【作者】 韩颖超；

【导师】 李世普；

【作者基本信息】 武汉理工大学 ， 生物材料学， 2007， 博士

【摘要】 羟基磷灰石(HAP)的化学成分和晶体结构与人体骨骼中的无机盐十分相似,具有良好的生物相容性和骨传导性,在临床上得到了广泛的应用。但是,人工合成的HAP骨缺损修复材料与自然骨相比存在力学性能差、无法达到生物学磷灰石所具有的溶解性和再结晶产生的连续骨再生性的水平,这大大限制了其在承重部位骨缺损的应用以及修复质量的提高。纳米尺度HAP表现出的不同于非纳米尺度HAP的独特性能,对于解决HAP目前存在的问题有望提供可行的方法。目前有多种方法可以用于纳米尺度HAP的制备,但是,对于稳定的HAP纳米粒子体系和HAP纳米结构的制备还需要进一步的研究。另外,对于纳米尺度HAP所表现出的独特纳米特性也需要深入的分析。因此,本论文主要针对纳米尺度HAP的制备技术及其纳米特性进行研究。对于纳米尺度HAP制备技术的研究主要包括两个方面。首先,形成了一种制备稳定的HAP纳米粒子体系的超声辅助GAGs调控沉淀法。研究了该工艺两个重要的影响因素GAGs浓度和超声时间对HAP纳米粒子体系形成和性能的影响,并探讨了超声辅助GAGs调控沉淀法的机理。其次,形成了一种制备纳米尺度HAP长棒状晶体以及束状纳米结构的BSA前驱体热分解法。研究了BSA浓度对胶态前驱体形成和性能的影响以及前驱体在热处理过程中产物的相组成和微观形貌等的变化,并探讨了BSA胶态前驱体热分解法的机理。对于纳米尺度HAP的纳米特性主要从对生物大分子的吸附和与红细胞的作用两个方面进行研究。首先,以肝素和BSA为吸附对象,与非纳米尺度HAP粒子对比,通过吸附等温线和吸附量的变化研究了HAP纳米粒子对肝素和BSA的吸附纳米特性。其次,选择四种不同特性的HAP粒子:HAP纳米粒子、非纳米尺度HAP粒子、GAG改性纳米粒子和BSA改性纳米粒子,与红细胞进行作用,在微米尺度和纳米尺度研究了HAP纳米粒子对红细胞聚集和膜变形的影响,初步分析了其对红细胞影响的纳米特性。从与红细胞膜表面唾液酸的作用入手,结合红细胞聚集模型,对HAP纳米粒子所表现出的引起红细胞变化的机理进行探讨,为纳米材料的血液相容性评价提供一定的参考和帮助。更多还原

【Abstract】 Hydroxyapatite has been widely used in clinic due to its good biocompatibility and osteoconductivity derived from the most similar composition and crystal structure with mineral in bone. However, the artificially synthesized HAP materials for the repairing of bone defects are greatly restricted to apply in the load-bearing situation because of its lower mechanical properties compared with natural bone. Moreover, the artificially synthesized HAP materials can’t reach the solubility of biological apatites and realize the continuous bone regeneration with constant dissolution-crystallisation cycles resulted from the smaller size below 50nm of biological apatite crystals, which will influence the repaired results. Nanoscaled HAP has specific physical or chemical properties differing substantially from those bulk HAP materials, which is hopeful to provide feasible means to resolve the above problems. Now there are many methods for the preparing of nanoscaled HAP. Nevertheless, it is required to study the preparation methodology of stable HAP nanoparticles system and HAP nanostructure further. In addition, the unique nano characteristics of nanoscaled HAP should also be deeply analyzed. Therefore, the main content of this paper is to study the preparation technology and nano characteristics of nanoscaled HAP.The study of preparation technology of nanoscaled HAP included two aspects. Firstly, ultrasound assisting and GAGs controlling precipitation method was provided for the preparation of stable HAP nanoparticles. The effects of two important impact factors of GAGs concentration and ultrasound time on the formation and properties of HAP nanoparticles were researched, and the mechanism of this method was also discussed. Secondly, BSA precursor thermolysis method was also provided to fabricate nanoscaled HAP rod-like crystals and bundle-like nanostructure. The impact factors such as BSA concentration and thermal treatment procedure were studied, and the mechanism of this method was also discussed.The study of nano characteristics of nanoscaled HAP was carried out in two aspects. One was the adsorption to biomacromolecule, the other was the interaction with red blood cells (RBCs). Firstly, the adsorbing characteristics of HAP nanoparticles to heparin and BSA were studied by the adsorption isotherms and adsorption rate of heparin and BSA on different size HAP particles. Secondly, four kinds HAP particles such as HAP nanoparticles, non-nano HAP particles, heparin modified nanoparticles and BSA modified nanoparticles were selected to interact with RBCs. The effects of HAP nanoparticles on the aggregation and membrane morphology change of RBCs were studied at micrometer scale and nanometer scale respectively in order to analyze the nano characteristics of nanoparticles to RBCs. Combined with the aggregation models of RBCs, the nano characteristics of HAP nanoparticles inducing the change of RBCs was discussed by the research of interaction between HAP nanoparticles and sialic acid on the membrane surface of RBCs. This can provide some experimental references for the evaluation of blood compatibility of nanomaterials.更多还原