+publisher:"Georgia Tech" +contributor:("Taylor, W. Robert")

Georgia Tech

1. Rathan, Swetha. Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification.

Degree: PhD, Chemical and Biomolecular Engineering, 2016, Georgia Tech

URL: http://hdl.handle.net/1853/58144

► Calcific aortic valve (AV) disease is a strong risk factor for cardiovascular related deaths and is a significant source of mortality worldwide, with the number… (more)

▼ Calcific aortic valve (AV) disease is a strong risk factor for cardiovascular related deaths and is a significant source of mortality worldwide, with the number of patients requiring AV surgery expected to increase from 250,000 to 850,000 by 2050. However, the molecular mechanisms underlying AV disease have not been well studied or understood. Further, identification of biomarkers that can be used to detect early stage AV disease is also understudied but vital to successfully preventing and/or treating AV disease. It was hypothesized that sclerosis, inflammation and calcification preferentially occurs in the fibrosa compared to the ventricularis due to differential gene expression and oscillatory shear stress. Freshly isolated porcine AV leaflets and an ex vivo shear stress bioreactor was used to test this hypothesis. The low magnitude oscillatory shear stress (OS) appeared to predispose fibrosa to side-dependent calcification via increasing collagen turnover (Col1a1), and thickening of the extracellular matrix (ECM) (fibrosis) and decreasing the expression of genes that protect endothelial function (Klf4 and Enos). The unidirectional pulsatile shear, LS, however, preserved the ECM and gene expression in the ventricularis. The involvement of miRNAs in OS mediated AV pathogenesis was also investigated in a shear- and side-dependent manner. The miR-214 was found to play a role in this OS induced pathogenesis in fibrosa but not ventricularis. Using an ex vivo miRNA silencing protocol, anti-miRNA was delivered to both endothelial and interstitial cells of the AV tissue without compromising the cell viability. Silencing of miR-214 showed that the OS induced pathology in the fibrosa is likely to be mediated via miR-214, klf4 and Tgfβ1 dependent pathway that can lead to AV fibrosis, endothelial-to-mesenchymal transition and eventually sclerosis. The miR-214, however, did not play a role in shear-induced inflammation and calcification. The miR-214, as such, is likely to play a key role in the early onset of side- and shear- dependent AV disease and has a potential to serve as a disease biomarker. Further, an ex vivo AV calcification model was also developed to understand the role of endogenous pro- and anti-calcification factors, such as inorganic pyrophosphate, orthophosphate, and alkaline phosphatase. The functional studies carried out in this dissertation aim to link the mechanosensitive miRNAs to the genes involved in inflammation, endothelial-to-mesenchymal transition, and cell apoptosis etc, which eventually causes AV leaflets to calcify. Thus improved understanding of AV disease mechanisms under different hemodynamic conditions will enable us to improve the design of tissue-engineered valves and develop non-surgical treatment options. Advisors/Committee Members: Yoganathan, Ajit P. (advisor), Jo, Hanjoong (committee member), Taylor, W. Robert (committee member), Champion, Julie A. (committee member), Nerem, Robert M. (committee member).

Subjects/Keywords: Aortic valve; Hemodynamics; Mechanobiology; MicroRNA; Calcification

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APA (6^th Edition):

Rathan, S. (2016). Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58144

Chicago Manual of Style (16^th Edition):

Rathan, Swetha. “Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification.” 2016. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/58144.

MLA Handbook (7^th Edition):

Rathan, Swetha. “Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification.” 2016. Web. 15 Apr 2021.

Vancouver:

Rathan S. Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/58144.

Council of Science Editors:

Rathan S. Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/58144

2. Bhutani, Srishti. Investigating scaffold designs for progenitor cells-based cell therapy for cardiac repair.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2017, Georgia Tech

URL: http://hdl.handle.net/1853/58277

► Cell therapy for congestive heart failure has shown promising results in preclinical studies, but results of clinical trials suggest the need for this modality to… (more)

▼ Cell therapy for congestive heart failure has shown promising results in preclinical studies, but results of clinical trials suggest the need for this modality to be optimized. C-kit+ cardiac progenitor cells (CPCs) are adult stem cells that have been shown to differentiate toward lineages of the heart and exert beneficial paracrine effects. Their injection in humans resulted in moderate but insufficient improvements in cardiac function after myocardial infarction. In this project, we studied two strategies for enhancing CPC based-cell therapy using tunable maleimide-crosslinked poly(ethylene glycol) (PEG-MAL) hydrogels. In the first strategy, CPCs were encapsulated in PEG-MAL hydrogels presenting vascular endothelial growth factor (VEGF). Although activation of ERK signaling was observed in CPCs encapsulated in VEGF presenting PEG gels, this strategy failed to induce endothelial differentiation or modulate paracrine effects of CPCs in vitro. Different growth factor doses, cell populations and biomaterial density and degradation rates were tested. In the second strategy, CPCs were encapsulated in integrin-specific hydrogels. α2β1-specific hydrogels induced cardiomyocyte differentiation of CPCs accompanied by a reduction in expression of secreted factors in vitro. Interestingly, following injection in rats undergoing ischemia-reperfusion, treatment with CPCs encapsulated in non-adhesive hydrogels resulted in the greatest preservation of cardiac contractility and attenuation of post-infarct remodeling. Overall, this work adds to our knowledge of CPC behavior in presence of stimuli relevant to pragmatic design of regenerative therapies, as well as broadens our understanding of design principles that may be used to augment effects of cell therapy for myocardial repair. Advisors/Committee Members: Davis, Michael E. (advisor), García, Andrés J. (committee member), Taylor, W. Robert (committee member), Xia, Younan (committee member), Xu, Chunhui (committee member).

Subjects/Keywords: Cardiac repair; Biomaterials; Cardiac progenitor cells

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APA (6^th Edition):

Bhutani, S. (2017). Investigating scaffold designs for progenitor cells-based cell therapy for cardiac repair. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58277

Chicago Manual of Style (16^th Edition):

Bhutani, Srishti. “Investigating scaffold designs for progenitor cells-based cell therapy for cardiac repair.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/58277.

MLA Handbook (7^th Edition):

Bhutani, Srishti. “Investigating scaffold designs for progenitor cells-based cell therapy for cardiac repair.” 2017. Web. 15 Apr 2021.

Vancouver:

Bhutani S. Investigating scaffold designs for progenitor cells-based cell therapy for cardiac repair. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/58277.

Council of Science Editors:

Bhutani S. Investigating scaffold designs for progenitor cells-based cell therapy for cardiac repair. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/58277

Georgia Tech

3. Headen, Devon M. Microfluidics-based microgel synthesis for immunoisolation and immunomodulation in pancreatic islet transplantation.

Degree: PhD, Mechanical Engineering, 2017, Georgia Tech

URL: http://hdl.handle.net/1853/59763

► Encapsulation of islets in hydrogel microspheres (microgels) before transplantation into diabetic recipients can establish an adequate immuno-isolation barrier to mitigate allogeneic rejection. The synthetic hydrogel… (more)

▼ Encapsulation of islets in hydrogel microspheres (microgels) before transplantation into diabetic recipients can establish an adequate immuno-isolation barrier to mitigate allogeneic rejection. The synthetic hydrogel macromer PEG-4MAL (4-arm polyethylene glycol terminated with maleimides) is an ideal candidate polymer for immunoisolation applications, since it can be easily modified with thiolated bioactive molecules, allowing precise control of islet microenvironment. Alginate microencapsulation dominates in literature even though alginate provides limited control of islet microenvironment, because no technique exists for islet encapsulation in synthetic microgels. Therefore, a microfluidic platform for the encapsulation of islets in size-controlled PEG-4MAL microgels was developed, and hydrogel composition was optimized to support encapsulated islet function. Islets microencapsulated in optimized PEG-4MAL restored glycemic control better than islets microencapsulated in alginate and equally as well as unencapsulated islets when delivered to epididymal fat pads in diabetic syngeneic mice within bulk vasculogenic hydrogels. Improved function was partially attributed to decreased microgel size vs. alginate, and therefore reduced diffusional barrier. Immuno-isolation potential of this strategy is currently being investigated in allogeneic recipients. In a separate scheme, PEG-4MAL microgels were designed which could capture and display the chimeric immunomodulatory protein SA-FasL in its bioactive form. Simple cotransplantation of SA-FasL presenting microgels with unmodified allogeneic islets under the kidney capsule of diabetic mice resulted in long term graft acceptance without long term immunosuppression. Regulatory T cells mediated this acceptance since their ablation on day 50 post-transplantation prompted rapid graft rejection. Effective control or mitigation of immune responses is critical for successful outcomes in islet transplantation, and this work presents the development of two novel strategies for achieving long term function of allogeneic islet grafts. Advisors/Committee Members: García, Andrés J. (advisor), Thulé, Peter (committee member), Lu, Hang (committee member), Taylor, W. Robert (committee member), Roy, Krishnendu (committee member).

Subjects/Keywords: Microfluidics; Cell encapsulation; Microencapsulation; Protein delivery; Pancreatic islet; Mesenchymal stem cell; Biomaterials

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APA (6^th Edition):

Headen, D. M. (2017). Microfluidics-based microgel synthesis for immunoisolation and immunomodulation in pancreatic islet transplantation. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/59763

Chicago Manual of Style (16^th Edition):

Headen, Devon M. “Microfluidics-based microgel synthesis for immunoisolation and immunomodulation in pancreatic islet transplantation.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/59763.

MLA Handbook (7^th Edition):

Headen, Devon M. “Microfluidics-based microgel synthesis for immunoisolation and immunomodulation in pancreatic islet transplantation.” 2017. Web. 15 Apr 2021.

Vancouver:

Headen DM. Microfluidics-based microgel synthesis for immunoisolation and immunomodulation in pancreatic islet transplantation. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/59763.

Council of Science Editors:

Headen DM. Microfluidics-based microgel synthesis for immunoisolation and immunomodulation in pancreatic islet transplantation. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/59763

Georgia Tech

4. Garcia, Jose. Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells.

Degree: PhD, Mechanical Engineering, 2018, Georgia Tech

URL: http://hdl.handle.net/1853/61618

► Since the discovery of adult human mesenchymal stem cells in the late 1900’s, the potential of utilizing these cells in the clinic for cell-therapy applications… (more)

▼ Since the discovery of adult human mesenchymal stem cells in the late 1900’s, the potential of utilizing these cells in the clinic for cell-therapy applications has been an ever-present goal. Unfortunately, clinical trials using these cells have garnered lackluster results with a high degree of variability in patient outcome and in many cases no difference between patients who received these adult stem cell or placebo. Various factors account for such results including the inability to properly control cell presence via the routine method of intravenous administration, the inability to control cell phenotype once the cells are injected into the patient and the harsh microenvironment cells are injected into. Biomaterials can provide solutions for these factors through engineering scaffolds to present needed signals to both encapsulated stem cells and the surrounding microenvironment. The objective of this project is to engineer bioartificial hydrogels presenting specific signals in the form of integrin-specific ligands and covalently-bound proteins to enhance mesenchymal stem cell activity and efficacy in wound and disease models. We investigated the application of these bioarticifial hydrogels towards two different goals: 1) to enhance vascularization and associated stem cell survival in a critical size bone defect and 2) to enhance immunomodulation of stem cells in a wound regeneration model. For our first goal, we found that hydrogels presenting the α2β1 ligand ‘GFOGER’ resulted in enhanced vascularization of bone defects compared to hydrogels presenting the αvβ3 ligand ‘RGD’ in the absence of vasculogenic protein. For our second goal, we found that hydrogels functionalized tethered IFN-γ enhanced the immunomodulatory properties of encapsulated hMSCs which led to enhanced tissue resolution in a colonic wound model. Together, our findings elucidate novel ways to enhance adult stem cell efficacy and further the applicability of these cells in clinical settings. Advisors/Committee Members: Garcia, Andres J. (advisor), Guldberg, Robert E. (committee member), Botchwey, Edward (committee member), Taylor, W. Robert (committee member), Fernandez-Nieves, Alberto (committee member).

Subjects/Keywords: Mesenchymal stem cells; Hydrogel; Biomaterials; Vascularization; Bone engineering; Immunomodulation

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APA (6^th Edition):

Garcia, J. (2018). Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61618

Chicago Manual of Style (16^th Edition):

Garcia, Jose. “Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/61618.

MLA Handbook (7^th Edition):

Garcia, Jose. “Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells.” 2018. Web. 15 Apr 2021.

Vancouver:

Garcia J. Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/61618.

Council of Science Editors:

Garcia J. Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/61618

Georgia Tech

5. Kassis, Timothy. Quantifying the role of lymphatics in lipid transport and lymphatic filariasis using novel engineering approaches.

Degree: PhD, Electrical and Computer Engineering, 2015, Georgia Tech

URL: http://hdl.handle.net/1853/53921

► The lymphatic system has fundamental physiological roles in maintaining fluid homeostasis, immune cell trafficking and lipid transport from the small intestine to the venous circulation.… (more)

▼ The lymphatic system has fundamental physiological roles in maintaining fluid homeostasis, immune cell trafficking and lipid transport from the small intestine to the venous circulation. Lymphatic vessels are the main functional organ responsible for the diverse transport roles the system plays. Unlike the blood vasculature, the lymphatic system does not have a central pump, such as the heart, and relies on a variety of factors to move lymph through. It was long thought that only external factors, such as skeletal muscle contraction and lymph formation, played a role in the functional transport capacity of these vessels. With the advancement of imaging capabilities (both hardware and software), it has become clear in the past two decades or so that the main factor in driving lymph transport is the ability of these vessels to intrinsically contract whereby each vessel is comprised of a chain of ‘mini pumps’ in series. The functional capacity of these vessels is thus now understood to be primarily determined by this pumping activity that has been shown to be regulated by various mechanical and biochemical cues. Lymphatic vessel dysfunction has been implicated in a variety of diseases including many lipid related pathologies and a neglected tropical disease known as lymphatic filariasis. While it has been possible to study the vessel function in the context of fluid drainage and immune cell trafficking, the capability to understand the role of lymphatic vessels in lipid transport has not been available due to the lack of experimental animal models and acquisition systems. As part of this thesis, we sought to develop an experimental animal model along with hardware and software tools to investigate the interplay between lymphatics and their lipid content. We report the first functional measurements of how vessels respond to elevated lipid loads. We further utilized our engineering expertise to develop an experimental platform allowing us to further understand the parasite known as B. malayi that migrates to and resides in lymphatic vessels. Advisors/Committee Members: Dixon, J. Brandon (advisor), Taylor, W. Robert (committee member), Gashev, Anatoliy (committee member), Santangelo, Philip (committee member), O'Farrell, Laura (committee member).

Subjects/Keywords: Lymphatics; B. malayi; Lymphatic imaging; Filariasis; Biomechanics; Lipid uptake; Lipid transport

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APA (6^th Edition):

Kassis, T. (2015). Quantifying the role of lymphatics in lipid transport and lymphatic filariasis using novel engineering approaches. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/53921

Chicago Manual of Style (16^th Edition):

Kassis, Timothy. “Quantifying the role of lymphatics in lipid transport and lymphatic filariasis using novel engineering approaches.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/53921.

MLA Handbook (7^th Edition):

Kassis, Timothy. “Quantifying the role of lymphatics in lipid transport and lymphatic filariasis using novel engineering approaches.” 2015. Web. 15 Apr 2021.

Vancouver:

Kassis T. Quantifying the role of lymphatics in lipid transport and lymphatic filariasis using novel engineering approaches. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/53921.

Council of Science Editors:

Kassis T. Quantifying the role of lymphatics in lipid transport and lymphatic filariasis using novel engineering approaches. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/53921

Georgia Tech

6. Fernandez Esmerats, Joan. The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2018, Georgia Tech

URL: http://hdl.handle.net/1853/62206

► Calcific Aortic Valve Disease (CAVD), characterized by aortic valve (AV) stenosis and insufficiency (regurgitation), is a major cause of cardiac-related deaths worldwide, especially in the… (more)

▼ Calcific Aortic Valve Disease (CAVD), characterized by aortic valve (AV) stenosis and insufficiency (regurgitation), is a major cause of cardiac-related deaths worldwide, especially in the aging population in advanced countries. Once developed, it is treated mainly with AV repair or replacement by surgical or transcathether methods; however, there are currently no pharmacological treatment options for these patients. This is largely due to a relative paucity in molecular mechanistic understanding of the disease. CAVD was once thought to be a passive degenerative disease, but overwhelming evidence demonstrates that it is actively regulated by cellular and molecular pathways that lead to AV inflammation, sclerosis (thickening and fibrosis), and calcific lesions. MicroRNAs (miRNAs) are a large class of evolutionarily conserved, noncoding RNAs which function as post-transcriptional regulators by interacting with the 3’ untranslated region (3’UTR) of specific target mRNAs in a sequence-specific manner. A single miRNA can typically target hundreds of mRNAs. These miRNAs negatively regulate gene expression through translational repression or mRNA cleavage, depending on the degree of complementarity. Flow-sensitive miRNAs have been mostly characterized in vitro however, their role in human disease has not been fully studied. Previous work in our laboratory has focused on identifying shear-sensitive and side-specific (ventricularis compared to fibrosa layers of the AV) miRNAs relevant to CAVD. To this end, we conducted two independent microRNA array studies. First, we isolated human aortic valve endothelial cells (HAVECs) from each side of the leaflet and exposed them to high-magnitude unidirectional laminar shear stress (LS) or low-magnitude oscillatory shear stress (OS) conditions for 24 hours to discover shear-sensitive miRNAs. Second, we isolated endothelial-enriched total RNAs from each side of the leaflet from porcine AVs to discover side-specific miRNAs. These studies allowed us to identify miR-181b and miR-483 as potential miRNAs for further studies. In Aim 1, we focused on studying shear-sensitive miR-181b. We showed that miR-181b was upregulated in OS conditions and that it regulates matrix metalloproteinases (MMP) activity in valvular endothelium. We conducted an in silico analysis combining predicted gene targets of miR-181b and shear-sensitive target genes from our in vitro HAVEC array and identified tissue inhibitor of metalloproteinases 3 (TIMP3) as a shear-sensitive target of miR-181b responsible for the role of miR-181b in extracellular matrix (ECM) degradation. Therefore, we showed that ECM degradation, a critical step in CAVD, might be mediated by the miR-181b/TIMP3 pathway. In Aim 2, we focused on studying the novel shear-sensitive miR-483-3p. We discovered that it regulated inflammation and endothelial-to-mesenchymal transition (EndMT) in HAVECs. In HAVECs we identified UBE2C as a novel shear-sensitive gene targeted by miR-483; which regulates endothelial inflammation and EndMT. Additionally, UBE2C exerts… Advisors/Committee Members: Jo, Hanjoong (advisor), Taylor, W. Robert (committee member), Nerem, Robert M. (committee member), Yoganathan, Ajit P. (committee member), Wilkinson, Keith D. (committee member), Garcia, Andres (committee member).

Subjects/Keywords: OS; miRNA; HAVECs; LS; TIMP3; UBE2C; HIF1A; pVHL; KLF2; Inflammation; Aortic valve; Calcification

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fernandez Esmerats, J. (2018). The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62206

Chicago Manual of Style (16^th Edition):

Fernandez Esmerats, Joan. “The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/62206.

MLA Handbook (7^th Edition):

Fernandez Esmerats, Joan. “The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease.” 2018. Web. 15 Apr 2021.

Vancouver:

Fernandez Esmerats J. The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/62206.

Council of Science Editors:

Fernandez Esmerats J. The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/62206

Georgia Tech

7. Yap, Choon Hwai. The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification.

Degree: PhD, Biomedical Engineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/45742

► Calcific aortic valve disease is highly prevalent, especially in the elderly. Currently, the exact mechanism of the calcification process is not completely understood, limiting our… (more)

▼ Calcific aortic valve disease is highly prevalent, especially in the elderly. Currently, the exact mechanism of the calcification process is not completely understood, limiting our ability to prevent or cure the disease. Ex vivo investigations, however, have provided evidence that the aortic valve's biological response is sensitive to mechanical forces, including fluid shear stresses, leading to the hypothesis that adverse fluid shear stress environment play a role in leading to valve calcification. This thesis seeks to investigate this hypothesis. A method for performing experimental measurement of time-varying shear stress on aortic valve leaflets under physiologic flow conditions was first developed, based on the Laser Doppler Velocimetry technique, and was systematically validated. This method was then applied to both the aortic surface and the ventricular surface of a normal tricuspid the aortic valve, and then on a congenital bicuspid aortic valve, using suitable in vitro valve models and an in vitro pulsatile flow loop. It was found that in the tricuspid valve, the peak shear stress on the aortic surface under adult resting condition was approximately 15-19 dyn/cm². Aortic surface shear stresses were elevated during mid- to late-systole, with the development of the sinus vortex, and were low during all other instances. Aortic surface shear stresses were observed to increase with increasing stroke volume and with decreasing heart rate. On the ventricular surface, shear stresses had a systolic peak of approximately 64-71 dyn/cm² under adult resting conditions. During late systole, due to the Womersley effect, shear stresses were observed to reverse in direction to a substantial magnitude for a substantial period of time. Further, it was found that a moderately stenotic bicuspid aortic valve can experience excessive unsteadiness in shear stress experienced by its leaflets, most likely due to the turbulent forward flow resulting from the stenosis, and due to the skewed forward flow. To demonstrate that the measured shear stresses can have an effect on the aortic valve biology, ex vivo experiments were performed in specific to determine the effects of these various shear stress characteristics on the biological response of porcine aortic valve leaflets, using the cone and plate bioreactor. It was found that unsteady shear stress measured in the bicuspid valve resulted in increased calcium accumulation. Further, it was found that low shear stresses and high frequency shear stresses resulted in increased calcium accumulation. Thus, shear stress was found to affect aortic valve pathology, and low and unsteady fluid shear stresses can enhance pathology. Advisors/Committee Members: Yoganathan, Ajit P. (Committee Chair), Giddens, Don P. (Committee Member), Gleason, Rudolph L. Jr. (Committee Member), Glezer, Ari (Committee Member), Jo, Hanjoong (Committee Member), Taylor, W. Robert (Committee Member).

Subjects/Keywords: Bicuspid aortic valve; Laser doppler velocimetry; Cone and plate bioreactor; Shear stress; Fluid mechanics; Aortic valve; Aortic valve calcification disease; Aortic valve Diseases; Aortic valve insufficiency; Aortic valve Stenosis; Mitral valve

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yap, C. H. (2011). The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45742

Chicago Manual of Style (16^th Edition):

Yap, Choon Hwai. “The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/45742.

MLA Handbook (7^th Edition):

Yap, Choon Hwai. “The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification.” 2011. Web. 15 Apr 2021.

Vancouver:

Yap CH. The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/45742.

Council of Science Editors:

Yap CH. The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/45742

Georgia Tech

8. Spinner, Erin M. Tricuspid valve mechanics: understanding the effect of annular dilatation and papillary muscle displacement.

Degree: PhD, Biomedical Engineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/45754

► Tricuspid regurgitation (TR), back flow of blood from the right ventricle to the right atrium, has been reported in approximately 85% of the population, with… (more)

▼ Tricuspid regurgitation (TR), back flow of blood from the right ventricle to the right atrium, has been reported in approximately 85% of the population, with 16% having mild or severe TR. Patients with untreated moderate to severe TR are likely to experience decreased exercise capacity and have increased morbidity and mortality, thus affecting the patient's quality of life. Current methods of repair offer limited rates of success, and many patients require further operations to correct returning levels of TR. Incomplete repair may be due to incomplete understanding of the functional anatomy and mechanics of the TV and the underlying causes of TR. It was hypothesized that alterations in the geometry of tricuspid valve annular and subvalvular apparatus induced by ventricular dilatation determine the severity of TR. In vivo measurements of papillary muscle (PM) position in patients with single or biventricular dilatation revealed PM displacement away from the center of the annulus as compared to control patients. Additionally, pulmonary arterial pressure, annulus area, ventricular size and apical displacement of the anterior PM were highly correlated with the severity of TR. An in vitro right-heart simulator was developed to investigate isolated mechanics of TR. Through these in vitro studies it was demonstrated that the tricuspid valve begins to leak at only 40% dilation, much lower than the mitral valve. Additionally, it was shown that isolated PM displacement resulted in significant TR. The highest levels of TR were achieved with a combination of annular dilatation and PM displacement. Alterations in leaflet coaptation, as quantified by measuring the amount of leaflet available for coaptation and leaflet mobility were observed with annular dilatation and PM displacement, both isolated and combined. The changes in leaflet coaptation resulted in redistribution of the forces on the chords originating from the anterior PM and inserting into the anterior and posterior leaflets. The findings herein provide the clinical and scientific community with a mechanistic understanding of the tricuspid valve to further improve intervention and repair of TV disease. Advisors/Committee Members: Yoganathan, Ajit P. (Committee Chair), Adams, David H. (Committee Member), Gleason, Rudoplh (Committee Member), Lerakis, Stamatios (Committee Member), Oshinski, John (Committee Member), Taylor, W. Robert (Committee Member).

Subjects/Keywords: Tricuspid valve; Right heart; Tricuspid valve Diseases; Tricuspid valve insufficiency; Heart Dilatation; Heart Diseases

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APA (6^th Edition):

Spinner, E. M. (2011). Tricuspid valve mechanics: understanding the effect of annular dilatation and papillary muscle displacement. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45754

Chicago Manual of Style (16^th Edition):

Spinner, Erin M. “Tricuspid valve mechanics: understanding the effect of annular dilatation and papillary muscle displacement.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/45754.

MLA Handbook (7^th Edition):

Spinner, Erin M. “Tricuspid valve mechanics: understanding the effect of annular dilatation and papillary muscle displacement.” 2011. Web. 15 Apr 2021.

Vancouver:

Spinner EM. Tricuspid valve mechanics: understanding the effect of annular dilatation and papillary muscle displacement. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/45754.

Council of Science Editors:

Spinner EM. Tricuspid valve mechanics: understanding the effect of annular dilatation and papillary muscle displacement. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/45754

Georgia Tech

9. Martinez, Mario Daniel. Targeted drug delivery for the treatment and diagnosis of cardiovascular disease.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2017, Georgia Tech

URL: http://hdl.handle.net/1853/59201

► Cardiovascular disease has accounted for more deaths than any other major cause of death in the United States every year since 1900, with the exception… (more)

▼ Cardiovascular disease has accounted for more deaths than any other major cause of death in the United States every year since 1900, with the exception of 1918. Despite improvements in the management of cardiovascular disease, there is still a need for new and improved treatments and diagnostics. In peripheral artery disease (PAD), treatment with pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF), is currently being explored. However, there is a need to overcome limitations of this therapy, such as the growth factor’s short half-life, inadequate delivery to target tissue, and inadequate retention at target tissue. In myocarditis, a large number of patients go undiagnosed due to the disease’s heterogeneous etiology, pathophysiology, and clinical presentation. Current diagnostic techniques, such as endomyocardial biopsy and cardiac magnetic resonance, are inadequate, and there is a need for new technologies for the appropriate diagnosis and timely treatment of myocarditis. This dissertation aims to explore two different targeting techniques for the treatment and diagnosis of PAD and myocarditis. In PAD, ischemic tissue undergoes necrosis and releases cellular contents, including DNA, into extracellular space. A modified Hoechst compound has been previously used to target extracellular DNA in an animal model of myocardial infarction. We explored using a similar modified Hoechst compound to target extracellular DNA in an animal model PAD and deliver VEGF to ischemic tissue. Despite promising initial results, we did not observe any improvements in the retention or targeting of our compound to ischemic tissue when compared to non-Hoechst controls. Myocarditis is characterized by the presence of localized or diffuse inflammation in the myocardium. In an animal model of myocarditis, we used an in vivo phage display library to identify peptides that preferentially targeted this diseased myocardium. Ex vivo screening of potential peptides was then used to identify two peptides whose binding correlated with disease severity. In vivo screening was used to demonstrate that one of these peptides identified animals with severe myocarditis. Immunohistochemistry and proteonomic analysis was then used to identify potential cell and protein targets of this peptide. Through these approaches, two different techniques for the treatment and diagnosis of cardiovascular disease have been explored. These insights will advance the development of new techniques for the better treatment and diagnosis of cardiovascular disease. Advisors/Committee Members: Davis, Michael E. (committee member), Taylor, W Robert (committee member), Prausnitz, Mark R. (committee member), Botchwey, Edward A. (committee member), Brewster, Luke P. (committee member).

Subjects/Keywords: Peripheral artery disease; Hoechst; VEGF; Myocariditis; Imaging; Peptide; Phage display; Molecular imaging

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APA (6^th Edition):

Martinez, M. D. (2017). Targeted drug delivery for the treatment and diagnosis of cardiovascular disease. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/59201

Chicago Manual of Style (16^th Edition):

Martinez, Mario Daniel. “Targeted drug delivery for the treatment and diagnosis of cardiovascular disease.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/59201.

MLA Handbook (7^th Edition):

Martinez, Mario Daniel. “Targeted drug delivery for the treatment and diagnosis of cardiovascular disease.” 2017. Web. 15 Apr 2021.

Vancouver:

Martinez MD. Targeted drug delivery for the treatment and diagnosis of cardiovascular disease. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/59201.

Council of Science Editors:

Martinez MD. Targeted drug delivery for the treatment and diagnosis of cardiovascular disease. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/59201

10. Qu, Zheng. Biologically active assemblies that attenuate thrombosis on blood-contacting surfaces.

Degree: PhD, Biomedical Engineering, 2012, Georgia Tech

URL: http://hdl.handle.net/1853/50119

► All artificial organ systems and medical devices that operate in direct contact with blood elicit activation of coagulation and platelets, and their long-term use often… (more)

Subjects/Keywords: Thrombomodulin; Medical devices; Thrombosis; Biomaterials; Blood compatibility; Biomedical materials; Implants, Artificial; Biomedical engineering; Blood coagulation factors

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APA (6^th Edition):

Qu, Z. (2012). Biologically active assemblies that attenuate thrombosis on blood-contacting surfaces. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/50119

Chicago Manual of Style (16^th Edition):

Qu, Zheng. “Biologically active assemblies that attenuate thrombosis on blood-contacting surfaces.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/50119.

MLA Handbook (7^th Edition):

Qu, Zheng. “Biologically active assemblies that attenuate thrombosis on blood-contacting surfaces.” 2012. Web. 15 Apr 2021.

Vancouver:

Qu Z. Biologically active assemblies that attenuate thrombosis on blood-contacting surfaces. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/50119.

Council of Science Editors:

Qu Z. Biologically active assemblies that attenuate thrombosis on blood-contacting surfaces. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/50119

11. Saikus, Christina Elena. Towards mri-guided cardiovascular interventions.

Degree: PhD, Biomedical Engineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/44912

► Imaging guidance may allow minimally invasive alternatives to open surgical exposure and help reduce procedure risk and morbidity. The inherent vascular and soft-tissue contrast of… (more)

Subjects/Keywords: MRI; Cardiovascular interventions; Device safety; Magnetic resonance imaging; Cardiovascular system; Cardiovascular system Diseases Treatment; Interventional magnetic resonance imaging

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APA (6^th Edition):

Saikus, C. E. (2011). Towards mri-guided cardiovascular interventions. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/44912

Chicago Manual of Style (16^th Edition):

Saikus, Christina Elena. “Towards mri-guided cardiovascular interventions.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/44912.

MLA Handbook (7^th Edition):

Saikus, Christina Elena. “Towards mri-guided cardiovascular interventions.” 2011. Web. 15 Apr 2021.

Vancouver:

Saikus CE. Towards mri-guided cardiovascular interventions. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/44912.

Council of Science Editors:

Saikus CE. Towards mri-guided cardiovascular interventions. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/44912

12. Hansen, Laura Marie. Mechanical and structural effects of HIV-1 proteins and highly active antiretroviral therapy (HAART) drugs on murine arteries.

Degree: PhD, Biomedical Engineering, 2012, Georgia Tech

URL: http://hdl.handle.net/1853/45791

► The overall goals of this project were to develop microstructurally based constitutive models to characterize the mechanical behavior of arteries and to investigate the effects… (more)

▼ The overall goals of this project were to develop microstructurally based constitutive models to characterize the mechanical behavior of arteries and to investigate the effects of HIV proteins and antiretroviral drugs on the microstructure and mechanical behavior. To this end we created several constitutive models in aim 1 using a rule of mixtures approach, investigated the role of viral proteins in aim 2 through the use a transgenic mouse model, and studied the effects of the antiretroviral drug AZT administered to mice in aim 3. It is well known that the local mechanical environment which cells experience mediates growth and remodeling and that subsequent growth and remodeling can change that mechanical environment. This remodeling includes changes in the content and organization of the constituents of arteries (collagen, elastin, and smooth muscle cells). The first aim thus created models that incorporated the content and organization of these constituents using a rule-of-mixtures approach. The models we developed were able to capture the mechanical behavior of the arteries as well as previously developed phenomenological models while providing more physical meaning to the parameters, some which can be measured experimentally for incorporation into future models. Aims 2 and 3 investigated the mechanical and microstructural changes to murine arteries in response to HIV proteins or the drug AZT. While the development of antiretroviral therapy has greatly increased the life expectancy of patients with HIV, a number of other complications and co-morbidities including cardiovascular disease have become apparent. While clinical data has implicated both the virus and the antiretroviral drugs as playing roles, this work addressed the need of investigating these effects in a controlled manner. Specifically we used mouse models and focused on the two subclinical markers of increased intima-media thickness and arterial stiffening. Aim 2 used a transgenic mouse that expressed most of the human HIV proteins. We observed both intima-media thickening and arterial stiffening in alignment with clinical data. Other changes that also support a proatherogenic phenotype included decreased elastin content and changes in cathepsin activity. Aim 3 administered the antiretroviral drug AZT to healthy mice and we also observed the same subclinical markers of atherosclerosis including intima-media thickening and arterial stiffening as well as the other proatherogenic changes of decreased elastin and changes in cathepsin activity. Several other parameters including axial behavior, opening angles, collagen content, and collagen fiber angles were also quantified. These were important to fully characterize the vessel and may also be incorporated in the future into the constitutive models developed in aim1. In conclusion, in aim 1 we developed a microstructurally based constitutive model of arteries that effectively captures the mechanical behavior and includes parameters that have more physical meaning and some of which… Advisors/Committee Members: Gleason, Rudolph L. (Committee Chair), Guldberg, Robert (Committee Member), Platt, Manu (Committee Member), Sutliff, Roy (Committee Member), Taylor, W. Robert (Committee Member).

Subjects/Keywords: Microstructure; Vascular mechanics; Atherosclerosis; HIV; Arteries; Antiretroviral agents; Arteriosclerosis

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APA (6^th Edition):

Hansen, L. M. (2012). Mechanical and structural effects of HIV-1 proteins and highly active antiretroviral therapy (HAART) drugs on murine arteries. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45791

Chicago Manual of Style (16^th Edition):

Hansen, Laura Marie. “Mechanical and structural effects of HIV-1 proteins and highly active antiretroviral therapy (HAART) drugs on murine arteries.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/45791.

MLA Handbook (7^th Edition):

Hansen, Laura Marie. “Mechanical and structural effects of HIV-1 proteins and highly active antiretroviral therapy (HAART) drugs on murine arteries.” 2012. Web. 15 Apr 2021.

Vancouver:

Hansen LM. Mechanical and structural effects of HIV-1 proteins and highly active antiretroviral therapy (HAART) drugs on murine arteries. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/45791.

Council of Science Editors:

Hansen LM. Mechanical and structural effects of HIV-1 proteins and highly active antiretroviral therapy (HAART) drugs on murine arteries. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/45791

13. Phelps, Edward Allen. Bio-functionalized peg-maleimide hydrogel for vascularization of transplanted pancreatic islets.

Degree: PhD, Bioengineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/45899

► Type 1 diabetes affects one in every 400-600 children and adolescents in the US. Standard therapy with exogenous insulin is burdensome, associated with a significant… (more)

▼ Type 1 diabetes affects one in every 400-600 children and adolescents in the US. Standard therapy with exogenous insulin is burdensome, associated with a significant risk of dangerous hypoglycemia, and only partially efficacious in preventing the long term complications of diabetes. Pancreatic islet transplantation has emerged as a promising therapy for type 1 diabetes. However, this cell-based therapy is significantly limited by inadequate islet supply (more than one donor pancreas is needed per recipient), instant blood-mediated inflammatory reaction, and loss of islet viability/function during isolation and following implantation. In particular, inadequate revascularization of transplanted islets results in reduced islet viability, function, and engraftment. Delivery of pro-vascularization factors has been shown to improve vascularization and islet function, but these strategies are hindered by insufficient and/or complex release pharmacokinetics and inadequate delivery matrices as well as technical and safety considerations. We hypothesized that controlled presentation of angiogenic cues within a bioartificial matrix could enhance the vascularization, viability, and function of transplanted islets. The primary objective of this dissertation was to enhance allogenic islet engraftment, survival and function by utilizing synthetic hydrogels as engineered delivery matrices. Polyethylene glycol (PEG)-maleimide hydrogels presenting cell adhesive motifs and vascular endothelial growth factor (VEGF) were designed to support islet activities and promote vascularization in vivo. We analyzed the material properties and cyto-compatibility of these engineered materials, islet engraftment in a transplantation model, and glycemic control in diabetic subjects. The rationale for this project is to establish novel biomaterial strategies for islet delivery that support islet viability and function via the induction of local vascularization. Advisors/Committee Members: García, Andrés (Committee Chair), Murthy, Niren (Committee Member), Sambanis, Athanassios (Committee Member), Taylor, W Robert (Committee Member), Temenoff, Johnna (Committee Member), Thulé, Peter (Committee Member).

Subjects/Keywords: Vascularization; Transplantation; Polyethylene glycol; Hydrogel; Pancreatic islet; Maleimide; Colloids; Islands of Langerhans; Pancreas; Regenerative medicine

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APA (6^th Edition):

Phelps, E. A. (2011). Bio-functionalized peg-maleimide hydrogel for vascularization of transplanted pancreatic islets. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45899

Chicago Manual of Style (16^th Edition):

Phelps, Edward Allen. “Bio-functionalized peg-maleimide hydrogel for vascularization of transplanted pancreatic islets.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/45899.

MLA Handbook (7^th Edition):

Phelps, Edward Allen. “Bio-functionalized peg-maleimide hydrogel for vascularization of transplanted pancreatic islets.” 2011. Web. 15 Apr 2021.

Vancouver:

Phelps EA. Bio-functionalized peg-maleimide hydrogel for vascularization of transplanted pancreatic islets. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/45899.

Council of Science Editors:

Phelps EA. Bio-functionalized peg-maleimide hydrogel for vascularization of transplanted pancreatic islets. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/45899

14. Holliday, Casey Jane. Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium.

Degree: PhD, Biomedical Engineering, 2012, Georgia Tech

URL: http://hdl.handle.net/1853/47517

► Aortic valve (AV) disease is a major cause of cardiovascular-linked deaths globally. In addition, AV disease is a strong risk factor for additional cardiovascular events;… (more)

▼ Aortic valve (AV) disease is a major cause of cardiovascular-linked deaths globally. In addition, AV disease is a strong risk factor for additional cardiovascular events; however, the mechanism by which it initiates and progresses is not well-understood. We hypothesize that low and oscillatory flow is present on the fibrosa side of the AV and stimulates ECs to differentially regulate microRNA (miRNA) and mRNAs and influence AV disease progression. This hypothesis was tested employing both in vitro and in vivo approaches, high throughput microarray and pathway analyses, as well as a variety of functional assays. First, we isolated and characterized side-dependent, human aortic valvular endothelial cells (HAVECs). We found that HAVECs express both endothelial cell markers (VE-Cadherin, vWF, and PECAM) as well as smooth muscle cell markers (SMA and basic calponin). Using microarray analysis on sheared, side-specific HAVECs, we identified side- and shear-induced changes in miRNA and mRNA expression profiles. More specifically, we identified over 1000 shear-responsive mRNAs which showed robust validation (93% of those tested). We then used Ingenuity Pathway Analysis to identify key miRNAs, including those with many relationships to other genes (for example, thrombospondin and I&B) and those that are members of over-represented pathways and processes (for example, sulfur metabolism). Furthermore, we validated five shear-sensitive miRNAs: miR-139-3p, miR-148a, miR-187, miR-192, and miR-486-5p and one side-dependent miRNA, miR-370. To prioritize these miRNAs, we performed in silico analysis to group these key miRNAs by cellular functions related to AV disease (including tissue remodeling, inflammation, and calcification). Next, to compare our in vitro HAVEC results in vivo, we developed a method to isolate endothelial-enriched, side-dependent total RNA and identify and validate side-dependent (fibrosa vs. ventricularis) miRNAs in porcine aortic valvular endothelium. From this analysis, we discovered and validated eight side-dependent miRNAs in porcine endothelial-enriched AV RNA, including one miRNA previously identified in vitro, miR-486-5p. Lastly, we determined the relationship between important miRNAs (specifically miR-187 and miR-486-5p) and AV disease by modulating levels of miRNAs and performing functional assays. Preliminary studies overexpressing miR-187 in HAVECs have shown a reduction in inflammatory state through monocyte adhesion (p<0.05). Further, miR-486-5p overexpression reveals an increase in migration (p<0.05) and a trend for a decrease in early apoptosis, linking miR-486-5p to tissue remodeling in the AV. Better understanding of AV biology and disease in terms of gene-regulation under different hemodynamic conditions will facilitate the design of a tissue-engineered valve and provide alternative treatment options. Advisors/Committee Members: Jo, Hanjoong (Committee Co-Chair), Nerem, Robert. M (Committee Co-Chair), Eskin, Suzanne (Committee Member), Taylor, W. Robert (Committee Member), Thourani, Vinod (Committee Member), Yoganathan, Ajit (Committee Member).

Subjects/Keywords: Aortic valve; Endothelium; MicroRNAs; Shear stress; Microarrays; MRNAs; Aortic valve Diseases; Aortic valve Stenosis; Messenger RNA; Vascular endothelium

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APA (6^th Edition):

Holliday, C. J. (2012). Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/47517

Chicago Manual of Style (16^th Edition):

Holliday, Casey Jane. “Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/47517.

MLA Handbook (7^th Edition):

Holliday, Casey Jane. “Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium.” 2012. Web. 15 Apr 2021.

Vancouver:

Holliday CJ. Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/47517.

Council of Science Editors:

Holliday CJ. Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/47517

15. Parker, Ivana Kennedy. The role of HIV-1 tat and antiretrovirals in cathepsin mediated arterial remodeling.

Degree: PhD, Mechanical Engineering, 2015, Georgia Tech

URL: http://hdl.handle.net/1853/53574

► Major advances in highly active antiretroviral therapies (ARVs) have extended the lives of people living with HIV, but there still remains an increased risk of… (more)

Subjects/Keywords: HIV; Cardiovascular disease; Arterial remodeling; Cathepsins; antiretroviral therapy; Shear stress; Endothelial cell; Tat

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APA (6^th Edition):

Parker, I. K. (2015). The role of HIV-1 tat and antiretrovirals in cathepsin mediated arterial remodeling. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/53574

Chicago Manual of Style (16^th Edition):

Parker, Ivana Kennedy. “The role of HIV-1 tat and antiretrovirals in cathepsin mediated arterial remodeling.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/53574.

MLA Handbook (7^th Edition):

Parker, Ivana Kennedy. “The role of HIV-1 tat and antiretrovirals in cathepsin mediated arterial remodeling.” 2015. Web. 15 Apr 2021.

Vancouver:

Parker IK. The role of HIV-1 tat and antiretrovirals in cathepsin mediated arterial remodeling. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/53574.

Council of Science Editors:

Parker IK. The role of HIV-1 tat and antiretrovirals in cathepsin mediated arterial remodeling. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/53574

16. Angsana, Julianty. The role of syndecan-1 in the resolution of chronic inflammatory responses.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2013, Georgia Tech

URL: http://hdl.handle.net/1853/52947

► Inflammation is an integral part of the body defense mechanism that occurs in vascularized tissue in response to harmful stimuli that is perceived as being… (more)

▼ Inflammation is an integral part of the body defense mechanism that occurs in vascularized tissue in response to harmful stimuli that is perceived as being a threat to tissue homeostasis. It is a complex physiological host response that is designed to neutralize and eliminate harmful agents, initiate tissue healing, and orchestrate a return to tissue homeostasis. While inflammation is designed to be an acute event that resolves following the elimination of harmful stimuli and tissue healing, there are instances where inflammation fails to resolve and instead evolves into chronic inflammation. It is now well understood that ongoing inflammation can serve as the underlying cause of many chronic inflammatory diseases, including atherosclerosis. In fact, one of the most pressing issues that is currently faced in the field of inflammation research, one that has also become the focus of numerous ongoing investigations, is how to turn this excessive, unwarranted and undesirable inflammation response off. Once thought to be a passive and simple process, resolution is now understood to be an active and complex process that is orchestrated by various inflammatory mediators, signaling pathways and biophysical processes. The discovery of novel biosynthetic pathways that turn on the pro-resolution signals has lead to a surge in research aimed at taking a closer look at processes that can stimulate the resolution of inflammation. While major advances in the field have resulted in a better understanding of the proactive nature of resolution, many of the mechanisms involved are still unknown. To date, the repertoire of chemokine receptors that participate in macrophage clearance during resolution, for the most part, remain unidentified. Overall, there is a growing appreciation that the discovery of mechanisms involved in the resolution responses can lead to the development of novel therapeutic approaches to resolve many chronic inflammatory diseases. Syndecan-1 (Sdc-1), a member of a family of cell surface proteoglycans, has been previously shown to regulate events relevant to tissue repair and chronic injury responses. Macrophage Sdc-1 expression during inflammation has been reported to be protective in various inflammatory models. Given these observations, we hypothesize that Sdc-1 expression on macrophages is a critical component of an anti-inflammatory, pro resolution program necessary for the successful resolution of inflammatory response. In this dissertation, we report the presence of a unique population of macrophages expressing Sdc-1 that are present within the vascular wall of mice undergoing atherosclerosis. Consistent with previous publications, the presence of Sdc-1 expressing macrophages was found to limit atherosclerosis progression. In addition, Sdc-1 expression on macrophages was associated with anti-inflammatory M2 polarization state and high intrinsic motility. Macrophage Sdc-1 expression was also linked with efferocytosis and enhanced macrophage egress from the site of inflammation to the… Advisors/Committee Members: Chaikof, Elliot L. (advisor), Haller, Carolyn (committee member), Babensee, Julia E. (committee member), Dixon, J. Brandon (committee member), McIntire, Larry V. (committee member), Taylor, W. Robert (committee member).

Subjects/Keywords: Atherosclerosis; Macrophage; Polarization state; Motility; Efferocytosis; Resolution; Syndecan-1; Cxcr4; Chemokine receptor; Chronic inflammation

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APA (6^th Edition):

Angsana, J. (2013). The role of syndecan-1 in the resolution of chronic inflammatory responses. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/52947

Chicago Manual of Style (16^th Edition):

Angsana, Julianty. “The role of syndecan-1 in the resolution of chronic inflammatory responses.” 2013. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/52947.

MLA Handbook (7^th Edition):

Angsana, Julianty. “The role of syndecan-1 in the resolution of chronic inflammatory responses.” 2013. Web. 15 Apr 2021.

Vancouver:

Angsana J. The role of syndecan-1 in the resolution of chronic inflammatory responses. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/52947.

Council of Science Editors:

Angsana J. The role of syndecan-1 in the resolution of chronic inflammatory responses. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/52947

17. Ju, Lining. Single-molecue study on GPIb-alpha and von Willebrand factor mediated platelet adhesion and signal triggering.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2013, Georgia Tech

URL: http://hdl.handle.net/1853/52953

► The binding between the 45 kDa N-terminal domain of the a subunit of the GPIb-IX-V complex (GPIbαN) on the platelet membrane and the A1 domain… (more)

Subjects/Keywords: Platelet; GPIb; VWF; Single molecule; BFP; Mechanotransduction

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APA (6^th Edition):

Ju, L. (2013). Single-molecue study on GPIb-alpha and von Willebrand factor mediated platelet adhesion and signal triggering. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/52953

Chicago Manual of Style (16^th Edition):

Ju, Lining. “Single-molecue study on GPIb-alpha and von Willebrand factor mediated platelet adhesion and signal triggering.” 2013. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/52953.

MLA Handbook (7^th Edition):

Ju, Lining. “Single-molecue study on GPIb-alpha and von Willebrand factor mediated platelet adhesion and signal triggering.” 2013. Web. 15 Apr 2021.

Vancouver:

Ju L. Single-molecue study on GPIb-alpha and von Willebrand factor mediated platelet adhesion and signal triggering. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/52953.

Council of Science Editors:

Ju L. Single-molecue study on GPIb-alpha and von Willebrand factor mediated platelet adhesion and signal triggering. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/52953

18. Wan, William. The role of fibulin-5 in the growth and remodeling of mouse carotid arteries.

Degree: PhD, Mechanical Engineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/42877

► The evolution of biomechanical behavior of arteries plays a key role in the onset and progression of cardiovascular disease. Biomechanical behavior is governed by the… (more)

▼ The evolution of biomechanical behavior of arteries plays a key role in the onset and progression of cardiovascular disease. Biomechanical behavior is governed by the content and organization of the key structural constituents (e.g., collagen, elastin, and smooth muscle) and vessel geometry. The evolution of biomechanical behavior of arteries is governed by biologically-mediated synthesis, degradation, and reorganization of these key structural constituents. A hallmark goal in biomechanics is quantifying the relationship between the microstructure of tissues and their mechanical response throughout tissue growth and remodeling; this will provide a crucial link in understanding the tissue level effects of biological processes involved in disease and normal growth Fibulin-5 (fbln5) is an ECM protein that binds tropoelastin and interacts with integrins. Arteries from fbln5 knockout mice lack functional elastic fibers and provide a system for investigating the link between an artery's microstructure and its mechanical response. The overall goal of this project was to develop multi-scaled theoretical and experimental frameworks to quantify the relationship between microstructural content and organization and tissue level material properties of arteries from fbln5 null mice and littermate controls and to quantify the effects of fbln5 on the in vivo maturation of mouse carotid arteries. We found significant differences in the mechanical properties of carotid arteries of fbln5 null mice, and these differences were correlated with altered extracellular matrix organization. We also developed a microstructurally-motivated 3-dimensional constrained mixture model for vascular growth and remodeling. Using physiological rates of constituent growth and turnover, the model captured the salient findings found in the literature. Incorporating experimentally measured fiber angle data into constitutive relations yielded greater predictive accuracy. This dissertation incorporates experimental data quantified at the micro (microstructural-level fiber distributions) and macro (tissue-level mechanical response) scale and incorporates these data into microstructurally motivated constitutive relations. The use of structurally motivated constitutive relations and experimentally measured microstructural data provides a foundation for future work in further understanding the relationship between processes governing microstructure and the tissue level effects of disease and normal growth. Advisors/Committee Members: Gleason, Rudolph (Committee Chair), Guldberg, Robert (Committee Member), Platt, Manu (Committee Member), Taylor, W. Robert (Committee Member), Zamir, Evan (Committee Member).

Subjects/Keywords: Growth and remodeling; Arteries; Carotid; Mouse; Fibulin-5; Extracellular matrix proteins; Arteries Mechanical properties; Microstructure

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APA (6^th Edition):

Wan, W. (2011). The role of fibulin-5 in the growth and remodeling of mouse carotid arteries. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/42877

Chicago Manual of Style (16^th Edition):

Wan, William. “The role of fibulin-5 in the growth and remodeling of mouse carotid arteries.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/42877.

MLA Handbook (7^th Edition):

Wan, William. “The role of fibulin-5 in the growth and remodeling of mouse carotid arteries.” 2011. Web. 15 Apr 2021.

Vancouver:

Wan W. The role of fibulin-5 in the growth and remodeling of mouse carotid arteries. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/42877.

Council of Science Editors:

Wan W. The role of fibulin-5 in the growth and remodeling of mouse carotid arteries. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/42877

19. Mancini, Michael C. Biomedical instrumentation and nanotechnology for image-guided cancer surgery.

Degree: PhD, Biomedical Engineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/43657

► Once diagnosed, cancer is treated by surgical resection, chemotherapy, radiation therapy, or a combination of these therapies. It is intuitive that physically and completely removing… (more)

▼ Once diagnosed, cancer is treated by surgical resection, chemotherapy, radiation therapy, or a combination of these therapies. It is intuitive that physically and completely removing a solid tumor would be an effective treatment. A complete resection of the tumor mass, defined by surgical margins that are clear of neoplasia, is prognostic for a decreased chance of cancer recurrence and an increased survival rate. In practice, complete resection is difficult. A surgeon primarily has only their senses of touch and sight to provide "real-time" guidance in the removal of a tumor while in the operating room. Preoperative imaging can guide a surgeon to a tumor but does not give a continuous update of surgical progress. Intraoperative pathology is limited to a few slides worth of samples: a product of its time-consuming nature and the limited time a patient can remain under general anesthesia. Technologies to guide a surgeon in effecting complete resection of a tumor mass during the surgical procedure would greatly increase cancer survival rates by lowering rates of cancer recurrence; such a technology would also reduce the need for follow-up chemotherapy or radiation therapy. Here, we describe a prototype instrumentation system that can provide intraoperative guidance with exogenous optical contrast agents. The instrumentation combines interactive point excitation, local spectroscopy, and widefield fluorescence imaging to enable low-cost surgical guidance using FDA-approved fluorescent dyes, semiconductor quantum dots (QDs), or surface-enhanced Raman scattering (SERS) nanoparticles. The utility of this surgical system is demonstrated in rodent tumor models using an FDA-approved fluorescent dye, indocyanine green (ICG), and is then more extensively demonstrated with a pre-clinical study of spontaneous tumors in companion canines. The pre-clinical studies show a high sensitivity in detecting a variety of canine tumors with a low false positive rate, as verified by pathology. We also present a fundamental study on the behavior of quantum dots. QDs are a promising fluorophore for biological applications, including as a surgical contrast agent. To use QDs for in vivo human imaging, toxicity concerns must be addressed first. Although it is suspected that QDs may be toxic to an organism based on the heavy-metal elemental composition of QDs, overt organism toxicity is not seen in long-term animal model studies. We have found that some reactive oxygen species (ROS) generated by the host inflammatory response can rapidly degrade QDs; in the case of hypochlorous acid, optical changes to the QDs are suggestive of degradation occurring within seconds. It is well-known that QDs are sequestered by the immune system when used in vivo – we therefore believe that QD degradation through an inflammatory response may represent a realizable in vivo mechanism for QD degradation. We demonstrate in an in vitro cell culture model that immune cells can degrade QDs through ROS exposure. Knowledge of the degradative processes that QDs… Advisors/Committee Members: Nie, Shuming (Committee Chair), El-Sayed, Mostafa (Committee Member), Provenzale, James (Committee Member), Santangelo, Philip (Committee Member), Taylor, W. Robert (Committee Member).

Subjects/Keywords: Cancer imaging; Instrumentation; Nanotechnology; Surgical guidance; Quantum dots; Computer-assisted surgery; Cancer Imaging; Semiconductors; Raman effect; Cancer

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APA (6^th Edition):

Mancini, M. C. (2011). Biomedical instrumentation and nanotechnology for image-guided cancer surgery. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/43657

Chicago Manual of Style (16^th Edition):

Mancini, Michael C. “Biomedical instrumentation and nanotechnology for image-guided cancer surgery.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/43657.

MLA Handbook (7^th Edition):

Mancini, Michael C. “Biomedical instrumentation and nanotechnology for image-guided cancer surgery.” 2011. Web. 15 Apr 2021.

Vancouver:

Mancini MC. Biomedical instrumentation and nanotechnology for image-guided cancer surgery. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/43657.

Council of Science Editors:

Mancini MC. Biomedical instrumentation and nanotechnology for image-guided cancer surgery. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/43657

20. Fornwalt, Brandon Kenneth. New methods for quantifying the synchrony of contraction and relaxation in the heart.

Degree: PhD, Biomedical Engineering, 2008, Georgia Tech

URL: http://hdl.handle.net/1853/24800

► Synchronous contraction and relaxation of the myocardium is required to optimize cardiac function. Regional timing of contraction and relaxation is dyssynchronous in many patients with… (more)

▼ Synchronous contraction and relaxation of the myocardium is required to optimize cardiac function. Regional timing of contraction and relaxation is dyssynchronous in many patients with heart failure. Cardiac resynchronization therapy (CRT) is a highly successful treatment for dyssynchronous heart failure. Patients are currently selected for CRT using surface electrocardiogram QRS duration as a measure of dyssynchrony. However, up to 30% of patients selected for CRT show no improvement. This poor response rate may in part be explained by the poor correlation between mechanical dyssynchrony and QRS duration. Thus, better methods to quantify mechanical dyssynchrony in the heart may improve the poor CRT response rate. The overall goal of this project was to develop better methods to diagnose dyssynchrony in the left ventricle (LV). We developed two new methods with different approaches. The first method improved upon existing tissue-Doppler based echocardiographic diagnosis of dyssynchrony by utilizing a cross-correlation (XC) function to quantify dyssynchrony during post-processing as opposed to the quantitatively simplistic time-to-peak analysis that is currently utilized. The second method utilized standard cine cardiac magnetic resonance (CMR) images to quantify the dyssynchrony in the flow of blood within the LV, which may represent a more direct, physiologically relevant measure of dyssynchrony. Specific aim 1 demonstrated that the new XC delay parameters can be quantified accurately with a stationary region of interest and therefore require significantly less post-processing time to calculate compared to the time-to-peak dyssynchrony parameters. Specific aim 2 showed that XC delays are superior to existing time-to-peak dyssynchrony parameters at discriminating patients with LV dyssynchrony from those with normal function. The time-to-peak parameters showed dyssynchrony in approximately half of the normal, healthy volunteers while the XC delay parameters had nearly perfect diagnostic accuracy. The results of specific aim 3 showed that XC delays could diagnose acute, pacing-induced dyssynchrony in young, healthy children with 79% accuracy while the time-to-peak parameters showed accuracies of 71%, 57% and 57%. Specific aim 4 showed that CMR-based quantification of LV internal flow can be used to discriminate patients with dyssynchronous heart failure from normal controls with 95% accuracy. Advisors/Committee Members: Oshinski, John N. (Committee Chair), Fyfe, Derek A. (Committee Member), León, Angel R. (Committee Member), Skrinjar, Oskar (Committee Member), Taylor, W. Robert (Committee Member).

Subjects/Keywords: Tissue doppler; Echocardiography; Heart failure; Magnetic resonance imaging; Ventricular asynchrony; Ventricular dyssynchrony; Cardiac resynchronization; Coincidence; Heart beat; Heart Contraction; Diastole (Cardiac cycle); Cardiac pacing; Heart Left ventricle Diseases Treatment

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APA (6^th Edition):

Fornwalt, B. K. (2008). New methods for quantifying the synchrony of contraction and relaxation in the heart. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/24800

Chicago Manual of Style (16^th Edition):

Fornwalt, Brandon Kenneth. “New methods for quantifying the synchrony of contraction and relaxation in the heart.” 2008. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/24800.

MLA Handbook (7^th Edition):

Fornwalt, Brandon Kenneth. “New methods for quantifying the synchrony of contraction and relaxation in the heart.” 2008. Web. 15 Apr 2021.

Vancouver:

Fornwalt BK. New methods for quantifying the synchrony of contraction and relaxation in the heart. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/24800.

Council of Science Editors:

Fornwalt BK. New methods for quantifying the synchrony of contraction and relaxation in the heart. [Doctoral Dissertation]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/24800

21. Uhrig, Brent A. Tissue regeneration in composite injury models of limb trauma.

Degree: PhD, Mechanical Engineering, 2013, Georgia Tech

URL: http://hdl.handle.net/1853/49080

► Severe extremity trauma often involves significant damage to multiple tissue types, including bones, skeletal muscles, peripheral nerves, and blood vessels. Such injuries present unique challenges… (more)

▼ Severe extremity trauma often involves significant damage to multiple tissue types, including bones, skeletal muscles, peripheral nerves, and blood vessels. Such injuries present unique challenges for reconstruction, and improving structural and functional outcomes of intervention remains a pressing, unmet clinical need. While tissue engineering/regenerative medicine (TE/RM) therapeutics offer promising potential to overcome the status quo limitations of surgical reconstruction, very few products have transitioned to clinical practice. Improving treatment options will likely require advancing our understanding of the biological interactions occurring in the repair of damaged tissues. Bone tissue is known to be innervated and highly vascularized, and both tissue types are involved in normal bone physiology. However, the degree to which these tissue relationships influence the repair of large, multi-tissue defects remains unknown. Accordingly, the goal of this thesis was to investigate tissue regeneration in two novel composite injury models. First, we characterized interactions in a composite bone and nerve injury model where a segmental bone defect was combined with a peripheral nerve gap. Our results indicated that although tissue regeneration was not impaired, the composite injury group experienced a marked functional deficit in the operated limb compared to single-tissue injury. Second, we developed a model of composite bone and vascular extremity trauma by combining a critically-sized segmental bone defect with surgically-induced hind limb ischemia to evaluate the effects on BMP-2-mediated bone repair. Interestingly, our results demonstrated a stimulatory effect of the recovery response to ischemia on bone regeneration. Finally, we investigated early vascular growth and gene expression as potential mechanisms coupling the response to ischemia with bone defect repair. Although the response to ischemia promoted robust vascular growth in the thigh, it did not directly augment vascularization at the site of bone regeneration. In addition, the stimulatory effects of ischemia on bone regeneration could not be explained by gene expression alone based on the genes and time points investigated. Taken together, this thesis presents pioneering work on a new thrust of TE/RM research – tissue regeneration in models of composite injury. This work has provided new insights on the complexity of composite tissue repair, specifically in regard to the relationship between vascular tissue growth and bone healing. Going forward, successful leverage of models of composite tissue injuries will provide valuable test beds for screening new technologies, advance the understanding of tissue repair biology, and ultimately, may produce new therapeutic interventions for limb salvage and reconstruction that improve outcomes for extremity trauma patients. Advisors/Committee Members: Guldberg, Robert E. (advisor), Bellamkonda, Ravi V. (committee member), Gilbert, Shawn R. (committee member), Taylor, W. Robert (committee member), Temenoff, Johnna S. (committee member).

Subjects/Keywords: Composite tissue injury; Tissue engineering; Bone regeneration; Hind limb ischemia; Vascularization; Nerve regeneration; Regenerative medicine; Nervous system Regeneration; Regeneration (Biology); Wound healing

…my time at Georgia Tech was all work and no play, I also developed some phenomenal…

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APA (6^th Edition):

Uhrig, B. A. (2013). Tissue regeneration in composite injury models of limb trauma. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/49080

Chicago Manual of Style (16^th Edition):

Uhrig, Brent A. “Tissue regeneration in composite injury models of limb trauma.” 2013. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/49080.

MLA Handbook (7^th Edition):

Uhrig, Brent A. “Tissue regeneration in composite injury models of limb trauma.” 2013. Web. 15 Apr 2021.

Vancouver:

Uhrig BA. Tissue regeneration in composite injury models of limb trauma. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/49080.

Council of Science Editors:

Uhrig BA. Tissue regeneration in composite injury models of limb trauma. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/49080

22. Birjiniuk, Joav. Investigation of fluid dynamic effects of endovascular intervention in a model of descending aortic dissection.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2017, Georgia Tech

URL: http://hdl.handle.net/1853/58687

► With advances in endovascular technology and technique, Thoracic EndoVascular Aortic Repair (TEVAR) has emerged as an integral component of the management of Stanford Type B… (more)

▼ With advances in endovascular technology and technique, Thoracic EndoVascular Aortic Repair (TEVAR) has emerged as an integral component of the management of Stanford Type B dissection of the descending aorta. Whereas this modality is considered vital in the treatment of patients experiencing severe complications as a result of dissection, it has not been shown to be demonstratively superior to treatment with medical therapy alone in the absence of malperfusion, rupture, or aneurysmal degeneration. However, results from various clinical studies on the relative benefits of these therapies may be confounded by the vast heterogeneity in dissection anatomy and hemodynamics. Therefore, little is known regarding which patients should undergo TEVAR, as well as the effect of stent-graft deployment on the functional status of the aorta. In order to address this knowledge gap, compliant models of the aorta possessing a mobile intimal flap mimicking dissection were fabricated and imaged via four-dimensional phase contrast magnetic resonance (4D PCMR) imaging sensitive to fluid flow. We aimed to understand how the fluid flow varies with changes to the dissection anatomy as well as the effect of varying anatomies on the fluid shear rate, which has been related to the thrombotic potential of blood-contacting surfaces. Furthermore, we aimed to study the effects of graft deployment on these hemodynamic effects. Dissection induced flow reversal in the aorta, with concomitant low and oscillatory shear zones, which were reduced in dissections with multiple tears. Device deployment was found to restore normal hemodynamics locally, while preserving distal hemodynamic alterations. These findings suggest a potential for risk-stratification based on anatomical and functional imaging as well as more aggressive intervention to rectify aberrant fluid mechanics of the dissected aorta. Advisors/Committee Members: Ku, David N (advisor), Oshinski, John N (advisor), Veeraswamy, Ravi K (committee member), Taylor, W. Robert (committee member), Sun, Wei (committee member), Dixon, J. B (committee member).

Subjects/Keywords: aortic dissection; fluid mechanics; hemodynamics; experimental model

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APA (6^th Edition):

Birjiniuk, J. (2017). Investigation of fluid dynamic effects of endovascular intervention in a model of descending aortic dissection. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58687

Chicago Manual of Style (16^th Edition):

Birjiniuk, Joav. “Investigation of fluid dynamic effects of endovascular intervention in a model of descending aortic dissection.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/58687.

MLA Handbook (7^th Edition):

Birjiniuk, Joav. “Investigation of fluid dynamic effects of endovascular intervention in a model of descending aortic dissection.” 2017. Web. 15 Apr 2021.

Vancouver:

Birjiniuk J. Investigation of fluid dynamic effects of endovascular intervention in a model of descending aortic dissection. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/58687.

Council of Science Editors:

Birjiniuk J. Investigation of fluid dynamic effects of endovascular intervention in a model of descending aortic dissection. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/58687

23. Caulk, Alexander Wilson. Biomechanics and modeling methods for quantifying mechanically-mediated disease progression in neglected populations.

Degree: PhD, Mechanical Engineering, 2015, Georgia Tech

URL: http://hdl.handle.net/1853/55490

► It is well known that biological tissue grows and remodels in response to changes in mechanical loading. Arteries and lymphatic vessels share many similar mechanical… (more)

Subjects/Keywords: Biomechanics; HIV; HAART; lymphedema; growth and remodeling; constitutive modeling

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APA (6^th Edition):

Caulk, A. W. (2015). Biomechanics and modeling methods for quantifying mechanically-mediated disease progression in neglected populations. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/55490

Chicago Manual of Style (16^th Edition):

Caulk, Alexander Wilson. “Biomechanics and modeling methods for quantifying mechanically-mediated disease progression in neglected populations.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/55490.

MLA Handbook (7^th Edition):

Caulk, Alexander Wilson. “Biomechanics and modeling methods for quantifying mechanically-mediated disease progression in neglected populations.” 2015. Web. 15 Apr 2021.

Vancouver:

Caulk AW. Biomechanics and modeling methods for quantifying mechanically-mediated disease progression in neglected populations. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/55490.

Council of Science Editors:

Caulk AW. Biomechanics and modeling methods for quantifying mechanically-mediated disease progression in neglected populations. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/55490

24. Sy, Jay Christopher. Novel strategies for cardiac drug delivery.

Degree: PhD, Biomedical Engineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/39531

► The American Heart Association (AHA) estimates that at least one American will die from a coronary event every minute, costing over $150 billion in 2008… (more)

Subjects/Keywords: Cardiac dysfunction; Myocardial infarction; Necrosis; Hoechst; Nitrilotriacetic acid; Polyketals; Biomaterials; Heart disease; Drug delivery; Drug delivery systems; Guided tissue regeneration

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APA (6^th Edition):

Sy, J. C. (2011). Novel strategies for cardiac drug delivery. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/39531

Chicago Manual of Style (16^th Edition):

Sy, Jay Christopher. “Novel strategies for cardiac drug delivery.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/39531.

MLA Handbook (7^th Edition):

Sy, Jay Christopher. “Novel strategies for cardiac drug delivery.” 2011. Web. 15 Apr 2021.

Vancouver:

Sy JC. Novel strategies for cardiac drug delivery. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/39531.

Council of Science Editors:

Sy JC. Novel strategies for cardiac drug delivery. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/39531

25. Zaucha, Michael Thomas. Biomechanics and biaxial mechanical stimulation of self-assembly tissue engineered blood vessels.

Degree: PhD, Bioengineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/39532

► Despite efforts by clinicians and scientists world-wide, coronary artery disease remains to be the leading cause of morbidity and mortality in industrialized nations. Development of… (more)

▼ Despite efforts by clinicians and scientists world-wide, coronary artery disease remains to be the leading cause of morbidity and mortality in industrialized nations. Development of a tissue engineered coronary by-pass graft with low thrombogenicity and immune responses, suitable mechanical properties, and a capacity to remodel to their environment could have a significant impact on the treatment of coronary artery disease. While many methods for the tissue engineering of blood vessels have been developed, one promising approach is the self-assembly method. Using autologous cells that produce an endogenous extracellular matrix (ECM), the potential for therapeutic success is high due to biocompatibility. However, despite these advantages, improvements can be made which will give the grafts an even higher rate of patency. This dissertation presents a study of the characterization of the biaxial mechanical properties of self-assembly tissue engineered blood vessels (SA-TEBV), as well as developing a framework for fabrication strategies of SA-TEBV. Native arteries are exposed to multiaxial mechanical loads, including (a pulsatile) blood pressure that causes the vessel to cyclically distend circumferentially, blood flow that induces a shearing load along the luminal surface, and an axial extending load; the latter is relieved upon excision, causing the vessel to retract. These mechanical loads introduce intramural wall stresses and flow induced wall shear stresses that play a key role in mechano-biological signaling and tissue homeostasis. Until now, the mechanical properties of SA-TEBV have only been characterized in the circumferential direction (i.e. burst pressure and circumferential elastic modulus). The objective of this work is to characterize the biaxial mechanical properties of SA-TEBV to quantify their mechanical behavior and local intramural stresses under physiological loading. The work will show that while the global mechanical response of the SA-TEBV is similar to that of native arteries (and potentially sufficient), the local intramural stresses (using the current fabrication techniques) differ greatly from native coronary arteries. Therefore, a novel approach to fabricate the self-assembly derived tissue sheets is developed and tested which utilizes biaxial mechanical stimulation to alter the microstructure, thereby controlling their mechanical response. Advisors/Committee Members: Gleason, Rudolph (Committee Chair), Dixon, J. Brandon (Committee Member), Rachev, Alexander (Committee Member), Taylor, W. Robert (Committee Member), Williams, Chrysanthi (Committee Member).

Subjects/Keywords: Arteries; TEBV; Fibroblast; Smooth muscle cells; Blood vessel prosthesis Mechanical properties; Self-organizing systems; Micromechanics

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APA (6^th Edition):

Zaucha, M. T. (2011). Biomechanics and biaxial mechanical stimulation of self-assembly tissue engineered blood vessels. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/39532

Chicago Manual of Style (16^th Edition):

Zaucha, Michael Thomas. “Biomechanics and biaxial mechanical stimulation of self-assembly tissue engineered blood vessels.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/39532.

MLA Handbook (7^th Edition):

Zaucha, Michael Thomas. “Biomechanics and biaxial mechanical stimulation of self-assembly tissue engineered blood vessels.” 2011. Web. 15 Apr 2021.

Vancouver:

Zaucha MT. Biomechanics and biaxial mechanical stimulation of self-assembly tissue engineered blood vessels. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/39532.

Council of Science Editors:

Zaucha MT. Biomechanics and biaxial mechanical stimulation of self-assembly tissue engineered blood vessels. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/39532

26. Boerckel, Joel David. Mechanical regulation of bone regeneration and vascular growth in vivo.

Degree: PhD, Mechanical Engineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/41063

► Regeneration of large bone defects presents a critical challenge to orthopaedic clinicians as the current treatment strategies are severely limited. Tissue engineering has therefore emerged… (more)

▼ Regeneration of large bone defects presents a critical challenge to orthopaedic clinicians as the current treatment strategies are severely limited. Tissue engineering has therefore emerged as a promising alternative to bone grafting techniques. This approach features the delivery of bioactive agents such as stem cells, genes, or proteins using biomaterial delivery systems which together stimulate endogenous repair mechanisms to regenerate the tissue. Because bone is a highly mechanosensitive tissue which responds and adapts dynamically to its mechanical environment, application of mechanical stimuli may enhance endogenous tissue repair. While mechanical loading has been shown to stimulate bone fracture healing, the ability of loading to enhance large bone defect regeneration has not been evaluated. The goal of this thesis was to evaluate the ability of sustained osteogenic growth factor delivery and functional biomechanical loading to stimulate vascularized repair of large bone defects in a rat segmental defect model. First, we evaluated the hypothesis that the relationship between protein dose and regenerative efficacy depends on delivery system. We determined the dose-response relationship between dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) and bone regeneration in a hybrid alginate-based protein delivery system and compared with the current clinically-used collagen sponge. The hybrid delivery system improved bone formation and reduced the effective dose due to its sustained delivery properties in vivo. Next, we tested the hypothesis that transfer of compressive ambulatory loads during segmental defect repair enhances bone formation and subsequent limb regeneration. We found that delayed application of axial loads enhanced bone regeneration by altering bone formation, tissue differentiation and remodeling, and local strain distribution. Finally, we evaluated the hypothesis that in vivo mechanical loading can enhance neovascular growth to influence bone formation. We found that early mechanical loading disrupted neovascular growth, resulting in impaired bone healing, while delayed loading induced vascular remodeling and enhanced bone formation. Together, this thesis presents the effects of dose and delivery system on BMP-mediated bone regeneration and demonstrates for the first time the effects of in vivo mechanical loading on vascularized regeneration of large bone defects. Advisors/Committee Members: Guldberg, Robert (Committee Chair), Garcia, Andres (Committee Member), Gleason, Rudolph (Committee Member), Taylor, W. Robert (Committee Member), Zamir, Evan (Committee Member).

Subjects/Keywords: Bone regeneration; Vascular growth; Mechanical loading; Bone regeneration; Guided tissue regeneration; Drug delivery systems; Loads (Mechanics)

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APA (6^th Edition):

Boerckel, J. D. (2011). Mechanical regulation of bone regeneration and vascular growth in vivo. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/41063

Chicago Manual of Style (16^th Edition):

Boerckel, Joel David. “Mechanical regulation of bone regeneration and vascular growth in vivo.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/41063.

MLA Handbook (7^th Edition):

Boerckel, Joel David. “Mechanical regulation of bone regeneration and vascular growth in vivo.” 2011. Web. 15 Apr 2021.

Vancouver:

Boerckel JD. Mechanical regulation of bone regeneration and vascular growth in vivo. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/41063.

Council of Science Editors:

Boerckel JD. Mechanical regulation of bone regeneration and vascular growth in vivo. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/41063

27. Broiles, JoSette Leigh Briggs. The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype.

Degree: PhD, Mechanical Engineering, 2008, Georgia Tech

URL: http://hdl.handle.net/1853/22652

► An increase in coronary disease prevalence and mortality highlights the growing need for therapies to treat atherosclerotic vessels. While current bypass procedures utilize autologous vessels… (more)

Subjects/Keywords: Tissue engineering; Smooth muscle cells; Tropoelastin; Versican; Muscle cells; Tissue engineering; Blood vessel prosthesis; Elastin

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APA (6^th Edition):

Broiles, J. L. B. (2008). The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/22652

Chicago Manual of Style (16^th Edition):

Broiles, JoSette Leigh Briggs. “The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype.” 2008. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/22652.

MLA Handbook (7^th Edition):

Broiles, JoSette Leigh Briggs. “The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype.” 2008. Web. 15 Apr 2021.

Vancouver:

Broiles JLB. The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/22652.

Council of Science Editors:

Broiles JLB. The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype. [Doctoral Dissertation]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/22652

28. Campbell, Ian Christopher. Plaque erosion and murine plaque stability: a biomechanical examination of exceptions to the phenomenon of plaque rupture.

Degree: PhD, Biomedical Engineering, 2013, Georgia Tech

URL: http://hdl.handle.net/1853/47741

► Atherosclerotic plaque disruption leading to thrombosis has traditionally been studied as a rupture of a thin fibrous cap over a lipid-laden necrotic core. However, two… (more)

▼ Atherosclerotic plaque disruption leading to thrombosis has traditionally been studied as a rupture of a thin fibrous cap over a lipid-laden necrotic core. However, two noteworthy categories of plaques that do not rupture have presented themselves: 1) in mice, plaque rupture is rare if not absent, and 2) in humans, some plaques erode and form a thrombus without rupturing. Current understanding of the biomechanical differences between plaques that rupture and those that do not is incomplete. In this research, we used patient-specific computational biomechanics tools to study differences among these groups. Lesion-specific solid mechanical modeling of murine plaques revealed that the relative distribution of stresses differs considerably between mice and man. In human vulnerable plaques, peak stresses are on the thin fibrous cap over a necrotic core, but in mice the highest stresses are in the media and adventitia, away from the plaque. Whereas atherosclerotic human arteries usually experience neointima formation around the entire circumference of the vessel, mouse plaques tend to be punctate and adjacent lesion-free regions. The difference in mechanical environment suggests that plaque rupture, if possible in mice, is likely not driven by mechanics in the same manner as humans. Similar mechanical modeling of human ruptured and eroded plaques and comparison to histological staining revealed that ruptured plaques exhibit increased levels of inflammatory markers in response to strain in ruptured plaques, but no such response was observed in plaque erosion. This suggests that treatment of inflammation, a current paradigm for care of atherosclerotic patients, may not be an effective approach to mediate plaque erosion. Computational fluid dynamics modeling of patients with plaque erosion revealed no relation between wall shear stress magnitude or direction, further suggesting that the mechanism of plaque erosion differs considerably from that of plaque rupture. Together, these findings suggest that biomechanics can help explain why not all plaques rupture and that different clinical approaches are necessary to address different phenotypes of lesions. Advisors/Committee Members: Oshinski, John N. (Committee Co-Chair), Taylor, W. Robert (Committee Co-Chair), Giddens, Don P. (Committee Member), Veneziani, Alessandro (Committee Member), Virmani, Renu (Committee Member), Vito, Raymond P. (Committee Member).

Subjects/Keywords: Biomechanics immunohistochemistry; Immunohistochemistry; Atherosclerotic plaque; Cardiovascular system Diseases; Thrombosis

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APA (6^th Edition):

Campbell, I. C. (2013). Plaque erosion and murine plaque stability: a biomechanical examination of exceptions to the phenomenon of plaque rupture. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/47741

Chicago Manual of Style (16^th Edition):

Campbell, Ian Christopher. “Plaque erosion and murine plaque stability: a biomechanical examination of exceptions to the phenomenon of plaque rupture.” 2013. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/47741.

MLA Handbook (7^th Edition):

Campbell, Ian Christopher. “Plaque erosion and murine plaque stability: a biomechanical examination of exceptions to the phenomenon of plaque rupture.” 2013. Web. 15 Apr 2021.

Vancouver:

Campbell IC. Plaque erosion and murine plaque stability: a biomechanical examination of exceptions to the phenomenon of plaque rupture. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/47741.

Council of Science Editors:

Campbell IC. Plaque erosion and murine plaque stability: a biomechanical examination of exceptions to the phenomenon of plaque rupture. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/47741

Georgia Tech

29. Carnell, Peter Hamilton. Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach.

Degree: PhD, Mechanical Engineering, 2004, Georgia Tech

URL: http://hdl.handle.net/1853/4811

► Hypertension is a major risk factor for coronary artery disease, stroke, and kidney disease. Many studies suggest that elevated intramural stresses caused by hypertension may… (more)

▼ Hypertension is a major risk factor for coronary artery disease, stroke, and kidney disease. Many studies suggest that elevated intramural stresses caused by hypertension may stimulate inflammatory changes, but little has been done to ascertain whether inflammation and stress are spatially correlated. Such correlations are a first step in identifying the mechanisms that may relate intramural stress to disease so that more effective clinical treatments may be developed. Arterial branches exhibit local stress peaks and are focal points for the onset of disease. They are thus a logical place to examine whether high stresses spatially correlate with increased inflammation. This research seeks to 1) develop a histology-based method to reconstruct small arterial branches; 2) use finite element analysis to evaluate intramural stresses where experimental testing is of limited use; 3) quantify biological measures of inflammation; and 4) visually and statistically compare the distribution of stress with the distribution of inflammation. Hypertension was induced in Sprague-Dawley rats by implanting Angiotensin II pumps for 7 days or 21 days. Normotensive rats were used as controls. To preserve morphology the mesentery was pressure-fixed in situ, harvested, processed, and embedded in glycol methacrylate resin. Branch geometry was reconstituted from serial sections. This involved: correcting deformations caused by sectioning; aligning sections into an image stack; identifying vessel boundaries; creating a surface suitable for finite element analysis; reducing the branch geometry to a midplane surface; and using Ansys (Ansys, Inc.) to mesh the midplane surface with a variable-thickness shell element. The pattern of inflammation was characterized by measuring the local density of monocytes and macrophages. Cell density was expressed as a distribution on the branch surface, which simplified visualization and facilitated statistical comparisons of inflammation with stress. Both intramural stresses and inflammation were greater near branches during hypertension. In most cases, however, high stresses and high cell density were not spatially collocated. The onset of an adaptive response may reduce the strength of this correlation. Maximal wall tension, defined as the maximal midplane stress multiplied by the wall thickness, was elevated near branches and strongly correlated with cell density. Advisors/Committee Members: Vito, Raymond P. (Committee Chair), Giddens, Don P. (Committee Member), Guldberg, Robert E. (Committee Member), Levenston, Marc E. (Committee Member), Taylor, W. Robert (Committee Member).

Subjects/Keywords: Statistical analysis; 3D reconstruction; Hypertension

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Carnell, P. H. (2004). Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/4811

Chicago Manual of Style (16^th Edition):

Carnell, Peter Hamilton. “Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach.” 2004. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/4811.

MLA Handbook (7^th Edition):

Carnell, Peter Hamilton. “Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach.” 2004. Web. 15 Apr 2021.

Vancouver:

Carnell PH. Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach. [Internet] [Doctoral dissertation]. Georgia Tech; 2004. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/4811.

Council of Science Editors:

Carnell PH. Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach. [Doctoral Dissertation]. Georgia Tech; 2004. Available from: http://hdl.handle.net/1853/4811

Georgia Tech

30. Johnson, Kevin Robert. In Vivo Coronary Wall Shear Stress Determination Using CT, MRI, and Computational Fluid Dynamics.

Degree: PhD, Biomedical Engineering, 2007, Georgia Tech

URL: http://hdl.handle.net/1853/14482

► Wall shear stress (WSS) has long been identified as a factor in the development of atherosclerotic lesions. Autopsy studies have revealed a strong tendency for… (more)

▼ Wall shear stress (WSS) has long been identified as a factor in the development of atherosclerotic lesions. Autopsy studies have revealed a strong tendency for lesion development at arterial branch sites and along the inner walls of curvature areas that, in theory, should experience low WSS. Calculations of coronary artery WSS have typically been based upon average models of coronary artery geometry with average flow conditions and then compared to average lesion distributions. With all the averaging involved, a more detailed knowledge of the correlation between WSS and atherosclerotic lesion development might be obscured. Recent advancements in hemodynamic modeling now enable the calculation of WSS in individual subjects. An image-based approach for patient-specific calculation of in vivo WSS using computational fluid dynamics (CFD) would allow a more direct study of this correlation. New state-of-the-art technologies in multi-detector computed tomography (CT) and 3.0 Tesla magnetic resonance imaging (MRI) offer potential improvements for the measurement of coronary artery geometry and blood flow. The overall objective of this research was to evaluate the quantitative accuracy of multi-detector CT and 3.0 Tesla MRI and incorporate those imaging modalities into a patient-specific CFD model of coronary artery WSS. Using a series of vessel motion phantoms, it has been shown that 64-detector CT can provide accurate measurements of coronary artery geometry for heart rates below 70 beats per minute. A flow phantom was used to validate the use of navigator-echo gated, phase contrast MRI at 3.0 Tesla to measure velocity of coronary blood flow. Patient-specific, time-resolved CFD models of coronary WSS were created for two subjects. Furthermore, it was determined that population-average velocity curves or steady state velocities can predict locations of high or low WSS with high degrees of accuracy compared to the use of patient-specific blood flow velocity measurements as CFD boundary conditions. This work is significant because it constitutes the first technique to non-invasively calculate in vivo coronary artery WSS using image-based, patient-specific modeling. Advisors/Committee Members: Oshinski, John (Committee Chair), Giddens, Don (Committee Member), Karellas, Andrew (Committee Member), Taylor, W. Robert (Committee Member), Tigges, Stefan (Committee Member).

Subjects/Keywords: Computed tomography; Computational fluid dynamics; Magnetic resonance imaging; Atherosclerosis; Modeling; Coronary arteries; Hemodynamics; Medical imaging; Imaging systems in medicine; Tomography; Blood flow Measurement Mathematical models; Coronary arteries; Hemodynamics Data processing

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Johnson, K. R. (2007). In Vivo Coronary Wall Shear Stress Determination Using CT, MRI, and Computational Fluid Dynamics. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/14482

Chicago Manual of Style (16^th Edition):

Johnson, Kevin Robert. “In Vivo Coronary Wall Shear Stress Determination Using CT, MRI, and Computational Fluid Dynamics.” 2007. Doctoral Dissertation, Georgia Tech. Accessed April 15, 2021. http://hdl.handle.net/1853/14482.

MLA Handbook (7^th Edition):

Johnson, Kevin Robert. “In Vivo Coronary Wall Shear Stress Determination Using CT, MRI, and Computational Fluid Dynamics.” 2007. Web. 15 Apr 2021.

Vancouver:

Johnson KR. In Vivo Coronary Wall Shear Stress Determination Using CT, MRI, and Computational Fluid Dynamics. [Internet] [Doctoral dissertation]. Georgia Tech; 2007. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1853/14482.

Council of Science Editors:

Johnson KR. In Vivo Coronary Wall Shear Stress Determination Using CT, MRI, and Computational Fluid Dynamics. [Doctoral Dissertation]. Georgia Tech; 2007. Available from: http://hdl.handle.net/1853/14482

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