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
to Zotero / EndNote / Reference
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 13, 2021.
MLA Handbook (7th Edition):
Kinney, Ramsey Christian. “The role of sexual dimorphism in cartilage tissue regeneration.” 2008. Web. 13 Apr 2021.
Kinney RC. The role of sexual dimorphism in cartilage tissue regeneration. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Apr 13].
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