Rapid low-cost assembly of modular microvessel-on-a-chip with benchtop xurography

Blood and lymphatic vessels in the body are central to molecular and cellular transport, tissue repair, and pathophysiology. Several approaches have been employed for engineering microfabricated blood and lymphatic vessels in vitro, yet these approaches invariably require specialized equipment, facilities, and research training beyond the capabilities of most biomedical laboratories. Here we present xurography as an inexpensive, accessible, and versatile rapid prototyping technique for engineering cylindrical and lumenized microvessels. Using a benchtop xurographer, or a cutting plotter, we fabricated modular multi-layer poly(dimethysiloxane) (PDMS) -based microphysiological systems (MPS) that house endothelial-lined microvessels approximately 260μm in diameter embedded within a user-defined 3-D extracellular matrix (ECM). We validated the vascularized MPS (or vessel-on-a-chip) by quantifying changes in blood vessel permeability due to the pro-angiogenic chemokine CXCL12. Moreover, we demonstrated the reconfigurable versatility of this approach by engineering three different vessel-ECM arrangements, which were obtained by minor adjustments to one or two steps of the fabrication process. Several of these arrangements, such as ones that incorporate close-ended vessel structures and spatially distinct ECM compartments along the same microvessel, cannot be readily achieved with other microfabrication strategies. Therefore, we anticipate that our low-cost and easy-to-implement fabrication approach will facilitate wider accessibility of MPS with tunable vascular architectures and ECM components while reducing the turnaround time required for iterative designs.