Self-Standing Photo-Crosslinked Hydrogel Construct: in vitro Microphysiological Vascular Model

Abstract

Modeling of the human vascular microphysiological system (MPS) has gained attention due to precise prediction of drug response and toxicity during drug screening process. Developing a physiologically equivalent vascular MPS still remains complex as it demands the recapitulation of dynamic structural and biological microenvironment similar to native vasculature. Hence, an ideal MPS would involve developing perfusable 3D in vitro models with multilayered human vascular cells encapsulated in a matrix to regulate the vascular tone resembling the native. Several attempts to model such anatomically accurate physiological and pathological blood vessels often fail to harmonize the essential vascular microenvironment. For instance, conventional microfluidic-based approaches employed for vascular MPS, though offering creation of perfusable channel, do not replicate the vascular hierarchical cellular arrangement due to planar geometry and confluent monolayered cell seeding. Also, recent advances with 3D biofabrication strategies are still limited by fabrication of small-diameter constructs and scalability besides post-processing techniques that indirectly distort the structural integrity of the hydrogel tubular constructs. These existing limitations toward fabricating a relevant vascular MPS demand a facile and mechanically stable construct. Hence, the present study is aimed toward developing a stable viable self-standing perfusable hydrogel construct by a rapid and scalable strategy toward vascular MPS application. The fabricated tubular constructs were found to be structurally stable with end-to-end perfusability exhibiting their potential as self-standing perfusable structures. Also, the construct exhibited nonhemolytic behavior with perfusion of red blood cells inside the luminal channel. The present study evidences creation of a dual-crosslinked stable, viable self-standing hydrogel construct with multilayered homogenous distribution of viable smooth muscle cells throughout the construct, thereby demonstrating its applicability as a promising 3D in vitro vascular microphysiological system.