Tissue engineering offers a potential alternative therapy to overcome the limitations of organ transplantation, by employing biomaterials as scaffold for cell growth. For example, poly-lactic-co-glycolic acid (PLGA) is a synthetic biomaterial widely used in tissue engineering. However, the hydrophobicity of PLGA results in scaffolds that are poorly wettable, and which, therefore, possess poor mass transfer properties for the delivery of nutrients and the removal of waste. The present work aimed to develop more hydrophilic PLGA scaffolds, specifically hollow fibre membranes, within a bioreactor system, which enables co-culture of cells in order to direct stem cell differentiation. Large quantities of costly growth factors are required over long periods for stem cell differentiation. Therefore, this project also aimed to use a cell line as a “factory” for the inexpensive, in situ growth factor production. Hollow fibres were fabricated by wet spinning and a hydrophilic polymer, polyvinyl alcohol (PVA), was added to the PLGA solution at three different concentrations (1.25, 2.5, 5% w/w) in order to obtain a more hydrophilic membrane. Results indicated that 5% PVA-PLGA hollow fibres were the only membranes which allowed permeation of water, BSA and cell-secreted hepatocyte growth factor (HGF), thus indicating that they are the most suitable membranes for use in bioreactor devices. However, these membranes failed to improve cell-attachment. Cell secreted HGF was shown to be more stable in a dynamic culture environment than commercial HGF, thus suggesting its suitability for applications in bioreactor devices. However, using both commercial and cell-secreted HGF, mesenchymal stem cell differentiation was unsuccessful. In conclusion, this work has developed a hollow fibre membrane which is more permeable to water and proteins for a higher mass transfer of nutrients, and has realised a model system for the inexpensive production of growth factors for use in bioreactor devices and the differentiation of stem cells.
|Date of Award||1 Jul 2010|
|Supervisor||Paul De Bank (Supervisor) & Julian Chaudhuri (Supervisor)|
- stem cells
- hollow fibre