You searched for +publisher:"Georgia Tech" +contributor:("Guldberg, Robert E.").
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Georgia Tech
1.
Priddy, Lauren B.
Biomaterial strategies for improved bone healing with bone morphogenetic protein-2 delivery.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2015, Georgia Tech
URL: http://hdl.handle.net/1853/55531 
► This thesis investigated hybrid biomaterial systems with controlled strategies for bone morphogenetic protein-2 (BMP-2) delivery to promote structural and functional restoration of segmental bone defects.…
(more)
▼ This thesis investigated hybrid biomaterial systems with controlled strategies for bone morphogenetic protein-2 (BMP-2) delivery to promote structural and functional restoration of segmental bone defects. Using a critically sized rat segmental bone defect model, we (i) evaluated the effects of alginate hydrogel oxidation on BMP-2 release and bone regeneration, (ii) elucidated the spatiotemporal effects of high dose BMP-2 on bone healing and gene expression, and (iii) investigated the ability of amniotic membrane to attenuate heterotopic mineralization in critically sized bone defects. Importantly, our rat model recapitulated adverse effects observed clinically with orthotopic high dose BMP-2 delivery, specifically heterotopic mineralization, prolonged local inflammation, and systemic inflammatory effects. By identifying specific alterations in gene expression as a function of time and BMP-2 dose, this thesis contributes to our understanding of the complex process of bone healing during the early stages of large bone defect regeneration. Although the hybrid alginate-PCL delivery system did not reduce heterotopic ossification with high dose BMP-2, extracellular matrix-derived amniotic membrane surrounding collagen sponge scaffolds resulted in less heterotopic mineralization compared to collagen sponge alone, which motivates the accelerated translation of amniotic membrane for bone regeneration applications. The findings here support the overall hypothesis that a biomaterial delivery vehicle that allows for localized growth factor availability and minimal heterotopic bone formation would facilitate structural and functional restoration of segmental bone defects. By considering these fundamental biomaterial parameters, we may more effectively harness endogenous repair mechanisms for successful bone regeneration.
Advisors/Committee Members: Guldberg, Robert E (advisor).
Subjects/Keywords: Bone regeneration; Bone morphogenetic protein-2 (BMP-2); Heterotopic mineralization; Biomaterials
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APA (6th Edition):
Priddy, L. B. (2015). Biomaterial strategies for improved bone healing with bone morphogenetic protein-2 delivery. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/55531
Chicago Manual of Style (16th Edition):
Priddy, Lauren B. “Biomaterial strategies for improved bone healing with bone morphogenetic protein-2 delivery.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/55531.
MLA Handbook (7th Edition):
Priddy, Lauren B. “Biomaterial strategies for improved bone healing with bone morphogenetic protein-2 delivery.” 2015. Web. 10 Apr 2021.
Vancouver:
Priddy LB. Biomaterial strategies for improved bone healing with bone morphogenetic protein-2 delivery. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/55531.
Council of Science Editors:
Priddy LB. Biomaterial strategies for improved bone healing with bone morphogenetic protein-2 delivery. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/55531
Georgia Tech
2.
Rojas Pena, Monica Lisseth.
Gene expression profiling approach towards enhancement of malaria vaccine development.
Degree: PhD, Biology, 2016, Georgia Tech
URL: http://hdl.handle.net/1853/56252
► Malaria continues to be one of the highest morbidity and mortality infectious diseases in the world, posing an enormous public health burden with significant economic…
(more)
▼ Malaria continues to be one of the highest morbidity and mortality infectious diseases in the world, posing an enormous public health burden with significant economic consequences. The development of vaccines that provide sterile protection against pathogenic infection by the Plasmodium parasites that cause malaria is thus a major global public health priority. This dissertation describes three gene expression profiling experiments using RNA sequencing technology (RNASeq) applied to samples collected during clinical trials performed at the CAUCASECO research center in Cali, Colombia. In each case, peripheral blood samples from volunteers and patients enrolled in studies addressing different aspects of immunity against P. vivax malaria were studied, namely the effect of prior exposure, the efficacy of an attenuated parasite vaccine, and resolution of complicated disease. The results presented explore how gene expression profiling of the complex mixture of cells present in whole blood can nevertheless reveal the cellular nature and duration of the immune response to P. vivax infection, while also highlighting subsets of genes that may mediate adaptive immunity. These results demonstrate the potential value of RNASeq for studying the response of the host transcriptome of a malaria infection, and represent a step toward genomic profiling as a component of personalized clinical diagnostics for malaria treatment.
Advisors/Committee Members: Gibson, Greg (advisor), Kubanek, Julia (advisor), Jordan, King (advisor), Streelman, Todd (advisor), Guldberg, Robert E. (advisor).
Subjects/Keywords: Malaria; Plasmodim vivax; Vaccine; Gene expression; RNA-seq
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APA (6th Edition):
Rojas Pena, M. L. (2016). Gene expression profiling approach towards enhancement of malaria vaccine development. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/56252
Chicago Manual of Style (16th Edition):
Rojas Pena, Monica Lisseth. “Gene expression profiling approach towards enhancement of malaria vaccine development.” 2016. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/56252.
MLA Handbook (7th Edition):
Rojas Pena, Monica Lisseth. “Gene expression profiling approach towards enhancement of malaria vaccine development.” 2016. Web. 10 Apr 2021.
Vancouver:
Rojas Pena ML. Gene expression profiling approach towards enhancement of malaria vaccine development. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/56252.
Council of Science Editors:
Rojas Pena ML. Gene expression profiling approach towards enhancement of malaria vaccine development. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/56252
Georgia Tech
3.
Rabbah, Jean Pierre.
Surgical management of ischemic mitral regurgitation: an in-vitro investigation.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2014, Georgia Tech
URL: http://hdl.handle.net/1853/53412
► Owing to its complex structure and dynamic loading, surgical repair of the heart’s mitral valve poses a significant clinical burden. Specifically, repair of ischemic mitral…
(more)
▼ Owing to its complex structure and dynamic loading, surgical repair of the heart’s mitral valve poses a significant clinical burden. Specifically, repair of ischemic mitral regurgitation, which is caused by the geometric disruption of the mitral apparatus in the setting of ventricular dysfunction, results in poor long-term patient survival. Clinical data have shown that the preferred surgical treatment, restrictive mitral annuloplasty, may result in 15-30% early (< 6 months) recurrence of mitral regurgitation; this may exceed 70% after five years. Studies have suggested that isolated annuloplasty may not be a comprehensive repair suitable for all patients because ischemic pathology is multi-factorial and results in variable ventricular and valvular geometric distortions. Therefore, in this thesis, a new surgical planning paradigm was developed through three specific aims. In specific aim 1, in collaboration with Philips Healthcare, a novel tool to more accurately and quantitatively assess mitral valve insufficiency was developed and rigorously validated using the
Georgia Tech Left Heart Simulator. This tool was found to be more efficacious and robust than the current clinical standard. Ultimately, this improved diagnostics may better inform surgical indication, specifically, to identify patients that may not benefit from simple ring annuloplasty. In specific aim 2, targeted adjunctive surgical repair for such patients were investigated. Anterior leaflet augmentation and basal papillary muscle relocation were observed to restore mitral valve function while reducing the leaflet-subvalvular tethering associated with ischemic left ventricular remodeling. These efficacious repairs were found to be robust to variability in surgical implementation, which may encourage more widespread clinical adaptation. Finally, in specific aim 3, an integrative experimental framework was developed to promote pre-operative patient specific evaluation of mitral valve surgical repair using novel computational methods. The experimental framework combined high-resolution state of the art imaging with clinical imaging to provide the most realistic anatomical reconstructions possible. For the first time, ventricular flow fields through and proximal to a native mitral valve were acquired using stereoscopic particle image velocimetry. These data were combined with measurements of leaflet dynamics and subvalvular forces to create a comprehensive database for the rigorous validation of mitral valve finite element and fluid-structure interaction models. Collectively, these studies comprise a surgical planning paradigm that may better inform repair of mitral valve insufficiency.
Advisors/Committee Members: Yoganathan, Ajit P. (advisor), Gleason, Rudolph (committee member), Gorman, Joseph H. (committee member), Guldberg, Robert E. (committee member), Taylor, Robert (committee member).
Subjects/Keywords: Mitral valve; Mechanics
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APA (6th Edition):
Rabbah, J. P. (2014). Surgical management of ischemic mitral regurgitation: an in-vitro investigation. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/53412
Chicago Manual of Style (16th Edition):
Rabbah, Jean Pierre. “Surgical management of ischemic mitral regurgitation: an in-vitro investigation.” 2014. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/53412.
MLA Handbook (7th Edition):
Rabbah, Jean Pierre. “Surgical management of ischemic mitral regurgitation: an in-vitro investigation.” 2014. Web. 10 Apr 2021.
Vancouver:
Rabbah JP. Surgical management of ischemic mitral regurgitation: an in-vitro investigation. [Internet] [Doctoral dissertation]. Georgia Tech; 2014. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/53412.
Council of Science Editors:
Rabbah JP. Surgical management of ischemic mitral regurgitation: an in-vitro investigation. [Doctoral Dissertation]. Georgia Tech; 2014. Available from: http://hdl.handle.net/1853/53412
Georgia Tech
4.
Douglas, Alison McKissock.
Engineering fibrin matrices for enhanced vascularization and cell infiltration.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2015, Georgia Tech
URL: http://hdl.handle.net/1853/59111
► Wound healing and revascularization of tissues at sites of injury are fundamental problems in the field of regenerative medicine. One promising approach to supporting vascularization…
(more)
▼ Wound healing and revascularization of tissues at sites of injury are fundamental problems in the field of regenerative medicine. One promising approach to supporting vascularization is the use of fibrin polymers, the natural blood clotting protein, as an injectable biomaterial construct. Current fibrin matrices/sealants for wound healing applications use high concentrations of fibrinogen and thrombin, forming a dense matrix to facilitate stable clot formation. However, this limits the ability for endogenous cells to infiltrate the wound site for adequate tissue repair. The overall goal of this work is to design materials that are mechanically robust for ease of handling and clot stability, but allow for increased cell infiltration and tissue regeneration by modifying the fibrin network ultrastructure. This is achieved using colloidal assemblies of ultra low cross-linked poly(N-isopropylacrylamide) pNIPAm microgels (microgels), which we have shown can alter network architecture and mechanics. We hypothesized that by modifying microscale network structure we would enhance infiltrating cell motility, endogenous cell recruitment and angiogenesis, and tissue regeneration. Ultimately, it was shown that microgels enabled enhanced cell motility and infiltration in vitro, and in-growth of small diameter vessels in vivo. While, enabling larger vessel vascularization and multicellular processes involving collective cell migration still remain to be realized, this novel system represents a new method of modifying dense biomaterial systems for enhanced regenerative outcomes.
Advisors/Committee Members: Barker, Thomas H. (advisor), Fernandez-Nieves, Alberto (committee member), García, Andrés J. (committee member), Lyon, Andrew (committee member), Guldberg, Robert E. (committee member).
Subjects/Keywords: Fibrin; Microgels; Angiogenesis; Biomaterials; Cell migration; Infiltration
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APA (6th Edition):
Douglas, A. M. (2015). Engineering fibrin matrices for enhanced vascularization and cell infiltration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/59111
Chicago Manual of Style (16th Edition):
Douglas, Alison McKissock. “Engineering fibrin matrices for enhanced vascularization and cell infiltration.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/59111.
MLA Handbook (7th Edition):
Douglas, Alison McKissock. “Engineering fibrin matrices for enhanced vascularization and cell infiltration.” 2015. Web. 10 Apr 2021.
Vancouver:
Douglas AM. Engineering fibrin matrices for enhanced vascularization and cell infiltration. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/59111.
Council of Science Editors:
Douglas AM. Engineering fibrin matrices for enhanced vascularization and cell infiltration. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/59111
Georgia Tech
5.
Tsang, Melissa.
The development of MEMS based biodegradable strain sensors and energy sources for monitoring bone healing.
Degree: PhD, Electrical and Computer Engineering, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/60236
► A sensor that lasts forever is not always desirable. In recent years, the field of biodegradable electronics has developed to dually address transient disease states…
(more)
▼ A sensor that lasts forever is not always desirable. In recent years, the field of biodegradable electronics has developed to dually address transient disease states and to minimize environmental waste. This presentation focuses on the development of MEMS based biodegradable strain sensors and energy sources for monitoring bone healing. Current demonstrations of biodegradable devices in literature have been limited by materials and fabrication. As such, this research emphasizes the expansion of materials and fabrication schemes for the micropatterning and integration of biodegradable materials in MEMS. The non aqueous electrodeposition of magnesium (Mg), passivation schemes with pulse plated zinc (PP Zn) and fluorinated hydroxyapatite (FHA), barrier encapsulation strategies, as well as degradable conductive composites are examined and, subsequently, harnessed for the development of biodegradable piezoresistive strain sensors and galvanic energy sources. Analogous non degradable strain sensors were developed to provide a basis for comparison, as well as to better understand the intended design space. The results culminated in the in vivo deployment of a wireless strain sensing system within a rodent femoral defect model and cytotoxicity results confirming the biocompatibility of the examined materials. Together, this research demonstrated electroplated Mg based strain sensors and energy sources as a trajectory towards a fully biodegradable system and, beyond the scope of bone healing, supported the field of biodegradable MEMS through the expansion of materials fabrication and characterization for use in widgets not intended to last forever.
Advisors/Committee Members: Allen, Mark G. (advisor), Brand, Oliver (committee member), Ayazi, Farrokh (committee member), Guldberg, Robert E. (committee member), Temenoff, Johnna S. (committee member).
Subjects/Keywords: Biodegradable; bioMEMS
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APA ·
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APA (6th Edition):
Tsang, M. (2018). The development of MEMS based biodegradable strain sensors and energy sources for monitoring bone healing. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60236
Chicago Manual of Style (16th Edition):
Tsang, Melissa. “The development of MEMS based biodegradable strain sensors and energy sources for monitoring bone healing.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/60236.
MLA Handbook (7th Edition):
Tsang, Melissa. “The development of MEMS based biodegradable strain sensors and energy sources for monitoring bone healing.” 2018. Web. 10 Apr 2021.
Vancouver:
Tsang M. The development of MEMS based biodegradable strain sensors and energy sources for monitoring bone healing. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/60236.
Council of Science Editors:
Tsang M. The development of MEMS based biodegradable strain sensors and energy sources for monitoring bone healing. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/60236
Georgia Tech
6.
Torstrick, Frederick Brennan.
Effects of surface chemistry and surface topography on polyether-ether-ketone osseointegration.
Degree: PhD, Mechanical Engineering, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/60711
► Osseointegration of a novel porous polymer material made from polyether-ether-ketone (PEEK) was investigated using in vitro cell models and in vivo small animal models. Porous…
(more)
▼ Osseointegration of a novel porous polymer material made from polyether-ether-ketone (PEEK) was investigated using in vitro cell models and in vivo small animal models. Porous PEEK was compared to conventional smooth PEEK surfaces and plasma-sprayed titanium coated PEEK surfaces. The relative effects of surface material and surface topography were also investigated utilizing nano-scale atomic layer deposition (ALD) coatings. Histological, micro-computed tomography and biomechanical outcomes support that the porous PEEK material facilitated bone ingrowth and implant fixation compared to other surfaces. These results could provide valuable insight for the development of more effective devices for spinal fusions and other orthopaedic applications.
Advisors/Committee Members: Guldberg, Robert E. (advisor), Gall, Ken (advisor), Boden, Scott (committee member), Garcia, Andres (committee member), Murphy, William (committee member).
Subjects/Keywords: PEEK; Osseointegration; Porous; Orthopaedics; Spinal fusion
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APA (6th Edition):
Torstrick, F. B. (2017). Effects of surface chemistry and surface topography on polyether-ether-ketone osseointegration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60711
Chicago Manual of Style (16th Edition):
Torstrick, Frederick Brennan. “Effects of surface chemistry and surface topography on polyether-ether-ketone osseointegration.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/60711.
MLA Handbook (7th Edition):
Torstrick, Frederick Brennan. “Effects of surface chemistry and surface topography on polyether-ether-ketone osseointegration.” 2017. Web. 10 Apr 2021.
Vancouver:
Torstrick FB. Effects of surface chemistry and surface topography on polyether-ether-ketone osseointegration. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/60711.
Council of Science Editors:
Torstrick FB. Effects of surface chemistry and surface topography on polyether-ether-ketone osseointegration. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/60711
Georgia Tech
7.
Pierce, Eric L.
Design parameters and physiologic factors governing mitral valve annular loading following device implantation.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2018, Georgia Tech
URL: http://hdl.handle.net/1853/61600
► The range of implantable devices to correct mitral regurgitation (MR) is diverse and continually expanding. It consists mainly of annuloplasty rings, which restore native valve…
(more)
▼ The range of implantable devices to correct mitral regurgitation (MR) is diverse and continually expanding. It consists mainly of annuloplasty rings, which restore native valve competency, and prosthetic valve replacements. Both attach to the mitral annulus via suture anchoring. Additionally, many transcatheter mitral valve (TMV) replacements, in which anchoring and sealing often rely on radial expansion against the mitral annulus, are now developing rapidly. The mechanical interactions of all such devices with the annulus remain poorly studied, yet are critical for device safety and performance. In this work, custom measurement techniques were applied to study device-annulus interactions in clinically and industrially relevant in vivo, ex vivo, and in vitro models. First, the impacts of mitral annuloplasty ring shape, size, and stiffness on suture dehiscence likelihood were assessed across 37 ovine subjects and a series of benchtop tests. A critical role of ring flexibility was uncovered, which suggested a promising new design concept to improve suture retention without compromising effectiveness. Second, TMV radial expansion forces and paravalvular leakage dynamics were quantified in explanted porcine hearts, as functions of the device’s profile. Findings quantitatively demonstrated key advantages of a non-circular TMV shape, implications of annular oversizing, and criteria for industrial TMV test system performance. Taken together, these studies yield significant new insights into best practices for MR device design, assessment, and usage.
Advisors/Committee Members: Yoganathan, Ajit P. (advisor), Gorman, Joseph H. (committee member), Wu, Changfu (committee member), Sun, Wei (committee member), Guldberg, Robert E. (committee member).
Subjects/Keywords: Mitral valve; Forces; In vivo; Ex vivo; In vitro; Annuloplasty; TMVR; Transducer; Sutures; Dehiscence; Paravalvular leak; PVL
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APA (6th Edition):
Pierce, E. L. (2018). Design parameters and physiologic factors governing mitral valve annular loading following device implantation. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61600
Chicago Manual of Style (16th Edition):
Pierce, Eric L. “Design parameters and physiologic factors governing mitral valve annular loading following device implantation.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/61600.
MLA Handbook (7th Edition):
Pierce, Eric L. “Design parameters and physiologic factors governing mitral valve annular loading following device implantation.” 2018. Web. 10 Apr 2021.
Vancouver:
Pierce EL. Design parameters and physiologic factors governing mitral valve annular loading following device implantation. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/61600.
Council of Science Editors:
Pierce EL. Design parameters and physiologic factors governing mitral valve annular loading following device implantation. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/61600
Georgia Tech
8.
Garcia, Jose.
Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells.
Degree: PhD, Mechanical Engineering, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/61618
► Since the discovery of adult human mesenchymal stem cells in the late 1900’s, the potential of utilizing these cells in the clinic for cell-therapy applications…
(more)
▼ Since the discovery of adult human mesenchymal stem cells in the late 1900’s, the potential of utilizing these cells in the clinic for cell-therapy applications has been an ever-present goal. Unfortunately, clinical trials using these cells have garnered lackluster results with a high degree of variability in patient outcome and in many cases no difference between patients who received these adult stem cell or placebo. Various factors account for such results including the inability to properly control cell presence via the routine method of intravenous administration, the inability to control cell phenotype once the cells are injected into the patient and the harsh microenvironment cells are injected into. Biomaterials can provide solutions for these factors through engineering scaffolds to present needed signals to both encapsulated stem cells and the surrounding microenvironment. The objective of this project is to engineer bioartificial hydrogels presenting specific signals in the form of integrin-specific ligands and covalently-bound proteins to enhance mesenchymal stem cell activity and efficacy in wound and disease models. We investigated the application of these bioarticifial hydrogels towards two different goals: 1) to enhance vascularization and associated stem cell survival in a critical size bone defect and 2) to enhance immunomodulation of stem cells in a wound regeneration model. For our first goal, we found that hydrogels presenting the α2β1 ligand ‘GFOGER’ resulted in enhanced vascularization of bone defects compared to hydrogels presenting the αvβ3 ligand ‘RGD’ in the absence of vasculogenic protein. For our second goal, we found that hydrogels functionalized tethered IFN-γ enhanced the immunomodulatory properties of encapsulated hMSCs which led to enhanced tissue resolution in a colonic wound model. Together, our findings elucidate novel ways to enhance adult stem cell efficacy and further the applicability of these cells in clinical settings.
Advisors/Committee Members: Garcia, Andres J. (advisor), Guldberg, Robert E. (committee member), Botchwey, Edward (committee member), Taylor, W. Robert (committee member), Fernandez-Nieves, Alberto (committee member).
Subjects/Keywords: Mesenchymal stem cells; Hydrogel; Biomaterials; Vascularization; Bone engineering; Immunomodulation
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APA (6th Edition):
Garcia, J. (2018). Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61618
Chicago Manual of Style (16th Edition):
Garcia, Jose. “Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/61618.
MLA Handbook (7th Edition):
Garcia, Jose. “Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells.” 2018. Web. 10 Apr 2021.
Vancouver:
Garcia J. Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/61618.
Council of Science Editors:
Garcia J. Hydrogel engineering for enhancing vascularization and augmenting immunomodulation of encapsulated mesenchymal stem cells. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/61618
Georgia Tech
9.
Salazar-Noratto, Giuliana Eva.
Elucidating pathological mechanisms of joint degenerative disorders.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2018, Georgia Tech
URL: http://hdl.handle.net/1853/61627
► Joint degenerative disorders impose a large burden on lifestyle and the healthcare system. The goals of this thesis were to elucidate pathological mechanisms in osteoarthritis…
(more)
▼ Joint degenerative disorders impose a large burden on lifestyle and the healthcare system. The goals of this thesis were to elucidate pathological mechanisms in osteoarthritis (OA) and juvenile osteochondritis dissecans (JOCD) in order to improve understanding of these diseases, and to provide well-characterized platforms for therapeutic development and testing. In order to bridge the gap in knowledge between preclinical and clinical studies, we characterized molecular events that occur in the rat medial meniscus transection model of post-traumatic OA as the disease develops and progresses. We then used this platform to investigate the mechanisms of action of micronized dehydrated human amnion/chorion membrane in order to elucidate potential disease-modifying mechanisms of this therapeutic. By utilizing cutting edge induced pluripotent stem cell technology, we established JOCD-specific models of chondrogenic and endochondral ossification differentiation, as well as endoplasmic reticulum-stress induction models. Our results shed light on pathological mechanisms of OA and JOCD and provided compelling data for the development of more targeted approaches for disease treatments.
Advisors/Committee Members: Guldberg, Robert E. (advisor), Gibson, Greg (committee member), Willett, Nick J. (committee member), Temenoff, Johnna (committee member), Willimon, Clifton (committee member).
Subjects/Keywords: Osteoarthritis; Juvenile osteochondritis dissecans; Animal models; Induced pluripotent stem cells; Patient-specific disease modeling; Organoids
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APA (6th Edition):
Salazar-Noratto, G. E. (2018). Elucidating pathological mechanisms of joint degenerative disorders. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61627
Chicago Manual of Style (16th Edition):
Salazar-Noratto, Giuliana Eva. “Elucidating pathological mechanisms of joint degenerative disorders.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/61627.
MLA Handbook (7th Edition):
Salazar-Noratto, Giuliana Eva. “Elucidating pathological mechanisms of joint degenerative disorders.” 2018. Web. 10 Apr 2021.
Vancouver:
Salazar-Noratto GE. Elucidating pathological mechanisms of joint degenerative disorders. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/61627.
Council of Science Editors:
Salazar-Noratto GE. Elucidating pathological mechanisms of joint degenerative disorders. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/61627
Georgia Tech
10.
Evans, Nathan Timothy.
Processing-structure-property relationships of surface porous polymers for orthopaedic applications.
Degree: PhD, Materials Science and Engineering, 2016, Georgia Tech
URL: http://hdl.handle.net/1853/55004
► The use of polymers in orthopaedics is steadily increasing. In some markets, such as spinal fusion and soft tissue anchors, the polymer polyetheretherketone (PEEK) is…
(more)
▼ The use of polymers in orthopaedics is steadily increasing. In some markets, such as spinal fusion and soft tissue anchors, the polymer polyetheretherketone (PEEK) is already the material of choice in the majority of implants. Despite PEEK’s widespread use, it is often associated with poor osseointegration, which can lead to implant loosening and ultimately failure of the device. Many attempts have been explored to improve the osseointegration of PEEK but none have had widespread clinical success. In this dissertation, a novel surface porous structure has been created, where limiting the porosity to the surface maintains adequate mechanical properties for load bearing applications while providing a surface for improved osseointegration. Careful control of the processing parameters resulted in tunable porous microstructures optimized for bone ingrowth: highly interconnected 200-500µm pores with porosity ranging from 60-85% and pore layers from 300-6000µm thick. Mechanical characterization, including monotonic tensile and compression, tensile fatigue, shear, and abrasion tests, were used to probe the effects of the surface porosity on the relevant mechanical properties of the material. In addition, the effect of surface porosity and surface roughness on the mechanical properties of a range of thermoplastics with varying chemistries and crystallinities was explored. This research showed that there is a great disparity in the notch sensitivity of polymers that correlates to the polymers fracture toughness as well as trends in the monotonic stress-strain curve. The results illustrate that care must be taken in the design of polymeric implants, especially when introducing topographical changes to promote osseointegration, in order to ensure they maintain adequate load-bearing capacity. Finally, preliminary in vitro and in vivo data demonstrated the ability of surface porous PEEK (PEEK-SP) to promote osseointegration. Cells grown on PEEK-SP demonstrated enhanced mineralization and differentiation, suggesting the ability of PEEK-SP to facilitate bone ingrowth. The potential of PEEK-SP was further demonstrated by implantation in a rat femoral segmental defect model which demonstrated bone ingrowth and reduced formation of a fibrous capsule.
Advisors/Committee Members: Gall, Ken (advisor), Guldberg, Robert E. (committee member), McDowell, David L. (committee member), Shofner, Meisha L. (committee member), Kumar, Satish (committee member).
Subjects/Keywords: Polyetheretherketone; Biomaterials; Polymers; Porosity; Osseointegration; Fatigue; Strength
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APA (6th Edition):
Evans, N. T. (2016). Processing-structure-property relationships of surface porous polymers for orthopaedic applications. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/55004
Chicago Manual of Style (16th Edition):
Evans, Nathan Timothy. “Processing-structure-property relationships of surface porous polymers for orthopaedic applications.” 2016. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/55004.
MLA Handbook (7th Edition):
Evans, Nathan Timothy. “Processing-structure-property relationships of surface porous polymers for orthopaedic applications.” 2016. Web. 10 Apr 2021.
Vancouver:
Evans NT. Processing-structure-property relationships of surface porous polymers for orthopaedic applications. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/55004.
Council of Science Editors:
Evans NT. Processing-structure-property relationships of surface porous polymers for orthopaedic applications. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/55004
Georgia Tech
11.
Allen, Ashley.
Modulation of stem cell delivery strategy by platelet lysate utilization and cell aggregation for enhanced bone regeneration.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2015, Georgia Tech
URL: http://hdl.handle.net/1853/55519
► Challenges to control delivered cell behavior, including viability and differentiation, remain a significant barrier to the translation of cell-based bone tissue engineering strategies. Our research…
(more)
▼ Challenges to control delivered cell behavior, including viability and differentiation, remain a significant barrier to the translation of cell-based bone tissue engineering strategies. Our research objectives were to evaluate a bioluminescent imaging (BLI) technique for the longitudinal monitoring of delivered mesenchymal stem cell (MSC) number and subsequently evaluate the effect of two MSC delivery strategies on cell survival and facilitated bone regeneration. A BLI protocol for tracking MSCs implanted subcutaneously within an alginate/mesh delivery platform was successfully established, during which the potential role of confounding factors, including fibrotic and vascular tissue development, on BLI signal correlation strength was highlighted. The utility of human platelet lysate (hPL) as a pre-treatment or co-delivery strategy was subsequently evaluated. While hPL utilization did not improve delivered hMSC survival nor promote construct vasculature within an immunocompromised rat model, limitations in the applicability of hPL pre-clinical testing via rodent testbeds were identified. Finally, the effect of MSC aggregation was investigated. Within an immunocompromised rat model, delivery of spheroids had no impact on cell survival, construct vascularization, nor critically-sized bone defect repair. When examined within a syngeneic rodent model, rMSC aggregates elicited a surviving cell fraction and construct vasculature comparable to that of single cell delivery. Despite in vitro observation that the osteoinductive potential of alginate/mesh constructs was increased with rMSC seeding, delivery of rMSC-containing treatments to the femoral defect space attenuated bone repair. Overall, this research implemented a novel imaging platform to relate key cell-based tissue regeneration metrics, namely delivered cell survival, construct vasculature, and functional outcomes, in an effort to elucidate fundamental principles for development of an effective MSC-based large bone defect therapeutic strategy. Importantly, this body of work also drew attention to several aspects of rodent model selection including xenogenicity, cross-reactivity, and biological variability.
Advisors/Committee Members: Guldberg, Robert E. (advisor), García, Andrés J. (committee member), Copland, Ian B. (committee member), Gazit, Zulma (committee member), McDevitt, Todd C. (committee member).
Subjects/Keywords: Mesenchymal stem cells; Bioluminescent imaging; Bone regeneration; Human platelet lysate; Cell Aggregation
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APA (6th Edition):
Allen, A. (2015). Modulation of stem cell delivery strategy by platelet lysate utilization and cell aggregation for enhanced bone regeneration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/55519
Chicago Manual of Style (16th Edition):
Allen, Ashley. “Modulation of stem cell delivery strategy by platelet lysate utilization and cell aggregation for enhanced bone regeneration.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/55519.
MLA Handbook (7th Edition):
Allen, Ashley. “Modulation of stem cell delivery strategy by platelet lysate utilization and cell aggregation for enhanced bone regeneration.” 2015. Web. 10 Apr 2021.
Vancouver:
Allen A. Modulation of stem cell delivery strategy by platelet lysate utilization and cell aggregation for enhanced bone regeneration. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/55519.
Council of Science Editors:
Allen A. Modulation of stem cell delivery strategy by platelet lysate utilization and cell aggregation for enhanced bone regeneration. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/55519
Georgia Tech
12.
Tellier, Liane Elizabeth.
Controlled heparin-based delivery strategies to promote musculoskeletal tissue regeneration after injury.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2018, Georgia Tech
URL: http://hdl.handle.net/1853/62183
► Despite the prevalence of musculoskeletal disorders, one of the leading causes of work- related disability in the United States, effective therapeutic delivery to the affected…
(more)
▼ Despite the prevalence of musculoskeletal disorders, one of the leading causes of work- related disability in the United States, effective therapeutic delivery to the affected musculoskeletal tissues such as bone, cartilage, and muscle remains a significant challenge. Thus, the long term goal of this research was to develop a tunable biomaterial-based system for the delivery of regenerative therapeutics to musculoskeletal tissues. This goal was approached through the engineering of a heparin-based microparticle (MP) system with tunable heparin sulfation, heparin content, and hydrolytic degradation, which was subsequently employed for in vitro release of an osteoinductive growth factor and in vivo delivery of a chondroprotective anti-inflammatory protein and a chemokine capable of recruiting pro-regenerative cells to muscle. In aim 1, hydrolytically-degradable, heparin-based MPs were fabricated containing heparin derivatives of varying levels of sulfation, and N-desulfated heparin MPs were found to efficiently load and release an osteoinductive growth factor, bone morphogenetic protein-2 (BMP-2), in vitro. In aim 2, heparin-based MPs were loaded with tumor necrosis factor- stimulated gene-6 (TSG-6), an anti-inflammatory protein known to inhibit plasmin, and delivered via intra-articular injection to rat knees in the context of post-traumatic osteoarthritis. After 21 days, TSG-6 loaded MPs reduced cartilage damage following injury, whereas a 3X higher dose of soluble TSG-6 did not, suggesting that Hep-N can enhance TSG-6 bioactivity in vivo and that Hep-N-based MPs can effectively deliver a chondroprotective protein for cartilage regeneration. Finally, in aim 3, heparin-based MPs were loaded with the chemokine stromal cell-derived factor- 1 (SDF-1) and delivered via local injection to the supraspinatus muscle in combination with systemic delivery of the bone marrow mobilizing agent, VPC01091, following severe rotator cuff injury in rats. Co-delivery of SDF-1 loaded MPs and VPC01091 led to significant modulation of the inflammatory cellular milieu and mesenchymal stem cell population in muscle 3 and 7 days following injury, along with significantly more regenerating muscle fibers compared to either treatment alone.
Overall, in this thesis, heparin-based MPs were utilized to deliver therapeutics capable of stimulating endogenous healing processes in two unique contexts of cartilage and muscle degeneration. Given the tunability of the MP system and the ability for heparin to bind and interact with a myriad of proteins, the application of heparin-based MPs extends beyond cartilage and muscle, and may be used for a wide range of applications where controlled release of bioactive positively-charged therapeutics is required.
Advisors/Committee Members: Temenoff, Johnna S. (advisor), Willett, Nick J. (committee member), Guldberg, Robert E. (committee member), Jarrett, Claude D. (committee member), Botchwey, Edward A. (committee member).
Subjects/Keywords: Heparin; Microparticles; Drug delivery; Endogenous healing
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APA (6th Edition):
Tellier, L. E. (2018). Controlled heparin-based delivery strategies to promote musculoskeletal tissue regeneration after injury. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62183
Chicago Manual of Style (16th Edition):
Tellier, Liane Elizabeth. “Controlled heparin-based delivery strategies to promote musculoskeletal tissue regeneration after injury.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/62183.
MLA Handbook (7th Edition):
Tellier, Liane Elizabeth. “Controlled heparin-based delivery strategies to promote musculoskeletal tissue regeneration after injury.” 2018. Web. 10 Apr 2021.
Vancouver:
Tellier LE. Controlled heparin-based delivery strategies to promote musculoskeletal tissue regeneration after injury. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/62183.
Council of Science Editors:
Tellier LE. Controlled heparin-based delivery strategies to promote musculoskeletal tissue regeneration after injury. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/62183
Georgia Tech
13.
Wang, Jason Lee.
Skeletal development and bone healing in HIV-1 transgenic animal models.
Degree: PhD, Mechanical Engineering, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/62245
► HIV and AIDS have drastically compromised the quality of life and lifespan for millions of people worldwide. The increasing effectiveness of and access to antiretroviral…
(more)
▼ HIV and AIDS have drastically compromised the quality of life and lifespan for millions of people worldwide. The increasing effectiveness of and access to antiretroviral therapy has dramatically increased the life expectancy of those infected with HIV to nearly that of the general population. Once considered a death sentence, a positive HIV diagnosis with appropriate treatment is now a chronic condition bringing with it the premature onset of disorders traditionally associated with the natural aging process including cardiovascular disease, neurocognitive decline, kidney disease, and osteoporosis. It is well understood that HIV infection is a risk factor for osteopenia and osteoporosis and subsequently for fragility fractures. More recently, studies have established an increase in fracture prevalence in the HIV-infected population. However, the effects of HIV infection on bone are difficult to investigate in the clinical setting. Traditional risk factors for osteoporosis – such as vitamin D deficiency, drug use, smoking, and alcohol use – can complicate any observed effects that HIV may have. Despite the increased risk for fracture and fracture prevalence in the HIV-infected population, relatively few clinical studies and no pre-clinical studies have investigated the potential for HIV infection to adversely affect fracture healing. The main goal of this work was to investigate the effects of HIV on skeletal growth and bone healing as exhibited by HIV-1 transgenic rodent models, specifically the mouse and the rat. In addition to the extensive body of bone research conducted in mouse and rat models, the transgenic rodent models offer significant advantages for pre-clinical research over the more recognized non-human primate and humanized mouse models, including less time and expense. Additionally, HIV-1 transgenic rodent models have been used to study various comorbidities associated with HIV infection. Thus, we first characterized the skeletal phenotype in the HIV-1 transgenic mouse model by evaluating bone microarchitecture and biomechanics. We further assessed whether HIV mice present with impairment in long bone fracture healing. Second, we characterized the longitudinal skeletal changes in the growing HIV-1 transgenic rat. Finally, we investigated alterations to bone healing in the HIV-1 transgenic rat using a critically-sized segmental bone defect model. This work presents findings supporting an HIV associated skeletal phenotype that is exhibited by both HIV-1 transgenic mice and rats that reflects the clinical literature. Specifically, HIV animals have reduced cortical and trabecular bone mass and altered bone microarchitecture at multiple skeletal sites. These deleterious effects on bone structure resulted in decreased whole bone mechanics and may be age-dependent in HIV-1 transgenic rodents. More significantly, we present the first pre-clinical investigation into fracture healing in the HIV-1 transgenic rodents showing impaired bone healing in both HIV-1 transgenic mice and rats. Our findings support the…
Advisors/Committee Members: Guldberg, Robert E. (advisor), Weitzmann, M. Neale (committee member), Gleason, Rudolph L. (committee member), Platt, Manu O. (committee member), Temenoff, Johnna S. (committee member).
Subjects/Keywords: HIV; Transgenic rodent models; Bone microarchitecture; Bone biomechanics; Bone healing
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APA (6th Edition):
Wang, J. L. (2018). Skeletal development and bone healing in HIV-1 transgenic animal models. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62245
Chicago Manual of Style (16th Edition):
Wang, Jason Lee. “Skeletal development and bone healing in HIV-1 transgenic animal models.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/62245.
MLA Handbook (7th Edition):
Wang, Jason Lee. “Skeletal development and bone healing in HIV-1 transgenic animal models.” 2018. Web. 10 Apr 2021.
Vancouver:
Wang JL. Skeletal development and bone healing in HIV-1 transgenic animal models. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/62245.
Council of Science Editors:
Wang JL. Skeletal development and bone healing in HIV-1 transgenic animal models. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/62245
Georgia Tech
14.
Sutha, Ken.
Osteoinductive material derived from differentiating embryonic stem cells.
Degree: PhD, Biomedical Engineering, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/51722
► The loss of regenerative capacity of bone, from fetal to adult to aged animals, has been attributed not only to a decline in the function…
(more)
▼ The loss of regenerative capacity of bone, from fetal to adult to aged animals, has been attributed not only to a decline in the function of cells involved in bone formation but also to alterations in the bone microenvironment that occur through development and aging, including extracellular matrix (ECM) composition and growth/trophic factor content. In the development of novel treatments for bone repair, one potential therapeutic goal is the restoration of a more regenerative microenvironment, as found during embryonic development. One approach to creating such a microenvironment is through the use of stem cells. In addition to serving as a differentiated cell source, pluripotent stem cells, such as embryonic stem cells (ESCs), may possess the unique potential to modulate tissue environments via local production of ECM and growth factors. ESC-produced factors may be harnessed and delivered to promote functional tissue regeneration. Such an approach to generate a naturally derived, acelluar therapy has been employed successfully to deliver osteoinductive factors found within adult bone, in the form of demineralized bone matrix (DBM), but the development of treatments derived instead from developing, more regenerative tissues or cells remains attractive. Furthermore, the derivation of regenerative materials from an ESC source also presents the added benefit of eliminating donor to donor variability of adult, cadaveric tissue derived materials, such as DBM. Thus, the objective of this project was to examine the osteoinductive potential harbored within the embryonic microenvironment, in vitro and in vivo. The osteogenic differentiation of mouse ESCs as embryoid bodies (EBs) was evaluated in response to phosphate treatment, in vitro, including osteoinductive growth factor production. The osteoinductivity of EB-derived material (EBM) was then compared to that of adult tissue-derived DBM, in vivo. Phosphate treatment enhanced osteogenic differentiation of EBs. EBM derived from phosphate treated EBs retained bioactive, osteoinductive factors and induced new bone formation, demonstrating that the microenvironment within osteogenic EBs can be harnessed in an acellular material to yield in vivo osteoinductivity. This work not only provides new insights into the dynamic microenvironments of differentiating stem cells but also establishes an approach for the development of an ESC-derived, tissue specific therapy.
Advisors/Committee Members: McDevitt, Todd C. (advisor), Guldberg, Robert E. (committee member), Schwartz, Zvi (committee member), Boyan, Barbara D. (committee member), O'Connell, Julie (committee member), Temenoff, Johanna S. (committee member).
Subjects/Keywords: Regenerative medicine; Regenerative therapy; Bone therapy; Embryonic stem cells; Embryonic stem cells; Bone regeneration
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APA (6th Edition):
Sutha, K. (2012). Osteoinductive material derived from differentiating embryonic stem cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/51722
Chicago Manual of Style (16th Edition):
Sutha, Ken. “Osteoinductive material derived from differentiating embryonic stem cells.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/51722.
MLA Handbook (7th Edition):
Sutha, Ken. “Osteoinductive material derived from differentiating embryonic stem cells.” 2012. Web. 10 Apr 2021.
Vancouver:
Sutha K. Osteoinductive material derived from differentiating embryonic stem cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/51722.
Council of Science Editors:
Sutha K. Osteoinductive material derived from differentiating embryonic stem cells. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/51722
Georgia Tech
15.
Hettiaratchi, Marian Hirushika.
Heparin microparticle-mediated delivery of BMP-2 and pluripotent stem cell morphogens for bone repair.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2016, Georgia Tech
URL: http://hdl.handle.net/1853/59144
► The delivery of bone morphogenetic protein-2 (BMP-2) offers a promising means of stimulating endogenous repair mechanisms to heal severe bone injuries. However, clinical application of…
(more)
▼ The delivery of bone morphogenetic protein-2 (BMP-2) offers a promising means of stimulating endogenous repair mechanisms to heal severe bone injuries. However, clinical application of growth factor therapy is hindered by the lack of adequate biomaterials to localize BMP-2 delivery. Glycosaminoglycans, such as heparin, have the capacity to strongly bind BMP-2 and other growth factors implicated in bone regeneration, and present the opportunity to locally deliver growth factors to injury sites. Moreover, pluripotent stem cells (PSCs) secrete many potent heparin-binding growth factors that have been implicated in tissue regeneration following cell transplantation and may provide cues for repair. Thus, heparin can also be used to concentrate and deliver PSC-derived morphogens to tissue injury sites, thereby overcoming challenges associated with PSC transplantation. The goal of this work was to improve growth factor delivery for bone repair by both (1) creating an effective biomaterial for BMP-2 delivery and (2) investigating PSC morphogens as a novel source of therapeutic growth factors. We developed heparin-based microparticles that could bind and retain large amounts of bioactive BMP-2 in vitro and improve BMP-2 retention in vivo, resulting in spatially localized bone formation in a critically sized rat femoral defect. Furthermore, heparin microparticles could also sequester and concentrate complex mixtures of bioactive PSC-secreted proteins, which may be developed into cell-free therapies in the future. Overall, this work broadens current understanding of bone tissue engineering, biomaterial delivery strategies, and stem cell-based therapeutics, and provides valuable insight into developing affinity-based biomaterials for clinical applications.
Advisors/Committee Members: Guldberg, Robert E. (advisor), McDevitt, Todd C. (advisor), Boden, Scott D. (committee member), Botchwey, Edward A. (committee member), García, Andrés J. (committee member), Temenoff, Johnna S. (committee member).
Subjects/Keywords: Heparin microparticles; Bone morphogenetic protein-2; Embryonic stem cells; Bone repair
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APA (6th Edition):
Hettiaratchi, M. H. (2016). Heparin microparticle-mediated delivery of BMP-2 and pluripotent stem cell morphogens for bone repair. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/59144
Chicago Manual of Style (16th Edition):
Hettiaratchi, Marian Hirushika. “Heparin microparticle-mediated delivery of BMP-2 and pluripotent stem cell morphogens for bone repair.” 2016. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/59144.
MLA Handbook (7th Edition):
Hettiaratchi, Marian Hirushika. “Heparin microparticle-mediated delivery of BMP-2 and pluripotent stem cell morphogens for bone repair.” 2016. Web. 10 Apr 2021.
Vancouver:
Hettiaratchi MH. Heparin microparticle-mediated delivery of BMP-2 and pluripotent stem cell morphogens for bone repair. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/59144.
Council of Science Editors:
Hettiaratchi MH. Heparin microparticle-mediated delivery of BMP-2 and pluripotent stem cell morphogens for bone repair. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/59144
Georgia Tech
16.
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 10, 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. 10 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 10].
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
Georgia Tech
17.
Li, Mon Tzu.
Treatment strategy for composite tissue limb trauma.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2015, Georgia Tech
URL: http://hdl.handle.net/1853/54837
► A majority of all fractures in current US armed conflicts are open fractures, in which a soft tissue injury is sustained along with the bone…
(more)
▼ A majority of all fractures in current US armed conflicts are open fractures, in which a soft tissue injury is sustained along with the bone fracture. Even with gold standard treatment, in which muscle flaps are used to cover bony defects, patients often do not regain normal function of their extremity, highlighting the necessity for tissue engineering strategies for this complex clinical problem. Due to a substantial amount of tissue damage and debridement treatment in composite injuries, a large volume of cells and extracellular matrix (ECM) proteins that are necessary for tissue healing are removed from the body. In the replacement of large volumes of tissue, nutrient transfer necessitates a vascular supply to maintain the viability of delivered cells. The objective of this project was to examine the regenerative potential of engineered matrix constructs and stem cells on composite bone & muscle defects. We hypothesized that stem cells delivered on engineered matrix constructs into the muscle defect will aid in muscle regeneration and promote bone healing, ultimately resulting in superior functional limb recovery. These studies established multiple preclinical platforms for testing tissue engineering strategies as well as models that can be used to gain insights on the healing of VML and composite VML/bone defects. From some of the insights gained on the vascularization of the defect sites, a vascular treatment strategy was tested within these platforms and shown to have varying results in the treatment of complex multi-tissue injuries.
Advisors/Committee Members: Guldberg, Robert E. (advisor), Warren, Gordon L. (committee member), García, Andrés J. (committee member), Temenoff, Johnna S. (committee member), Cendales, Linda C. (committee member).
Subjects/Keywords: Tissue engineering; Composite tissue injury; Animal models; Microvascular constructs; Muscle functional testing
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APA (6th Edition):
Li, M. T. (2015). Treatment strategy for composite tissue limb trauma. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/54837
Chicago Manual of Style (16th Edition):
Li, Mon Tzu. “Treatment strategy for composite tissue limb trauma.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/54837.
MLA Handbook (7th Edition):
Li, Mon Tzu. “Treatment strategy for composite tissue limb trauma.” 2015. Web. 10 Apr 2021.
Vancouver:
Li MT. Treatment strategy for composite tissue limb trauma. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/54837.
Council of Science Editors:
Li MT. Treatment strategy for composite tissue limb trauma. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/54837
Georgia Tech
18.
Lei, Jennifer.
The development of glycosaminoglycan coatings for mesenchymal stem cell-based culture applications.
Degree: PhD, Mechanical Engineering, 2016, Georgia Tech
URL: http://hdl.handle.net/1853/54949
► Mesenchymal stem cells are multipotent cells that have the ability to differentiate down multiple lineages as well as secrete trophic and anti-inflammatory factors. These qualities…
(more)
▼ Mesenchymal stem cells are multipotent cells that have the ability to differentiate down multiple lineages as well as secrete trophic and anti-inflammatory factors. These qualities make MSCs a promising cell source for cell-based therapies to treat a variety of injuries and pathologies. Biomaterials are often used to control and direct stem cell behavior by engineering a desired environment around the cells. Recent research has focused on using the naturally derived sulfated glycosaminoglycan (GAG), heparin as a biomaterial due to its negative charge and ability to sequester and bind positively charged growth factors. Engineering a heparin coating that can mimic the native heparan sulfate proteoglycan structure found at cell surfaces can be used as a novel platform to present GAGs to cells to direct cell behavior. The overall goal of this dissertation was to develop GAG-based coatings on MSC spheroids in order to study the role of heparin and its derivatives on MSC culture applications. To investigate the role of heparin in coating form on MSC behavior, the ability of the coating to sequester positively charged growth factors was characterized. Given the role of sulfation in the negative charge density of heparin and growth factor interactions, a desulfated heparin coating was develop and used to examine how presentation of coatings with native and no sulfation levels could potentiate response to growth factors in the surrounding environment. Additionally, heparin and growth factor binding in coating presentation was explored to develop a novel platform to assemble MSC-based microtissues. Together these studies provided valuable insight into a novel approach to direct cell behavior by engineering a coating that harnesses heparin interactions with the surrounding environment.
Advisors/Committee Members: Temenoff, Johnna S. (advisor), Botchwey, Edward A. (committee member), Guldberg, Robert E. (committee member), McDevitt, Todd C. (committee member), Murphy, William L. (committee member).
Subjects/Keywords: Heparin; Mesenchymal stem cells
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APA (6th Edition):
Lei, J. (2016). The development of glycosaminoglycan coatings for mesenchymal stem cell-based culture applications. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/54949
Chicago Manual of Style (16th Edition):
Lei, Jennifer. “The development of glycosaminoglycan coatings for mesenchymal stem cell-based culture applications.” 2016. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/54949.
MLA Handbook (7th Edition):
Lei, Jennifer. “The development of glycosaminoglycan coatings for mesenchymal stem cell-based culture applications.” 2016. Web. 10 Apr 2021.
Vancouver:
Lei J. The development of glycosaminoglycan coatings for mesenchymal stem cell-based culture applications. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/54949.
Council of Science Editors:
Lei J. The development of glycosaminoglycan coatings for mesenchymal stem cell-based culture applications. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/54949
19.
Johnson, Christopher T.
Lysostaphin-delivering hydrogels to treat orthopaedic device infections.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2018, Georgia Tech
URL: http://hdl.handle.net/1853/61143
► Orthopaedic hardware infections are a significant clinical problem with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with…
(more)
▼ Orthopaedic hardware infections are a significant clinical problem with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with high anti-staphylococcal activity. We engineered a lysostaphin-delivering injectable poly(ethylene glycol) (PEG) hydrogel to treat Staphylococcus aureus infections in bone fractures and segmental defections. The injectable hydrogel formulation conforms and adheres to the injury and surrounding tissue, ensuring efficient, local delivery of lysostaphin. The objective of this work is to engineer novel lysostaphin-delivering hydrogels to reduce infection and enhance bone repair in murine models of implant-associated orthopaedic infection. The central hypothesis is that controlled delivery of lysostaphin from our osseo-repartive hydrogels will reduce infection and allowing for bone repair to occur. We engineered PEG hydrogels that release active lysostaphin in response to local environmental cues. The hydrogel delivery vehicle enhances lysostaphin stability thereby preserving antimicrobial activity. Lysostaphin-delivering hydrogels eradicate S. aureus infection and support fracture healing of a pin-stabilized fracture infection model. Co-delivery of lysostaphin and BMP-2 to a model of segmental bone defect infection results in the simultaneous elimination of bacteria and bone regeneration. BMP-2 loaded lysostaphin-delivering hydrogels regenerated bone with mechanical integrity. Importantly, these hydrogels restore the local inflammatory environment, as assessed by cytokine and inflammatory cell profiling, to that of a sterile wound by one week. Administration of lysostaphin-delivering hydrogel therapy to established S. aureus infections results in an infection reduction that is potentiated with the addition of systemic antibiotic therapy. These findings support the further development of lysostaphin delivering hydrogels to treat device associated infections. This work is innovative and significant because it establishes a local strategy to effectively reduce bacterial infections while simultaneously supporting bone healing.
Advisors/Committee Members: García, Andrés J. (advisor), Donlan, Rodney M. (committee member), Guldberg, Robert E. (committee member), Westblade, Lars F. (committee member), Botchwey, Edward A. (committee member).
Subjects/Keywords: Orthopaedic implant infection; Biomaterials associated infection; Lysostaphin; Hydrogel; Bone repair; Drug delivery
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APA (6th Edition):
Johnson, C. T. (2018). Lysostaphin-delivering hydrogels to treat orthopaedic device infections. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61143
Chicago Manual of Style (16th Edition):
Johnson, Christopher T. “Lysostaphin-delivering hydrogels to treat orthopaedic device infections.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/61143.
MLA Handbook (7th Edition):
Johnson, Christopher T. “Lysostaphin-delivering hydrogels to treat orthopaedic device infections.” 2018. Web. 10 Apr 2021.
Vancouver:
Johnson CT. Lysostaphin-delivering hydrogels to treat orthopaedic device infections. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/61143.
Council of Science Editors:
Johnson CT. Lysostaphin-delivering hydrogels to treat orthopaedic device infections. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/61143
Georgia Tech
20.
Ruehle, Marissa Ashley.
Cell-Based Vascular Therapeutics for Bone Regeneration.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2019, Georgia Tech
URL: http://hdl.handle.net/1853/63520
► Bone is a highly vascularized tissue, and adequate vascularity is an essential requirement for proper bone healing. Revascularization is a challenge in critical-sized defects, especially…
(more)
▼ Bone is a highly vascularized tissue, and adequate vascularity is an essential requirement for proper bone healing. Revascularization is a challenge in critical-sized defects, especially those with concomitant muscle damage typical of traumatic injury. Patients with these injuries heal slowly and exhibit higher rates of infection and non-union, underscoring the critical importance of vasculature to bone healing. Additionally, the bone defect environment is a complex niche, involving mechanical cues in addition to a host of biochemical signals. It is well known that mechanical loading affects bone growth and remodeling, and while flow-mediated mechanics influence the vasculature, remarkably little is known about the effects of bulk matrix deformation on neovascularization. The overall objective of this thesis was to leverage mechanical cues to enhance vascular network formation and to use enhanced vascularization to improve bone regeneration.
First, we evaluated the effect of multicellular microvascular fragments (MVF) co- delivered with BMP-2 to a model of composite bone-muscle trauma using collagen sponge, the clinically available BMP-2 delivery vehicle. MVF did not improve bone healing as hypothesized; however, we also investigated the effect of a modestly increased BMP-2 dose, which did significantly improve functional healing. While MVF maintained viability within the collagen sponge in vitro, they first dissociated to single cells, which we speculated may have prevented their inosculation with the host vasculature. Next, we developed and characterized decorin-supplemented collagen gels for use as both an in vivo co-delivery vehicle for MVF and BMP-2 and as a dimensionally stable biomaterial scaffold to investigate the effects of compressive loading on MVF growth in vitro. Despite in vitro results demonstrating synergistic effects of BMP-2 and MVF, there was no effect of MVF on bone healing, and MVF significantly decreased early revascularization following injury. However, the addition of decorin increased the compressive properties and dimensional stability of collagen while still supporting robust in vitro MVF growth.
We then evaluated the effects of dynamic compressive loading on MVF growth. While the vasculature has long been recognized as mechanosensitive, the effects of abluminal forces experienced by healing tissues on angiogenesis are poorly understood. We demonstrated that delayed compressive loading led to longer, more extensively branched microvascular networks than early loading at all strain magnitudes tested. Across strain magnitudes, delayed loading increased vascular network length and branching compared to non-loaded controls; however, early high strain loading inhibited network formation. Gene expression analysis revealed differential mechanoregulation of gene expression profiles by early vs. delayed loading. Genes associated with angiogenic sprout tip cells were downregulated by early loading and upregulated by delayed loading. Delayed loading also led to the upregulation of genes involved in…
Advisors/Committee Members: Guldberg, Robert E (advisor), Willett, Nick J (advisor), Boerckel, Joel D (committee member), Garcia, Andres J (committee member), Hoying, James B (committee member), Levit, Rebecca D (committee member).
Subjects/Keywords: Angiogenesis; Tissue Engineering; Regenerative Medicine; Bone Regeneration
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APA (6th Edition):
Ruehle, M. A. (2019). Cell-Based Vascular Therapeutics for Bone Regeneration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/63520
Chicago Manual of Style (16th Edition):
Ruehle, Marissa Ashley. “Cell-Based Vascular Therapeutics for Bone Regeneration.” 2019. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/63520.
MLA Handbook (7th Edition):
Ruehle, Marissa Ashley. “Cell-Based Vascular Therapeutics for Bone Regeneration.” 2019. Web. 10 Apr 2021.
Vancouver:
Ruehle MA. Cell-Based Vascular Therapeutics for Bone Regeneration. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/63520.
Council of Science Editors:
Ruehle MA. Cell-Based Vascular Therapeutics for Bone Regeneration. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/63520
Georgia Tech
21.
Klosterhoff, Brett S.
Mechanobiological Regulation of Early Stage Bone Repair.
Degree: PhD, Mechanical Engineering, 2019, Georgia Tech
URL: http://hdl.handle.net/1853/63531
► Each year in the United States alone, several hundred thousand people suffer skeletal fractures that do not heal from the original treatment, resulting in non-union.…
(more)
▼ Each year in the United States alone, several hundred thousand people suffer skeletal fractures that do not heal from the original treatment, resulting in non-union. To improve patient outcomes, there is a clinical need for therapeutic strategies that stimulate bone repair. The skeleton dynamically adapts its structure and composition to mechanical loads, and controlled loading via rehabilitation represents a non-pharmacologic target with the potential to stimulate endogenous bone regeneration.
The primary objectives of this thesis were to develop technical approaches to longitudinally monitor dynamic mechanical cues during bone healing and elucidate how specific magnitudes promote repair. Our overall hypothesis was that moderate mechanical stimulation exerted via periodic walking could enhance bone regeneration. To test this hypothesis, we engineered a fully implantable wireless strain sensor platform that enabled real-time non-invasive monitoring of mechanical cues in a pre-clinical model of skeletal repair. We discovered that early-stage strain magnitudes correlated with significantly improved healing outcomes. We also observed that osteogenic mechanical loading exerted effects on early stage biological processes that precede mineralization, including immune cytokine signaling and angiogenesis.
At the conclusion of the experiments, we attained a deeper understanding of how specific mechanical cues regulate bone repair, and established a novel sensor platform to further investigate mechanobiology. The knowledge gained by this thesis aids the development of integrative therapeutic strategies that stimulate bone repair via functional rehabilitation. In addition, the technological outcomes of this thesis serve as foundational support for the expanded development of implantable medical sensor technologies with broad implications to enhance diagnostics, therapeutic development, and interventional surveillance.
Advisors/Committee Members: Guldberg, Robert E (advisor), Willett, Nick J (advisor), Botchwey, Edward A (committee member), Ong, Keat Ghee (committee member), Hollister, Scott J (committee member), Weiss, Jeffrey A (committee member).
Subjects/Keywords: bone regeneration; biomedical sensors; mechanobiology; rehabilitation
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APA (6th Edition):
Klosterhoff, B. S. (2019). Mechanobiological Regulation of Early Stage Bone Repair. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/63531
Chicago Manual of Style (16th Edition):
Klosterhoff, Brett S. “Mechanobiological Regulation of Early Stage Bone Repair.” 2019. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/63531.
MLA Handbook (7th Edition):
Klosterhoff, Brett S. “Mechanobiological Regulation of Early Stage Bone Repair.” 2019. Web. 10 Apr 2021.
Vancouver:
Klosterhoff BS. Mechanobiological Regulation of Early Stage Bone Repair. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/63531.
Council of Science Editors:
Klosterhoff BS. Mechanobiological Regulation of Early Stage Bone Repair. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/63531
22.
Seto, Song P.
The development of heparin-based materials for tissue engineering applications to treat rotator cuff tendon injuries.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2014, Georgia Tech
URL: http://hdl.handle.net/1853/51898
► Surgical repair of torn rotator cuff tendons have a high rate of failure and does not address the underlying pathophysiology. Tissue engineering strategies, employing the…
(more)
▼ Surgical repair of torn rotator cuff tendons have a high rate of failure and does not address the underlying pathophysiology. Tissue engineering strategies, employing the use of multipotent progenitor cells or growth factors, represent potential therapies to improve the outcome of rotator cuff surgery. The use of glycosaminoglycan-based biomaterials in these therapies may enhance the effectiveness of cell and growth factor delivery techniques. Furthermore, understanding the cellular and molecular mediators in tendon overuse can help elucidate the causes of tendon degeneration. Thus the overall goals of this dissertation were to 1) develop heparin-based biomaterials to enhance cell pre-culture and maintain growth factor bioactivity and 2) characterize the histological and enzymatic changes in a supraspinatus tendon overuse model. To investigate the use of heparin in enhancing dynamic signaling, mesenchymal stem cells (MSCs) were encapsulated in heparin-containing hydrogels and evaluated for differentiation markers when cocultured with a small population of differentiated cells. To probe the effect of sulfation of heparin on the interactions with protein, selectively desulfated heparin species were synthesized and evaluated for their ability to bind and protect proteins. Finally, to develop a tendon overuse model that can become a test bed for testing future targeted therapeutics, an animal model was evaluated for tissue damage and protease activity. Together these studies represent a multi-pronged approach to understanding how tendon tissues become degenerative and for developing technologies to improve the biological fixation of tendon to bone in order to reduce the need for revision surgeries.
Advisors/Committee Members: Temenoff, Johnna S. (advisor), Guldberg, Robert E. (committee member), Peister, Alexandra (committee member), Platt, Manu O. (committee member), Sambanis, Athanassios (committee member).
Subjects/Keywords: Rotator cuff; Heparin-containing hydrogels; Tendon overuse; Growth factor bioactivity; Supraspinatus tendon; Coculture of mesenchymal stem cells; Tissue engineering; Shoulder joint Rotator cuff; Tendons Wounds and injuries Healing; Heparin; Biomedical materials
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APA (6th Edition):
Seto, S. P. (2014). The development of heparin-based materials for tissue engineering applications to treat rotator cuff tendon injuries. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/51898
Chicago Manual of Style (16th Edition):
Seto, Song P. “The development of heparin-based materials for tissue engineering applications to treat rotator cuff tendon injuries.” 2014. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/51898.
MLA Handbook (7th Edition):
Seto, Song P. “The development of heparin-based materials for tissue engineering applications to treat rotator cuff tendon injuries.” 2014. Web. 10 Apr 2021.
Vancouver:
Seto SP. The development of heparin-based materials for tissue engineering applications to treat rotator cuff tendon injuries. [Internet] [Doctoral dissertation]. Georgia Tech; 2014. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/51898.
Council of Science Editors:
Seto SP. The development of heparin-based materials for tissue engineering applications to treat rotator cuff tendon injuries. [Doctoral Dissertation]. Georgia Tech; 2014. Available from: http://hdl.handle.net/1853/51898
23.
Lee, Christopher S. D.
Directing the paracrine actions of adipose stem cells for cartilage regeneration.
Degree: PhD, Biomedical Engineering, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/44713
► Current cartilage repair methods are ineffective in restoring the mechanical and biological functions of native hyaline cartilage. Therefore, using the paracrine actions of stem cell…
(more)
▼ Current cartilage repair methods are ineffective in restoring the mechanical and biological functions of native hyaline cartilage. Therefore, using the paracrine actions of stem cell therapies to stimulate endogenous cartilage regeneration has gained momentum. Adipose stem cells (ASCs) are an attractive option for this endeavor because of their accessibility, chondrogenic potential, and secretion of factors that promote connective tissue repair. In order to use the factors secreted by ASCs to stimulate cartilage regeneration, the signaling pathways that affect postnatal cartilage development and morphology need to be understood. Next, approaches need to be developed to tailor the secretory profile of ASCs to promote cartilage regeneration. Finally, delivery methods that localize ASCs within a defect site while facilitating paracrine factor secretion need to be optimized.
The overall objective of this thesis was to develop an ASC therapy that could be effectively delivered in cartilage defects and stimulate regeneration via its paracrine actions. The general hypothesis was that the secretory profile of ASCs can be tailored to enhance cartilage regeneration and be effectively delivered to regenerate cartilage in vivo. The overall approach used the growth plate as an initial model to study changes in postnatal cartilage morphology and the molecular mechanisms that regulate it, different media treatments and microencapsulation to tailor growth factor production, and alginate microbeads to deliver ASCs in vivo to repair cartilage focal defects.
Advisors/Committee Members: Boyan, Barbara D. (Committee Chair), Guldberg, Robert E. (Committee Member), Murphy, Mary (Committee Member), Sambanis, Anthanassios (Committee Member), Schwartz, Zvi (Committee Member).
Subjects/Keywords: Stem cells; Cartilage; Paracrine factors; Connective tissues; Connective tissues Growth; Chondrogenesis
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APA (6th Edition):
Lee, C. S. D. (2012). Directing the paracrine actions of adipose stem cells for cartilage regeneration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/44713
Chicago Manual of Style (16th Edition):
Lee, Christopher S D. “Directing the paracrine actions of adipose stem cells for cartilage regeneration.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/44713.
MLA Handbook (7th Edition):
Lee, Christopher S D. “Directing the paracrine actions of adipose stem cells for cartilage regeneration.” 2012. Web. 10 Apr 2021.
Vancouver:
Lee CSD. Directing the paracrine actions of adipose stem cells for cartilage regeneration. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/44713.
Council of Science Editors:
Lee CSD. Directing the paracrine actions of adipose stem cells for cartilage regeneration. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/44713
24.
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 ·
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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 10, 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. 10 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 10].
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
25.
Uhrig, Brent A.
Tissue regeneration in composite injury models of limb trauma.
Degree: PhD, Mechanical Engineering, 2013, Georgia Tech
URL: http://hdl.handle.net/1853/49080
► Severe extremity trauma often involves significant damage to multiple tissue types, including bones, skeletal muscles, peripheral nerves, and blood vessels. Such injuries present unique challenges…
(more)
▼ Severe extremity trauma often involves significant damage to multiple tissue types, including bones, skeletal muscles, peripheral nerves, and blood vessels. Such injuries present unique challenges for reconstruction, and improving structural and functional outcomes of intervention remains a pressing, unmet clinical need. While tissue engineering/regenerative medicine (TE/RM) therapeutics offer promising potential to overcome the status quo limitations of surgical reconstruction, very few products have transitioned to clinical practice. Improving treatment options will likely require advancing our understanding of the biological interactions occurring in the repair of damaged tissues.
Bone tissue is known to be innervated and highly vascularized, and both tissue types are involved in normal bone physiology. However, the degree to which these tissue relationships influence the repair of large, multi-tissue defects remains unknown. Accordingly, the goal of this thesis was to investigate tissue regeneration in two novel composite injury models. First, we characterized interactions in a composite bone and nerve injury model where a segmental bone defect was combined with a peripheral nerve gap. Our results indicated that although tissue regeneration was not impaired, the composite injury group experienced a marked functional deficit in the operated limb compared to single-tissue injury. Second, we developed a model of composite bone and vascular extremity trauma by combining a critically-sized segmental bone defect with surgically-induced hind limb ischemia to evaluate the effects on BMP-2-mediated bone repair. Interestingly, our results demonstrated a stimulatory effect of the recovery response to ischemia on bone regeneration. Finally, we investigated early vascular growth and gene expression as potential mechanisms coupling the response to ischemia with bone defect repair. Although the response to ischemia promoted robust vascular growth in the thigh, it did not directly augment vascularization at the site of bone regeneration. In addition, the stimulatory effects of ischemia on bone regeneration could not be explained by gene expression alone based on the genes and time points investigated.
Taken together, this thesis presents pioneering work on a new thrust of TE/RM research – tissue regeneration in models of composite injury. This work has provided new insights on the complexity of composite tissue repair, specifically in regard to the relationship between vascular tissue growth and bone healing. Going forward, successful leverage of models of composite tissue injuries will provide valuable test beds for screening new technologies, advance the understanding of tissue repair biology, and ultimately, may produce new therapeutic interventions for limb salvage and reconstruction that improve outcomes for extremity trauma patients.
Advisors/Committee Members: Guldberg, Robert E. (advisor), Bellamkonda, Ravi V. (committee member), Gilbert, Shawn R. (committee member), Taylor, W. Robert (committee member), Temenoff, Johnna S. (committee member).
Subjects/Keywords: Composite tissue injury; Tissue engineering; Bone regeneration; Hind limb ischemia; Vascularization; Nerve regeneration; Regenerative medicine; Nervous system Regeneration; Regeneration (Biology); Wound healing
…my time at Georgia Tech was all work and no play,
I also developed some phenomenal…
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APA (6th Edition):
Uhrig, B. A. (2013). Tissue regeneration in composite injury models of limb trauma. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/49080
Chicago Manual of Style (16th Edition):
Uhrig, Brent A. “Tissue regeneration in composite injury models of limb trauma.” 2013. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/49080.
MLA Handbook (7th Edition):
Uhrig, Brent A. “Tissue regeneration in composite injury models of limb trauma.” 2013. Web. 10 Apr 2021.
Vancouver:
Uhrig BA. Tissue regeneration in composite injury models of limb trauma. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/49080.
Council of Science Editors:
Uhrig BA. Tissue regeneration in composite injury models of limb trauma. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/49080
26.
Miller, Andrew Todd.
Fatigue and cyclic loading of 3D printed soft polymers for orthopedic applications.
Degree: PhD, Mechanical Engineering, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/58292
► Processing-structure-property relationships were developed for several popular, soft biomedical polymers under fatigue loading to assist in the use and success of such polymers in load-bearing…
(more)
▼ Processing-structure-property relationships were developed for several popular, soft biomedical polymers under fatigue loading to assist in the use and success of such polymers in load-bearing orthopedic applications. Results demonstrated that materials with sufficient energy dissipation at the testing temperature, such as polycarbonate urethane (PCU), resisted fatigue fracture under cyclic compressive loading however also demonstrated cyclic ratcheting. Bovine meniscal tissue demonstrated similar ratcheting behavior with a lack of fatigue fracture. Further studies on PCU demonstrated an increase in monotonic stiffness, shear failure stress, and improvements in tensile fatigue from a stress-based standpoint with increasing hard segment content. Effects of hard segment content on tensile failure strain, and strain-based fatigue performance, were more complex and seemingly influenced by interaction between phases. Results demonstrated that the fused deposition modeling (FDM) printing process is a very effective processing method for PCU as printed samples matched or exceeded injection molded samples in terms of monotonic tension, compression, shear, and tensile fatigue performance. Lastly, the effects of printed architecture on fatigue performance were examined for FDM PCU as well as an elastomeric polyurethane (EPU) printed via continuous liquid interface production. Results indicated that both materials were relatively tolerant of architectures and notches. Introduction of porosity led to a decrease in tensile failure stress based on gross area as expected, without a significant effect on tensile failure strain. Effects on fatigue performance were small and were found to be dependent on notch severity, with the largest effects in the high cycle regime.
Advisors/Committee Members: Guldberg, Robert E. (advisor), Gall, Ken (committee member), Temenoff, Johnna S. (committee member), Willett, Nick (committee member), Shofner, Meisha L. (committee member).
Subjects/Keywords: Elastomer; Fatigue; 3D printing; Fused deposition modeling; Continuous liquid interface production; Printed architecture; Biomedical polymers; Orthopedic polymers
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APA (6th Edition):
Miller, A. T. (2017). Fatigue and cyclic loading of 3D printed soft polymers for orthopedic applications. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58292
Chicago Manual of Style (16th Edition):
Miller, Andrew Todd. “Fatigue and cyclic loading of 3D printed soft polymers for orthopedic applications.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/58292.
MLA Handbook (7th Edition):
Miller, Andrew Todd. “Fatigue and cyclic loading of 3D printed soft polymers for orthopedic applications.” 2017. Web. 10 Apr 2021.
Vancouver:
Miller AT. Fatigue and cyclic loading of 3D printed soft polymers for orthopedic applications. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/58292.
Council of Science Editors:
Miller AT. Fatigue and cyclic loading of 3D printed soft polymers for orthopedic applications. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/58292
27.
Reece, David Sterling.
In vivo and in vitro evaluation of an ECM-based OA therapy.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2017, Georgia Tech
URL: http://hdl.handle.net/1853/60694
► Osteoarthritis (OA) is a disease estimated to affect 10-12% of the adult US population and there are currently no clinically proven disease modifying therapies. Micronized…
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▼ Osteoarthritis (OA) is a disease estimated to affect 10-12% of the adult US population and there are currently no clinically proven disease modifying therapies. Micronized dehydrated human amnion/chorion membrane (μ-dHACM) is an extracellular matrix (ECM)-based therapy that has been shown to attenuate OA progression in rats but many of the underlying mechanisms and design variables involved with μ-dHACM are not well understood. The primary objective of this proposed research is to investigate factors that influence the therapeutic benefit of potential disease modifying OA therapies. Specifically this work (i) developed a technological platform using contrast enhanced µCT to quantify cartilage surface roughness and utilized this platform to characterize early articular joint tissue changes in a rat OA model (Chapter 3), (ii) used contrast enhanced µCT and near-infrared fluorescent tracking to evaluate the effect of μ-dHACM particle size on the intra-articular residence time and therapeutic efficacy in a rat OA model (Chapter 4), and (iii) characterized and utilized synoviocyte and cartilage co-culture models to investigate the effect of interactions between synovium and μ-dHACM on OA disease progression (Chapter 5). This work increased the scientific community’s understanding of the factors influencing the efficacy of μ-dHACM treatment for OA. It also increased the characterization and understanding of the in vivo and in vitro models used to investigate these factors.
Advisors/Committee Members: Guldberg, Robert E. (advisor), Temenoff, Johnna S. (committee member), Roy, Krishnendu (committee member), Ethier, C. Ross (committee member), Koob, Thomas J. (committee member).
Subjects/Keywords: Osteoarthritis; MicroCT imaging; Pre-clinical models; Cellular models; Amniotic membrane; ECM therapies
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APA (6th Edition):
Reece, D. S. (2017). In vivo and in vitro evaluation of an ECM-based OA therapy. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60694
Chicago Manual of Style (16th Edition):
Reece, David Sterling. “In vivo and in vitro evaluation of an ECM-based OA therapy.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/60694.
MLA Handbook (7th Edition):
Reece, David Sterling. “In vivo and in vitro evaluation of an ECM-based OA therapy.” 2017. Web. 10 Apr 2021.
Vancouver:
Reece DS. In vivo and in vitro evaluation of an ECM-based OA therapy. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/60694.
Council of Science Editors:
Reece DS. In vivo and in vitro evaluation of an ECM-based OA therapy. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/60694
Georgia Tech
28.
Carnell, Peter Hamilton.
Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach.
Degree: PhD, Mechanical Engineering, 2004, Georgia Tech
URL: http://hdl.handle.net/1853/4811
► Hypertension is a major risk factor for coronary artery disease, stroke, and kidney disease. Many studies suggest that elevated intramural stresses caused by hypertension may…
(more)
▼ Hypertension is a major risk factor for coronary artery disease, stroke, and kidney disease. Many studies suggest that elevated intramural stresses caused by hypertension may stimulate inflammatory changes, but little has been done to ascertain whether inflammation and stress are spatially correlated. Such correlations are a first step in identifying the mechanisms that may relate intramural stress to disease so that more effective clinical treatments may be developed.
Arterial branches exhibit local stress peaks and are focal points for the onset of disease. They are thus a logical place to examine whether high stresses spatially correlate with increased inflammation. This research seeks to 1) develop a histology-based method to reconstruct small arterial branches; 2) use finite element analysis to evaluate intramural stresses where experimental testing is of limited use; 3) quantify biological measures of inflammation; and 4) visually and statistically compare the distribution of stress with the distribution of inflammation.
Hypertension was induced in Sprague-Dawley rats by implanting Angiotensin II pumps for 7 days or 21 days. Normotensive rats were used as controls. To preserve morphology the mesentery was pressure-fixed in situ, harvested, processed, and embedded in glycol methacrylate resin. Branch geometry was reconstituted from serial sections. This involved: correcting deformations caused by sectioning; aligning sections into an image stack; identifying vessel boundaries; creating a surface suitable for finite element analysis; reducing the branch geometry to a midplane surface; and using Ansys (Ansys, Inc.) to mesh the midplane surface with a variable-thickness shell element.
The pattern of inflammation was characterized by measuring the local density of monocytes and macrophages. Cell density was expressed as a distribution on the branch surface, which simplified visualization and facilitated statistical comparisons of inflammation with stress.
Both intramural stresses and inflammation were greater near branches during hypertension. In most cases, however, high stresses and high cell density were not spatially collocated. The onset of an adaptive response may reduce the strength of this correlation. Maximal wall tension, defined as the maximal midplane stress multiplied by the wall thickness, was elevated near branches and strongly correlated with cell density.
Advisors/Committee Members: Vito, Raymond P. (Committee Chair), Giddens, Don P. (Committee Member), Guldberg, Robert E. (Committee Member), Levenston, Marc E. (Committee Member), Taylor, W. Robert (Committee Member).
Subjects/Keywords: Statistical analysis; 3D reconstruction; Hypertension
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APA (6th Edition):
Carnell, P. H. (2004). Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/4811
Chicago Manual of Style (16th Edition):
Carnell, Peter Hamilton. “Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach.” 2004. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/4811.
MLA Handbook (7th Edition):
Carnell, Peter Hamilton. “Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach.” 2004. Web. 10 Apr 2021.
Vancouver:
Carnell PH. Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach. [Internet] [Doctoral dissertation]. Georgia Tech; 2004. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/4811.
Council of Science Editors:
Carnell PH. Intramural Stress and Inflammation in Arterial Branches: A Histology-Based Approach. [Doctoral Dissertation]. Georgia Tech; 2004. Available from: http://hdl.handle.net/1853/4811
Georgia Tech
29.
Sucosky, Philippe.
Flow Characterization and Modeling of Cartilage Development in a Spinner-Flask Bioreactor.
Degree: PhD, Mechanical Engineering, 2005, Georgia Tech
URL: http://hdl.handle.net/1853/6875
► Bioreactors are devices used for the growth of tissues in a laboratory environment. They exist in many different forms, each designed to enable the production…
(more)
▼ Bioreactors are devices used for the growth of tissues in a laboratory environment. They exist in many different forms, each designed to enable the production of high-quality tissues. The dynamic environment within bioreactors is known to significantly affect the growth and development of the tissue. Chondrocytes, the building blocks of articular cartilage, for example, are stimulated by mechanical stresses such as shear, as compared with those in tissues grown under static incubation conditions. On the other hand, high shear can damage cells. Consequently the shear-stress level has to be controlled in order to optimize the design and the operating conditions of bioreactors.
Spinner flasks have been used for the production of articular cartilage in vitro. Assuming the existence of a relation between the cellular glycosaminoglycan (GAG) synthesis and the local shear stresses on the construct surfaces, this research focuses on the development of a model for cartilage growth in such devices. The flow produced in a model spinner flask is characterized experimentally using particle-image velocimetry (PIV). A computational fluid dynamic (CFD) model validated with respect to the laboratory measurements is constructed in order to predict the local shear stresses on the construct surfaces. Tissue growth experiments conducted in the prototype bioreactor permit construct histologies and GAG contents to be analyzed and then correlated with the shear-stress predictions. The integration of this relation into the CFD model enables the prediction of GAG synthesis through convective effects. Coupling this convective model to an existing diffusive model produces a complete cartilage-growth model for use in aiding the optimization of existing bioreactors, and in the design of new ones.
Advisors/Committee Members: Neitzel, G. Paul (Committee Chair), Guldberg, Robert E. (Committee Member), Smith, Marc K. (Committee Member), Vunjak-Novakovic, Gordana (Committee Member), Yeung, Pui-Kuen (Committee Member).
Subjects/Keywords: Tissue engineering; Cartilage; Computational fluid dynamics; Tissue growth model; Spinner-flask bioreactor; Particle image velocimetry; Bioreactors Design and construction; Tissues; Articular cartilage Mechanical properties
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APA ·
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APA (6th Edition):
Sucosky, P. (2005). Flow Characterization and Modeling of Cartilage Development in a Spinner-Flask Bioreactor. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/6875
Chicago Manual of Style (16th Edition):
Sucosky, Philippe. “Flow Characterization and Modeling of Cartilage Development in a Spinner-Flask Bioreactor.” 2005. Doctoral Dissertation, Georgia Tech. Accessed April 10, 2021.
http://hdl.handle.net/1853/6875.
MLA Handbook (7th Edition):
Sucosky, Philippe. “Flow Characterization and Modeling of Cartilage Development in a Spinner-Flask Bioreactor.” 2005. Web. 10 Apr 2021.
Vancouver:
Sucosky P. Flow Characterization and Modeling of Cartilage Development in a Spinner-Flask Bioreactor. [Internet] [Doctoral dissertation]. Georgia Tech; 2005. [cited 2021 Apr 10].
Available from: http://hdl.handle.net/1853/6875.
Council of Science Editors:
Sucosky P. Flow Characterization and Modeling of Cartilage Development in a Spinner-Flask Bioreactor. [Doctoral Dissertation]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/6875
Georgia Tech
30.
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 ·
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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 April 10, 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. 10 Apr 2021.
Vancouver:
Reyes CD. Collagen- and Fibronectin-Mimetic Integrin-Specific Surfaces That Promote Osseointegration. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Apr 10].
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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