Collagen densification as a model for cardiac fibrosis
Cardiac fibrosis is a disease state characterized by excessive collagenous matrix accumulation within the myocardium that can lead to ventricular dilation and systolic failure. Current treatment options are severely lacking due in part to the poor understanding of the complexity of molecular pathways involved in cardiac fibrosis. Therefore, a need exists for an in-vitro model system that recapitulates the defining features of a fibrotic cellular environment, namely extracellular mechanics and composition. Type I collagen, as the major matrix component of fibrotic tissue, is an attractive matrix choice for a fibrosis model, but demonstrates poor mechanical strength due to solubility limits. However, plastic compression of collagen matrices has been shown to significantly increase their mechanical properties. Here, we utilized confined compression of collagen oligomer matrices to achieve constructs with increased surface fibril concentration (3.07 fold increase to 13.4 mg/mL) and mean thickness (1.4 fold increase to 1.39 µm) that were subsequently used to study the spontaneous cardiomyocyte beating response on compressed gels. Beating intensity was shown to be significantly decreased in compressed collagen matrices, with a 2.4 fold decrease seen in calcium stain intensity. These results were consistent with the expected beating response on a pathologically stiff substrate. Plastic compression of collagen matrices therefore shows potentially as a mechanically and physiochemically relevant platform for in-vitro study of cardiac fibrosis.
Neu, Purdue University.
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