Engineering biomimetic coronary artery equivalents for Kawasaki disease modeling and drug screening

Kawasaki disease (KD) is an acute vasculitis that primarily affects the pediatric population, and the development of coronary artery lesions constituting its most severe clinical sequela. Although investigated for decades, the precise etiology and pathogenesis of this syndrome remains elusive. This critical knowledge gap stems from the absence of robust in vitro platforms capable of accurately recreating the complex pathophysiological dynamics of pediatric coronary arteries. To overcome this challenge, we developed hollow hydrogel fibers using microfluidic coaxial printing, which were then seeded with human coronary artery smooth muscle cells (HCASMCs) and human umbilical vein endothelial cells (HUVECs) to generate biomimetic coronary artery construct. The physiological responsiveness of the model was validated through stimulation with TNF-α, and a KD-specific pathological model was established by introducing serum from KD patients. Using this biomimetic platform, we evaluated the therapeutic potential of Atorvastatin (ATOR) and the NLRP3 inflammasome inhibitor MCC950, and explored their underlying mechanisms in attenuating vascular inflammation. Overall, this work introduces a structurally relevant in vitro platform that offers new opportunities for studying KD pathogenesis and accelerating the development of targeted therapies.