微孔发泡注射成型制备三维多孔聚乳酸骨组织工程支架研究

发布时间：2018-06-22 07:00

本文选题：微孔发泡注射成型 + 骨组织工程支架　；参考：《华南理工大学》2013年博士论文

【摘要】：微孔发泡注射成型采用超临界CO_2/N_2做为物理发泡剂，具有可显著减轻制品重量、缩短成型周期和极大改善制品翘曲变形和尺寸稳定性等特点，将微孔发泡注射成型技术应用于制备三维多孔连通结构的生物可降解骨组织工程支架，不涉及任何有机溶剂且批量生产显著降低成本，对人类骨组织重建和再生医学的发展具有重要的现实意义和科学研究价值。聚乳酸强度高、成本低廉、生物相容性好且可降解，，目前在组织工程领域已得到广泛应用。然而将聚乳酸这种半结晶性聚合物应用微孔发泡注射成型制备真三维连通结构且具有高孔隙率的支架仍存在较多加工难题，因此研究聚乳酸的微孔发泡注射成型成核机理和加工特性，对于制备理想结构的生物骨组织工程支架具有重要的指导意义。据此，本文从结晶、流变特性和异相成核等角度着手，做了以下几方面的工作：首先，介绍了微孔发泡注射成型过程泡孔成核和长大的机理，研究了超临界流体作用下结晶对聚合物流变特性和发泡形态结构的影响。针对半结晶型聚合物气体溶解和扩散相对困难、溶解度低，发泡温度窗口窄，熔体强度对温度敏感等特点，以及超临界流体注入会降低聚合物熔体粘度的客观实际情况，研究了结晶对半结晶型聚合物泡孔成核和长大的影响机理。研究发现，结晶有助于提高聚合物熔体的储能模量和熔体弹性，对制备良好形态结构的发泡制品具有积极作用。结晶不仅可以增加成核点数目，而且作为一种异相成核剂存在能够促进泡孔成核使得泡孔密度增大，同时还可以有效阻止泡孔长大从而减小泡孔的平均尺寸。其次，为了克服气熔混合不足和纳米粒子在复合材料中分散不均带来的制品“皮芯”结构和力学性能下降的问题，将预发泡技术引入微孔发泡注射成型工艺中，开发了一种气熔混合效果好、可有效改善发泡结构和性能的方法。采用挤出发泡制备的含气发泡粒料，使得纳米复合材料在进入微孔发泡注射成型机之前已经基本充分形成了分散均匀的微纳结构，而且提高了超临界流体与聚合物熔体的配混效果。实验结果表明，采用预发泡颗粒制备的微孔注射成型纳米复合材料，皮芯层的均匀度明显改善，泡孔平均尺寸减小，泡孔密度增大，提高了发泡制品的力学性能。然后，根据理想骨组织工程支架的结构特征，利用共混法调控了聚乳酸共混体系的降解速率和力学性能，研究了它们的热性能、动态热机械性能和发泡形态结构。通过调整加工工艺参数，制备了具有双尺度模式泡孔结构的高孔隙率发泡制品。人类骨髓间质干细胞的培养实验结果表明，所制备的支架酸碱度适当，无毒性，细胞附着和生长繁殖良好，在PLA/PHBV(55:45)支架上培育14天的细胞呈现骨髓前体细胞典型树突结构。MTS分析测定结果表明，细胞在所制备的支架上繁殖速度较快，数目多，其中PLA/PHBV(55:45)试样尤为突出，验证了该种配方和工艺条件下制备的双尺度连通发泡结构的支架适合细胞培养，具有良好的载体作用。最后，从熔体粘弹特性、结晶和异相成核机理等三重角度研究了纳米粒子改善发泡制品泡孔形态结构的机理和方法，讨论了纳米粒子对泡孔成核和结晶成核的双重作用，分析了纳米粒子增强复合材料的流变特性的响应规律。对制备真三维多孔连通、可调控的力学性能和降解速率的纳米填充复合高分子骨组织工程支架具有重要的研究价值。实验结果表明：聚乳酸纳米复合材料在整个频率扫描范围内呈现非常明显的剪切变稀现象，这种pseudo solid like行为充分说明了纳米粘土与高分子之间形成很强的界面作用，这种类似于物理交联点的作用限制了高分子链的松弛和滑移，增强了熔体粘度。
[Abstract]:Microcellular foaming injection molding using supercritical CO_2/N_2 as a physical foaming agent, which can significantly reduce the weight of products, shorten the molding cycle and greatly improve the warpage and dimensional stability of products. Microporous foam injection molding technology is applied to the biodegradable scaffold for the preparation of three-dimensional porous connected structure. It is of great practical significance and scientific research value for human bone tissue reconstruction and the development of regenerative medicine that any organic solvent is involved and the cost of mass production is significantly reduced.
Polylactic acid has high strength, low cost, good biocompatibility and degradability. It has been widely used in the field of tissue engineering. However, there are still many difficult problems in preparing the semi crystalline polymer of polylactic acid by microporous foam injection molding for the preparation of a truly three-dimensional connected structure with high porosity. The nucleation mechanism and processing characteristics of the injection molding of the orifice are of great guiding significance for the preparation of the scaffold for the ideal structure of biological bone tissue engineering. Accordingly, the following work has been done from the angles of crystallization, rheological properties and heterogenous nucleation.
Firstly, the mechanism of nucleation and growth of foam holes in microcellular foaming injection molding was introduced. The influence of crystallization on the rheological properties and foam morphology of polymer under the action of supercritical fluid was studied. The solubility and diffusion of the semi crystalline polymer gas were relatively difficult, the solubility was low, the foaming temperature window was narrow, and the melt strength was sensitive to temperature. Characteristics, as well as the objective reality of reducing the viscosity of polymer melt by supercritical fluid injection, the influence mechanism of crystallization on the nucleation and growth of semi crystalline polymer bubble holes is studied. It is found that crystallization helps to improve the energy storage modulus and melt elasticity of the polymer melts, and has a positive effect on the foaming products with good morphology and structure. It is used not only to increase the number of nucleation points, but also as an hetero nucleating agent, which can promote the nucleation of the bubble hole to increase the pore density, and can also effectively prevent the bubble hole growth and reduce the average size of the bubble hole.
Secondly, in order to overcome the problem of the "skin core" structure and the mechanical properties of the products caused by uneven gas melting and the uneven dispersion of nanoparticles in the composite materials, the pre foaming technology is introduced into the microcellular foaming injection molding process, and a method for improving the mixing effect of gas melt and improving the foaming structure and properties is developed. The foaming granular materials prepared by foaming make the nano composite basically fully formed the dispersed homogeneous microstructure before entering the microcellular foam injection molding machine, and improve the mixing effect of the supercritical fluid and the polymer melt. The experimental results show that the microporous injection molding nanocomposite prepared by the pre foaming particles has been shown. The uniformity of the core layer is obviously improved, the average size of the foams is reduced, and the density of the foams increases, which improves the mechanical properties of the foaming products.
Then, according to the structural characteristics of the ideal bone tissue engineering scaffold, the degradation rate and mechanical properties of the polylactic acid blends were controlled by blending, and their thermal properties, dynamic thermal mechanical properties and foam morphology were studied. By adjusting the processing parameters, the high porosity foaming with a double scale mode bubble structure was prepared. The results of cultured human bone marrow mesenchymal stem cells showed that the prepared scaffolds were properly acidity, non-toxic, cell adhesion and growth were good. The.MTS analysis of the typical dendritic structure of bone marrow precursor cells for 14 days on the PLA/PHBV (55:45) scaffold showed that the cells were propagated on the prepared stents. The PLA/PHBV (55:45) sample is particularly prominent, which proves that the scaffold of double scale connected foaming structure prepared under the formula and process conditions is suitable for cell culture and has good carrier effect.
Finally, the mechanism and methods of nano particles to improve the morphology and structure of foam holes in foaming products were studied from the three angles of viscoelastic properties, crystallization and heterogeneous nucleation mechanism. The double effects of nanoparticles on the nucleation and nucleation of the bubbles were discussed, and the response laws of the rheological properties of the nano particles reinforced composites were analyzed. The preparation of the true three was true. The experimental results show that the pseudo solid like behavior shows a very obvious shear thinning phenomenon in the range of frequency scanning, and the behavior of this kind of nanocomposites is fully explained. There is a strong interfacial interaction between the clay and the polymer. This action, similar to the physical crosslinking point, restricts the relaxation and slip of the polymer chain and enhances the viscosity of the melt.
【学位授予单位】：华南理工大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R318.08

【引证文献】