+publisher:"Rice University" +contributor:("Grande-Allen, Jane")

Rice University

1. Connell, Patrick Sean. Investigating Mitral Valve Disease Progression Using a Flow Loop Bioreactor.

Degree: PhD, Engineering, 2015, Rice University

URL: http://hdl.handle.net/1911/107994

► Mitral regurgitation is a common but highly varied clinical disease that can have profound impacts on patient morbidity and mortality. While the effects of regurgitation… (more)

▼ Mitral regurgitation is a common but highly varied clinical disease that can have profound impacts on patient morbidity and mortality. While the effects of regurgitation on the rest of the cardiovascular system have been widely investigated, the direct effects on valve remodeling are understudied. From previous studies of mitral valve interstitial cells conducted using a variety of biomaterial and bioreactor platforms, it was established that valve interstitial cells respond to altered mechanical stimulation by changing their phenotype and remodeling the extracellular matrix. Here I sought to take advantage of an existing flow loop bioreactor capable of intact organ culture of porcine mitral valves, in order to investigate the remodeling response of valve tissues to the altered mechanics of the two main etiologies of mitral regurgitation. My global objective was to understand the specific changes to the biomechanical properties and extracellular matrix composition that occur in response to the altered mechanics of mitral regurgitation. The first aim successfully recreated the hemodynamic environment of non-regurgitant valves, valves experiencing mitral valve prolapse, and valves experiencing functional mitral regurgitation. Redesigning the flow loop system to enable precise control of the geometry of the valve annulus and papillary muscles enabled the creation of these models. The second aim of this study showed that previously healthy porcine mitral valves subjected to mitral valve prolapse hemodynamics undergo myxomatous remodeling, while valves placed in functional mitral regurgitation geometry and hemodynamics undergo fibrotic remodeling compared to non-regurgitant controls. The third aim showed that the pathophysiologic fibrotic remodeling of functional mitral regurgitation conditioned valves is partially reversible if valves previously cultured in functional mitral regurgitation conditions for a week are placed in non-regurgitant conditions for a subsequent week. Here the pattern of remodeling reversal was interesting, as those regions most affected both in our one-week FMR studies and in clinical samples were those that experienced reversal of fibrotic remodeling and more closely resembled controls. The impact of this thesis is to: 1) establish that the natural response of valve tissues to being placed in disease hemodynamics is to remodel in a way that resembles the disease phenotype; 2) demonstrate that this remodeling can be partially reversed if normal hemodynamics are reestablished; and 3) establish an experimental platform that can be used to explore directly the impact of physiological mechanical stimuli on valve biological functioning. Advisors/Committee Members: Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (advisor).

Subjects/Keywords: mitral valve; mitral regurgitation; functional mitral regurgitation; mitral valve prolapse; remodeling; flow loop; bioreactor

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APA (6^th Edition):

Connell, P. S. (2015). Investigating Mitral Valve Disease Progression Using a Flow Loop Bioreactor. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/107994

Chicago Manual of Style (16^th Edition):

Connell, Patrick Sean. “Investigating Mitral Valve Disease Progression Using a Flow Loop Bioreactor.” 2015. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/107994.

MLA Handbook (7^th Edition):

Connell, Patrick Sean. “Investigating Mitral Valve Disease Progression Using a Flow Loop Bioreactor.” 2015. Web. 08 Mar 2021.

Vancouver:

Connell PS. Investigating Mitral Valve Disease Progression Using a Flow Loop Bioreactor. [Internet] [Doctoral dissertation]. Rice University; 2015. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/107994.

Council of Science Editors:

Connell PS. Investigating Mitral Valve Disease Progression Using a Flow Loop Bioreactor. [Doctoral Dissertation]. Rice University; 2015. Available from: http://hdl.handle.net/1911/107994

Rice University

2. Vekilov, Dragoslava P. Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves.

Degree: PhD, Engineering, 2019, Rice University

URL: http://hdl.handle.net/1911/106021

► Each tissue of the cardiovascular system exhibits a unique pattern of composition and material properties, which are matched to the tissue’s mechanical environment and required… (more)

▼ Each tissue of the cardiovascular system exhibits a unique pattern of composition and material properties, which are matched to the tissue’s mechanical environment and required function. My global objective was to characterize such patterns in mitral valves and the central venous system with the goal of understanding how anatomical locations within each tissue differ and how they vary in their pathological responses. In the first aim, I employed a novel mechanical analysis method, optical coherence elastography, to assess the spatial pattern of elasticity along the surface of the porcine mitral valve leaflets. This analysis revealed heterogeneity within and differences between the leaflets at a higher resolution than previously reported and broadened our understanding of mitral valve mechanics as they relate to the tissue’s finely tuned composition. The second aim explored the mitral valve leaflets’ differing responses to alterations in mechanical environment. Previously, the Grande-Allen lab established that mimicking mitral regurgitation in a pseudo-physiological flow loop can lead to fibrotic remodeling and increased stiffness in cultured porcine mitral valves. I utilized this system to explore whether elimination of regurgitation would lead the leaflets to reverse remodel toward a healthy state. The finding of leaflet- and orientation-dependent remodeling revealed the complex interplay between valve composition, forces experienced by the valve, and responses to alterations in these forces. In the last aim, I shifted focus to exploring anatomical variation in the central venous system. Tensile testing was performed on healthy porcine veins and veins harvested from a porcine model of deep vein thrombosis (DVT). Detected location-specific differences in the thickness, stiffness, failure strength, and remodeling in response to DVT revealed previously understudied variation in venous system mechanics and pathological response. To further analyze the effects of DVT, I developed a pressurized digital image correlation system to examine the pressure- displacement relationship of veins. This system provides a platform to further investigate venous mechanics in their natural geometry. Together, this dissertation reveals heterogeneity in the material properties and pathological remodeling of mitral valves and veins, thereby underscoring the need for the consideration of anatomical variation in the study and treatment of cardiovascular disease. Advisors/Committee Members: Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (advisor).

Subjects/Keywords: Mitral valve; vein; elastic properties; heterogeneity

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

APA (6^th Edition):

Vekilov, D. P. (2019). Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/106021

Chicago Manual of Style (16^th Edition):

Vekilov, Dragoslava P. “Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves.” 2019. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/106021.

MLA Handbook (7^th Edition):

Vekilov, Dragoslava P. “Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves.” 2019. Web. 08 Mar 2021.

Vancouver:

Vekilov DP. Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves. [Internet] [Doctoral dissertation]. Rice University; 2019. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/106021.

Council of Science Editors:

Vekilov DP. Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves. [Doctoral Dissertation]. Rice University; 2019. Available from: http://hdl.handle.net/1911/106021

Rice University

3. Vekilov, Dragoslava P. Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves.

Degree: PhD, Engineering, 2019, Rice University

URL: http://hdl.handle.net/1911/106020

► Each tissue of the cardiovascular system exhibits a unique pattern of composition and material properties, which are matched to the tissue’s mechanical environment and required… (more)

▼ Each tissue of the cardiovascular system exhibits a unique pattern of composition and material properties, which are matched to the tissue’s mechanical environment and required function. My global objective was to characterize such patterns in mitral valves and the central venous system with the goal of understanding how anatomical locations within each tissue differ and how they vary in their pathological responses. In the first aim, I employed a novel mechanical analysis method, optical coherence elastography, to assess the spatial pattern of elasticity along the surface of the porcine mitral valve leaflets. This analysis revealed heterogeneity within and differences between the leaflets at a higher resolution than previously reported and broadened our understanding of mitral valve mechanics as they relate to the tissue’s finely tuned composition. The second aim explored the mitral valve leaflets’ differing responses to alterations in mechanical environment. Previously, the Grande-Allen lab established that mimicking mitral regurgitation in a pseudo-physiological flow loop can lead to fibrotic remodeling and increased stiffness in cultured porcine mitral valves. I utilized this system to explore whether elimination of regurgitation would lead the leaflets to reverse remodel toward a healthy state. The finding of leaflet- and orientation-dependent remodeling revealed the complex interplay between valve composition, forces experienced by the valve, and responses to alterations in these forces. In the last aim, I shifted focus to exploring anatomical variation in the central venous system. Tensile testing was performed on healthy porcine veins and veins harvested from a porcine model of deep vein thrombosis (DVT). Detected location-specific differences in the thickness, stiffness, failure strength, and remodeling in response to DVT revealed previously understudied variation in venous system mechanics and pathological response. To further analyze the effects of DVT, I developed a pressurized digital image correlation system to examine the pressure- displacement relationship of veins. This system provides a platform to further investigate venous mechanics in their natural geometry. Together, this dissertation reveals heterogeneity in the material properties and pathological remodeling of mitral valves and veins, thereby underscoring the need for the consideration of anatomical variation in the study and treatment of cardiovascular disease. Advisors/Committee Members: Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (advisor).

Subjects/Keywords: Mitral valve; vein; elastic properties; heterogeneity

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

APA (6^th Edition):

Vekilov, D. P. (2019). Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/106020

Chicago Manual of Style (16^th Edition):

Vekilov, Dragoslava P. “Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves.” 2019. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/106020.

MLA Handbook (7^th Edition):

Vekilov, Dragoslava P. “Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves.” 2019. Web. 08 Mar 2021.

Vancouver:

Vekilov DP. Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves. [Internet] [Doctoral dissertation]. Rice University; 2019. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/106020.

Council of Science Editors:

Vekilov DP. Resolving Spatial Heterogeneity of Elastic Properties in Veins and Mitral Valves. [Doctoral Dissertation]. Rice University; 2019. Available from: http://hdl.handle.net/1911/106020

Rice University

4. Puperi, Daniel. Biomimetic heterogeneous scaffolds for a layered tissue engineered heart valve.

Degree: PhD, Engineering, 2016, Rice University

URL: http://hdl.handle.net/1911/96554

► This dissertation describes strategies that I have developed to introduce mechanical and biochemical heterogeneity into synthetic tissue engineering scaffolds for heart valves. For a tissue… (more)

▼ This dissertation describes strategies that I have developed to introduce mechanical and biochemical heterogeneity into synthetic tissue engineering scaffolds for heart valves. For a tissue engineered heart valve to work well, it must meet the mechanical demands of the natural heart valve and support healthy valve cell behavior. Natural heart valve leaflets have a heterogeneous structure with distinct layers that provide the valve with unique mechanical functions. My research focused on mimicking the mechanics and biochemical signaling of each layer so that the entire scaffold will function similar to the natural valve. Three specific strategies to add heterogeneity into tissue engineered heart valve scaffolds are described in this thesis. First, I designed an innovative method to direct the proper spatial arrangement of cell adhesive peptides in order to promote the correct organization of the two different cell types in the valve (valve endothelial cells and valve interstitial cells). Second, hyaluronan hydrogels were utilized as a mechanical and biochemical mimic of the middle, spongiosa layer of heart valves. Third, I learned how valve interstitial cells respond to synthetic fibrous structure in 3D culture by designing a composite scaffold made from poly(ethylene glycol) hydrogels and electrospun polyurethane fibers. The electrospun fibers were incorporated to give the valve scaffold the anisotropic, viscoelastic, and non-linear mechanical behavior similar to native valves, while the hydrogel material functioned as a cell-friendly substrate. These specific research projects provide methods and results that advance the heart valve tissue engineering field while having broad applicability to other tissue engineering applications, especially for tissues which have a layered structure and a stratified distribution of multiple cell types. The results of this research also lay the groundwork for constructing heart valve scaffolds for the purpose of in vitro disease modeling. A synthetic heart valve model based on this research would be more consistent than explant animal valves and could be used to study the initiation and progression of heart valve disease. Advisors/Committee Members: Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (advisor).

Subjects/Keywords: heart valves; tissue engineering; biomimetic; bimaterials

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

APA (6^th Edition):

Puperi, D. (2016). Biomimetic heterogeneous scaffolds for a layered tissue engineered heart valve. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/96554

Chicago Manual of Style (16^th Edition):

Puperi, Daniel. “Biomimetic heterogeneous scaffolds for a layered tissue engineered heart valve.” 2016. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/96554.

MLA Handbook (7^th Edition):

Puperi, Daniel. “Biomimetic heterogeneous scaffolds for a layered tissue engineered heart valve.” 2016. Web. 08 Mar 2021.

Vancouver:

Puperi D. Biomimetic heterogeneous scaffolds for a layered tissue engineered heart valve. [Internet] [Doctoral dissertation]. Rice University; 2016. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/96554.

Council of Science Editors:

Puperi D. Biomimetic heterogeneous scaffolds for a layered tissue engineered heart valve. [Doctoral Dissertation]. Rice University; 2016. Available from: http://hdl.handle.net/1911/96554

Rice University

5. Bieritz, Shelby A. Resolving Flow Properties of Spiral Groove Bearings to Improve Mechanical Circulatory Support Hemocompatibility.

Degree: PhD, Engineering, 2020, Rice University

URL: http://hdl.handle.net/1911/108799

► Rotary blood pumps are utilized as bridge to transplant, bridge to destination, and bridge to recovery devices to support a failing heart. These pumps unload… (more)

▼ Rotary blood pumps are utilized as bridge to transplant, bridge to destination, and bridge to recovery devices to support a failing heart. These pumps unload the ventricles (ventricular assist devices) or replace the heart entirely (total artificial hearts), using impellers, or a rotating set of blades, to drive blood flow to the systemic and/or pulmonary circulation. These pumps have been used in the clinic for decades, supporting patients for 1.5 years on average, but the complication rate while on pump support remains high, with 60% of patients returning to the hospital with a major adverse event within 6 months. Much of these complications arise from damage to blood components due to the supraphysiologic shear stresses within a rotary blood pump. This work aims to explore a method of controlling red blood cell flow in a rotary blood pump by means of a spiral groove bearing, a hydrodynamic bearing that generates lift by pumping fluid along a set of grooves. The application of these bearings to rotary blood pump design will be explored in two contexts; first, as a means of generating washout flow in a miniature axial left ventricular assist device, and second, as a tool to reduce red blood cell shear stress exposure in a centrifugal blood pump. The salient findings of this work include i) the applicability of an analytical model to predict spiral groove bearing flow in an axial pump; ii) the induction of cell exclusion in a spiral groove bearing gap, allowing manipulation of red blood cell flow in rotary blood pumps to limit shear exposure; iii) the ability to track red blood cell flow in a complex pump geometry using erythrocyte ghosts as a blood analog solution, and iv) the implications of cell exclusion on red blood cell and von Willebrand Factor damage. Spiral groove bearings cab be utilized to reduce both the magnitude and duration of red blood cell exposure to supraphysiologic shear stress, thereby providing an additional tool to improve rotary blood pump hemocompatibility and patient outcomes. Advisors/Committee Members: Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (advisor).

Subjects/Keywords: Heart failure; hemocompatibility; rotary blood pump; ventricular assist device; spiral groove bearing

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

APA (6^th Edition):

Bieritz, S. A. (2020). Resolving Flow Properties of Spiral Groove Bearings to Improve Mechanical Circulatory Support Hemocompatibility. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/108799

Chicago Manual of Style (16^th Edition):

Bieritz, Shelby A. “Resolving Flow Properties of Spiral Groove Bearings to Improve Mechanical Circulatory Support Hemocompatibility.” 2020. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/108799.

MLA Handbook (7^th Edition):

Bieritz, Shelby A. “Resolving Flow Properties of Spiral Groove Bearings to Improve Mechanical Circulatory Support Hemocompatibility.” 2020. Web. 08 Mar 2021.

Vancouver:

Bieritz SA. Resolving Flow Properties of Spiral Groove Bearings to Improve Mechanical Circulatory Support Hemocompatibility. [Internet] [Doctoral dissertation]. Rice University; 2020. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/108799.

Council of Science Editors:

Bieritz SA. Resolving Flow Properties of Spiral Groove Bearings to Improve Mechanical Circulatory Support Hemocompatibility. [Doctoral Dissertation]. Rice University; 2020. Available from: http://hdl.handle.net/1911/108799

Rice University

6. Biswas, Rajoshi. Data-Driven Modeling of Lung Deposition of Aerosol Medication Delivered by Metered Dose Inhalers.

Degree: PhD, Engineering, 2018, Rice University

URL: http://hdl.handle.net/1911/105804

► Chronic pulmonary diseases such as Asthma and COPD (Chronic Obstructive Pulmonary Disease) affect over 510 million worldwide. The most common form of treatment for the… (more)

▼ Chronic pulmonary diseases such as Asthma and COPD (Chronic Obstructive Pulmonary Disease) affect over 510 million worldwide. The most common form of treatment for the management of the diseases is a Metered Dose Inhaler (MDI). Numerous large-scale studies have demonstrated that 70-90% of patients misuse their MDIs leading to wasted medication and poor health outcomes. Due to the nature of inhaled therapy and delayed impact of MDI misuse on health outcomes, patients are unaware of their MDI use technique as well as the resulting lung deposition. In this thesis, I have developed and validated a predictive model of lung deposition corresponding to any MDI technique in three phases. Phase I: I conducted the first pilot study that quantitatively measured MDI technique from 23 physician-diagnosed asthma and COPD adult patients in an outpatient clinic setting. Our results showed that all patients made at least one technique error and 74% made at least three; our quantitative method of measurement recorded 60% more errors than the current gold standard method (using observation alone). Further, I derived an MDI technique model using a parameterized model with a trapezoidal approximation to inspiration curves and includes actuation timing and instantaneous flow-based parameterization. Phase II: To derive lung deposition for any MDI technique (ground truth estimation), I constructed and validated the first in vitro experimental testbed designed to emulate both inspiration and actuation mechanisms of any MDI use in a lab setting. Using this testbed, I determined the significance of inspiration and actuation parameters on in vitro lung deposition of aerosols delivered by Ventolin MDIs. Our results demonstrated that actuation parameters affected lung deposition more significantly (23% difference in lung deposition) than inspiratory flow parameters (<5%). Phase III: With a training dataset of MDI techniques and corresponding in vitro lung deposition, I determined that the model specification for a linear mixed effects model of lung deposition of aerosol from Ventolin MDIs was a function of quadratic inspiration and actuation parameters. I validated the model against in vitro lung deposition measured for the MDI techniques (non-trapezoidal) recorded from patients and had a testing RMSE of 2.3% lung deposition. Hence, we demonstrated the methodology and validation for developing a data-driven model of lung deposition of aerosol medication delivered by any MDI, based on patient representative inhaler use techniques. Advisors/Committee Members: Sabharwal, Ashutosh (advisor), Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (committee member).

Subjects/Keywords: Asthma; COPD; Metered Dose Inhaler; Modeling; Aerosol; Linear Mixed Effects Model; Inhaler technique; Lung deposition

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

APA (6^th Edition):

Biswas, R. (2018). Data-Driven Modeling of Lung Deposition of Aerosol Medication Delivered by Metered Dose Inhalers. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/105804

Chicago Manual of Style (16^th Edition):

Biswas, Rajoshi. “Data-Driven Modeling of Lung Deposition of Aerosol Medication Delivered by Metered Dose Inhalers.” 2018. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/105804.

MLA Handbook (7^th Edition):

Biswas, Rajoshi. “Data-Driven Modeling of Lung Deposition of Aerosol Medication Delivered by Metered Dose Inhalers.” 2018. Web. 08 Mar 2021.

Vancouver:

Biswas R. Data-Driven Modeling of Lung Deposition of Aerosol Medication Delivered by Metered Dose Inhalers. [Internet] [Doctoral dissertation]. Rice University; 2018. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/105804.

Council of Science Editors:

Biswas R. Data-Driven Modeling of Lung Deposition of Aerosol Medication Delivered by Metered Dose Inhalers. [Doctoral Dissertation]. Rice University; 2018. Available from: http://hdl.handle.net/1911/105804

Rice University

7. Spurlin, James W. A novel paradigm for non-fibrotic regeneration of the cornea: The role of TGF-beta superfamily during embryonic cornea regeneration.

Degree: PhD, Natural Sciences, 2015, Rice University

URL: http://hdl.handle.net/1911/88164

► Damage to the cornea results in fibrotic scarring, leading to the loss of tissue transparency and reduced visual acuity. In fact, corneal opacity is the… (more)

▼ Damage to the cornea results in fibrotic scarring, leading to the loss of tissue transparency and reduced visual acuity. In fact, corneal opacity is the world’s third leading cause of blindness. Other than transplantation of the affected tissue, there is no treatment to prevent corneal scarring. For these reasons, there is a need to develop anti-fibrotic therapies to promote corneal regeneration after injury. Embryonic tissue has a remarkable regenerative capacity. However, prior to this study, it was not known if the embryonic cornea possessed the ability to regenerate. I hypothesized wounded embryonic corneas wound exhibit non-fibrotic regeneration, and could be used to elucidate novel mechanisms of cornea regeneration. I developed a multistep microdissection method that allows access to the embryonic cornea and several other tissues undergoing organogenesis. Utilizing this methodology, I found embryonic corneal wounds induce a transient population of scar-forming myofibroblast, and ultimately regenerate scar-free. Immunohistological analysis of wounded embryonic corneas revealed transient change in expression of ECM components, which is restored to normal levels in the healed corneas. Furthermore, I showed that Sema3A mRNA is elevated and innervation of wounded embryonic corneas is inhibited during healing, but regenerated corneas are fully innervated. These findings contribute to the understanding of the events that orchestrate scar-free regeneration of wounded corneas. Since embryonic corneas possess an intrinsic regenerative capacity, the embryonic wound healing model serves as a great tool to study regulatory mechanisms that facilitate non-fibrotic healing. Because scar associated myofibroblasts are inherently transient in the embryonic cornea wound, I sought to determine mechanistic regulation of this cell population during cornea regeneration. I hypothesized the embryonic cornea wound would exhibit unique regulation of myofibroblast inductive growth factor, TGF-beta, during regeneration. Through studying gene expression profiles in the embryonic cornea wound healing model, I determined the spatiotemporal distribution of TGF-beta transcripts and the subsequent activation of the myofibroblast population. Moreover, I identified the expression of candidate TGF-beta antagonists when myofibroblasts are found to exit the regenerating cornea. My data shows BMP3 as a novel antagonist to TGF-beta mediated myofibroblast differentiation in isolated embryonic corneal cells. Interestingly, TGF-beta mediated accumulation of focal adhesion appears to be attenuated by BMP3, implicating the role of cellular adhesion in promoting the myofibroblast phenotype. Collectively, this work demonstrates the utility of the embryonic cornea wound healing model to identify novel mechanisms of scar-free cornea regeneration. Additionally, this novel mechanism of BMP3 antagonism on TGF-beta mediated fibrotic response suggests targeting aspects of cellular adhesion signaling may provide viable therapeutics to mitigate corneal fibrosis. Advisors/Committee Members: Farach-Carson, Mary C (advisor), Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (committee member), Lwigale, Peter Y (committee member), McNew, James A (committee member), Stern, Micheal (committee member).

Subjects/Keywords: cornea; wound healing; organogenesis; regeneration; development; embryonic manipulations; TGF-beta; myofibroblasts; BMP; ECM

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

APA (6^th Edition):

Spurlin, J. W. (2015). A novel paradigm for non-fibrotic regeneration of the cornea: The role of TGF-beta superfamily during embryonic cornea regeneration. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/88164

Chicago Manual of Style (16^th Edition):

Spurlin, James W. “A novel paradigm for non-fibrotic regeneration of the cornea: The role of TGF-beta superfamily during embryonic cornea regeneration.” 2015. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/88164.

MLA Handbook (7^th Edition):

Spurlin, James W. “A novel paradigm for non-fibrotic regeneration of the cornea: The role of TGF-beta superfamily during embryonic cornea regeneration.” 2015. Web. 08 Mar 2021.

Vancouver:

Spurlin JW. A novel paradigm for non-fibrotic regeneration of the cornea: The role of TGF-beta superfamily during embryonic cornea regeneration. [Internet] [Doctoral dissertation]. Rice University; 2015. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/88164.

Council of Science Editors:

Spurlin JW. A novel paradigm for non-fibrotic regeneration of the cornea: The role of TGF-beta superfamily during embryonic cornea regeneration. [Doctoral Dissertation]. Rice University; 2015. Available from: http://hdl.handle.net/1911/88164

8. Wilson, Reid Laurence. Novel biomaterial and biomaterial platforms for studying small intestinal biology.

Degree: PhD, Engineering, 2018, Rice University

URL: http://hdl.handle.net/1911/105852

► The small intestine is the site of numerous pathologies that contribute significantly to the disease burden of both the developing and the developed world. Investigation… (more)

▼ The small intestine is the site of numerous pathologies that contribute significantly to the disease burden of both the developing and the developed world. Investigation into the pathological mechanisms contributing to small intestinal disease is complicated by the complexity and dynamism of organ’s physiology. The small intestinal mucosa has an intricate microanatomy that includes fine topographical features that organize its epithelium into distinct proliferative and differentiated compartments. A steep oxygen gradient extends from the intestinal wall into the lumen and supports complex colonies of anaerobic microorganisms in close proximity to the aerobic cells of the mucosa. Finally, the contractions of the intestinal wall and the movement of luminal chyme create a dynamic mechanical environment that contributes to normal intestinal homeostasis and influences the crosstalk between the mucosal surface and the luminal microbiota. Despite their importance in both intestinal biology and pathology, these aforementioned features are often not included in in vitro experimental models of the small intestine. Thus, the objective of this thesis was to apply a variety of bioengineering techniques to develop biomaterial and biomechanical platforms that incorporate these important elements of the intestinal environment, and in so doing, improve the study of small intestinal biology. First, a modular hydrogel platform that mimics the stiffness, extracellular matrix cues, and villous topography of the small intestinal mucosa was designed as an advanced culture platform for human intestinal epithelial cells. Second, oxygen-sensing hydrogel microparticles were developed to measure oxygen concentrations from in vitro experimental models non-invasively and in real time. Third, a millifluidic perfusion device that is both simple to fabricate and easy to operate was created to investigate how the application of flow affects the pathophysiology of enteric infection. Taken together, the three technologies in this thesis expand the capabilities of in vitro models of the intestinal mucosa to probe important questions in intestinal biology and lay the foundation for a better understanding of the pathophysiology of intestinal disease. Advisors/Committee Members: Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (advisor), Estes, Mary (committee member).

Subjects/Keywords: Intestine; human intestinal enteroids; engineering; bioengineering; hydrogel; basement membrane; molding; topography; oxygen; tissue engineering; three-dimensional; norovirus; E. coli; host-pathogen interaction; shear stress; peristalsis; biofilm; perfusion

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APA (6^th Edition):

Wilson, R. L. (2018). Novel biomaterial and biomaterial platforms for studying small intestinal biology. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/105852

Chicago Manual of Style (16^th Edition):

Wilson, Reid Laurence. “Novel biomaterial and biomaterial platforms for studying small intestinal biology.” 2018. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/105852.

MLA Handbook (7^th Edition):

Wilson, Reid Laurence. “Novel biomaterial and biomaterial platforms for studying small intestinal biology.” 2018. Web. 08 Mar 2021.

Vancouver:

Wilson RL. Novel biomaterial and biomaterial platforms for studying small intestinal biology. [Internet] [Doctoral dissertation]. Rice University; 2018. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/105852.

Council of Science Editors:

Wilson RL. Novel biomaterial and biomaterial platforms for studying small intestinal biology. [Doctoral Dissertation]. Rice University; 2018. Available from: http://hdl.handle.net/1911/105852

9. Gao, Yang. Use of Human Pediatric Cardiac Progenitor Cells in an Engineered Heart Patch.

Degree: PhD, Engineering, 2015, Rice University

URL: http://hdl.handle.net/1911/88349

► Congenital heart defects (CHD) are the most common birth defects in the US and the leading cause of death in newborns. Some of the most… (more)

▼ Congenital heart defects (CHD) are the most common birth defects in the US and the leading cause of death in newborns. Some of the most prevalent CHD require surgical interventions with patch materials. However, current commercial patch materials are acellular, non-conductive, and non-contractile; they can induce arrhythmias and require reoperations. We envision an engineered cardiac patch seeded with autologous cells from the patient. However, mature cardiomyocytes (CM) rarely proliferate. This research examined the ability of primary pediatric cardiac cells (PPCC) isolated from pediatric CHD biopsy samples supplied by Texas Children’s Hospital to differentiate into CM or induce CM differentiation in stem cells. Previous studies indicated evidence of cardiogenesis in Amniotic fluid-derived stem cells (AFSC) when directly mixed with neonatal rat ventricle myocytes. We hypothesized that co-culturing with human PPCC will induce cardiac differentiation in human AFSC (hAFSC). hAFSC co-cultured in contact with PPCC showed a statistically significant increase in cTnT expression compared to non-contact conditions but did not have functional or morphological characteristics of mature cardiomyocytes. This result suggests that contact is a necessary but not sufficient condition for AFSC cardiac differentiation in co-culture with PPCC. Cardiac progenitor cells (CPC) are proliferating cells with the ability to differentiate into cardiac cells. CPC can be identified from cardiac cells by the expression of Isl-1, SSEAs, and c-Kit. We hypothesized that there are potential CPC in PPCC. We found a small subpopulation (1%-4%) of the primary cells expressing Isl-1, SSEA-4, and c-Kit. However, when exposed to oxytocin, PPCC did not differentiate into functional CM as shown with murine CPC in literature. Extracellular matrix proteins isolated from adult cardiac tissue have been shown to promote CM maturation in vitro. PPCC can be expanded in vitro and cultured in PEGylated fibrin hydrogels. PPCC conditioned gels can then be decellularized. We found that PPCC could be cultured in fibrin hydrogels and that stem cell derived CM were viable when cultured on these conditioned gels. Overall, this research demonstrated that PPCC are a potential tool for CM differentiation and maturation in the development of a tissue engineered cardiac patch for repair of CHD. Advisors/Committee Members: Jacot, Jeffrey G (advisor), Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (committee member), Harrington, Daniel (committee member).

Subjects/Keywords: Tissue Engineering; Cardiac; Pediatric; Congenital Heart Defects; Stem Cells; Cardiac Progenitor Cells

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

APA (6^th Edition):

Gao, Y. (2015). Use of Human Pediatric Cardiac Progenitor Cells in an Engineered Heart Patch. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/88349

Chicago Manual of Style (16^th Edition):

Gao, Yang. “Use of Human Pediatric Cardiac Progenitor Cells in an Engineered Heart Patch.” 2015. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/88349.

MLA Handbook (7^th Edition):

Gao, Yang. “Use of Human Pediatric Cardiac Progenitor Cells in an Engineered Heart Patch.” 2015. Web. 08 Mar 2021.

Vancouver:

Gao Y. Use of Human Pediatric Cardiac Progenitor Cells in an Engineered Heart Patch. [Internet] [Doctoral dissertation]. Rice University; 2015. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/88349.

Council of Science Editors:

Gao Y. Use of Human Pediatric Cardiac Progenitor Cells in an Engineered Heart Patch. [Doctoral Dissertation]. Rice University; 2015. Available from: http://hdl.handle.net/1911/88349

Rice University

10. Natoli, Roman M. Impact loading and functional tissue engineering of articular cartilage.

Degree: PhD, Engineering, 2009, Rice University

URL: http://hdl.handle.net/1911/88472

► This thesis presents two advances for alleviating the problem of articular cartilage degeneration: mitigating degradative changes that follow mechanically induced injuries and growing functional neo-cartilage… (more)

▼ This thesis presents two advances for alleviating the problem of articular cartilage degeneration: mitigating degradative changes that follow mechanically induced injuries and growing functional neo-cartilage for diseased tissue replacement. Experiments demonstrate that cartilage subjected to a single, non-surface disrupting 1.1 J (Low) impact experiences sufficient degeneration over 4 weeks to become functionally equivalent to tissue subjected to a single, surface disrupting 2.8 J (High) impact. By 24 hrs post High impact, cell death and sulfated glycosaminoglycan (sGAG) release increased, changes in gene expression distinguished injured from adjacent tissue, and compressive stiffness decreased. In contrast, Low impacted tissue did not show decreased compressive stiffness until 4 weeks, revealing that Low impacted tissue experiences a delayed biological response. Post-injury treatment with the polymer P188, growth factor IGF-I, or matrix metalloproteinase inhibitor doxycycline partially ameliorated cell death and sGAG loss, two detrimental changes that occurred following either Low or High impact. With 1 week of treatment after Low impact, P188 reduced cell death 75% and IGF-I decreased sGAG release 49%. Following High impact, doxycycline treatment reduced 1 and 2 week sGAG release by 30% and 38%, respectively. As a novel method for engineering functional replacement tissue to use in cases of established disease, the GAG degrading enzyme chondroitinase ABC (C-ABC) improved the tensile integrity of articular cartilage constructs grown with a scaffold-less approach. C-ABC application increased ultimate tensile strength and tensile stiffness, reaching values of 1.4 and 3.4 MPa, respectively. Moreover, construct collagen concentration was ∼22% by wet weight. Though C-ABC temporarily depleted sGAG, by 6 weeks no significant differences in compressive stiffness remained. Furthermore, chondrocyte phenotype was maintained, as constructs contained collagen type II, but not collagen type I. Decorin decreased following C-ABC treatment, but recovered during subsequent culture. The known ability of decorin to control collagen fibrillogenesis suggests a putative mechanism for C-ABC's effects. Diseased articular cartilage heals poorly. For patients, the last resort is total joint replacement, though its associated morbidity and the limited lifespan of its results drive the need for alternate treatment strategies. Decreasing degradative changes post-injury and increasing functional properties of engineered cartilage are two significant improvements. Advisors/Committee Members: Athanasiou, Kyriacos (advisor), Allen%2C%20Jane%22%29&pagesize-30">Grande-Allen, Jane (committee member), Gustin, Michael (committee member).

Subjects/Keywords: Biomedical engineering; Medicine; Physiology; Health and environmental sciences; Applied sciences; Biological sciences; Tissue engineering; Articular cartilage; Mechanobiology; Biomechanics; Mechanotransduction; Osteoarthritis; Chondroitinase ABC

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

APA (6^th Edition):

Natoli, R. M. (2009). Impact loading and functional tissue engineering of articular cartilage. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/88472

Chicago Manual of Style (16^th Edition):

Natoli, Roman M. “Impact loading and functional tissue engineering of articular cartilage.” 2009. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/88472.

MLA Handbook (7^th Edition):

Natoli, Roman M. “Impact loading and functional tissue engineering of articular cartilage.” 2009. Web. 08 Mar 2021.

Vancouver:

Natoli RM. Impact loading and functional tissue engineering of articular cartilage. [Internet] [Doctoral dissertation]. Rice University; 2009. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/88472.

Council of Science Editors:

Natoli RM. Impact loading and functional tissue engineering of articular cartilage. [Doctoral Dissertation]. Rice University; 2009. Available from: http://hdl.handle.net/1911/88472

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