Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration

Abstract

Linköping 2015Cover: Scanning Electron Microscopy image of a mesenchymal cell on polycaprolactone fibers.During the course of the research presented in this thesis, Abeni Wickham, was enrolled in Forum Scientium, a multidisciplinary graduate school at Linköping University. ColophonThis thesis is not only the summation of 5 years of research, but also a material manifestation of my happiness.It has not been straightforward and I have had numerous failures, disappointments and doubts. These have always been positive moments, as each difficult moment gave me the chance to choose a different path to still achieve my research goals.I have spent the past few years fighting for what I love the most; answering the questions that I ask myself every day. I have been lucky to have two supervisors, Daniel and Bo who pushed me to be better scientifically and family/friends who kept me grounded.During this work, I found who I really am; this thesis is a representation of me.ii Abstract Nature has had millions of years to perfect the structural components of the human body, but has also produced the dysfunctions that result in the cancers and diseases, which ruin that perfection. Congenital heart defects, and myocardial infarction lead to scarring that remodels heart muscle, decreasing the contractility of the heart, with profound consequences for the host. Regenerative medicine is the study of strategies to return diseased body parts to their evolutionarily optimum structure.Cells alone cannot develop into functional tissue, as they require mechanical support and chemical signals from the extracellular matrix in order to play the correct role in the body. In order to imitate the process of tissue formation optimized by nature, scaffolds are developed as the architectural support for tissue regeneration. To mimic the elasticity and strength seen in the heart muscle is one of the major scientific conundrums of our time. The development of new multifunctional materials for scaffolds is an accepted solution for repairing failing heart muscle. In this thesis I accept the notion that endogenous cardiac cells can play a major role in addressing this problem, if we can attract them to the site of defect or injury and make them proliferate. I then proceed to show how improving on a commonly used synthetic polymer was used to develop two new biomaterials.Polycaprolactone (PCL) fibers and sheets were studied for their ability to adsorb proteins based on their surface energies. We found that although the wettability of the PCL might be similar to positive controls for cell attachment, the large differences in surface energies may account for the increased serum protein adsorption and limit cell adhesion. The effect of fiber morphology was then investigated with respect to proliferation of mesenchymal stem cells and cardiac progenitor cells. PCL was also mechanically enhanced with thiophene conjugated single walled carbon nanotubes (T-CNT); where small concentrations of the T-CNT allowed for a 2.5 fold increase in the percentage of elong...