Engineered Fibrin Scaffolds for Cardiac Tissue Repair

Abstract

Myocardial infarction (MI) causes significant cell loss and damage to myocardium. Cell-based therapies for treatment of MI aim to remuscularize the resultant scar, but the majority of transplanted cells do not survive or integrate with host tissue. Additionally, survival of tissue engineered constructs after implantation depends heavily on induction of a vascular response in host tissue in order to promote a quick anastomosis of the cellular graft. Scaffolds can improve cell retention following implantation, but often do little to enhance host-graft integration. Fibrin is an ideal biomaterial for cardiac tissue engineering as it is a natural, biodegradable polymer that can induce neovascularization, promote cell attachment, and has tunable mechanical properties. The research presented in this dissertation describes the development and characterization of a novel high density microtemplated fibrin scaffold with mechanical stiffness comparable to native myocardium, tunable degradation, and a microarchitecture designed to promote cellular organization within constructs. Acellular fibrin scaffolds demonstrated highly angiogenic properties when implanted. Cell seeding with a tri-cell mixture of cardiomyocytes, endothelial cells, and fibroblasts demonstrated the fibrin scaffolds promote cardiomyocyte alignment and the development of a pre-vascular network. The fibrin scaffolds are designed to promote graft cell organization and improve chances of construct survival and integration with host tissue upon implantation.