brain Vessels with a Mechanically Enhanced Extracellular Matrix Bioink for Investigating Hemodynamic Force‐Induced Endothelial Responses

Abstract Stenotic regions in cerebral vessels are implicated in diseases such as atherosclerosis, where shear‐responsive endothelial function is critical to disease progression. However, studying flow‐induced inflammation remains challenging due to the complexity of in vivo conditions, highlighting the need for a well‐engineered in vitro model. A physiologically relevant in vitro model of stenotic brain vessels using 3D‐coaxial bioprinting and a mechanically enhanced extracellular matrix (ECM) bioink is developed to investigate flow‐induced endothelial inflammation. The hybrid bioink, composed of vascular decellularized ECM, collagen, and alginate, exhibits an approximately 65‐fold increase in dynamic modulus, enabling stable formation of perfusable structures. Printing parameter optimization facilitates precise fabrication of stenotic vessels with a luminal diameter of 250–500 µm. Computational fluid dynamics simulations under an inlet flow rate of 3 mL min −1 predict disturbed fluid flow in stenotic regions. The bioprinted vessels exhibit continuous endothelial coverage, expression of junction proteins (CD31, ZO‐1, and VE‐cadherin), and size‐dependent permeability, indicating a mature vascular barrier formation. Under disturbed flow conditions, ICAM‐1 (approximately 2.2‐fold) and VCAM‐1 (approximately 1.5‐fold) are upregulated, confirming the hemodynamic stress‐induced inflammation. These findings highlight the potential of 3D bioprinting for modeling cerebrovascular disease in vitro and paving the way for future therapeutic innovation.