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Georgia Tech
1.
Ahmed, Faisal.
Microfluidic devices for stiffness dependent enrichment of red blood cell subpopulations.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2017, Georgia Tech
URL: http://hdl.handle.net/1853/60695 
► Microfluidic devices were designed, fabricated and tested for enriching red blood cell subpopulations based on their stiffness. First, stiffness dependent margination of red blood cells…
(more)
▼ Microfluidic devices were designed, fabricated and tested for enriching red blood cell subpopulations based on their stiffness. First, stiffness dependent margination of red blood
cells in high aspect ratio straight microchannels was studied with simulation tools. Stiff red blood cells marginate to channel walls whereas normal ones migrate to the central
core of the channel regardless whether cell-cell interactions are present or not. Cells of different stiffness reach their equilibrium locations faster in channels with smaller cross sections. Increasing flow Reynolds number and hence the shear rate and, cell volume fraction or hematocrit results in stronger segregation between normal and stiff red blood cells. Based on the results of the simulations, two types of cell enrichment devices were designed and fabricated, simple straight channel device and multistep device. The simple straight channel device was tested for a wide range of Reynolds number and hematocrit
values. Cell enrichment gets better with increasing flow Reynolds number and hematocrit up to certain threshold for each of them, and after that threshold no significant improvement
of performance is observed. Statistical analysis on experimental data found the effect of individual parameters, flow Reynolds number and hematocrit, to be strong. Significant interaction between these two factors implies that the extent of the effect of one factor
(e.g. flow Reynolds number) changes when the value of the other factor (e.g. volume fraction) varies and for best performance of the devices the combination of flow Reynolds number and hematocrit needs to be optimized. The multistep device performs more than three times better than the single step device. This research work revealed new information about stiffness dependent cell enrichment with straight channel microfluidic devices and improved their performance through optimizing flow parameters and new design.
Advisors/Committee Members: Aidun, Cyrus K. (advisor), Barabino, Gilda A. (advisor), Botchwey, Edward (committee member), Dixon, Brandon (committee member), Lam, Wilbur A. (committee member).
Subjects/Keywords: Microfluidic devices; Separation; Margination; Enrichment; Stiffness; RBC; Red blood cell; Internal viscosity; Red blood cell subpopulations
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APA (6th Edition):
Ahmed, F. (2017). Microfluidic devices for stiffness dependent enrichment of red blood cell subpopulations. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60695
Chicago Manual of Style (16th Edition):
Ahmed, Faisal. “Microfluidic devices for stiffness dependent enrichment of red blood cell subpopulations.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/60695.
MLA Handbook (7th Edition):
Ahmed, Faisal. “Microfluidic devices for stiffness dependent enrichment of red blood cell subpopulations.” 2017. Web. 13 Apr 2021.
Vancouver:
Ahmed F. Microfluidic devices for stiffness dependent enrichment of red blood cell subpopulations. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/60695.
Council of Science Editors:
Ahmed F. Microfluidic devices for stiffness dependent enrichment of red blood cell subpopulations. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/60695
Georgia Tech
2.
Awojoodu, Anthony O.
Sphingolipid dysregulation in erythrocytes during sickle cell disease contributes to pro-inflammatory microparticle generation and subsequent inflammatory cell activation.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2014, Georgia Tech
URL: http://hdl.handle.net/1853/54286
► Sickle cell disease is a hereditary blood disorder caused by a point mutation in the gene encoding hemoglobin. This mutation causes hemoglobin molecules to polymerize…
(more)
▼ Sickle cell disease is a hereditary blood disorder caused by a point mutation in the gene encoding hemoglobin. This mutation causes hemoglobin molecules to polymerize during de-oxygenation of erythrocytes producing rod-shaped polymers that bend and distort the red blood cell membrane, making it more rigid and “sickled”. This sickling causes red blood cells to lose their flexibility and ability to navigate small capillaries and also enhances the production of pro-inflammatory membrane-derived microparticles, leading to chronic inflammation and many complications such as peripheral artery disease, stroke, myocardial infarction, vasculitis and even death. Sphingolipids are a class of lipids containing a backbone of sphingoid bases and are integral components of erythrocyte and microparticle membranes. Many of these lipids are known to mediate biological processes, but their expression, distribution and orientation in erythrocytes during sickle cell disease has never been explored. Sphingomyelin, the most abundant sphingolipid in the red blood cell membrane is hydrolyzed by sphingomyelinase to produce ceramide, which has been shown to alter membrane dynamics and enhance microvessel formation. Additionally, ceramide can be further metabolized to form sphingosine and sphingosine 1-phosphate, which is a bioactive ligand for 5 known G-protein coupled receptors present on most blood and vascular cells that modulates cell motility, proliferation, migration and phenotype. Prior to this work, it was not understood how sphingolipid metabolism contributes to vascular inflammation in sickle cell disease. Together, this body of work has elucidated key enzymatic and lipidomic alterations in sphingolipid metabolism (i.e. the activation of acid sphingomyelinase on red blood cells) that result in the production of sphingolipid-rich erythrocyte-derived microparticles, which enhance inflammatory cell activation. Our work has elucidated novel pharmacological targets to reduce microparticle generation and subsequent vascular inflammation in sickle cell disease.
Advisors/Committee Members: Botchwey, Edward A. (advisor), Gibson, Greg (committee member), Barabino, Gilda (committee member), Platt, Manu O. (committee member), Peirce-Cottler, Shayn M. (committee member).
Subjects/Keywords: Sickle cell disease; Inflammation; Sphingolipid; Microparticles
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APA (6th Edition):
Awojoodu, A. O. (2014). Sphingolipid dysregulation in erythrocytes during sickle cell disease contributes to pro-inflammatory microparticle generation and subsequent inflammatory cell activation. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/54286
Chicago Manual of Style (16th Edition):
Awojoodu, Anthony O. “Sphingolipid dysregulation in erythrocytes during sickle cell disease contributes to pro-inflammatory microparticle generation and subsequent inflammatory cell activation.” 2014. Doctoral Dissertation, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/54286.
MLA Handbook (7th Edition):
Awojoodu, Anthony O. “Sphingolipid dysregulation in erythrocytes during sickle cell disease contributes to pro-inflammatory microparticle generation and subsequent inflammatory cell activation.” 2014. Web. 13 Apr 2021.
Vancouver:
Awojoodu AO. Sphingolipid dysregulation in erythrocytes during sickle cell disease contributes to pro-inflammatory microparticle generation and subsequent inflammatory cell activation. [Internet] [Doctoral dissertation]. Georgia Tech; 2014. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/54286.
Council of Science Editors:
Awojoodu AO. Sphingolipid dysregulation in erythrocytes during sickle cell disease contributes to pro-inflammatory microparticle generation and subsequent inflammatory cell activation. [Doctoral Dissertation]. Georgia Tech; 2014. Available from: http://hdl.handle.net/1853/54286
3.
Para, Andrea N.
Preventing rapid platelet accumulation under very high shear stress.
Degree: PhD, Mechanical Engineering, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/44726
► Atherosclerosis is a major cause of mortality in industrialized nations. Atherosclerosis is characterized by plaque deposition which decreases the lumen diameter into a stenosis. The…
(more)
▼ Atherosclerosis is a major cause of mortality in industrialized nations. Atherosclerosis is characterized by plaque deposition which decreases the lumen diameter into a stenosis. The creation of a restriction increases shear rates pathologic levels exceeding 3,500/s. Following plaque cap rupture, thrombus may form from the accumulation of millions of platelets, occluding the vessel, leading to heart attack and stroke. Studies of high shear thrombosis show that platelet activation, GPIIb/IIIa and vWF are involved. However, some recent studies also suggest that high shear aggregation is not dependent on activation or GPIIb/IIIa. Several antiplatelet pharmaceuticals against activation
and GPIIb/IIIa have been proposed, but their efficacy in patients remains mixed. The overall
objective of this project is to determine the factors necessary for thrombosis to occlusion in very high shear regions seen in diseased arteries. Our central hypotheses are that platelet activation and the subsequent conformational change in GPIIb/IIIa are
necessary for thrombosis, and that higher concentrations of vWF in the plasma will
increase thrombosis.
To this end, we developed a new high shear hemodynamic model utilizing 30mLs of whole blood and quantified thrombus thickness, volume accumulation and accumulation rates. We demonstrate that thrombosis to occlusion stems from a second phase of Rapid Platelet Accumulation (RPA). Thrombus accumulation is completely prevented by PGE1 inhibition of platelet activation. Similarly, GPIIb/IIIa blockade via abciximab prevented significant thrombus deposition and RPA. We also found that
increasing plasma vWF levels in high shear regions increased thrombus thickness and
suggestively increased RPA rates. The results clarify the need for activation of mural
platelets for long term thrombus accumulation without the activation of circulating platelets.
Advisors/Committee Members: Ku, David (Committee Chair), Barabino, Gilda (Committee Member), Deckmyn, Hans (Committee Member), Meeks, Shannon (Committee Member), Sulchek, Todd (Committee Member).
Subjects/Keywords: Atherosclerosis; Thrombosis; Platelet activation; Rapid platelet accumulation; Shear stress; Blood platelets Aggregation; Shear (Mechanics)
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APA (6th Edition):
Para, A. N. (2012). Preventing rapid platelet accumulation under very high shear stress. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/44726
Chicago Manual of Style (16th Edition):
Para, Andrea N. “Preventing rapid platelet accumulation under very high shear stress.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/44726.
MLA Handbook (7th Edition):
Para, Andrea N. “Preventing rapid platelet accumulation under very high shear stress.” 2012. Web. 13 Apr 2021.
Vancouver:
Para AN. Preventing rapid platelet accumulation under very high shear stress. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/44726.
Council of Science Editors:
Para AN. Preventing rapid platelet accumulation under very high shear stress. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/44726
4.
Sargent, Carolyn Yeago.
Effects of hydrodynamic culture on embryonic stem cell differentiation: cardiogenic modulation.
Degree: PhD, Biomedical Engineering, 2010, Georgia Tech
URL: http://hdl.handle.net/1853/34710
► Stem and progenitor cells are an attractive cell source for the treatment of degenerative diseases due to their potential to differentiate into multiple cell types…
(more)
▼ Stem and progenitor cells are an attractive cell source for the treatment of degenerative diseases due to their potential to differentiate into multiple cell types and provide large cell yields. Thus far, however, clinical applications have been limited due to inefficient differentiation into desired cell types with sufficient yields for adequate tissue repair and regeneration. The ability to spontaneously aggregate in suspension makes embryonic stem cells (ESCs) amenable to large-scale culture techniques for the production of large yields of differentiating cell spheroids (termed embryoid bodies or EBs); however, the introduction of hydrodynamic conditions may alter differentiation profiles within EBs and should be methodically examined. The work presented here employs a novel, laboratory-scale hydrodynamic culture model to systematically interrogate the effects of ESC culture hydrodynamics on cardiomyocyte differentiation through the modulation of a developmentally-relevant signaling pathway. The fluidic environment was defined using computational fluid dynamic modeling, and the effects of hydrodynamic conditions on EB formation, morphology and structure were assessed. Additionally, EB differentiation was examined through gene and protein expression, and indicated that hydrodynamic conditions modulate differentiation patterns, particularly cardiogenic lineage development. This work illustrates that mixing conditions can modulate common signaling pathways active in ESC differentiation and suggests that differentiation may be regulated via bioprocessing parameters and bioreactor design.
Advisors/Committee Members: McDevitt, Todd (Committee Chair), Anderson, Leonard (Committee Member), Barabino, Gilda (Committee Member), Jo, Hanjoong (Committee Member), Yoganathan, Ajit (Committee Member).
Subjects/Keywords: Embryonic stem cells; Embryoid body; Hydrodynamic; Bioprocessing; Differentiation; Cardiomyocyte; Heart cells; Degeneration (Pathology); Hydrodynamics; Embryonic stem cells Research
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APA (6th Edition):
Sargent, C. Y. (2010). Effects of hydrodynamic culture on embryonic stem cell differentiation: cardiogenic modulation. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/34710
Chicago Manual of Style (16th Edition):
Sargent, Carolyn Yeago. “Effects of hydrodynamic culture on embryonic stem cell differentiation: cardiogenic modulation.” 2010. Doctoral Dissertation, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/34710.
MLA Handbook (7th Edition):
Sargent, Carolyn Yeago. “Effects of hydrodynamic culture on embryonic stem cell differentiation: cardiogenic modulation.” 2010. Web. 13 Apr 2021.
Vancouver:
Sargent CY. Effects of hydrodynamic culture on embryonic stem cell differentiation: cardiogenic modulation. [Internet] [Doctoral dissertation]. Georgia Tech; 2010. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/34710.
Council of Science Editors:
Sargent CY. Effects of hydrodynamic culture on embryonic stem cell differentiation: cardiogenic modulation. [Doctoral Dissertation]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/34710
Georgia Tech
5.
Goldman, Stephen M.
Development and validation of a microfluidic hydrogel platform for osteochondral tissue engineering.
Degree: PhD, Mechanical Engineering, 2014, Georgia Tech
URL: http://hdl.handle.net/1853/54295
► Due to the inability of intra-articular injuries to adequately self-heal, current therapies are largely focused on palliative care and restoration of joint function rather than…
(more)
▼ Due to the inability of intra-articular injuries to adequately self-heal, current therapies are largely focused on palliative care and restoration of joint function rather than true regeneration. Subsequently tissue engineering of chondral and osteochondral tissue constructs has emerged as a promising strategy for the repair of partial and full-thickness intra-articular defects. Unfortunately, the fabrication of large tissue constructs is plagued by poor nutrient transport to the interior of the tissue resulting in poor tissue growth and necrosis. Further, for the specific case of osteochondral grafts, the presence of two distinct tissue types offers additional challenges related to cell sourcing, scaffolding strategies, and bioprocessing. To overcome these constraints, this dissertation was focused on the development and validation of a microfluidic hydrogel platform which reduces nutrient transport limitations within an engineered tissue construct through a serpentine microfluidic network embedded within the developing tissue. To this end, a microfluidic hydrogel was designed to meet the nutrition requirements of a developing tissue and validated through the cultivation of chondral tissue constructs of clinically relevant thicknesses. Additionally, optimal bioprocessing conditions with respect to morphogen delivery and hydrodynamic loading were pursued for the production of bony and cartilaginous tissue from bone marrow derived mesenchymal stem cells. Finally, the optimal bioprocessing conditions were implemented within MSC laden microfluidic hydrogels to spatially engineer the matrix composition of a biphasic osteochondral graft through directed differentiation.
Advisors/Committee Members: Barabino, Gilda A. (advisor), Sambanis, Athanassios (committee member), Botchwey, Edward A. (committee member), Guldberg, Robert E. (committee member), Karas, Spero G. (committee member), Temenoff, Johnna S. (committee member).
Subjects/Keywords: Osteochondral tissue engineering; Microfluidic hydrogels
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APA (6th Edition):
Goldman, S. M. (2014). Development and validation of a microfluidic hydrogel platform for osteochondral tissue engineering. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/54295
Chicago Manual of Style (16th Edition):
Goldman, Stephen M. “Development and validation of a microfluidic hydrogel platform for osteochondral tissue engineering.” 2014. Doctoral Dissertation, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/54295.
MLA Handbook (7th Edition):
Goldman, Stephen M. “Development and validation of a microfluidic hydrogel platform for osteochondral tissue engineering.” 2014. Web. 13 Apr 2021.
Vancouver:
Goldman SM. Development and validation of a microfluidic hydrogel platform for osteochondral tissue engineering. [Internet] [Doctoral dissertation]. Georgia Tech; 2014. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/54295.
Council of Science Editors:
Goldman SM. Development and validation of a microfluidic hydrogel platform for osteochondral tissue engineering. [Doctoral Dissertation]. Georgia Tech; 2014. Available from: http://hdl.handle.net/1853/54295
6.
Yang, Yueh-Hsun.
Development of hydrodynamically engineered cartilage in response to insulin-like growth factor-1 and transforming growth factor-beta1: formation and role of a type I collagen-based fibrous capsule.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2013, Georgia Tech
URL: http://hdl.handle.net/1853/49072
► Articular cartilage which covers the surfaces of synovial joints is designed to allow smooth contact between long bones and to absorb shock induced during joint…
(more)
▼ Articular cartilage which covers the surfaces of synovial joints is designed to allow smooth contact between long bones and to absorb shock induced during joint movement. Tissue engineering, a means of combining cells, biomaterials, bioreactors and bioactive agents to produce functional tissue replacements suitable for implantation, represents a potential long-term strategy for cartilage repair. The interplay between environmental factors, however, gives rise to complex culture conditions that influence the development of tissue-engineered constructs. A fibrous capsule that is composed of abundant type I collagen molecules and resembles fibrocartilage usually forms at the outer edge of neocartilage, yet the understanding of its modulation by environmental cues is still limited. Therefore, this dissertation was aimed to characterize the capsule formation, development and function through manipulation of biochemical parameters present in a hydrodynamic environment while a chemically reliable media preparation protocol for hydrodynamic cultivation of tissue-engineered cartilage was established. To this end, a novel wavy-wall bioreactor (WWB) that imparts turbulent flow-induced shear stress was employed as the model system and polyglycolic acid scaffolds seeded with bovine primary chondrocytes were cultivated under varied biochemical conditions.
The results demonstrated that tissue morphology, biochemical composition and mechanical strength of hydrodynamically engineered cartilage were maintained as the serum content decreased by 80% (from 10% to 2%). Transient exposure of the low-serum constructs to exogenous insulin-like growth factor-1 (IGF-1) or transforming growth factor-β1 (TGF-β1) further accelerated their development in comparison with continuous treatment with the same bioactive molecules. The process of the capsule formation was found to be activated and modulated by the concentration of serum which contains soluble factors that are able to induce fibrotic processes and the capsule development was further promoted by fluid shear stress. Moreover, the capsule formation in hydrodynamic cultures was identified as a potential biphasic process in response to concentrations of fibrosis-promoting molecules such as TGF-β. Comparison between the capsule-containing and the capsule-free constructs, both of which had comparable tissue properties and were produced by utilizing the WWB system in combination with IGF-1 and TGF-β1, respectively, showed that the presence of the fibrous capsule at the construct periphery effectively improved the ability of engineered cartilage to integrate with native cartilage tissues, but evidently compromised its tissue homogeneity.
Characterization of the fibrous capsule and elucidation of the conditions under which it is formed provide important insights for the development of tissue engineering strategies to fabricate clinically relevant cartilage tissue replacements that possess optimized tissue homogeneity and properties while retaining a minimal capsule thickness required to…
Advisors/Committee Members: Barabino, Gilda A. (advisor), Halper, Jaroslava (committee member), Eskin, Suzanne G. (committee member), Guldberg, Robert E. (committee member), McDevitt, Todd C. (committee member).
Subjects/Keywords: Cartilage tissue engineering; Fibrous capsule; Hydrodynamic; Wavy-walled bioreactor; Insulin-like growth factor-1; Transforming growth factor-beta1; Articular cartilege; Tissue engineering
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APA (6th Edition):
Yang, Y. (2013). Development of hydrodynamically engineered cartilage in response to insulin-like growth factor-1 and transforming growth factor-beta1: formation and role of a type I collagen-based fibrous capsule. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/49072
Chicago Manual of Style (16th Edition):
Yang, Yueh-Hsun. “Development of hydrodynamically engineered cartilage in response to insulin-like growth factor-1 and transforming growth factor-beta1: formation and role of a type I collagen-based fibrous capsule.” 2013. Doctoral Dissertation, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/49072.
MLA Handbook (7th Edition):
Yang, Yueh-Hsun. “Development of hydrodynamically engineered cartilage in response to insulin-like growth factor-1 and transforming growth factor-beta1: formation and role of a type I collagen-based fibrous capsule.” 2013. Web. 13 Apr 2021.
Vancouver:
Yang Y. Development of hydrodynamically engineered cartilage in response to insulin-like growth factor-1 and transforming growth factor-beta1: formation and role of a type I collagen-based fibrous capsule. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/49072.
Council of Science Editors:
Yang Y. Development of hydrodynamically engineered cartilage in response to insulin-like growth factor-1 and transforming growth factor-beta1: formation and role of a type I collagen-based fibrous capsule. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/49072
7.
Banton, Shereka.
Human peripheral reticulocyte isolation and exosome release in vitro.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2017, Georgia Tech
URL: http://hdl.handle.net/1853/58256
► The exosomes released by peripheral reticulocytes were originally thought to function as vehicles for protein clearance for the maturing cells. With the emergence of exosomes…
(more)
▼ The exosomes released by peripheral reticulocytes were originally thought to function as vehicles for protein clearance for the maturing cells. With the emergence of exosomes as mediators of intercellular communication, a new paradigm exists for the role of reticulocyte-derived exosomes in both healthy and disease states, particularly conditions whose pathology is driven by the red blood cell and its precursors. However, no standard or detailed method for the isolation of human peripheral CD71+ reticulocytes exists. A combination of density-dependent and immunomagnetic approaches was used to demonstrate a procedure to isolate human CD71+ reticulocytes from peripheral blood. Nearly 90% of the CD71+ cells were distinct from the CD71- population when measured with flow cytometry detection of RNA. CD71+ reticulocyte-derived exosomes were then isolated and analyzed after incubation in vitro, the first such demonstration of these phenomena using these cells. These findings form the basis for more targeted and mechanistic studies into the role of reticulocyte-derived exosomes in pathologies like sickle cell disease.
Advisors/Committee Members: Barabino, Gilda (advisor), Davis, Michael (advisor), Santangelo, Philip (committee member), Lam, Wilbur (committee member), Pace, Betty (committee member), Kutlar, Abdullah (committee member), Taite, Lakeshia (committee member).
Subjects/Keywords: Reticulocytes; Exosomes
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APA (6th Edition):
Banton, S. (2017). Human peripheral reticulocyte isolation and exosome release in vitro. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58256
Chicago Manual of Style (16th Edition):
Banton, Shereka. “Human peripheral reticulocyte isolation and exosome release in vitro.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/58256.
MLA Handbook (7th Edition):
Banton, Shereka. “Human peripheral reticulocyte isolation and exosome release in vitro.” 2017. Web. 13 Apr 2021.
Vancouver:
Banton S. Human peripheral reticulocyte isolation and exosome release in vitro. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/58256.
Council of Science Editors:
Banton S. Human peripheral reticulocyte isolation and exosome release in vitro. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/58256
8.
Hovell, Candice Megan.
Development of a novel In vitro blood brain barrier model for the evaluation of nanomedicines.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2017, Georgia Tech
URL: http://hdl.handle.net/1853/60667
► In this work, we present a novel microfluidic lumen system of the BBB (MLS-BBB) for the evaluation of multifunctional nanomedicines engineered for the treatment of…
(more)
▼ In this work, we present a novel microfluidic lumen system of the BBB (MLS-BBB) for the evaluation of multifunctional nanomedicines engineered for the treatment of medulloblastoma. Our MLS-BBB is designed to co-culture human astrocytes (HA) and human brain vascular pericytes (HBVP) around a cylindrical lumen of human brain microvascular endothelial cells (HBMEC) within a 3D hydrogel system tuned to mimic the properties of brain extracellular matrix (ECM). Our MLS-BBB facilitates the administration of tunable shear rates to a lumen of endothelial cells in direct contact with supporting astrocyte and pericyte cells within a hydrogel system optimized to facilitate the appropriate culture of astrocytes, and is to our knowledge, the first model to do so. We employed high throughput qPCR techniques to simultaneously analyze expression of 85 BBB relevant endothelial specializations such as junctional proteins (ZO-1, Claudins, JAMs, etc.), specialized transporters (GLUT-1, CAT1, TfR, etc.) and drug resistant proteins (PgP, ABCC1, ABCC4, etc.). Our results indicate that our system provides a marked increase in physiological relevance relative to transwell culture systems. Our model was further validated through comparison to BBB spheroids, by examination of model response to perturbations of the optimized ECM composition, and examination of response to the administration of TNFα, an inflammatory cytokine. Our model is currently being employed in parallel with traditional transwell systems and ex vivo brain slice cultures in the preliminary evaluation of a novel nanomedicine designed for the treatment of sonic hedgehog driven (SSH) medulloblastoma to evaluate its functional utility in such studies. The ultimate goal of organ-on-a-chip model development is eventual adaptation by the community for preclinical assessment of novel drug compounds. While our MLS-BBB could be improved in several ways, including modification to a high throughout design, by combining comprehensive characterization with an assessment of functional utility relative to standard in vitro controls, we believe our work constitutes a significant step towards the realization of this goal.
Advisors/Committee Members: Kim, YongTae (advisor), Taite, Lakeshia (advisor), Barabino, Gilda (advisor), Dixon, Brandon (advisor), Lu, Hang (advisor), Botchwey, Edward (advisor), Vazquez, Maribel (advisor).
Subjects/Keywords: Blood brain barrier; Organ on a chip
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APA (6th Edition):
Hovell, C. M. (2017). Development of a novel In vitro blood brain barrier model for the evaluation of nanomedicines. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60667
Chicago Manual of Style (16th Edition):
Hovell, Candice Megan. “Development of a novel In vitro blood brain barrier model for the evaluation of nanomedicines.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/60667.
MLA Handbook (7th Edition):
Hovell, Candice Megan. “Development of a novel In vitro blood brain barrier model for the evaluation of nanomedicines.” 2017. Web. 13 Apr 2021.
Vancouver:
Hovell CM. Development of a novel In vitro blood brain barrier model for the evaluation of nanomedicines. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/60667.
Council of Science Editors:
Hovell CM. Development of a novel In vitro blood brain barrier model for the evaluation of nanomedicines. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/60667
Georgia Tech
9.
Brown, Lola A.
The Effects of Sickle Erythrocytes on Endothelial Permeability.
Degree: MS, Biomedical Engineering, 2005, Georgia Tech
URL: http://hdl.handle.net/1853/6960
► Sickle cell anemia is a hematological disorder that is caused by a single point mutation in the beta-globin chain of hemoglobin. It results in several…
(more)
▼ Sickle cell anemia is a hematological disorder that is caused by a single point mutation in the beta-globin chain of hemoglobin. It results in several complications related to the small and large vessels in patients with the disease. Large vessel complications include cerebral infarcts, which are observed in children under ten years old. The mechanism behind this complication is not completely understood.
It is the goal of this project to begin to understand the role sickle erythrocytes may play in causing endothelial dysfunction as a precursor to sickle related complications. The hypothesis of this work is that exposure of large vessel endothelium to sickle erythrocytes causes an increase in endothelial permeability through loosening of adherens junctions.
In the first goal of this work, bovine aortic endothelial cells (BAECs) are grown on coverslips and exposed to sickle erythrocytes for 5 minutes and either immediately fixed or incubated in 30 minutes and then fixed. Immunofluorescent studies labeling VE cadherin show changes in VE cadherin dynamics, suggesting sickle erythrocytes may be involved in this observation.
Next, BAECs were grown on transwell inserts and exposed to sickle erythrocytes for 5 minutes. The erythrocytes are washed off and the BAEC are incubated with 10,000 MW dextran conjugated to lucifer yellow or FITC-BSA or to determine BAEC permeability. When dextran is used as the test molecule, endothelial permeability did not show a significant change from baseline. However, when BSA is used as the test molecule, increases in endothelial permeability are observed. Explanations into the differences between the transport mechanisms of the two molecules are discussed.
These experiments show changes in VE cadherin localization due to sickle erythrocyte exposure. This may cause increases in endothelial permeability and an experimental model and preliminary studies are performed. This study provides potential mechanisms to explain the changes in VE cadherin localization and provide suggestions for further studies to test the effect of sickle erythrocytes on endothelial permeability. This work provides a strong foundation for continuing studies on the effects of sickle erythrocytes on endothelial dysfunction within the confines of sickle related complications.
Advisors/Committee Members: Wick, Timothy (Committee Chair), Barabino, Gilda (Committee Co-Chair), Eckman, James (Committee Member), Nerem, Robert (Committee Member).
Subjects/Keywords: Permeability coefficient; VE cadherin; Stroke; Endothelial cells; Sickle cell anemia
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APA (6th Edition):
Brown, L. A. (2005). The Effects of Sickle Erythrocytes on Endothelial Permeability. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/6960
Chicago Manual of Style (16th Edition):
Brown, Lola A. “The Effects of Sickle Erythrocytes on Endothelial Permeability.” 2005. Masters Thesis, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/6960.
MLA Handbook (7th Edition):
Brown, Lola A. “The Effects of Sickle Erythrocytes on Endothelial Permeability.” 2005. Web. 13 Apr 2021.
Vancouver:
Brown LA. The Effects of Sickle Erythrocytes on Endothelial Permeability. [Internet] [Masters thesis]. Georgia Tech; 2005. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/6960.
Council of Science Editors:
Brown LA. The Effects of Sickle Erythrocytes on Endothelial Permeability. [Masters Thesis]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/6960
. 
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