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You searched for +publisher:"Georgia Tech" +contributor:("Sambanis, Anthanassios"). Showing records 1 – 3 of 3 total matches.

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1. Kinney, Ramsey Christian. The role of sexual dimorphism in cartilage tissue regeneration.

Degree: PhD, Biomedical Engineering, 2008, Georgia Tech

Osteoarthritis is a degenerative joint disease characterized by progressive erosion of the articular cartilage. Epidemiological studies have established a relationship between osteoarthritis and menopause suggesting that estrogen may be important in the development of cartilage regeneration therapies. The overall goal of this research project was to advance the field of cartilage tissue regeneration by investigating the role of 17 ß -estradiol (E2), an active estrogen metabolite, on the chondrocyte phenotype. The central hypothesis was that E2 plays an important and sex-specific role in regulating chondrogenesis. Specific Aim-1 focused on establishing and characterizing a primary human articular chondrocyte (HAC) cell source, and then examining the response of the cells in culture to E2. It was demonstrated that the response of HACs to E2 treatment was sex-specific despite both male and females cells expressing estrogen receptors. Female HACs showed changes in proliferation, matrix production, and differentiation while male cells did not. In addition, the female response was regulated through a rapid membrane signaling pathway mediated by protein kinase C. Specific Aim-2 involved establishing an ovariectomized animal model to investigate the effects of E2 on orthopaedic tissue implants. Human demineralized bone matrix (DBM) was implanted intramuscularly into female nude mice and rats. Ovariectomy was shown to reduce the ability of DBM to induce the formation of cartilage and bone tissue. Moreover, the inductive properties of DBM were reestablished with subcutaneous E2 supplementation. Specific Aim-3 entailed developing and characterizing a microencapsulation method for in vitro culture and in vivo delivery of chondrocytes to study the effects of E2 on chondrogenesis. Rat growth plate chondrocytes and HACs were microencapsulated in alginate using an extrusion method in conjunction with high electrostatic potential. Chondrocytes maintained their phenotype in alginate suspension but were unable to form cartilage tissue when implanted into our animal model. Further optimization of the system is required before the role of E2 on chondrogenesis of tissue engineered constructs can be determined. In summary, our results suggest that the successful production of tissue engineered therapies will likely depend on understanding and manipulating the actions of sex hormones in both the in vitro and in vivo environment. Advisors/Committee Members: Boyan, Barbara (Committee Chair), Bonassar, Lawrence (Committee Member), Sambanis, Anthanassios (Committee Member), Schwartz, Zvi (Committee Member), Wick, Timothy (Committee Member).

Subjects/Keywords: Estrogen; Chondrocyte; Tissue engineering; Sex-specific; Alginate; Electrostatic microencapsulation; Sexual dimorphism (Animals); Articular cartilage; Regeneration (Biology); Osteoarthritis; Estrogen

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

APA (6th Edition):

Kinney, R. C. (2008). The role of sexual dimorphism in cartilage tissue regeneration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/28225

Chicago Manual of Style (16th Edition):

Kinney, Ramsey Christian. “The role of sexual dimorphism in cartilage tissue regeneration.” 2008. Doctoral Dissertation, Georgia Tech. Accessed April 16, 2021. http://hdl.handle.net/1853/28225.

MLA Handbook (7th Edition):

Kinney, Ramsey Christian. “The role of sexual dimorphism in cartilage tissue regeneration.” 2008. Web. 16 Apr 2021.

Vancouver:

Kinney RC. The role of sexual dimorphism in cartilage tissue regeneration. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1853/28225.

Council of Science Editors:

Kinney RC. The role of sexual dimorphism in cartilage tissue regeneration. [Doctoral Dissertation]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/28225

2. Lee, Christopher S. D. Directing the paracrine actions of adipose stem cells for cartilage regeneration.

Degree: PhD, Biomedical Engineering, 2012, Georgia Tech

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

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 16, 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. 16 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 16]. 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


Georgia Tech

3. Gersbach, Charles Alan. Runx2-Genetically Engineered Skeletal Myoblasts for Bone Tissue Engineering.

Degree: PhD, Biomedical Engineering, 2006, Georgia Tech

Bone tissue engineering is a promising approach to address the limitations of currently used bone tissue substitutes. However, an optimal cell source for the production of osteoblastic matrix proteins and mineral deposition has yet to be defined. In response to this deficiency, ex vivo gene therapy of easily accessible non-osteogenic cells, such as skeletal myoblasts, has become a prevalent strategy for inducing an osteoblastic phenotype. The majority of these approaches focus on constitutive overexpression of soluble osteogenic growth factors such as bone morphogenetic proteins (BMPs). In order to avoid aberrant effects of unregulated growth factor secretion, this work focuses on delivery of the osteoblastic transcription factor Runx2 as an autocrine osteogenic signal under the control of an inducible expression system. The overall objective of this research was to engineer an inducible cell source for bone tissue engineering that addresses the limitations of current cell-based approaches to orthopedic regeneration. Our central hypothesis was that inducible Runx2 overexpression in skeletal myoblasts would stimulate differentiation into a regulated osteoblastic phenotype. We have demonstrated that Runx2 overexpression stimulates transdifferentiation of primary skeletal myoblasts into a mineralizing osteoblastic phenotype. Furthermore, we have established Runx2-engineered skeletal myoblasts as a potent cell source for bone tissue engineering applications in vitro and in vivo, similar to BMP-2-overexpressing controls. Finally, we exogenously regulated osteoblastic differentiation by myoblasts engineered to express a tetracycline-inducible Runx2 transgene. This conversion into an osteoblastic phenotype was inducible, repressible, recoverable after suppression, and dose-dependent with tetracycline concentration. This work is significant because it addresses cell sourcing limitations of bone tissue engineering, develops controlled and effective gene therapy methods for orthopedic regeneration, and establishes a novel strategy for regulating the magnitude and kinetics of osteoblastic differentiation. Advisors/Committee Members: Garcia, Andres (Committee Chair), Boyan, Barbara (Committee Member), Guldberg, Robert (Committee Member), Le Doux, Joseph (Committee Member), Pavlath, Grace (Committee Member), Sambanis, Anthanassios (Committee Member).

Subjects/Keywords: Cell therapy; Regenerative medicine; Gene therapy; Genetic engineering; Tissue engineering; Bone repair

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

APA (6th Edition):

Gersbach, C. A. (2006). Runx2-Genetically Engineered Skeletal Myoblasts for Bone Tissue Engineering. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/11600

Chicago Manual of Style (16th Edition):

Gersbach, Charles Alan. “Runx2-Genetically Engineered Skeletal Myoblasts for Bone Tissue Engineering.” 2006. Doctoral Dissertation, Georgia Tech. Accessed April 16, 2021. http://hdl.handle.net/1853/11600.

MLA Handbook (7th Edition):

Gersbach, Charles Alan. “Runx2-Genetically Engineered Skeletal Myoblasts for Bone Tissue Engineering.” 2006. Web. 16 Apr 2021.

Vancouver:

Gersbach CA. Runx2-Genetically Engineered Skeletal Myoblasts for Bone Tissue Engineering. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1853/11600.

Council of Science Editors:

Gersbach CA. Runx2-Genetically Engineered Skeletal Myoblasts for Bone Tissue Engineering. [Doctoral Dissertation]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/11600

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