Design of Blood Vessel Models using Magnetic-Responsive Vascular Platforms

The design of physiologically relevant blood vessel in vitro models has been impaired by the difficulty to reproduce the complex architecture of native blood vessels and the mechanisms mediating key cellular functions within miniaturized perfusable systems. Aiming to simulate blood vessel walls, in this work innovative 2D platforms are designed and patterned with magnetic-responsive gelatin for enabling in situ co-culture of mesenchymal stromal cells (MSCs) and human umbilical vein endothelial cells (HUVECs) within confined compartments. The performance of the 2D chips is evaluated based on HUVECs migration, adherence, and angiogenic behavior (proliferation and sprouting), as well as production of Endothelin-1 (endothelium marker), and compared with the results of 3D single channel models, designed to mimic the morphology of native arteries and veins. The 2D chips obtain better cell adhesion and angiogenic performance, which is attributed to flow profiles and VEGF concentration gradients. Magnetic stimulation is then used as a novel strategy to increase cell sprouting and endothelization ≈1.5 times above the control condition. These bio-inspired devices advance the exploration of magnetism for a finer convergence to the native vascular conditions in vitro and improved modulation of angiogenesis, showing promising contributions to the development of sophisticated therapeutics for vascular ischemia-related diseases.