Micropatterned fibrin scaffolds increase cardiomyocyte alignment and contractility for the fabrication of engineered myocardial tissue.

Cardiovascular disease is the leading cause of death in the United States, which can result in blockage of a coronary artery, triggering a myocardial infarction (MI), scar tissue formation in the myocardium, and ultimately heart failure. Currently, the gold-standard solution for total heart failure is a heart transplantation. 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 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. Toward the development of a cardiac patch, our laboratory previously developed a cell-populated composite fibrin scaffold and aligned microthreads to recapitulate the mechanical properties of native myocardium. In this study, we explore micropatterning the surfaces of fibrin gels to mimic anisotropic native tissue architecture and promote cellular alignment of human induced pluripotent stem cell cardiomyocytes (hiPS-CM), which is crucial for increasing scaffold contractile properties. hiPS-CMs seeded on micropatterned surfaces exhibit cellular elongation, distinct sarcomere alignment, and circumferential connexin-43 staining at 14 days of culture, which are necessary for mature contractile properties. Constructs were also subject to electrical stimulation during culture 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 micropatterned topographic cues on fibrin scaffolds may be a promising strategy for creating engineered cardiac tissue.