"Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model

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Abstract Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder that results in premature and accelerated aging, while accumulation of progerin also occurs during physiological aging. Our paratal project seeks to optimize a biomimetic HGPS-on-a-chip system generated with patient-derived fibroblasts (FBs), smooth muscle cells (SMCs), and endothelial cells (ECs) that allow application of relevant cyclic stretch for performing ‘clinical trials’ or informing clinical trial designs for HGPS patients. Given the unique microgravity environment of the International Space Station-National Lab (ISS-NL), which has been shown before to pose various negative effects on vascular cell phenotypes, this supplement further aims at developing a methodology to enable in-space bioprinting of multi-layered, high-cell-density, bioreactor-integrated vascular conduits through Techshot’s BioFabrication Faclity (BFF) at the International Space Station-National Laboratory (ISS-NL), and studying premature vascular aging under microgravity. Successful completion of the proposed supplement project will be transformative in multiple aspects. First, it will demonstrate a unique in-space BFF utility through the use of new bioink formulations for the bioprinting of a new tissue type not previously done. Yet, while we target vascular bioprinting, we anticipate that the technology is applicable to many other tissue types with necessary modifications. Second, the biological study will benefit life both in space and on Earth. Vascular aging is a pressing medical problem that affects millions of people, and is potentially also a major pathological manifestation for astronauts especially for future deep-space missions. Under our hypothesis that vascular conduits bioprinted with HGPS cells will manifest a pathologically relevant premature aging phenotype that is more severely affected by the space microgravity environment than those with healthy cells and those on Earth, we anticipate grasping additional fundamental knowledge regarding the underlying mechanisms of vascular aging in both children and adults in association with developmental biology, which will further instruct prevention and therapeutic interventions in the future in HGPS and beyond.