Auxetic iPSC-Cardiomyocyte Patches for Heart Repair After Myocardial Infarction
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Brazhkina, Olga
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Abstract
Myocardial infarction is one of the largest contributors to cardiovascular disease and reduces the ability of the heart to pump blood. One promising therapeutic approach to address the diminished function is the use of cardiac patches, including new designs such auxetic geometries that can expand in multiple directions when stretched longitudinally, can have high energy absorption, and can be modified to suit the mechanics of the infarct and surrounding cardiac tissue. This project developed an auxetic composite polycaprolactone and fibrin cardiac patch that can support induced cardiomyocyte (iCM) function. Aim 1 focuses on designing an auxetic cardiac patch capable of supporting iCM function, highlighting that a 3D printed polycaprolactone missing rib auxetic pattern can support basic cell viability, contractility, and electrical propagation after 14 days of culture. Aim 2 examines maturation potential of iCMs encapsulated within the auxetic cardiac patch under cyclic loading conditions. We showed how continuous unidirectional 10% mechanical strain of the auxetic patch upregulated key maturation markers of iCMs, created syncytium electrical propagation across the whole patch, and led to more organized ultrastructure and increased mitochondrial presence. Finally, aim 3 evaluated therapeutic cardiac function in vivo after patch delivery following a chronic myocardial infarction model and showed increased global functional outcomes and increased regenerative potential of the iCM auxetics. Taken together these aims demonstrate the validity of using auxetics for long-term cardiomyocyte culture and maturation, as well as broadening the impact of auxetics in tissue engineering approaches to treating cardiac disease.
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2024-12-03
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Dissertation (PhD)