Modeling of the dispensing-based tissue scaffold fabrication processes
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Tissue engineering is an emerging area with an aim to create artificial tissues or organs by employing methods of biology, engineering and material science. In tissue engineering, scaffolds are three-dimensional (3D) structure made from biomaterials with highly interconnected pore networks or microstructure, and are used to provide the mechanical and biological cues to guide cell differentiation in order to form desired three-dimensional tissues or functional organs. Hence, tissue scaffold plays a critical role in tissue engineering. However, fabrication of such scaffolds has proven to be a challenge task. One important barrier is the inability to fabricate scaffolds with designed pore size and porosity to mimic the microstructure of native tissue. Another issue is the prediction of process-induced cell damage in the cell-involved scaffold fabrication processes. By addressing these key issues involved in the scaffold fabrication, this research work is aimed at developing methods and models to represent the dispensing-based solid free form scaffold fabrication process with and without the presence of living cells. The microstructure of scaffolds, featured by the pore size and porosity, has shown to significantly affect the biological and mechanical properties of formed tissues. As such, during fabrication process the ability to predict and determine scaffold pore size and porosity is of great importance. In the first part of this research, the flow behaviours of the scaffold materials were investigated and a model of the flow rate of material dispensed during the scaffold fabrication was developed. On this basis, the pore size and porosity of the scaffolds fabricated were represented by developing a mathematical model. Scaffold fabrication experiments using colloidal gels with different hydroxylapatite volume fractions were carried out and the results obtained agreed with those from model simulations, indicating the effectiveness of the models developed. The availability of these models makes it possible to control the scaffold fabrication process rigorously, instead of relying upon a trial and error process as previously reported. In the scaffold fabrication process with the presence of living cells, cells are continuously subjected to mechanical forces. If the forces exceed certain level and/or the forces are applied beyond certain time periods, cell damage may result. In the second part of this research, a method to quantify the cell damage in the bio-dispensing process is developed. This method consists of two steps: one step is to establish cell damage models or laws to relate cell damage to the hydrostatic pressure / shear stress that is applied on cells; and the second step is to represent the process-induced forces that cells experience during the bio-dispensing process and then apply the established cell damage law to model the percent cell damage in the process. Based on the developed method, the cell damage percents in the scaffold fabrication processes that employ two types of dispensing needles, i.e., tapered and cylindrical needles, respectively, were investigated and compared. Also, the difference in cell damage under the high and low shear stress conditions was investigated, and a method was developed to establish the cell damage law directly from the bio-dispensing process. To validate the aforementioned methods and models, experiments of fabricating scaffolds incorporating Schwann cells or 3T3 fibroblasts were carried out and the percent cell damage were measured and compared with the simulation results. The validated models allow one to determine of the influence of process parameters, such as the air pressure applied to the process and the needle geometry, on cell damage and then optimize these values to preserve cell viability and/or achieve the desired cell distribution within the scaffolds.
DegreeDoctor of Philosophy (Ph.D.)
CommitteeGander, Bob; Rinker, Kristina; Zhang, Chris; Bugg, Jim
Copyright DateJuly 2010