【作者】 张俊川；

【导师】 丁建东；

【作者基本信息】 复旦大学 ， 高分子化学与物理， 2005， 博士

【摘要】 组织工程将在一定程度上改变21世纪的外科学,本身是一个典型的交叉学科研究。在组织工程中,预塑形多孔支架为细胞粘附、增殖、分化以及营养物质输入与废物的排放提供场所,引导细胞生长和组织再生,并最终影响到组织的结构和功能,在组织工程中起着重要的作用。多孔支架的外形、孔结构形态、孔隙率、力学性能、降解速率等基本性质对实现其细胞外基质的功能起到非常重要的作用。本博士论文的主题即为组织工程生物材料,尤其是组织工程多孔支架的制备技术。 论文合成了聚乳酸等可降解聚酯,并以其为支架材料,详细考察了不同致孔剂溶出方法对所制备多孔支架的影响;在此基础上,采用球形致孔剂并结合模压成型技术制成了具有规整球形孔结构的新型多孔支架,并系统地研究了该三维多孔支架的力学性能;且对该多孔支架的细胞相容性及动物皮下埋植进行了初步的评价。 我们的主要研究内容和实验结果如下: 1.可降解聚酯的合成。本文通过开环聚合制备了具有生物降解性的聚酯类化合物,包括消旋聚乳酸(PDLLA)、乙交酯—丙交酯共聚物(PLGA)、聚己内酯(PCL)等。该聚合可通过调节反应条件加以控制,其中PDLLA的分子量可高达40万以上。验证了该材料的体外降解行为。 2.盐粒致孔和常温模压相结合制备非规整孔结构的大尺寸多孔支架。以氯化钠粒子为致孔剂,分别采用溶剂浇铸与模压成型技术制备了高分子多孔支架,并系统地考察了致孔剂的影响。实验表明,采用模压成型技术可制备大尺寸的多孔支架,且成型精度高,所得支架孔隙率高达90%以上,孔形态可由致孔剂形念来调控,孔分布均匀。该法克服了溶剂浇铸法仅能制备小尺寸支架的弊端,且表面亦为为开孔结构,在组织工程的预塑形细胞支架领域可得到广泛应用。 3.球形孔的大尺寸支架的制备技术。以悬浮分散方法制备了不粘连的、单分散更多还原

【Abstract】 Tissue engineering is believed to revolutionize Surgery to some extent in this century. It is a native interdisciplinary research field. Three dimensional porous scaffolds play an important role in tissue engineering as an adhesive substrate for implanted cells and a physical support to form new tissues or organs. To be the temporary matrix, the scaffolds should facilitate cell adhesion, promote cell growth, and allow the retention of differentiated cell functions. It should thus be biocompatible, biodegradable, highly porous with a large surface-to-volume ratio, mechanically strong, and shapable. Some basic properties of porous scaffold such as shape, pore structure, porosity, mechanical properties and degradation rate are of great importance for realization its function. The theme of this thesis is research of tissue engineering biomaterials. Much attention was paid on improvement of fabrication technique of porous scaffolds.In this thesis, biodegradable polyesters were synthesized; and three-dimensional porous scaffolds were fabricated by particulate leaching methods. Combined with compression molding technique, novel spherical pore foams with ordered internal structure and complicated external shape were prepared. The compressive properties of such porous scaffolds were investigated. Cytotoxic and histological responses of the porous scaffolds have also been examined preliminarily.The main researches are listed as follows:1. Synthesis of biodegradable polyesters by ring opening polymerization. Biodegradable polyesters including poly（D,L-lactide） （PDLLA）, poly（D,L-lactide-co-glycolide） PLGA and poly（ε-caprolactone） （PCL） have been successfully synthesized by vacuum polymerization with Sn（Oct）₂ as catalyst. The molecular weight of PDLLA homopolymer can reach 400,000. Higher polymerization temperature and high GA content result in lower molecular weight of PLGA. In vitro degradation behaviors of polyesters have also beenconfirmed.2. Prepration and calibration of large scaffolds with irregular pores after combining salt-particulate leaching technique and compressive molding technique. Classic particulate leaching technique was improved to preparing large scaffold with porous structures, after combined with compressive molding at room temperature. The results revealed that larger-volume foams with highly porous three-dimensional structure could be achieved by the modified compression molding technique.3. Novel preparation method to fabricate large scaffolds with ordered spherical pores and well-defined interconnectivity between pores. Un-sticky and monodispersed paraffin microspheres were obtained via dispersion technique. Biodegradable PLGA85/15 porous foams with interconnected global pores were successfully fabricated using room temperature compression molding & particulate leaching technique based on paraffin spheres. SEM and light microscopic observations demonstrated ordered global pore structures and good pore interconnectivity. The porosity may be adjusted among 80%-95%, which covers application ranges in tissue engineering. Porosity and the pore size of the scaffolds could be controlled by modulating the ratio and the particle size of the salt porogens.4. Verify good mechanical property of scaffolds with spherical pores. Compressive strength and modulus of pore scaffolds were measured on an Instron testing machine with cylindrical samples. Mechanical properties of porous scaffolds strongly depend on porosity, but modulus is in the order of magnitude of MPa even at high porosity. Compared with the scaffolds prepared by salt particles, the spherical pore foams possess higher compression modulus, especially at high porosity above 90%.5. Preliminary examination of biocompatibility of porous scaffolds. Due to very strict demands for biomedical materials applied in clinical applications, the new spherical porous foams should be testified by cell culture and animal implantation.更多还原