Coaxial Cell Printing of Freestanding, Perfusable, and Functional In Vitro Vascular Models for Recapitulation of Native Vascular Endothelium Pathophysiology

3D printing technology is used to produce channels within hydrogels followed by endothelial cells (ECs)-seeding to establish in vitro vascular models. However, as built-in bulk hydrogels, it is difficult to incorporate additional cells and molecules into the crosslinked matrix to study the pathophysiological responses of healthy endothelium. In this study, freestanding in vitro vascular models (VMs) are developed using the coaxial cell printing technique and a vascular tissue-specific bioink. It has various advantages in plotting tubular cell-laden vessels with designed patterns, providing pump-driven circulating perfusion, generating endothelium without ECs-seeding, and implementing further expansions to study vascular pathophysiology. Following the maturation of endothelium, the VMs exhibit representative vascular functions (i.e., selective permeability, antiplatelets/leukocytes adhesion, and vessel remodeling under shear stress). Moreover, with the expansions of the VMs, the directional angiogenesis and inflammatory responses are demonstrated by giving asymmetric distributions of proangiogenic factors and an airway inflammatory ambience, respectively. Therefore, the freestanding, perfusable, and functional VMs can be useful devices to engineer diverse in vitro platforms for a wide range of biomedical applications, from modeling blood vessel relevant diseases to building vascularized tissues/organs.