In Vitro Human Arteriole Microphysiological System with Physiological Scale and Functional Vasoactivity Enabled by a...

Arterioles are the principal regulators of vascular tone, yet their small size and deep tissue location hinder direct investigation of their roles in microvascular disease. To address this, we developed a human microphysiological arteriole distinguished from previous models by simultaneously integrating an arteriole-scale caliber (~200 μm), continuous perfusion culture, and active vasoactivity. The vessel autonomously forms and matures under flow through a spatially regulated coating strategy that eliminates post-seeding manipulation. The engineered vessels exhibit vasoactivity in response to both biochemical and metabolic cues. In particular, the metabolic response is a physiological form of vasoactivity rarely reproduced in previous in vitro systems. Leveraging the ease of sample harvesting, proteomic profiling and mechanical testing indicated that flow-induced maturation promotes a contractile phenotype consistent with arteriogenesis-like remodeling. This accessible platform provides a versatile tool for studying arteriolar physiology and microvascular remodeling.