Venkatasubramanian, Ramji T.2009-02-232009-02-232008-11https://hdl.handle.net/11299/47752University of Minnesota Ph.D. dissertation. November 2008. Major: Mechanical Engineering. Advisor: John Bischof. 1 computer file (PDF); xix, 142 pages, appendix A.Conventional treatments for arterial diseases, such as balloon angioplasty, often result in restenosis or re-narrowing of the arteries. In the last few years, the clinical importance of thermal therapies for atherosclerosis involving both freezing (cryoplasty) and heating (in-stent heating) has increased significantly because of their potential to control or minimize restenosis. An alternative to these therapies includes replacing the diseased artery through preserved arterial grafts which brings with it the need to effectively preserve them. Cryopreservation, i.e. preservation of tissues by freezing to very low temperatures, has therefore become an important problem in medicine. As mechanical properties of arteries play a large role in blood flow, a complete understanding of the biomechanical changes following thermal treatments and the underlying mechanisms is essential for further optimization of these treatments through controlling biomechanical changes. The objective of this dissertation was to quantify the biomechanical changes and investigate the underlying mechanisms post freeze-thaw. In this dissertation, the following specific aims were pursued: 1. Quantification of freeze-thaw induced biomechanical changes in arteries 2. Investigation of underlying mechanisms of thermobiomechanics SA1 involved quantification of freeze-thaw induced mechanical property changes in arteries using both uniaxial tensile tests and indentation. While uniaxial tensile tests were chosen for relatively easy sample preparation and testing, indentation was performed in order to study a more localized biomechanical response while characterizing the diseased artery response. SA2 involved investigation of the mechanisms underlying the biomechanical changes. This primarily involved understanding the changes to the collagen matrix and SMCs following thermal treatments. Changes to collagen matrix stability were assessed by quantifying the changes to the amide-III band using the FTIR spectroscopy. Changes in SMC function were studied from the response of arteries to norepinephrine and acetylcholine. Finally, MD simulations were performed as a tool to further investigate dehydration induced increase in thermal stability of the collagen matrix due to freeze-thaw at the molecular level. The important conclusions of this dissertation research are: 1. Freeze-thaw causes significant stiffening of the arteries. While, significant increase in the physiological elastic modulus (and reduction in toe region) was observed in the uniaxial tensile response, the peak and equilibrium modulus measured from indentation increased significantly following freeze-thaw. 2. Freeze-thaw induces significant changes in the collagen matrix and smooth muscle cells (SMCs) that are arguably the most important components of an artery. While dehydration accompanied by increased thermal stability was observed following freeze-thaw in the collagen matrix, it caused complete destruction of SMCs measured through loss in function. 3. At the molecular level, dehydration due to freeze-thaw (or any osmotic treatments) results in formation of new sidechain-backbone hydrogen bonds that are typically absent under hydrated conditions. These newly formed intra-protein hydrogen bonds in the absence of water molecules increase the thermal stability of the tropocollagen molecule.en-USBiomechanicsCollagenCryoplastyCryopreservationMolecular DynamicsSmooth Muscle CellsMechanical EngineeringThesis or Dissertation