Collagen-Glycosaminoglycan Scaffold Systems to Assess HL-1 Cardiomyocyte Beating and Alignment

cardiomyocyte;collagen;scaffold;biomaterial systems;cardiac tissue engineering

Gonnerman, Emily ; Harley ; Brendan A.

关键词: cardiomyocyte;    collagen;    scaffold;    biomaterial systems;    cardiac tissue engineering;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/29554/Gonnerman_Emily.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

With heart disease being the leading cause of death in the US and an estimated 1.3 million heart attacks occurring annually, the need for tissue-engineered strategies to regenerate damaged cardiac tissue has become increasingly important. This thesis discusses the development of scaffold systems to examine the alignment and beating potential of HL-1 cardiomyoctyes in a 3D environment. Collagen-glycosaminoglycan scaffolds have been used extensively to probe the behavior of mature cells in vitro, but have not yet been designed for cardiac applications. In order to recapitulate key properties of the cardiac extracellular matrix, most notably its high degree of organization and alignment, we fabricated scaffolds with a longitudinally anisotropic pore structure. A freeze-dry process promoting unidirectional heat transfer through the precursor suspension was employed to create scaffolds of various mean pore sizes, all with pores elongated in the direction of solidification. The effects of structural cues on cell number, metabolic activity, alignment, and beating potential were quantified. It was shown that scaffolds with longitudinally anisotropic pore structures promoted spontaneous HL-1 cardiomyocyte beating compared to isotropic controls. This effect was dependent on pore size, with scaffolds with larger mean pore sizes exhibiting the highest instances of spontaneous beating. In addition, anisotropic scaffold variants promoted gross cell alignment in the longitudinal plane. These results indicate that an anisotropic collagen-glycosaminoglycan scaffold with larger pores (> 150 μm), may be most suited for cardiac tissue engineering applications.