A Fundamental Study On The Preparation Of The Cell Scaffolds In Tissue Engineering By The Supercritical Fluid

Scaffolds fabrication technique is essential to tissue engineering research. Conventional techniques for scaffolds fabrication have their advantages, but they exist in one or more limitations as follows:residual organic solvent, low porosity and difficulty in controlling pore size. Recently, supercritical fluid has been introduced into scaffolds production, and several processes have been developed. Among these three processes stand out and gain more attention. One of these is the ScCO2foaming process and no solvent is used during the process, while the product obtained by this process has generally low porosity and closed-cells structure. Combing ScCO2with other processes can overcome some disadvantages, but it makes the process more complexited and time consumed. The SAS process has shown great application potential in preparing porous polymer with the advantages of no residual organic solvent and controllable pore size by adjusting process parameters. The present research work on the SAS process is still in the early stage on the process feasibility, and there are seldom reseach on the systemically theoretical research of the process.An improvement is made on the ScCO2foaming process. Porous PMMA scaffolds are produced by repeated heating and pressure reducing. The influences of the different operation parameters on the properties of porous scaffolds are examined and a comparison is made between conventional SCCO2foaming process and the improved one. The results show that the porosity, pore size and pore connectivity of PMMA scaffolds prepared by improved ScCO2foaming process are higher than those prepared by conventional one at the operation conditions of the same temperature, pressure, pressure release time, and different maitaining times.The scaffolds of PCL and PLLA polymer are successfully prepared by SAS process. The influences of operation parameters (polymer concentration, CO2pressure and temperature) on the scaffolds morphology, pore size and size distribution are investigated. The optimal operation conditions for these materials are obtained. In order to improve the porosity and the compressive strength of the PLLA scaffolds, the PLLA composite scaffolds are fabricated with PEG and β-TCP as additive respectively. The porosity increases with the adding of the PEG and the highest porosity of PLLA/PEG composite scaffolds can reach92%. The compressive strength increases with the adding of the β-TCP and the highest compressive strength of PLLA/β-TCP composite scaffolds can reach1.76MPa.Based on Flory-Huggins theory, a thermodynamic model suitable for SAS process is established. Through the calculation of binodal line, spinodal line and critical point, the ternary phase diagram is obtained. The thermodynamics behaviors of ScCO2/AC/PCL and ScCO2/CH2Cl2/PLLA systems in the process of preparing porous scaffolds are analyzed by means of the ternary phase diagram. The results show that both systems have liquid-liquid phase separation in the upper part of the critical point following the nuclear growth mechanism, and they are suitable for the preparation of porous scaffolds. The interaction parameters χ12and χ13reduce, but χ23remains unchanged with the increase of CO2pressure. As the temperature increases, the interaction parameters χ12and χ13increase, the change of χ23is very small. The calculation results of split phase point show that the solvent quantity of polymer solution increases gradually with the increase of pressure and the decrease temperature. Similar calculations are obtained in these two systems.Based on Reuvers model, a mass transfer dynamics model suitable for SAS process is established. The computing methods of model parameters are given, the mass transfer processes of ScCO2/AC/PCL and ScCO2/CH2Cl2/PLLA system are simulated, and the influences of the operation parameters on the scaffolds morphology, pore size and size distribution are investigated according to the mass transfer path obtained by the calculation. The result shows that the change of volume fraction of the different component is similar in the two systems. The diffusion coefficients decrease with the increase of CO2pressure, while they increase with the increase of temperature. The mass transfer path gradually becomes short with the increase of the polymer concentration or temperature or with the decrease of CO2pressure. So the speed of phase sepatation gradually accelerate, then the mean pore size of scaffolds gradually decrease. The formation of scaffolds is the result of the combination of the equilibrium thermodynamics and membrane formation kinetics. The different porous structures of these two scaffolds can be explained with different physical properties and component different diffusion coefficients of the polymers.