Development of hydrogel-based cell stretching devices as in vitro model of atherosclerotic vessel walls

Atherosclerosis, the hardening of arteries, is the leading cause of heart attacks and strokes. The disease is worsened by smooth muscle cell (SMC) dedifferentiation, but the cause is difficult to study in vitro because it involves coupling between multiple physical and chemical factors. We sought to improve SMC culture models by creating a device with independent control over substrate stiffness, mechanical stretch and cell attachment. This device was fabricated by embedding micro-heaters under temperature-responsive hydrogel with patterned creases on the surface, and one SMC was seeded between two neighboring creases by photo-lithographically patterned attachment of peptides in desired location. The actuation is achieved by driving the heaters at 1 Hz, which mimics the resting pulse rate, causing the cell to be cyclically stretched and released by the repeatable deepening and relaxation of the creases. The cell is stretched by a strain of 5-10%, which is comparable to the stretch ratio that it experiences in physiological environment. This device can be systematically engineered, avoids macroscopic deformation and can potentially be scaled to high-throughput arrays.