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Title:	Bacterial nanocellulose/acrylic acid hydrogel as a cell carrier for the delivery of keratinocytes and fibroblasts to promote healing in full-thickness skin wound
Authors:	Evelyn Loh Yun Xi (P86806)
Supervisor:	Cairul, Prof
Keywords:	Wound Bacterial Fibroblasts Dissertations, Academic -- Malaysia
Issue Date:	9-Jun-2019
Description:	While most skin wound can heal naturally, healing of larger and deeper wounds may take a long time and can result in complications. The gold standard of treatment for major skin loss is split-skin grafting but it is associated with certain disadvantages, including limited availability of healthy skin, formation of scarring, and risk of infection. Additionally, some of the limitation of current cell-based skin regenerative products available commercially are its high cost, use of allogeneic cells that carries the risk of rejection, and the long cell culturing duration. The main objective of this study was to investigate the potential of electron-beam irradiation crosslinked bacterial nanocellulose/acrylic acid (BNC/AA) hydrogel as cell carrier to deliver autologous human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) for immediate treatment of full-thickness skin loss. Gel fraction, swelling, water retention, hardness, adhesive force (swelled form), porosity, and hydrophilicity (dry) of 4 hydrogel formulations were found to differ based on the degree of cross-linking and the amount of AA grafted into it. Nevertheless, water vapor transmission rate, pore size distribution, hydrophilicity (semidry), and topography were comparable between all formulations, resulting in a similar cell attachment, viability, and proliferation characteristic. Collectively, the findings suggested that the 307045 hydrogel may be the most suitable formulation as both a cell carrier and wound dressing. The hydrogel was not compatible with HEK as viability was low even on day 1. Therefore, further studies were proceeded with only the use of HDF. The in vitro studies revealed that the hydrogel had excellent cell attachment of more than 80% at 4 hours, maintained cell viability and morphology of HDF with limited migration, facilitated rapid transfer of live HDF, upregulated 8 important wound healing genes (IL6, IL10, MMP2, CTSK, FGF7, GMCSF, TGFB1, and COX2) and downregulated 1 gene (F3). Analysis using bioinformatics predicted that these gene changes are favourable for wound healing. Peripheral blood mononuclear cell proliferation test showed no immune response towards the hydrogel. Although studies in athymic mice exhibited no significant changes in wound closure and histological aspect between no treatment, hydrogel alone, hydrogel with 50,000 HDF and hydrogel with 100,000 HDF groups, there were indication at the molecular and protein level on day 7 that wound healing was faster and better in the hydrogel with HDF group. By day 14, all groups yielded similar results as the wound were already healed. The hydrogel performed its function as a cell carrier because approximately 50% of HDF were transferred to the wound site on day 1 with traces of human cell found on day 7. In conclusion, since the wound size on the mice was relatively small, when no treatment was given, the wound had the ability to heal quickly but in larger and difficult to heal wounds, the small treatment benefits of hydrogel with HDF at the gene and protein level may potentially lead to a significant visible acceleration of wound healing.,Degree of Doctor of Philosophy
Pages:	205
Call Number:	Tesis Cd WO700.L833b 2019
Publisher:	UKM, Kuala Lumpur
Appears in Collections:	Faculty of Pharmacy / Fakulti Farmasi

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