Designing Modular Fibrin Composite Scaffolds for Enhanced Ventricular Myocardium Regeneration

Chrobak, Megan O'Brien

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Designing Modular Fibrin Composite Scaffolds for Enhanced Ventricular Myocardium Regeneration

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Cardiovascular diseases are the leading causes of death globally. One contributing factor that can lead to heart failure is a myocardial infarction. When an infarct occurs, an occlusion in the tissue vasculature prevents blood flow beyond this site. It results in scar tissue formation. The scar is non-contractile and reduces the working efficiency of the heart. To compensate, left ventricular remodeling will ensue resulting in enlarging of the left ventricle. This progression of events ultimately culminates in heart failure. One approach to assist patients who have suffered a heart attack is to implant a cardiac patch. Current patches are acellular and aim to retain the geometry of the left ventricle, limiting any ventricular remodeling from occurring. While these patches provide a passive support, it is hypothesized that incorporation of cells into the patches could result in functional support that could help to restore baseline function. To be effective, a cell-populated cardiac patch would need to integrate with the host tissue functionally and mechanically. In this thesis, we developed a fibrin microthread-based composite scaffold with material properties comparable to left ventricular myocardium that promotes regional cardiomyocyte alignment and physiologically relevant contractile strains. We hypothesized that a composite material could be developed where constituents of the material would complement one another to yield a mechanically reinforced scaffold that promotes cardiomyocyte function. Through manipulation of the volume fraction of the components, we manipulated the modulus of the layer without compromising contractile strain or contractile frequency of incorporated cells. Additionally, through strategic restraint of the scaffolds, we utilized cell-mediated compaction to induce a tension pattern that increased alignment of incorporated cells. This corresponded to an increase in contractile strain magnitudes, and an anisotropic contractile wave propagation through the engineered tissue. Finally, we laminated composite layers into a patch mimicking the architecture of ventricular myocardium and found that material properties of the patch were similar to properties of the target tissue. In summary, we designed a biomimetic composite patch with material properties similar to ventricular myocardium that supports cardiomyocyte alignment and contractility to promote functional and mechanical integration upon implantation.

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