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published_or_final_version / Dental Surgery / Master / Master of Dental Surgery

HA (Hyaluronan, hyaluronic acid) is a predominant component of the extracellular matrix and plays diverse roles in the process of wound healing. The major significance of the biological functions of HA in wound healing arise from early studies showing that rich and prolonged existence of HA is associated with the fetal scarless wound healing. It has been hypothesized that adult wound healing can be modulated by the application of exogenous HA to make the process of wound repair more like regeneration. / In this thesis, the effects of molecular weight and concentration of HA on the biological behavior of human fibroblasts and keratinocytes have been investigated in both monolayer and 3D culture models. In addition, the mechanism for the HA-induced biological effects has also been investigated. Previous laboratory studies have primarily focused on individual cell type, but in wound healing in vivo there is considerable interaction between the keratinocytes and fibroblasts. The role of HA in keratinocyte-fibroblast interactions is not clear, so an organotypical culture model was used to investigate the keratinocyte differentiation and stratification and basement membrane formation with and without fibroblasts to explore the effect of HA on keratinocyte-fibroblast interactions. / The experimental data suggest that exogenous application of HA modulates the process of wound healing so that it becomes more like regeneration by regulating the biological functions of human keratinocytes and fibroblasts, including their interaction. By further understanding the HA-induced cell biological phenomena and involved mechanisms new approaches for wound care may be revealed. / The skin is the largest organ in the body. It consists of an outer layer, the epidermis supported by a connective tissue matrix, the dermis. The keratinocyte and fibroblast are the major cell types in the epidermis and dermis respectively. When the skin is damaged, the body will active a cascade of mechanisms to restore the tissue integrity. If the damaged tissue is limited to the epidermis, it will be restored by the process of regeneration. Regeneration involves the replacement of injured tissue by new tissue which has both form and function identical to the original tissue. If the defect involves the dermis, healing is achieved by repair which results in permanent scar formation. Wound healing is an extremely complex biological process which involves several overlapping steps; inflammation, granulation tissue formation and remodeling which are coordinated by various cell types, growth factors, cytokines and extracellular matrix components including hyaluronan. / Whilst there have been many studies looking at the effect of HA on different cell types using varying molecular parameters, concentrations and sources of HA, the result are often contradictory. Even the endogenous or exogenous application of HA have been reported to have opposite effects on cell behavior. / Gu, Hua. / Adviser: Andrew Bard. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0216. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 116-135). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.