超臨界流體制備組織工程細(xì)胞支架工藝基礎(chǔ)研究
發(fā)布時(shí)間：2018-09-18 21:52
【摘要】：細(xì)胞支架的制備工藝是組織工程學(xué)研究的核心內(nèi)容。傳統(tǒng)細(xì)胞支架的制備工藝雖然各有其優(yōu)勢(shì),但存在著有機(jī)溶劑殘留、制備周期長和孔隙率低等不足。近年來,將超臨界流體(簡稱SCF)技術(shù)引入組織工程細(xì)胞支架的制備過程已引起研究者廣泛關(guān)注。利用現(xiàn)有的超臨界C02(簡稱ScCO2)發(fā)泡工藝制備細(xì)胞支架,雖然沒有有機(jī)溶劑的殘留,但其孔隙率較低、難以控制孔尺寸的范圍；利用ScCO2與其他工藝結(jié)合制備細(xì)胞支架,增加了原工藝的復(fù)雜性,使得制備周期延長；利用超臨界反溶劑(簡稱SAS)工藝制備細(xì)胞支架,既沒有有機(jī)溶劑的殘留,又可以通過改變工藝參數(shù)來控制支架的孔徑范圍,具有廣闊的應(yīng)用前景。目前對(duì)SAS工藝的研究僅停留在實(shí)驗(yàn)階段,主要探討相關(guān)工藝參數(shù)對(duì)支架性能的影響,缺乏深入系統(tǒng)的理論研究。 本論文首先對(duì)現(xiàn)有的ScCO2發(fā)泡工藝進(jìn)行改進(jìn),采用多次升溫和泄壓的方法,以典型的無定型類聚合物—PMMA為模型材料,制備了PMMA多孔支架,考察了主要工藝參數(shù)對(duì)多孔支架性能的影響,并與現(xiàn)有的ScCO2發(fā)泡工藝制備的支架進(jìn)行了比較。結(jié)果表明,與現(xiàn)有ScCO2發(fā)泡技術(shù)制備的PMMA細(xì)胞支架相比,在相同溫度、壓力、泄壓時(shí)間、不同保壓時(shí)間的條件下,改進(jìn)工藝制備的PMMA細(xì)胞支架具有孔徑范圍大、孔隙率高、孔與孔之間連通性好的特點(diǎn)。 利用SAS工藝,以PCL、PLLA為模型材料,進(jìn)行了SAS工藝制備細(xì)胞支架的實(shí)驗(yàn)研究,確定了聚合物濃度、CO2壓力和溫度對(duì)支架形態(tài)、孔徑分布的影響規(guī)律,得出了實(shí)驗(yàn)范圍內(nèi)制備上述材料支架的最佳工藝；為了提高單體PLLA支架的孔隙率與抗壓強(qiáng)度,分別以PEG和β-TCP為添加劑,在制備單體PLLA細(xì)胞支架的基礎(chǔ)上,成功制備了PLLA/PEG和PLLA/β-TCP復(fù)合材料支架。結(jié)果顯示,加入PEG后,可以提高支架的孔隙率,最高可達(dá)92%；加入β-TCP后,可以提高支架的抗壓強(qiáng)度,最高可達(dá)1.76MPa。 以Flory-Huggins理論為基礎(chǔ),對(duì)SAS工藝的熱力學(xué)行為進(jìn)行了研究,建立了適合SAS工藝過程的相平衡熱力學(xué)模型。利用模型中雙節(jié)線、旋節(jié)線和臨界點(diǎn)的計(jì)算方法,得到了三元體系相圖,分別分析了ScCO2/AC/PCL和ScCO2/CH2C12/PLLA三元體系在制備多孔支架過程中的相行為。結(jié)果表明,兩種三元體系均在臨界點(diǎn)的上方按成核生長機(jī)理發(fā)生液—液相分離,可制備出具有多孔結(jié)構(gòu)特征的聚合物。隨著CO2壓力的增加,相互作用參數(shù)χ12、χ13均減小,χ23保持不變；隨著溫度的升高,相互作用參數(shù)χ12χ13均增大,X23變化的趨勢(shì)很小；分相點(diǎn)的計(jì)算結(jié)果表明,隨著壓力的增加,非溶劑進(jìn)入聚合物溶液中的量逐漸增大,而隨著溫度的升高,非溶劑進(jìn)入聚合物溶液中的量逐漸減小,兩種體系計(jì)算結(jié)果一致。 基于Reuvers模型,建立了適合SAS工藝過程的傳質(zhì)動(dòng)力學(xué)模型,分別針對(duì)ScCO2/AC/PCL和ScCO2/CH2C12/PLLA三元體系給出了相關(guān)參數(shù)的求取方法,模擬了傳質(zhì)過程,得到了三元相圖中的傳質(zhì)路徑,描述了不同工藝參數(shù)對(duì)多孔結(jié)構(gòu)的影響趨勢(shì)。結(jié)果表明：兩種三元體系在不同工藝條件下各組分體積分?jǐn)?shù)的變化趨勢(shì)相似,組分間擴(kuò)散系數(shù)隨著CO2壓力的增加而減小,隨著溫度的升高而增大：隨著聚合物濃度的增加、CO2壓力的減小和溫度的升高,傳質(zhì)路徑逐漸變短,相分離速度逐漸加快,支架的平均孔徑呈逐漸減小的趨勢(shì)。支架平均孔徑的最終變化趨勢(shì)受相平衡熱力學(xué)和傳質(zhì)動(dòng)力學(xué)兩方面因素的影響；兩種三元體系中聚合物不同的物理性質(zhì)、組分間不同的擴(kuò)散系數(shù)造成了兩種支架截面孔結(jié)構(gòu)的不同。
[Abstract]:The preparation technology of cell scaffolds is the core of tissue engineering research. Although the traditional preparation technology of cell scaffolds has its own advantages, there are some shortcomings such as residual organic solvents, long preparation cycle and low porosity. ScCO2 foaming process is widely concerned. Although there is no residual organic solvent, its porosity is low and it is difficult to control the range of pore size. ScCO2 combined with other processes to prepare cell scaffolds increases the complexity of the original process and prolongs the preparation cycle. The preparation of cell scaffolds by boundary antisolvent (SAS) process has broad application prospects. There is no residual organic solvent, and the pore size of the scaffolds can be controlled by changing the technological parameters. At present, the research on SAS process is only in the experimental stage, mainly discussing the influence of related technological parameters on the performance of the scaffolds. Theoretical research.
In this paper, the existing ScCO2 foaming process was improved. The typical amorphous polymer-PMMA porous scaffolds were prepared by multiple heating and pressure relief methods. The effects of main process parameters on the properties of the scaffolds were investigated and compared with the scaffolds prepared by the existing ScCO2 foaming process. The results showed that, compared with the existing scaffolds prepared by ScCO2 foaming technology, the improved scaffolds had the characteristics of large pore size, high porosity and good pore-to-pore connectivity under the same temperature, pressure, pressure relief time and different holding time.
Using SAS process and PCL and PLLA as model materials, the SAS process was used to prepare cell scaffolds. The effects of polymer concentration, CO2 pressure and temperature on the morphology and pore size distribution of the scaffolds were determined, and the optimum process for preparing the scaffolds was obtained. The PLLA/PEG and PLLA/beta-TCP composite scaffolds were successfully prepared with PEG and beta-TCP as additives, respectively. The results showed that the porosity of the scaffolds could be increased up to 92% by adding PEG, and the compressive strength of the scaffolds could be increased up to 1.76MPa by adding beta-TCP.
Based on Flory-Huggins theory, the thermodynamic behavior of SAS process was studied, and a phase equilibrium thermodynamic model suitable for SAS process was established. The phase diagrams of ternary system were obtained by calculating the bi-nodal line, spindle line and critical point in the model. ScCO2/AC/PCL and SCCO2/CH2C12/PLLA ternary system were analyzed respectively. The results show that the polymer with porous structure can be prepared by the liquid-liquid phase separation of the two ternary systems above the critical point according to the nucleation growth mechanism. The number 1213 increases and the change trend of X23 is very small. The calculation results of phase separation point show that the amount of non-solvent entering the polymer solution increases with the increase of pressure, but decreases with the increase of temperature, and the results of the two systems are consistent.
Based on the Reuvers model, a mass transfer kinetic model suitable for SAS process was established. The method of calculating the relevant parameters for ScCO2/AC/PCL and SCCO2/CH2C12/PLLA ternary systems was given respectively. The mass transfer process was simulated, the mass transfer path in ternary phase diagram was obtained, and the influence trend of different process parameters on porous structure was described. Ming: The variation trend of volume fraction of each component in the two ternary systems under different process conditions is similar. The diffusion coefficient between components decreases with the increase of CO2 pressure and increases with the increase of temperature. With the increase of polymer concentration, the decrease of CO2 pressure and the increase of temperature, the mass transfer path becomes shorter and the phase separation rate increases. The final variation trend of the average pore size of the scaffolds is affected by two factors, namely, phase equilibrium thermodynamics and mass transfer kinetics. Different physical properties of polymers in two ternary systems and different diffusion coefficients between components result in different pore structures of the two scaffolds.
【學(xué)位授予單位】：大連理工大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.08
本文編號(hào)：2249188
[Abstract]:The preparation technology of cell scaffolds is the core of tissue engineering research. Although the traditional preparation technology of cell scaffolds has its own advantages, there are some shortcomings such as residual organic solvents, long preparation cycle and low porosity. ScCO2 foaming process is widely concerned. Although there is no residual organic solvent, its porosity is low and it is difficult to control the range of pore size. ScCO2 combined with other processes to prepare cell scaffolds increases the complexity of the original process and prolongs the preparation cycle. The preparation of cell scaffolds by boundary antisolvent (SAS) process has broad application prospects. There is no residual organic solvent, and the pore size of the scaffolds can be controlled by changing the technological parameters. At present, the research on SAS process is only in the experimental stage, mainly discussing the influence of related technological parameters on the performance of the scaffolds. Theoretical research.
In this paper, the existing ScCO2 foaming process was improved. The typical amorphous polymer-PMMA porous scaffolds were prepared by multiple heating and pressure relief methods. The effects of main process parameters on the properties of the scaffolds were investigated and compared with the scaffolds prepared by the existing ScCO2 foaming process. The results showed that, compared with the existing scaffolds prepared by ScCO2 foaming technology, the improved scaffolds had the characteristics of large pore size, high porosity and good pore-to-pore connectivity under the same temperature, pressure, pressure relief time and different holding time.
Using SAS process and PCL and PLLA as model materials, the SAS process was used to prepare cell scaffolds. The effects of polymer concentration, CO2 pressure and temperature on the morphology and pore size distribution of the scaffolds were determined, and the optimum process for preparing the scaffolds was obtained. The PLLA/PEG and PLLA/beta-TCP composite scaffolds were successfully prepared with PEG and beta-TCP as additives, respectively. The results showed that the porosity of the scaffolds could be increased up to 92% by adding PEG, and the compressive strength of the scaffolds could be increased up to 1.76MPa by adding beta-TCP.
Based on Flory-Huggins theory, the thermodynamic behavior of SAS process was studied, and a phase equilibrium thermodynamic model suitable for SAS process was established. The phase diagrams of ternary system were obtained by calculating the bi-nodal line, spindle line and critical point in the model. ScCO2/AC/PCL and SCCO2/CH2C12/PLLA ternary system were analyzed respectively. The results show that the polymer with porous structure can be prepared by the liquid-liquid phase separation of the two ternary systems above the critical point according to the nucleation growth mechanism. The number 1213 increases and the change trend of X23 is very small. The calculation results of phase separation point show that the amount of non-solvent entering the polymer solution increases with the increase of pressure, but decreases with the increase of temperature, and the results of the two systems are consistent.
Based on the Reuvers model, a mass transfer kinetic model suitable for SAS process was established. The method of calculating the relevant parameters for ScCO2/AC/PCL and SCCO2/CH2C12/PLLA ternary systems was given respectively. The mass transfer process was simulated, the mass transfer path in ternary phase diagram was obtained, and the influence trend of different process parameters on porous structure was described. Ming: The variation trend of volume fraction of each component in the two ternary systems under different process conditions is similar. The diffusion coefficient between components decreases with the increase of CO2 pressure and increases with the increase of temperature. With the increase of polymer concentration, the decrease of CO2 pressure and the increase of temperature, the mass transfer path becomes shorter and the phase separation rate increases. The final variation trend of the average pore size of the scaffolds is affected by two factors, namely, phase equilibrium thermodynamics and mass transfer kinetics. Different physical properties of polymers in two ternary systems and different diffusion coefficients between components result in different pore structures of the two scaffolds.
【學(xué)位授予單位】：大連理工大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.08
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