高分子三维多孔生物支架的成型及结构性能研究
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摘要
组织工程多孔生物支架作为种植细胞的场所和组织再生的模板,是组织工程领域重要研究方向之一,已经引起了越来越多的研究者重视。理想的多孔生物支架必须具备,高孔隙率、内部相互连通性、无毒性、良好的生物相容性和较好力学性能等,因此,如何制备符合及满足细胞需求的理想三维多孔生物支架是组织工程领域的前沿课题。基于可降解高分子生物支架具有在引导细胞生长的同时可被机体吸收的突出优点,使其成为生物支架研究方向的热点。
论文以可降解高分子生物支架的制备工艺一结构形态一性能为主线,通过选择合适的加工方法、设计合理的材料配方,调控泡孔形态、孔隙率、吸水率、内部连通性和力学性能等,加工制备新型的具有高孔隙率且内部相互连通的三维多孔可降解高分子生物支架。主要工作包括：
1、采用注塑成型／粒子沥滤技术加工PCL和PCL/HA三维多孔生物支架。基于不同材料配方控制支架的泡孔形态、孔隙率、力学性能、吸水性能和生物性能。分析NaCl颗粒和可溶性高分子聚合物PEO的沥滤过程,对比探讨了PCL和PCL/HA三维多孔生物支架的力学性能和生物相容性。研究结果表明,PEO的应用较大的提高了支架内部相互连通性；HA的使用不仅增强了支架的力学性能,而且促进了细胞的增殖生长。
2、利用微发泡注塑成型/粒子沥滤技术加工PCL三维多孔生物支架。对比探究了传统注塑成型和微发泡注塑成型技术所制备支架的内部孔洞结构形态、静态和动态力学性能、孔隙率和吸水率等。超临界N2的使用不仅作为物理发泡剂,而且起到增塑剂的作用,降低共混物的熔体粘度,使其易于加工成型,同时有效的提高了PCL生物支架的孔隙率。
3、基于注塑成型技术、弱酸沥滤方法和新材料配方(PCL/PEO/NaCl/壳聚糖纤维),首次利用壳聚糖纤维加工了具有微孔洞和微管道双重形态特征的三维多孔PCL生物支架。壳聚糖纤维的引入,不仅在支架中形成了微管道结构形态,而且提高了其孔隙率及内部连通性。分析了壳聚糖含量对PCL生物支架泡孔形态和力学性能影响。
4、采用单向冷冻干燥法和静电纺丝技术相结合,加工了具有微米级管道和纳米级微结构特征的高孔隙率三维壳聚糖/PLGA纳米复合生物支架。相比壳聚糖生物支架,PLGA纳米纤维的加入不仅使三维生物支架具有纳米级形态结构,而且使其具有较大的比表面积和更高的力学性能。并研究了壳聚糖溶液浓度和静电纺丝时间对支架结构形态和力学性能的影响。
5、研究了压缩成型聚酸酐样品的降解机理和降解速率。分析探究了样品加工温度和几何尺寸对其降解速率的影响。
The research on porous tissue engineering scaffold has been one of the major braches in tissue engineering field. Therefore, it has received considerable attention and many researchers have already focused on it due to its application as matrix of seeding cells and repairing the tissues. Ideally, these porous scaffolds should have the following characteristics:high porosity, an interconnected porous structure, nontoxic, biocompatible, and suitable mechanical strength. Therefore, How to fabricate the ideal three dimensional porous scaffolds is a front subject in the field of tissue engineering. The biodegradable polymer scaffolds have become the focal researcher of tissue engineering domain due to its outstanding advantage; for example, it would be resorbed by live tissue while guiding the cells growth.
This dissertation pays attention on the technology, morphology, and property of biodegradable polymer scaffolds in the process of their forming. The novel porous biodegradable polymer scaffolds were manufactured with high porosity, interconnected, and three dimensional by choosing suitable technique, designing rational material formula, controlling pores morphology, porosity, water absorption, interconnectivity, and mechanical porosity. The main works are as follow:
1、 To fabricate the three dimensional porous PCL and PCL/HA scaffolds by injection molding/particulate leaching method. To control the pores morphology, porosity, water absorption, and mechanical porosity of the scaffold by varying the material formula. The leaching process of NaCl particular and the soluble polymer PEO inside the scaffold were observed. The mechanical porosity and biocompatible of three dimensional porous PCL and PCL/HA scaffold were compared. The result shows that the application of HA not only enhance the mechanical porosity of scaffold, but also promote the proliferation ability of cells.
2、To fabricate the three dimensional porous PCL scaffolds by microcellular injection molding/particulate leaching. The morphology、static and dynamic mechanical properties, porosity, and water absorption of scaffold which formed by injection molding were compared with that of scaffold which fabricated by microcellular injection molding. The super critical N:not only used as physical blowing agent, but also used as plasticizer, which could decrease the viscosity of blend melt, resulting to easy to molded, as well as increasing the porosity of the PCL scaffold.
3、To fabricate the three dimensional porous PCL scaffolds with double morphology of micro pores and channels by using chitosan fiber at the first time based on adopting injection molding technique、weak acid leaching method and novel material formula (PCL/PEO/NaCl/chitosan fiber). The addition of chitosan fiber not only formed the micro channel inside scaffold, but also increased the porosity and interconnectivity of scaffold. In addition, the effection of chitosan fiber content in blend on the morphology and mechanical property of PCL scaffold were studied.
4、To fabricate the three dimensional highly porous chitosan/PLGA nario composite scaffolds with micro channels and nano-topography by combining unidirectional freeze drying and electrospinning technology. The chitosan/PLGA scaffold not only has nano-topography but also has bigger specific surface area and higher mechanical property compared with that of chitosan scaffold due to the addition of PLGA nano fiber. In addition, the effection of chitosan concentration and electrospinning time on the morphology and mechanical property of scaffold were investigated.
5、The degradation mechanism and degradation rate of compression molding polyanhydrides samples were investigated. Moreover, the effection of processing temperature and the geometry of samples on the degradation rate were studied.
论文以可降解高分子生物支架的制备工艺一结构形态一性能为主线,通过选择合适的加工方法、设计合理的材料配方,调控泡孔形态、孔隙率、吸水率、内部连通性和力学性能等,加工制备新型的具有高孔隙率且内部相互连通的三维多孔可降解高分子生物支架。主要工作包括：
1、采用注塑成型／粒子沥滤技术加工PCL和PCL/HA三维多孔生物支架。基于不同材料配方控制支架的泡孔形态、孔隙率、力学性能、吸水性能和生物性能。分析NaCl颗粒和可溶性高分子聚合物PEO的沥滤过程,对比探讨了PCL和PCL/HA三维多孔生物支架的力学性能和生物相容性。研究结果表明,PEO的应用较大的提高了支架内部相互连通性；HA的使用不仅增强了支架的力学性能,而且促进了细胞的增殖生长。
2、利用微发泡注塑成型/粒子沥滤技术加工PCL三维多孔生物支架。对比探究了传统注塑成型和微发泡注塑成型技术所制备支架的内部孔洞结构形态、静态和动态力学性能、孔隙率和吸水率等。超临界N2的使用不仅作为物理发泡剂,而且起到增塑剂的作用,降低共混物的熔体粘度,使其易于加工成型,同时有效的提高了PCL生物支架的孔隙率。
3、基于注塑成型技术、弱酸沥滤方法和新材料配方(PCL/PEO/NaCl/壳聚糖纤维),首次利用壳聚糖纤维加工了具有微孔洞和微管道双重形态特征的三维多孔PCL生物支架。壳聚糖纤维的引入,不仅在支架中形成了微管道结构形态,而且提高了其孔隙率及内部连通性。分析了壳聚糖含量对PCL生物支架泡孔形态和力学性能影响。
4、采用单向冷冻干燥法和静电纺丝技术相结合,加工了具有微米级管道和纳米级微结构特征的高孔隙率三维壳聚糖/PLGA纳米复合生物支架。相比壳聚糖生物支架,PLGA纳米纤维的加入不仅使三维生物支架具有纳米级形态结构,而且使其具有较大的比表面积和更高的力学性能。并研究了壳聚糖溶液浓度和静电纺丝时间对支架结构形态和力学性能的影响。
5、研究了压缩成型聚酸酐样品的降解机理和降解速率。分析探究了样品加工温度和几何尺寸对其降解速率的影响。
The research on porous tissue engineering scaffold has been one of the major braches in tissue engineering field. Therefore, it has received considerable attention and many researchers have already focused on it due to its application as matrix of seeding cells and repairing the tissues. Ideally, these porous scaffolds should have the following characteristics:high porosity, an interconnected porous structure, nontoxic, biocompatible, and suitable mechanical strength. Therefore, How to fabricate the ideal three dimensional porous scaffolds is a front subject in the field of tissue engineering. The biodegradable polymer scaffolds have become the focal researcher of tissue engineering domain due to its outstanding advantage; for example, it would be resorbed by live tissue while guiding the cells growth.
This dissertation pays attention on the technology, morphology, and property of biodegradable polymer scaffolds in the process of their forming. The novel porous biodegradable polymer scaffolds were manufactured with high porosity, interconnected, and three dimensional by choosing suitable technique, designing rational material formula, controlling pores morphology, porosity, water absorption, interconnectivity, and mechanical porosity. The main works are as follow:
1、 To fabricate the three dimensional porous PCL and PCL/HA scaffolds by injection molding/particulate leaching method. To control the pores morphology, porosity, water absorption, and mechanical porosity of the scaffold by varying the material formula. The leaching process of NaCl particular and the soluble polymer PEO inside the scaffold were observed. The mechanical porosity and biocompatible of three dimensional porous PCL and PCL/HA scaffold were compared. The result shows that the application of HA not only enhance the mechanical porosity of scaffold, but also promote the proliferation ability of cells.
2、To fabricate the three dimensional porous PCL scaffolds by microcellular injection molding/particulate leaching. The morphology、static and dynamic mechanical properties, porosity, and water absorption of scaffold which formed by injection molding were compared with that of scaffold which fabricated by microcellular injection molding. The super critical N:not only used as physical blowing agent, but also used as plasticizer, which could decrease the viscosity of blend melt, resulting to easy to molded, as well as increasing the porosity of the PCL scaffold.
3、To fabricate the three dimensional porous PCL scaffolds with double morphology of micro pores and channels by using chitosan fiber at the first time based on adopting injection molding technique、weak acid leaching method and novel material formula (PCL/PEO/NaCl/chitosan fiber). The addition of chitosan fiber not only formed the micro channel inside scaffold, but also increased the porosity and interconnectivity of scaffold. In addition, the effection of chitosan fiber content in blend on the morphology and mechanical property of PCL scaffold were studied.
4、To fabricate the three dimensional highly porous chitosan/PLGA nario composite scaffolds with micro channels and nano-topography by combining unidirectional freeze drying and electrospinning technology. The chitosan/PLGA scaffold not only has nano-topography but also has bigger specific surface area and higher mechanical property compared with that of chitosan scaffold due to the addition of PLGA nano fiber. In addition, the effection of chitosan concentration and electrospinning time on the morphology and mechanical property of scaffold were investigated.
5、The degradation mechanism and degradation rate of compression molding polyanhydrides samples were investigated. Moreover, the effection of processing temperature and the geometry of samples on the degradation rate were studied.
引文
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