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1.
Ravi, Swathi.
Recombinant elastin analogues as cell-adhesive matrices for vascular tissue engineering.
Degree: PhD, Biomedical Engineering, 2010, Georgia Tech
URL: http://hdl.handle.net/1853/42728 
► Biomimetic materials that recapitulate the complex mechanical and biochemical cues in load-bearing tissues are of significant interest in regenerative medicine and tissue engineering applications. Several…
(more)
▼ Biomimetic materials that recapitulate the complex mechanical and biochemical cues in load-bearing tissues are of significant interest in regenerative medicine and tissue engineering applications. Several investigators have endeavored to not only emulate the mechanical properties of the vasculature, but to also mimic the biologic responsiveness of the blood vessel in creating vascular substitutes. Previous studies in our lab generated the elastin-like protein polymer LysB10, which was designed with the capability of physical and chemical crosslinks, and was shown to display a range of elastomeric properties that more closely matched those of the native artery. While extensive validation of the mechanical properties of elastin-mimetic polymers has demonstrated their functionality in a number of tissue engineering applications, limited cell growth on the surfaces of the polymers has motivated further optimization for biological interaction. Recent biologically-inspired surface strategies have focused on functionalizing material surfaces with extracellular matrix molecules and bioactive motifs in order to encourage integrin-mediated cellular responses that trigger precise intracellular signaling processes, while limiting nonspecific biomaterial interactions. Consequently, this dissertation addresses three approaches to modulating cellular behavior on elastin-mimetic analogs with the goal of promoting vascular wall healing and tissue regeneration: genetic engineering of elastin-like protein polymers (ELPs) with cell-binding domains, biofunctionalization of elastin-like protein polymers via chemoselective ligation of bioactive ligands, and incorporation of matrix protein fibronectin for engineering of cell-seeded multilamellar collagen-reinforced elastin-like constructs.
The synthesis of recombinant elastin-like protein polymers that integrate biologic functions of the extracellular matrix provides a novel design strategy for generating clinically durable vascular substitutes. Ultimately, the synthesis of model protein networks provides new insights into the relationship between molecular architecture, biomimetic ligand presentation, and associated cellular responses at the cell-material interface. Understanding how each of these design parameters affects cell response will contribute significantly to the rational engineering of bioactive materials. Potential applications for polymer blends with enhanced mechanical and biological properties include surface coatings on vascular grafts and stents, as well as composite materials for tissue engineered scaffolds and vascular substitutes.
Advisors/Committee Members: Chaikof, Elliot L. (Committee Chair).
Subjects/Keywords: Surface modification; Vascular tissue engineering; Biomaterials; Polypeptides; Elastin like protein polymers; Recombinant proteins; Regenerative medicine; Biomedical materials; Vascular grafts; Tissue engineering; Implants, Artificial; Polymers in medicine
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APA (6th Edition):
Ravi, S. (2010). Recombinant elastin analogues as cell-adhesive matrices for vascular tissue engineering. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/42728
Chicago Manual of Style (16th Edition):
Ravi, Swathi. “Recombinant elastin analogues as cell-adhesive matrices for vascular tissue engineering.” 2010. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/42728.
MLA Handbook (7th Edition):
Ravi, Swathi. “Recombinant elastin analogues as cell-adhesive matrices for vascular tissue engineering.” 2010. Web. 03 Mar 2021.
Vancouver:
Ravi S. Recombinant elastin analogues as cell-adhesive matrices for vascular tissue engineering. [Internet] [Doctoral dissertation]. Georgia Tech; 2010. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/42728.
Council of Science Editors:
Ravi S. Recombinant elastin analogues as cell-adhesive matrices for vascular tissue engineering. [Doctoral Dissertation]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/42728
2.
Balderrama, Fanor Alberto.
Incorporation of recombinant fibronectin into genetically engineered elastin-based polymers.
Degree: MS, Bioengineering, 2009, Georgia Tech
URL: http://hdl.handle.net/1853/31640
► Cardiovascular disease is the main cause of death in the United States. Many of these conditions require the grafting or bypassing of compromised blood vessels.…
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▼ Cardiovascular disease is the main cause of death in the United States. Many of these conditions require the grafting or bypassing of compromised blood vessels. To this effect, biological vascular grafts (autografts and allografts) are the first line of action. However, when the patient lacks vasculature suitable for grafting use, several synthetic grafting options are available. The search for an inert biomaterial for vascular grafts has proven to be unsuccessful. This makes the interaction taking place on the blood-biomaterial interface critical for the success of the grafts.
This thesis introduces a new bio-inspired approach to tackle the mechanical and biological challenges of vascular material design. The hypothesis of this research is that recombinant fibronectin protein can be stably incorporated onto elastin-mimetic polymers to increase endothelialization. Recombinant elastin, designed to recreate the mechanical properties of natural elastin as a candidate material for vascular graft fabrication, was used as a model surface.
Recombinant fibronectin-functionalized elastin-mimetic polymer displayed significant improvement in cell adhesion. Quantification of surface bound recombinant fibronectin verified the concentration dependence of this cell adhesive behavior. Modified elastin-mimetic polymer also demonstrated an enhanced ability to support endothelial cell proliferation. Furthermore, the stability of recombinant fibronectin-modified polymers was assessed. These studies provide the foundation for fabricating elastin-mimetic vascular grafts with improved endothelialization and subsequent biological performance.
Advisors/Committee Members: Chaikof, Elliot (Committee Chair), Conticello, Vincent (Committee Member), Jo, Hanjoong (Committee Member).
Subjects/Keywords: Functionalization; Coating; Protein; Crosslinking; Genipin; HUVEC; Stability; Cell proliferation; Vascular graft; Elastin; FNIII7-10; Cell adhesion; Endothelialization; Endothelial; Fibronectins; Globulins; Biomedical materials; Vascular grafts
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APA (6th Edition):
Balderrama, F. A. (2009). Incorporation of recombinant fibronectin into genetically engineered elastin-based polymers. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/31640
Chicago Manual of Style (16th Edition):
Balderrama, Fanor Alberto. “Incorporation of recombinant fibronectin into genetically engineered elastin-based polymers.” 2009. Masters Thesis, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/31640.
MLA Handbook (7th Edition):
Balderrama, Fanor Alberto. “Incorporation of recombinant fibronectin into genetically engineered elastin-based polymers.” 2009. Web. 03 Mar 2021.
Vancouver:
Balderrama FA. Incorporation of recombinant fibronectin into genetically engineered elastin-based polymers. [Internet] [Masters thesis]. Georgia Tech; 2009. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/31640.
Council of Science Editors:
Balderrama FA. Incorporation of recombinant fibronectin into genetically engineered elastin-based polymers. [Masters Thesis]. Georgia Tech; 2009. Available from: http://hdl.handle.net/1853/31640
Georgia Tech
3.
Kumar, Vivek Ashok.
Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials.
Degree: PhD, Biomedical Engineering, 2011, Georgia Tech
URL: http://hdl.handle.net/1853/45869
► For small diameter (<6 mm) blood vessel replacements, lack of collaterals and vascular disease preclude homografts; while synthetic analogs, ePTFE, expanded polytetrafluoroethylene, and PET, polyethyleneterephathalate,…
(more)
▼ For small diameter (<6 mm) blood vessel replacements, lack of collaterals and vascular disease preclude homografts; while synthetic analogs, ePTFE, expanded polytetrafluoroethylene, and PET, polyethyleneterephathalate, are prone to acute thrombosis and restenosis. It is postulated that the hierarchical assembly of cell populated matrices fabricated from protein analogs provides a new design strategy for generating a structurally viable tissue engineered vascular graft. To this end, synthetic elastin and collagen fiber analogs offer a novel strategy for creating tissue engineered vascular grafts with mechanical and biological properties that match or exceed those of native vessels. This work details techniques developed for the fabrication of prosthetic vascular grafts from a series of extracellular matrix analogs composed of nanofibrous collagen matrices and elastin-mimetic proteins, with and without cells, and subsequent evaluation of their biocompatibility and mechanical properties. The work details the fabrication and mechanical analysis of vascular grafts made from aforementioned protein analogs. Subesequent studies detail seeding and proliferation of rodent mesenchymal stem cells on protein-based composites to recapitulate the media of native vasculature. Finally detailing in vivo biocompatibility and stability of tissue engineered vascular grafts.
Advisors/Committee Members: Chaikof, Elliot (Committee Chair), Allen, Mark (Committee Member), Gleason, Rudolph (Committee Member), Nerem, Robert (Committee Member), Stice, Steve (Committee Member).
Subjects/Keywords: Rat aortic interposition; Rat tail tendon; Vascular; Elastin; Collagen; Soft tissue; Blood vessels; Tissue engineering; Regenerative medicine; Arterial grafts; Tissue scaffolds
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APA (6th Edition):
Kumar, V. A. (2011). Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45869
Chicago Manual of Style (16th Edition):
Kumar, Vivek Ashok. “Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials.” 2011. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/45869.
MLA Handbook (7th Edition):
Kumar, Vivek Ashok. “Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials.” 2011. Web. 03 Mar 2021.
Vancouver:
Kumar VA. Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/45869.
Council of Science Editors:
Kumar VA. Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/45869
Georgia Tech
4.
Soon, Allyson Shook Ching.
Exploiting fibrin knob:hole interactions for the control of fibrin polymerization.
Degree: PhD, Biomedical Engineering, 2011, Georgia Tech
URL: http://hdl.handle.net/1853/45917
► The minimization of blood loss represents a significant clinical need in the arena of surgery, trauma, and emergency response medicine. Fibrinogen is our body's native…
(more)
▼ The minimization of blood loss represents a significant clinical need in the arena of surgery, trauma, and emergency response medicine. Fibrinogen is our body's native polymer system activated in response to tissue and vasculature injury, and forms the foundation of the most widely employed surgical sealant and hemostatic agent. Non-covalent knob:hole interactions are central to the assembly of fibrin that leads to network and clot formation. This project exploits these affinity interactions as a strategy to direct fibrin polymerization dynamics and network structure so as to develop a temperature-triggered polymerizing fibrin mixture for surgical applications.
Short peptides modeled after fibrin knob sequences have been shown to alter fibrin matrix structure by competing with native fibrin knobs for binding to the available holes on fibrinogen and fibrin. The fusion of such knob peptides to a non-native component should facilitate binding of the fused component to fibrinogen/fibrin, and may permit the concomitant modification of the fibrin matrix. We examined this hypothesis in a three-step approach involving (a) analyzing the ability of tetrapeptide knob sequences to confer fibrin(ogen) affinity on a non-fibrin protein, (b) investigating the effect of knob display architecture on fibrin(ogen) structure, and (c) designing a temperature-responsive knob-displaying construct to modulate fibrin(ogen) affinity at different temperature regimes, thus altering fibrin(ogen) structure.
Advisors/Committee Members: Barker, Thomas (Committee Chair), Chaikof, Elliot (Committee Member), Collier, Joel (Committee Member), Lyon, Andrew (Committee Member), Temenoff, Johnna (Committee Member).
Subjects/Keywords: Protein; Self-assembling; Polyethylene glycol; Fibrinogen; Elastin; Hematologic agents; Hemostatics; Hemorrhage; Proteins; Protein binding; Biomolecules
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APA (6th Edition):
Soon, A. S. C. (2011). Exploiting fibrin knob:hole interactions for the control of fibrin polymerization. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45917
Chicago Manual of Style (16th Edition):
Soon, Allyson Shook Ching. “Exploiting fibrin knob:hole interactions for the control of fibrin polymerization.” 2011. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/45917.
MLA Handbook (7th Edition):
Soon, Allyson Shook Ching. “Exploiting fibrin knob:hole interactions for the control of fibrin polymerization.” 2011. Web. 03 Mar 2021.
Vancouver:
Soon ASC. Exploiting fibrin knob:hole interactions for the control of fibrin polymerization. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/45917.
Council of Science Editors:
Soon ASC. Exploiting fibrin knob:hole interactions for the control of fibrin polymerization. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/45917
5.
Patel, Dhaval Pradipkumar.
Novel PEG-elastin copolymer for tissue engineered vascular grafts.
Degree: PhD, Chemical Engineering, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/45811
► The growing incidences of coronary artery bypass graft surgeries have triggered a need to engineer a viable small diameter blood vessel substitute. An ideal tissue…
(more)
▼ The growing incidences of coronary artery bypass graft surgeries have triggered a need to engineer a viable small diameter blood vessel substitute. An ideal tissue engineered vascular graft should mimic the microenvironment of a native blood vessel, while providing the adequate compliance post-implantation. Current vascular graft technologies lack the ability to promote vascular ECM deposition, leading to a compliance mismatch and ultimately, graft failure. Hence, in order to engineer suitable vascular grafts, this thesis describes the synthesis and characterization of novel elastin mimetic peptides, EM-19 and EM-23, capable of promoting vascular ECM deposition within a poly(ethylene glycol) diacrylate (PEG-DA) hydrogel. By combining the material properties of a synthetic and bio-inspired polymer, a suitable microenvironment for cell growth and ECM deposition can be engineered, leading to improved compliance.
As such, characterization of EM-19 and EM-23 was conducted in human vascular smooth muscle cell (SMC) cultures, and the peptides self-assembled with a growing elastic matrix. After grafting the peptides onto the surface of PEG-DA hydrogels, EM-23 increased SMC adhesion by 6000% over PEG-RGDS hydrogels, which have been the gold standard of cell adhesive PEG scaffolds. Moreover, EM-23 grafted surfaces were able to promote elastin deposition that was comparable to tissue cultured polystyrene (TCPS) surface even though TCPS had roughly 4.5 times more SMCs adhered. Once translated to a 3D model, EM-23 also stimulated increased elastin deposition and improved the mechanical strength of the scaffold over time. Moreover, degradation studies suggested that EM-23 may serve as a template that not only promotes ECM deposition, but also allows ECM remodeling over time. The characterization studies in this thesis suggest that this peptide is an extremely promising candidate for improving vascular ECM deposition within a synthetic substrate, and that it may be beneficial to incorporate EM-23 within polymeric scaffolds to engineer compliant vascular grafts.
Advisors/Committee Members: Taite, Lakeshia (Committee Chair), Chaikof, Elliot (Committee Member), Garcia, Andres (Committee Member), McIntire, Larry (Committee Member), Sambanis, Athanassios (Committee Member).
Subjects/Keywords: Extracellular matrix; Elastin; Peptides; Hydrogels; Tissue engineering; Biomedical engineering; Vascular grafts; Biopolymers; Synthetic biology; Bioengineering
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APA (6th Edition):
Patel, D. P. (2012). Novel PEG-elastin copolymer for tissue engineered vascular grafts. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45811
Chicago Manual of Style (16th Edition):
Patel, Dhaval Pradipkumar. “Novel PEG-elastin copolymer for tissue engineered vascular grafts.” 2012. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/45811.
MLA Handbook (7th Edition):
Patel, Dhaval Pradipkumar. “Novel PEG-elastin copolymer for tissue engineered vascular grafts.” 2012. Web. 03 Mar 2021.
Vancouver:
Patel DP. Novel PEG-elastin copolymer for tissue engineered vascular grafts. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/45811.
Council of Science Editors:
Patel DP. Novel PEG-elastin copolymer for tissue engineered vascular grafts. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/45811
6.
Jordan, Sumanas W.
A mathematical model of tissue factor-induced blood coagulation: discrete sites of initiation and regulation under conditions of flow.
Degree: PhD, Biomedical Engineering, 2010, Georgia Tech
URL: http://hdl.handle.net/1853/33907
► A mathematical model of blood coagulation under defined flow conditions, initiated and modulated by spatially discrete regions of surface bound tissue factor (TF) and thrombomodulin…
(more)
▼ A mathematical model of blood coagulation under defined flow conditions, initiated and modulated by spatially discrete regions of surface bound tissue factor (TF) and thrombomodulin (TM), respectively, is presented. The model incorporates fluid phase and surface-associated reactions of the extrinsic, intrinsic, and common pathways, as well as three inhibitory pathways. The spatially heterogeneous model is formulated by finite element method, and an effective prothrombotic zone, which quantifies the spatial propagation of thrombin generation is defined. Characteristic features of coagulation are simulated under physiologic conditions, and the behavior of the system in response to perturbations in TF and TM surface densities, TF site dimensions, and wall shear rate is explored. The major findings of these studies include: (i) The model system responds in an 'all-or-none', threshold-like manner to changes in model parameters. (ii) It was found that prothrombotic effects may extend significantly beyond the dimensions of the spatially discrete site of TF expression in both axial and radial directions. (iii) The relationship between the length of the effective prothrombotic zone and the interval distance between tandem sites of TF expression dictate the net response of the system. Additive prothrombotic effects of sub-clinical lesions as well as suppressive antithrombotic effects of intervening TM-containing regions were observed. Secondly, the computational model is applied to calculate an individualized, systems-based metric of clotting potential for 210 pre-menopausal women in the Leiden Thrombophilia Study (LETS). The simulated variable was found to be a highly predictive parameter for deep venous thrombosis risk.
Advisors/Committee Members: Chaikof, Elliot (Committee Chair), Federspiel, William (Committee Member), Hanson, Stephen (Committee Member), McIntire, Larry (Committee Member), Voit, Eberhard (Committee Member).
Subjects/Keywords: Protein C pathway; Tissue factor; DVT; APC; Thrombomodulin; FEM; Blood coagulation factors; Hemostatics; Thromboplastin; Thrombosis Diagnosis; Embolism
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APA (6th Edition):
Jordan, S. W. (2010). A mathematical model of tissue factor-induced blood coagulation: discrete sites of initiation and regulation under conditions of flow. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/33907
Chicago Manual of Style (16th Edition):
Jordan, Sumanas W. “A mathematical model of tissue factor-induced blood coagulation: discrete sites of initiation and regulation under conditions of flow.” 2010. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/33907.
MLA Handbook (7th Edition):
Jordan, Sumanas W. “A mathematical model of tissue factor-induced blood coagulation: discrete sites of initiation and regulation under conditions of flow.” 2010. Web. 03 Mar 2021.
Vancouver:
Jordan SW. A mathematical model of tissue factor-induced blood coagulation: discrete sites of initiation and regulation under conditions of flow. [Internet] [Doctoral dissertation]. Georgia Tech; 2010. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/33907.
Council of Science Editors:
Jordan SW. A mathematical model of tissue factor-induced blood coagulation: discrete sites of initiation and regulation under conditions of flow. [Doctoral Dissertation]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/33907
7.
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)
▼ 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 necessitates antithrombotic therapies that carry significant cost and bleeding risk. Thrombomodulin (TM) is a major endogenous inhibitor of blood coagulation localized on the endothelial cell surface. The overall objective of this research is to develop clinically durable synthetic materials by incorporating TM as a solid-supported film to actively and sustainably attenuate thrombus formation at the blood-contacting interface. During the course of this research, we developed site-specific approaches to covalently attach TM on the luminal surface of commercial vascular grafts using bioorthogonal chemistry that was compatible with ethylene oxide sterilization. Notably, we demonstrated the superior efficacy of TM to reduce platelet deposition compared with commercial heparin modified grafts using a non-human primate model of acute graft thrombosis. Finally, we optimized a novel reversible chemistry to rapidly and repeatedly regenerate immobilized TM, with the potential to significantly extend the lifetime of biologically active films.
Advisors/Committee Members: Chaikof, Elliot (advisor), Babensee, Julia (committee member), Hanson, Stephen (committee member), McIntire, Larry (committee member), Taylor, W. Robert (committee member).
Subjects/Keywords: Thrombomodulin; Medical devices; Thrombosis; Biomaterials; Blood compatibility; Biomedical materials; Implants, Artificial; Biomedical engineering; Blood coagulation factors
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APA ·
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APA (6th 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 (16th Edition):
Qu, Zheng. “Biologically active assemblies that attenuate thrombosis on blood-contacting surfaces.” 2012. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/50119.
MLA Handbook (7th Edition):
Qu, Zheng. “Biologically active assemblies that attenuate thrombosis on blood-contacting surfaces.” 2012. Web. 03 Mar 2021.
Vancouver:
Qu Z. Biologically active assemblies that attenuate thrombosis on blood-contacting surfaces. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Mar 03].
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
8.
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 (6th 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 (16th Edition):
Angsana, Julianty. “The role of syndecan-1 in the resolution of chronic inflammatory responses.” 2013. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/52947.
MLA Handbook (7th Edition):
Angsana, Julianty. “The role of syndecan-1 in the resolution of chronic inflammatory responses.” 2013. Web. 03 Mar 2021.
Vancouver:
Angsana J. The role of syndecan-1 in the resolution of chronic inflammatory responses. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Mar 03].
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
9.
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)
▼ 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 alone. Regenerating the myocardium of patients that survive the initial infarction has proven to be an elusive goal. A variety of factors - including the loss of contractile cells, inflammatory response following infarction, cardiac hypertrophy, and lack of suitable cues for progenitor cells - causes fibrosis in the heart and loss of cardiac function. This dissertation examines three drug delivery strategies aimed at improving conditions for cardiac regeneration: polyketal microspheres as non-inflammatory drug delivery vehicles; surface functionalization of microparticles with nitrilotriacetic acid-nickel (NTA-Ni) for non-covalent tethering of proteins; and using Hoechst-inspired ligands for targeting extracellular DNA in necrotic tissue.
Advisors/Committee Members: Davis, Michael (Committee Co-Chair), Murthy, Niren (Committee Co-Chair), Chaikof, Elliot (Committee Member), Griendling, Kathy (Committee Member), Jo, Hanjoong (Committee Member), Taylor, W. Robert (Committee Member).
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 (6th 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 (16th Edition):
Sy, Jay Christopher. “Novel strategies for cardiac drug delivery.” 2011. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/39531.
MLA Handbook (7th Edition):
Sy, Jay Christopher. “Novel strategies for cardiac drug delivery.” 2011. Web. 03 Mar 2021.
Vancouver:
Sy JC. Novel strategies for cardiac drug delivery. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Mar 03].
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
10.
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)
▼ 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 for small caliber grafts, there is a big push towards the use of engineered tissues to bypass diseased portions of arteries. Cardiovascular tissue engineering is the emerging discipline that aims to create a functional substitute. Ideally, a tissue engineered blood vessel would possess the relevant cells and matrix proteins that interact in a physiologic manner and will respond to the environmental cues of the host. A particular obstacle to achieving appropriate vessel structure is the inclusion of elastin in a tissue engineered media equivalent. Rat arterial smooth muscle cells that were retrovirally mediated to overexpress versican V3 have been shown to have an enhanced expression of tropoelastin in vitro as well as in injury models. The unique tropoelastin expression by these adult cells was studied in the context of tissue engineered media equivalents. Changes to the extracellular matrix architecture and composition, stimulation with medium additives, and cyclic distension, were shown to increase tropoelastin synthesis in V3 versican overexpressing cells. This study not only expanded the characterization of V3 versican overexpressing smooth muscle cells, it also explored the novel use of these cells as a tropoelastin source in a tissue engineered media equivalent.
Advisors/Committee Members: Nerem, Robert (Committee Chair), Chaikof, Elliot (Committee Member), Taylor, W. Robert (Committee Member), Vito, Raymond (Committee Member), Wight, Thomas (Committee Member).
Subjects/Keywords: Tissue engineering; Smooth muscle cells; Tropoelastin; Versican; Muscle cells; Tissue engineering; Blood vessel prosthesis; Elastin
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APA (6th 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 (16th 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 March 03, 2021.
http://hdl.handle.net/1853/22652.
MLA Handbook (7th 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. 03 Mar 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 Mar 03].
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
Georgia Tech
11.
Naik, Nisarga.
MEMS-based nozzles and templates for the fabrication of engineered tissue constructs.
Degree: PhD, Electrical and Computer Engineering, 2010, Georgia Tech
URL: http://hdl.handle.net/1853/42853
► This dissertation presents the application of MEMS-based approaches for the construction of engineered tissue substitutes. MEMS technology can offer the physical scale, resolution, and organization…
(more)
▼ This dissertation presents the application of MEMS-based approaches for the construction of engineered tissue substitutes. MEMS technology can offer the physical scale, resolution, and organization necessary for mimicking native tissue architecture. Micromachined nozzles and templates were explored for the fabrication of acellular, biomimetic collagenous fibrous scaffolds, microvascular tissue structures, and the combination of these structures with cell-based therapeutics. The influence of the microstructure of the tissue constructs on their macro-scale characteristics was investigated.
Advisors/Committee Members: Allen, Mark (Committee Chair), Bhatti, Pamela (Committee Member), Brand, Oliver (Committee Member), Chaikof, Elliot (Committee Member), Shamma, Jeff (Committee Member).
Subjects/Keywords: Microvascular scaffolds; Tissue scaffold; Collagen microfibers; MEMS; Micro/nanonozzles; Microelectromechanical systems; Tissue engineering; Microstructure
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APA (6th Edition):
Naik, N. (2010). MEMS-based nozzles and templates for the fabrication of engineered tissue constructs. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/42853
Chicago Manual of Style (16th Edition):
Naik, Nisarga. “MEMS-based nozzles and templates for the fabrication of engineered tissue constructs.” 2010. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/42853.
MLA Handbook (7th Edition):
Naik, Nisarga. “MEMS-based nozzles and templates for the fabrication of engineered tissue constructs.” 2010. Web. 03 Mar 2021.
Vancouver:
Naik N. MEMS-based nozzles and templates for the fabrication of engineered tissue constructs. [Internet] [Doctoral dissertation]. Georgia Tech; 2010. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/42853.
Council of Science Editors:
Naik N. MEMS-based nozzles and templates for the fabrication of engineered tissue constructs. [Doctoral Dissertation]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/42853
Georgia Tech
12.
Gross, Jeffrey David.
Non-invasive Monitoring of Oxygen Concentrations and Metabolic Function in Pancreatic Substitutes.
Degree: PhD, Biomedical Engineering, 2007, Georgia Tech
URL: http://hdl.handle.net/1853/14499
► Design and characterization of tissue engineered substitutes rely on robust monitoring techniques that provide information regarding viability and function when exposed to various environmental conditions.…
(more)
▼ Design and characterization of tissue engineered substitutes rely on robust monitoring techniques that provide information regarding viability and function when exposed to various environmental conditions. In vitro studies permit the direct monitoring of cellular and construct changes because these substitutes remain accessible. However, upon in vivo implantation, changes in cell viability and function are often detected using indirect or invasive methods that make assessing temporal changes challenging. . Thus, the development of non-invasive monitoring modalities may facilitate improved tissue substitute design and, ultimately, clinical outcome.
The overall objective of this thesis was to establish a method to monitor and track cells and the cellular environment within a tissue engineered substitute in vitro and in vivo. This was accomplished via 31P NMR spectroscopy and through the incorporation of perfluorocarbon (PFC) emulsions for the monitoring of DO concentration by 19F NMR spectroscopy. The first aim of this thesis was to develop a method that tracked the state of cells and of the cellular environment within alginate constructs during perfusion studies in which the perfusing medium DO concentrations were changed over time or cells were exposed to a cytotoxic antibiotic. Due to challenges in acquiring DO concentration gradient information within beads, a second aim was to develop a mathematical model that would calculate gradients from experimentally acquired volume averaged DO concentrations; thus, significantly enhancing the robustness of tracking the alginate beads. Lastly, since the PFC emulsions used in the study may affect cell viability and function, a third aim was to characterize, experimentally and via modeling, the effect of several PFC emulsion concentrations on the encapsulated and946;TC-tet cells.
Advisors/Committee Members: Sambanis, Athanassios (Committee Chair), Chaikof, Elliot (Committee Member), Constantinidis, Ioannis (Committee Member), Edmondson, Dale (Committee Member), Long, Jr., Robert (Committee Member).
Subjects/Keywords: 19F NMR; Perfluorocarbon; Pancreatic substitute; Oxygen
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APA (6th Edition):
Gross, J. D. (2007). Non-invasive Monitoring of Oxygen Concentrations and Metabolic Function in Pancreatic Substitutes. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/14499
Chicago Manual of Style (16th Edition):
Gross, Jeffrey David. “Non-invasive Monitoring of Oxygen Concentrations and Metabolic Function in Pancreatic Substitutes.” 2007. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/14499.
MLA Handbook (7th Edition):
Gross, Jeffrey David. “Non-invasive Monitoring of Oxygen Concentrations and Metabolic Function in Pancreatic Substitutes.” 2007. Web. 03 Mar 2021.
Vancouver:
Gross JD. Non-invasive Monitoring of Oxygen Concentrations and Metabolic Function in Pancreatic Substitutes. [Internet] [Doctoral dissertation]. Georgia Tech; 2007. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/14499.
Council of Science Editors:
Gross JD. Non-invasive Monitoring of Oxygen Concentrations and Metabolic Function in Pancreatic Substitutes. [Doctoral Dissertation]. Georgia Tech; 2007. Available from: http://hdl.handle.net/1853/14499
Georgia Tech
13.
Gumera, Christiane Bacolor.
New materials and scaffold fabrication method for nerve tissue engineering.
Degree: PhD, Biomedical Engineering, 2009, Georgia Tech
URL: http://hdl.handle.net/1853/28212
► Acetylcholine is a neurotransmitter that regulates neurite branching, induces neurite outgrowth, and synapse formation. Because of its various roles in neuronal activities, acetylcholine-based materials may…
(more)
▼ Acetylcholine is a neurotransmitter that regulates neurite branching, induces neurite outgrowth, and synapse formation. Because of its various roles in neuronal activities, acetylcholine-based materials may also be useful in nerve repair. We present a series of biodegradable polymers with varying concentrations of acetylcholine-like motifs. We hypothesize that neurite sprouting and extension can be enhanced by using materials to present biochemical and physical cues.
Acetylcholine-like motifs were incorporated by the polycondensation of diglycidyl sebacate, aminoethyl acetate, and leucine ethyl ester, which permitted control over acetylcholine motif concentration. Interactions between the polymers and neurons were characterized using rat dorsal root ganglia explants (DRG). We screened the potential application of these materials in nerve tissue engineering using the following criteria: 1) neurite sprouting, 2) neurite length, and 3) distribution of the neurite lengths. The ability of DRG to sprout neurites was influenced by the concentration of acetylcholine motifs of the polymer. Addition of acetylcholine receptor antagonists to DRG cultured on the polymers significantly decreased neurite sprouting, suggesting acetylcholine receptors mediate sprouting on the polymers. Future studies may examine how neurons on acetylcholine-based polymers exhibit changes in downstream signaling events and cell excitability that are associated with receptor activation.
In preparation for testing the acetylcholine-based polymers in vivo, porous scaffolds with longitudinally oriented channels were fabricated using fiber templating and salt leaching. Micro computed tomography, scanning electron microscopy, and cryo-sectioning revealed the presence of longitudinally oriented channels. Channel volume and average pore size of the scaffolds were controlled by the number of fibers and salt fusion time. Future studies may involve testing the effect of acetylcholine-motifs by coating polymers onto such scaffolds or assessing the effect of the scaffold's dimensional properties on nerve regeneration.
Advisors/Committee Members: Wang, Yadong (Committee Chair), Bao, Gang (Committee Member), Bellamkonda, Ravi (Committee Member), Boyan, Barbara (Committee Member), Chaikof, Elliot (Committee Member), Meredith, J. Carson (Committee Member).
Subjects/Keywords: Nerve regeneration; Polymers; Neurotransmitter; Acetylcholine; Nerve tissue engineering; Tissue engineering; Nerve tissue; Polymers in medicine
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APA (6th Edition):
Gumera, C. B. (2009). New materials and scaffold fabrication method for nerve tissue engineering. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/28212
Chicago Manual of Style (16th Edition):
Gumera, Christiane Bacolor. “New materials and scaffold fabrication method for nerve tissue engineering.” 2009. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/28212.
MLA Handbook (7th Edition):
Gumera, Christiane Bacolor. “New materials and scaffold fabrication method for nerve tissue engineering.” 2009. Web. 03 Mar 2021.
Vancouver:
Gumera CB. New materials and scaffold fabrication method for nerve tissue engineering. [Internet] [Doctoral dissertation]. Georgia Tech; 2009. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/28212.
Council of Science Editors:
Gumera CB. New materials and scaffold fabrication method for nerve tissue engineering. [Doctoral Dissertation]. Georgia Tech; 2009. Available from: http://hdl.handle.net/1853/28212
Georgia Tech
14.
Cheng, Shing-Yi.
Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells.
Degree: PhD, Chemical Engineering, 2005, Georgia Tech
URL: http://hdl.handle.net/1853/7160
► Genetically engineered cells have the potential to solve the cell availability problem in developing a pancreatic tissue substitute for the treatment of insulin-dependent diabetes (IDD).…
(more)
▼ Genetically engineered cells have the potential to solve the cell availability problem in developing a pancreatic tissue substitute for the treatment of insulin-dependent diabetes (IDD). These cells can be beta-cells genetically engineered so that they can be grown in culture, such as the betaTC3 and betaTC tet mouse insulinomas developed by Efrat et al; or, they can be non-beta cells genetically engineered to secrete insulin constitutively or under transcriptional regulation. The aim of this work was to thoroughly characterize and improve the secretion dynamics of pancreatic substitutes based on genetically engineered cells.
One issue involved with the continuous beta-cell lines is the remodeling of the cells inside an encapsulated cell system, which may affect the insulin secretion dynamics exhibited by the construct. To evaluate the effect of remodeling on the secretion properties of the construct, we used a single-pass perfusion system to characterize the insulin secretion dynamics of different alginate beads in response to step-ups and downs in glucose concentration. Results indicated that the secretion dynamics of beads indeed changed after long-term culture. On the other hand, data with a growth-regulated cell line, betaTC tet cells, showed that the secretion profile of beads can be retained if the cell growth is suppressed.
A major concern associated with genetically engineered cells of non-beta origin is that they generally exhibit sub-optimal insulin secretion characteristics relative to normal pancreatic islets. Instead of relying on molecular tools such as manipulating gene elements, our approach was to introduce a glucose-responsive material acting as a control barrier for insulin release from a device containing constitutively secreting cells. Proof-of-concept experiments were performed with a disk-shaped prototype based on recombinant HepG2 hepatomas or C2C12 myoblasts, which constitutively secreted insulin, and concanavalin A (con A)-based glucose-responsive material as the control barrier. Results demonstrated that the a hybrid pancreatic substitute consisting of constitutively secreting cells and glucose-responsive material has the potential to provide a more physiologic regulation of insulin release than the cells by themselves or in an inert material.
Advisors/Committee Members: Sambanis, Athanassios (Committee Chair), Chaikof, Elliot (Committee Member), Lyon, L. Andrew (Committee Member), Thule, Peter (Committee Member), Wick, Timothy (Committee Member).
Subjects/Keywords: Pancreatic substitute; Insulin secretion dynamics; Glucose-responsive; Genetically engineered cells
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APA (6th Edition):
Cheng, S. (2005). Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/7160
Chicago Manual of Style (16th Edition):
Cheng, Shing-Yi. “Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells.” 2005. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/7160.
MLA Handbook (7th Edition):
Cheng, Shing-Yi. “Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells.” 2005. Web. 03 Mar 2021.
Vancouver:
Cheng S. Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2005. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/7160.
Council of Science Editors:
Cheng S. Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells. [Doctoral Dissertation]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/7160
Georgia Tech
15.
Tseng, Po-Yuan.
Thrombomodulin/heparin functionalized membrane-mimetic assemblies: strategies for generating an actively anti-thrombogenic surface.
Degree: PhD, Chemical Engineering, 2005, Georgia Tech
URL: http://hdl.handle.net/1853/7236
► It has been postulated that the control of thrombus formation on molecularly engineered surfaces is an important step in developing clinically durable small-diameter vascular prostheses.…
(more)
▼ It has been postulated that the control of thrombus formation on molecularly engineered surfaces is an important step in developing clinically durable small-diameter vascular prostheses. This has led to designing a membrane-mimetic assembly that contains physiological regulators of blood coagulation, thrombomodulin (TM) and heparin, to provide strategies for generating actively antithrombogenic surfaces. The membrane-mimetic construct contains polymeric phospholipid monolayer on an alkylated polyelectrolyte multilayer supported by planar substrate such as glass or silicone. When incorporated with TM, the model platform exhibited the biological function by catalyzing activation of protein C. Surface TM activity was extensively investigated at physiologic shear rates (50 sec-1 and 500 sec-1). Significantly, reaction rates become saturated at TM surface densities greater than or equal to ~ 800 fmole/cm2 due to due to a transport limitation. Based on the similar membrane-mimetic construct, a functional heparinized surface was designed as an alternative anticoagulant system. Immobilization of heparin onto membrane-mimetic surfaces was achieved through biotin-streptavidin binding specificity. Activity of surface heparin to facilitate thrombin inactivation was investigated at shear rates of 50 and 500 sec-1. Significantly, rate of thrombin decay becomes saturated when the surface coverage of heparin is higher than 4.4 pmole of heparin per cm2. We further investigated the effects of surface bound TM and heparin on tissue factor (TF) -induced thrombin generation in a flow model. Specifically, TF positioned over a 2 x 6 mm2 upstream region as a trigger for thrombin generation and TM and/or heparin positioned over the remaining downstream (34 x 6 mm2) portion of the test film. Compared to TF alone surface, thrombin generation was profoundly reduced in the presence of surface bound TM and/or heparin. Significantly, thrombin production was maximally inhibited more than 85% in the presence of TM and heparin, possibly due to anticoagulant synergism of both anticoagulants. We believe that current membrane-mimetic systems can potentially create actively antithrombogenic surfaces.
Advisors/Committee Members: Chaikof, Elliot (Committee Chair), Hanson, Stephen (Committee Member), Lollar, John "Pete" (Committee Member), Sambanis, Athanassios (Committee Member), Yoganathan, Ajit (Committee Member).
Subjects/Keywords: Antithrombogenic; Anticoagulant; Membrane-mimetic; Heparin; Thrombomodulin; Tissue factor; Thrombomodulin; Membranes (Technology); Heparin; Fibrinolytic agents; Blood vessel prosthesis; Anticoagulants (Medicine)
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APA (6th Edition):
Tseng, P. (2005). Thrombomodulin/heparin functionalized membrane-mimetic assemblies: strategies for generating an actively anti-thrombogenic surface. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/7236
Chicago Manual of Style (16th Edition):
Tseng, Po-Yuan. “Thrombomodulin/heparin functionalized membrane-mimetic assemblies: strategies for generating an actively anti-thrombogenic surface.” 2005. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/7236.
MLA Handbook (7th Edition):
Tseng, Po-Yuan. “Thrombomodulin/heparin functionalized membrane-mimetic assemblies: strategies for generating an actively anti-thrombogenic surface.” 2005. Web. 03 Mar 2021.
Vancouver:
Tseng P. Thrombomodulin/heparin functionalized membrane-mimetic assemblies: strategies for generating an actively anti-thrombogenic surface. [Internet] [Doctoral dissertation]. Georgia Tech; 2005. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/7236.
Council of Science Editors:
Tseng P. Thrombomodulin/heparin functionalized membrane-mimetic assemblies: strategies for generating an actively anti-thrombogenic surface. [Doctoral Dissertation]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/7236
Georgia Tech
16.
Zern, Blaine Joseph.
A biocompatible, heparin-binding polycation for the controlled delivery of growth factors.
Degree: PhD, Biomedical Engineering, 2009, Georgia Tech
URL: http://hdl.handle.net/1853/28145
► The delivery of growth factors has been attempted for a number of different therapies. The approach of delivering therapeutic growth factors in a safe and…
(more)
▼ The delivery of growth factors has been attempted for a number of different therapies. The approach of delivering therapeutic growth factors in a safe and efficient manner is difficult and certain criteria should be met. These criteria include: binding the appropriate growth factors, maintaining their bioactivity, and delivering these proteins with controllable release kinetics for an extended period of time. These criteria encompass a set of guidelines that hope to mimic in vivo biological events such as neovascularization. The central goal of this thesis is to meet these criteria by introducing a novel delivery strategy for growth factors using a biocompatible polycation and heparin.
It was hypothesized that a polycation could interact with heparin to form a complex with the potential to deliver bioactive growth factors with an adaptable release. This hypothesis was tested by examining the release kinetics of bFGF from the complex and investigating whether the released bFGF maintained its bioactivity. The [polycation:heparin:bFGF] complex was formed by mixing the components in water, resulting in a precipitate. This precipitate was able to deliver bFGF with controllable release kinetics and the bioactivity of the released bFGF was higher than bolus bFGF and comparable to heparin stabilized bFGF. This system is expected to have the ability to bind and deliver numerous heparin-binding growth factors.
In conclusion, the delivery system developed in this research provides a novel mechanism for controlled release of growth factors. This delivery strategy has met the criteria listed earlier and this research has laid the foundation for a successful delivery vehicle. Further, a biocompatible polycation was synthesized, which is a critical component of the delivery system. This polycation exhibited in vitro and in vivo biocompatibility that was orders of magnitude higher than existing polycations and has the potential to be very useful in a variety of biomedical applications. This design principle is also expected to serve as a platform for the synthesis of other biocompatible polycations.
Advisors/Committee Members: Wang, Yadong (Committee Chair), Barker, Thomas (Committee Member), Boyan, Barbara (Committee Member), Chaikof, Elliot (Committee Member), Meredith, J. Carson (Committee Member), Prausnitz, Mark (Committee Member).
Subjects/Keywords: Polycation; Growth factor delivery; Heaprin; Growth factors; Drug delivery systems; Heparin; Biocompatibility
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APA ·
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MLA ·
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APA (6th Edition):
Zern, B. J. (2009). A biocompatible, heparin-binding polycation for the controlled delivery of growth factors. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/28145
Chicago Manual of Style (16th Edition):
Zern, Blaine Joseph. “A biocompatible, heparin-binding polycation for the controlled delivery of growth factors.” 2009. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/28145.
MLA Handbook (7th Edition):
Zern, Blaine Joseph. “A biocompatible, heparin-binding polycation for the controlled delivery of growth factors.” 2009. Web. 03 Mar 2021.
Vancouver:
Zern BJ. A biocompatible, heparin-binding polycation for the controlled delivery of growth factors. [Internet] [Doctoral dissertation]. Georgia Tech; 2009. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/28145.
Council of Science Editors:
Zern BJ. A biocompatible, heparin-binding polycation for the controlled delivery of growth factors. [Doctoral Dissertation]. Georgia Tech; 2009. Available from: http://hdl.handle.net/1853/28145
Georgia Tech
17.
Weaver, Jason David.
Development of a polyvinyl alcohol cryogel covered stent.
Degree: PhD, Biomedical Engineering, 2010, Georgia Tech
URL: http://hdl.handle.net/1853/41080
► Atherosclerosis is the number one cause of death in the United States and one of the most common treatments is the implantation of a stent.…
(more)
▼ Atherosclerosis is the number one cause of death in the United States and one of the most common treatments is the implantation of a stent. In order to eliminate the two most common complications - restenosis and thrombosis - a novel covered stent is investigated. A covered stent membrane should be able to undergo large stretch, prevent restenosis, and be relatively non-thrombogenic. Polyvinyl alcohol (PVA) cryogels are examined as a candidate material for covered stent membranes. Mechanical testing included uniaxial tensile testing, puncture testing, and the fabrication and expansion of PVA cryogel covered stents. Uniaxial testing showed PVA cryogels to have sufficient ultimate stretch which was similar to bare metal stents during deployment. Puncture testing revealed that PVA cryogels are not likely to puncture in vivo. No tears were seen in the PVA cryogel membrane after expansion of the covered stents. Finite element analysis was used to determine a PVA cryogel membrane's effect on artery wall stress. PVA cryogel covered stents reduced both artery wall stress and tissue prolapse when compared to equivalent uncovered stents. Migration assays were used to determine if PVA cryogels are able to block the smooth muscle cell migration seen during restenosis. PVA cryogels significantly reduced cellular migration in modified Boyden chambers - suggesting that they would be able to prevent restenosis in vivo. Thrombogenicity was tested in vitro with a gravity-fed flow loop using porcine blood and in vivo with a sheep model. PVA cryogels were found to be less thrombogenic than polyester controls with the flow loop system. The sheep study demonstrated the feasibility of implanting PVA cryogel covered stents and good early patency. After explantation, the PVA cryogel membranes were intact - providing in vivo evidence for the durability of PVA cryogel covered stents. Overall, this work provides evidence that covered stents made with PVA cryogels are a feasible device in terms of their mechanics, ability to prevent restenosis, and low thrombogenicity. This work represents a major advancement in the development of PVA cryogel covered stents and provides necessary safety and feasibility data for future clinical trials.
Advisors/Committee Members: Ku, David N. (Committee Co-Chair), Taylor, W. Robert (Committee Co-Chair), Chaikof, Elliot L. (Committee Member), Finn, Aloke V. (Committee Member), Gleason, Rudolph L. (Committee Member), McIntire, Larry V. (Committee Member).
Subjects/Keywords: Covered stent; Polyvinyl alcohol cryogel; Restenosis; Thrombosis; Mechanics; Atherosclerosis; Biomedical materials; Biomedical materials Research
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APA (6th Edition):
Weaver, J. D. (2010). Development of a polyvinyl alcohol cryogel covered stent. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/41080
Chicago Manual of Style (16th Edition):
Weaver, Jason David. “Development of a polyvinyl alcohol cryogel covered stent.” 2010. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/41080.
MLA Handbook (7th Edition):
Weaver, Jason David. “Development of a polyvinyl alcohol cryogel covered stent.” 2010. Web. 03 Mar 2021.
Vancouver:
Weaver JD. Development of a polyvinyl alcohol cryogel covered stent. [Internet] [Doctoral dissertation]. Georgia Tech; 2010. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/41080.
Council of Science Editors:
Weaver JD. Development of a polyvinyl alcohol cryogel covered stent. [Doctoral Dissertation]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/41080
Georgia Tech
18.
Reyes, Catherine Diane.
Collagen- and Fibronectin-Mimetic Integrin-Specific Surfaces That Promote Osseointegration.
Degree: PhD, Mechanical Engineering, 2006, Georgia Tech
URL: http://hdl.handle.net/1853/11599
► Cell adhesion to the extracellular matrix through cell-surface integrin receptors is essential to development, wound healing, and tissue remodeling and therefore represents a central theme…
(more)
▼ Cell adhesion to the extracellular matrix through cell-surface integrin receptors is essential to development, wound healing, and tissue remodeling and therefore represents a central theme in the design of bioactive surfaces that successfully interface with the body. This is especially significant in the areas of integrative implant coatings since adhesion triggers signals that regulate cell cycle progression and differentiation in multiple cellular systems. The interactions of osteoblasts with their surrounding extracellular matrix are essential for skeletal development and homeostasis and the maintenance of the mature osteoblastic phenotype. Our objective was to engineer integrin-specific bioactive surfaces that support osteoblastic differentiation and promote osseointegration by mimicking these interactions. We target two specific integrins essential to osteoblast differentiation the type I collagen receptor alpha2beta1 and the fibronectin receptor alpha5beta1. The central hypothesis of this project was that the controlled presentation of type I collagen and fibronectin binding domains onto well-defined substrates would result in integrin-specific bioadhesive surfaces that support osteoblastic differentiation, matrix mineralization, and osseointegration. We have demonstrated that these biomimetic peptides enhance bone formation and mechanical osseointegration on titanium implants in a rat tibia cortical bone model. We have also shown that the presentation of multiple integrin-binding ligands synergize to enhance intracellular signaling and proliferation. Finally, we demonstrate the advantage of the short biomimetic peptides over the native ECM proteins. This research is significant because it addresses current orthopaedic implant limitations by specifically targeting cellular responses that are critical to osteoblastic differentiation and bone formation. This biomolecular approach provides a versatile and robust strategy for developing bioactive surfaces that enhance bone repair and osseointegration of orthopaedic implants.
Advisors/Committee Members: Garcia, Andres J. (Committee Chair), Bellamkonda, Ravi (Committee Member), Boyan, Barbara D. (Committee Member), Chaikof, Elliot L. (Committee Member), Collard, David M. (Committee Member), Guldberg, Robert E. (Committee Member).
Subjects/Keywords: Biomimetics; Bone; Implants; Peptides; Cell adhesion; Titanium; Osteoblast; Biomaterials; Collagen; Fibronectin; Differentiation; Mineralization; Osseointegration; Osseointegration; Orthopedic implants; Integrins; Cell adhesion; Biomimetics; Biomedical materials; Adhesion
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APA (6th Edition):
Reyes, C. D. (2006). Collagen- and Fibronectin-Mimetic Integrin-Specific Surfaces That Promote Osseointegration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/11599
Chicago Manual of Style (16th Edition):
Reyes, Catherine Diane. “Collagen- and Fibronectin-Mimetic Integrin-Specific Surfaces That Promote Osseointegration.” 2006. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021.
http://hdl.handle.net/1853/11599.
MLA Handbook (7th Edition):
Reyes, Catherine Diane. “Collagen- and Fibronectin-Mimetic Integrin-Specific Surfaces That Promote Osseointegration.” 2006. Web. 03 Mar 2021.
Vancouver:
Reyes CD. Collagen- and Fibronectin-Mimetic Integrin-Specific Surfaces That Promote Osseointegration. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/1853/11599.
Council of Science Editors:
Reyes CD. Collagen- and Fibronectin-Mimetic Integrin-Specific Surfaces That Promote Osseointegration. [Doctoral Dissertation]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/11599
. 
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