Preston Le

Heart failure is characterized by immune cell recruitment and activation. Macrophages, a type of immune cell, can have a profound effect on the trajectory of heart failure based on their polarization towards pro-inflammatory or anti-inflammatory phenotypes. Conversely, macrophage behavior is modulated based on environmental cues. Macrophage behavior is commonly studied under the lens of traditional biological parameters, like the gene/protein expression and chemical signaling pathways of small molecules. Less commonly studied are the influences of the physical environment or chemical signaling pathways of large macromolecules. The study of hyaluronic acid, a native polysaccharide residing in the extracellular matrix, addresses these areas. Cardiac injury can promote increased extracellular rigidity and formation of shorter hyaluronic acid chains. Both factors have been shown to stimulate pro-inflammatory macrophage phenotypes, though direct ties of these findings to the trajectory of heart failure remain elusive. The current work of this project presents histochemistry experiments quantifying the amount of hyaluronic acid in heart tissues subjected to induced pressure overload modeling hypertensive heart failure. Additionally, the effect of hyaluronic acid concentration and molecular weight on bone marrow-derived macrophage proliferation and behavior in two-dimensional cell cultures is presented. Lastly, the prospectives and pilot studies of three-dimensional cell encapsulation cultures in hyaluronic acid-based hydrogels are discussed.