CHARACTERIZATION OF CALCIFICATIONS IN DISEASED HUMAN AORTIC VALVES: A RAMAN STUDY
ABSTRACT The formation of biogenic minerals in human aortic valves is an increasingly prevalent cardiovascular pathology lacking effective treatment options except valve replacement surgery. Much research has focused on cell signaling pathways and maladaptive remodeling of the valvular matrix. Little is known, however, about the pathological mineralization process from a materials science perspective, potentially due to a lack of appropriate characterization tools. In this thesis, excised human patient valves with varying degrees of calcification were scanned via micro-CT, processed, and analyzed via Raman microscopy in series with histological staining. Raman microscopy enabled characterization of mineral and organic matrix composition in the context of pathology. Carbonated hydroxyapatite was found to be the predominant phase of valvular calcification, though traces of whitlockite and octacalcium phosphate were also detected. We found that the mineral crystallinity of valvular calcification was higher for female than male patients. Though calcifications were extremely heterogeneous across and among patients in terms of size, mineralization density, matrix composition, etc., small calcifications tended to associate strongly with lipids, while large calcifications with collagen. The association of specific matrix species with calcifications size could reflect different events in the pathological progression of the disease (e.g., inflammation and fibrosis), and warranted further investigation. This thesis laid the groundwork for incorporating Raman microscopy into future studies of pathogenesis of calcific aortic valve disease.
Biomineralization; Calcific aortic valve disease; Raman microscopy
Estroff, Lara A.
Butcher, Jonathan T.
Materials Science and Engineering
M.S., Materials Science and Engineering
Master of Science
dissertation or thesis