【作者】 蔡志江；

【导师】 成国祥；

【作者基本信息】 天津大学 ， 材料学， 2003， 博士

【摘要】 组织工程学是运用工程科学与生命科学的基本原理和方法，研究生物学替代物来恢复、维持和改进组织功能的一门新兴交叉学科。支架材料作为细胞粘附生长模板，对工程化组织的构建起重要作用。而材料本体组成和结构、表面化学及表面拓扑结构、降解行为等对组织的生物特性产生重要影响。聚羟基丁酸酯(PHB)具有良好的生物相容性和生物降解性，还具有无毒性、压电性、结晶度高、球晶大、脆性大、加工温度范围窄、疏水性强等特点。本论文利用不同分子量的聚乙二醇为第二组分通过物理和化学的方法对PHB进行改性，研究了改性物的结构、力性和降解等特性，运用冷冻干燥法和模板法制备了组织工程用三维多孔支架材料，并对其生物相容性进行了评价。研究结果表明，通过物理共混和偶联法、热引发及紫外光引发三种化学方法分别制备得到了PHB/PEG共混物和共聚物。改性后，PHB球晶尺寸变小、结构规整度降低、结晶度下降、材料的亲水性、热稳定性和韧性都有所提高。采用冷冻干燥法和模板法制备的PHB支架，研究表明用冷冻干燥法制备的材料孔径在几百微米，而采用微乳液模板法可制备出大孔在几微米至几十微米、微孔在几百纳米的具多重孔径分布的纳米结构支架材料。摸拟体内环境对PHB及其改性材料进行了体外酶降解实验，结果表明：酶能加速材料的降解过程，同时降解环境、材料的组成及材料的孔隙度对降解速率都有一定的影响，通过调节这些影响因素能在一定程度上对材料的降解速度进行控制。生物相容性实验表明，PHB材料本身具的良好的生物相容性，随着改性材料亲水性的提高，PHB的血液相容性得到明显改善，细胞在材料表面的贴壁、生长都得到提高。更多还原

【Abstract】 Tissue engineering has emerged as a new multi-disciplinary field combing engineering science and life science to provide living tissue products that restore, maintain, or improve tissue function. Acting as templates for cell adhesion and growth, scaffolds play an important role in construct of engineering tissue. Thus, scaffold biomaterials should meet a series of physical, chemical and mechanical requirements such as surface and degradation characteristics, blood and cell compatibilities etc. Polyhydroxybutyrate(PHB) is a microbially produced materials with many excellent properties such as biodegradability, biocompatibility, non-toxicity, piezoelectricity etc. But due to its high crystallinity and large spherulite, it shows high brittleness and strong hydrophobic property. At the same time, its process window is rather narrow.In this paper, physical blend and chemical modification were used to improve the properties of PHB using Poly (ethylene glycol)(PEG) with different molecular weight as the second component. At the same time, three-dimensional scaffolds were prepared by freeze-drying techniques and templates method. The biodegradability and biocompatibility were also investigated. The results showed that the PHB/PEG blend and copolymer could be prepared by physical blend and chemical methods. The crystallinity and size of spherulite of PHB decreased after modification. Thus, the thermal stability, hydrophilicity and brittleness of PHB were improved by whether physical blend or chemical modification. PHB three-dimensional porous scaffolds were prepared by freeze-drying technique and microemulsion templates method. The pore size of scaffold prepared by freeze-drying was about several hundred micrometers. While, microemulsion templates was shown to be capable of producing scaffolds of PHB with median pore sizes ranging from 5μm to 30μm<WP=8>in diameter and with micro-pore size ranging from 100nm to 500nm inside the pore wall. This multi-distribution of pore size may be in favor of transferring nutrient fluid and waste effectively so as to benefit the cell growth in three-dimensional porous scaffolds. The degradation of PHB was tested in the presence of distilled water and　lysozyme/PBS buffer solution, respectively. The result revealed that enzyme accelerated the degradation and because of high specific surface area and the hydrophilic addition of PEG, the weight loss of scaffolds was larger than that of membranes. The biocompatibility test showed that biocompatibility of PHB was improved with the PEG content increasing.更多还原