Date of Award
Doctor of Philosophy (PhD)
Burg, Karen J.L.
The need for soft tissue reconstruction or augmentation has increased continuously over the years. This need is compounded by patients suffering from post-traumatic repair and congenital soft-tissue deformities. All the current options available to treat the soft tissue deformities have inherent difficulties associated with them. Hence, more research is needed to come up with a better solution to this problem which is only going to increase in magnitude. Tissue engineering is a relatively new technique which has the potential to deliver a cell-based device which can overcome the problems associated with traditional therapies. However, before it becomes clinically viable we need to understand several key issues. The goal of these studies is to employ the principles of tissue engineering to better comprehend the interaction between cells and the implant on which they are seeded and their surrounding environment in order to facilitate the design of improved devices. The long-term hypothesis, beyond the scope of the proposed work, is that through the control of the level of cellular differentiation in a tissue-engineered device, one can influence the viability of the device post-implantation. Specifically, the aim of these studies was to characterize different means by which the differentiation of adult stem cells could be modulated in a tissue engineered device. The first two studies explore the possibility of using the surface texture of a scaffold to control the level of cellular differentiation. In the first study, polymer scaffold with microgrooves were employed to study the role of the defined surface texture in the differentiation process. In the second study, similar scaffolds were used to investigate the onset of the differential rates of cellular differentiation in the adipose system and the amount of leptin secreted by these cells was compared. Polynomial models were proposed to model the leptin released over time. The next study investigated the possibility of using the scaffold material and cell size to modulate the differentiation of adult stem cells. Different ECM molecules (laminin and collagen I) were evaluated for their efficacy in controlling cellular proliferation and differentiation. Laminin was found to enhance adipogenesis more effectively than collagen I. The role of cell size in determining the functionality of differentiated adipocytes was also explored in this study. Modified inkjet printer was used to create controlled width of adhesive area for cellular adhesion surrounded by non-adhesive area. It was found that printed adhesive areas did not bind strongly enough to the glass substrate to support the, rather large, differentiated adipocytes leading to detachment of the cell sheet. The aim of the final study was to study the behavior of the differentiated adipocytes in a 3D environment. Three different scaffold types were investigated: collagen microcarriers, laminin-coated polylactide beads and control polylactide beads. It was found that cells seeded on collagen microcarriers accumulated the highest amount of lipid and that coating the surface of polylactide beads with laminin significantly enhanced their ability to affect adipogenesis and cellular adhesion. The proposed 3D system could also be use as a tunable, in vitro test system to study adipogenesis and its related pathologies.
Chaubey, Aditya, "Differentiation Modulation of Adult Stem Cells in an Adipose System" (2007). All Dissertations. 118.