Pulmonary Arterial Hypertension (PAH) is a deadly vascular disease, affecting the blood vessels of the lungs rather than the systemic circulation, with no existing cure. PAH is characterized by pulmonary arterial smooth muscle cell (PASMC) hypertrophy and hyperplasia, which increases resistance to blood flow within the pulmonary arteries and leads to rapid symptom progression and death from right heart failure over several years. We hypothesize that defects in PASMC differentiation and alignment may contribute to PAH. Prior work has shown that micropatterned scaffolds encourage vascular SMC alignment and differentiation towards a contractile phenotype. To test whether these responses differ in patients with PAH, we designed a micropatterned collagen scaffold atop a glass coverslip. Scaffoldings were imprinted with either alternating 10-µm wide x 10-µm deep microchannels or left unpatterned. Explanted PASMCs from patients with PAH or failed donors (controls) were cultured on patterned versus unpatterned constructs and alignment, protein expression, and cellular morphology were compared across conditions. I evaluated 3 PAH and 3 control subjects and have collected preliminary data for each condition (control versus PAH), with three technical replicates each. Through these preliminary studies, I have demonstrated success of my model with consistent alignment observed on patterned substrates. Excitingly, PASMCs from patients with PAH expressed significantly decreased levels of the contractile protein, Calponin, when compared with control cells, including after responding to cues that promote alignment and contractility. This suggests that PAH PASMCs remain in an inappropriately synthetic or proliferative state. Subsequent testing will include assessment of calcium signaling in response to contractile stimuli and transcriptomic evaluation of cellular responses to micropatterning. This work will enhance understanding of whether SMC abnormalities contribute to disease initiation and progression in PAH and will contribute to the broader effort of developing more complex models of pulmonary vascular disease.