THERMODYNAMICS OF POLYMER SOLUTION AND ITS APPLICATION IN 3D SCAFFOLD MANUFACTURING FOR USE IN TISSUE ENGINEERING

Lim, Sue Ann (2007). THERMODYNAMICS OF POLYMER SOLUTION AND ITS APPLICATION IN 3D SCAFFOLD MANUFACTURING FOR USE IN TISSUE ENGINEERING PhD Thesis, School of Engineering, University of Queensland.

       
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Author Lim, Sue Ann
Thesis Title THERMODYNAMICS OF POLYMER SOLUTION AND ITS APPLICATION IN 3D SCAFFOLD MANUFACTURING FOR USE IN TISSUE ENGINEERING
School, Centre or Institute School of Engineering
Institution University of Queensland
Publication date 2007
Thesis type PhD Thesis
Supervisor Professor Justin Cooper-White
Abstract/Summary Three dimensional polymeric scaffolds, which act as a cell transplant device, have been widely used in the field of tissue engineering as an approach to generate tissue replacements. This 3D construct plays an important role in determining the viability and functionality of the transplanted cells by providing a physical and chemical template for cells to attach, proliferate, migrate and finally restructure into functionalized tissue. In this study, a Thermally Induced Phase Separation (TIPS) technique is chosen as the main scaffold fabrication methodology. While this process is known to be a simple yet cost effective scaffold fabrication technique, a detailed understanding of the thermodynamic behaviour of polymer solutions undergoing thermal transition is required. By identifying the influence of scaffold processing conditions on the resultant scaffold morphology, a huge array of scaffold architectures could be created easily. Hence, the first aim of this thesis was to develop an understanding of the phase separation behaviour of a commonly used polymersolvent- nonsolvent system, that is PLGA-dioxane-water system. In the present study, the phase diagram of a PLGA-dioxane-water system was developed through simplifying a ternary system of PLGA-dioxane-water to a binary system of PLGA-dioxane and water as the two respective components. Flory’s lattice theory, together with the solution cloud point temperatures, were used to generate a complete phase diagram for this pseudo-binary system. Based on the calculated phase diagram, the effect of cooling rate, quenching temperature, polymer concentration and solvent/nonsolvent volume ratio on the expected morphology of the scaffold were described in detail. This resulting analysis method is seen to be very useful in defining the critical processing characteristics for manufacturing scaffolds using other polymer-solvent-nonsolvent systems. The second aim of the thesis was to develop a novel continuous scaffold fabrication procedure which incorporates traditional polymer extrusion processing (injection molding) in combination with TIPS. In an extrusion process, the final morphology of the product is controlled by the shear and pressure applied to the polymer blend or solution. Shear, in this study, was found to affect the scaffold morphology produced via a solid-liquid phase separation by disrupting the heat transfer gradient along the radius of the mold. Further, the influence of shear on the phase separation behaviour of a PLGA-dioxane-water system was also investigated. It was found that depending on the solution cloud point temperature, the shear rate applied and the polymer molecular weight, shear can induce either phase remixing or phase demixing behaviour. Generally, shear was found facilitate the formation of a bi-continuous structure by reducing the gap between the binodal and spinodal line. Overall, phase separation through spinodal decomposition was found to be encouraged by shear as it suppressed the formation of a dispersed droplet phase. This represents a significant outcome and allowed the production of layered scaffold structures in a one stage process. Pressure, similar to temperature can be used as a thermodynamic parameter to induce phase separation in an originally homogeneous polymer solution. Pressure has however, a significant advantage over temperature, as pressure changes can be brought about uniformly and very quickly throughout the bulk of a solution, thus potentially encouraging the formation of a uniform pore structure if this could be incorporated into a scaffold fabrication methodology. When looking at the influence of pressure on the phase separation behaviour of a PLGA-dioxane solution, it was found that pressure induced the crystallization of dioxane by shifting the solid-liquid equilibrium line to a higher temperature. The rate of crystallization was dependent on the pressure applied, the initial temperature of the solution, as well as the PLGA concentration. In the case of a liquid-liquid phase separating system, such as PLGAdioxane- water, depending on the interaction between the various component in the system, pressure could either induce phase remixing or phase demixing. The effect of scaffold morphology on cell behaviour was investigated in the last section of this study. Cell proliferation rate, cell morphology, cell cytoskeleton structure and extracellular matrix (ECM) protein orientation when cells were cultured on two different architectures within the same scaffold were compared. It is found that for all cell lines studied, cells proliferated at a higher rate when cultured in the region with directional pores. Further, the scaffold architecture was found to affect the overall cell morphology, as well as the orientation of the ECM protein (collagen I) deposited by cell. However, the relative influence of scaffold architecture on cell shape varied with the type of cell used.

 
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Created: Fri, 21 Nov 2008, 15:36:04 EST