Micropatterned Fibrin Hydrogels for Increased Cardiomyocyte Alignment

Cardiovascular disease is the leading cause of death in the US, which can result in blockage of a coronary artery, triggering a myocardial infarction (MI). After a MI, hypoxic ventricular myocardial tissue dies, resulting in the deposition of non-contractile scar tissue and remodeling of the ventricle, leading to decreased cardiac output and ultimately heart failure. Currently, the gold-standard solution for total heart failure is a heart transplant. As donor hearts are in short supply, an alternative to total-organ transplantation is surgically remodeling the ventricle with the implantation of a cardiac patch. Acellular cardiac patches have previously been investigated using synthetic or decellularized native materials in effort to improve cardiac function. However, a limitation of this strategy is that acellular cardiac patches only reshape the ventricle and do not increase cardiac contractile function. By incorporating the use of a clinically relevant cell type and by matching native architecture, we propose the use of a highly aligned fibrin scaffold to support the maturation of human induced pluripotent stem cell cardiomyocytes (hiPS-CM) for use as a cell-populated cardiac patch. By micropatterning fibrin hydrogels, hiPS-CM seeded on the surface of this scaffold become highly aligned, which is crucial for increased contractile output. Our lab previously developed a composite fibrin hydrogel and microthread cardiac patch matching mechanical properties of native myocardium. By micropatterning fibrin hydrogel alone, we were able to match cellular alignment of hiPS-CM to that of native myocardium. hiPS-CMs seeded on this surface were found to express distinct sarcomere alignment and circumferential connexin-43 staining at 14 days of culture as well as cellular elongation, which are necessary for mature contractile properties. Constructs were also cultured under electrical stimulation to promote increased contractile properties. After 7 days of stimulation, contractile strains of micropatterned constructs were significantly higher than unpatterned controls. These results suggest that the use of topographical cues on fibrin scaffolds may be a promising strategy for creating engineered myocardial tissue to repair damaged myocardium