【作者】 季金苟；

【导师】 冉均国；

【作者基本信息】 四川大学 ， 生物医学工程， 2004， 博士

【摘要】 多孔β-TCP／HA生物活性陶瓷，不仅具有良好的生物相容性，还具有独特的可控制降解性能，因而成为材料工作者研究的热点之一。然而，作为骨组织替换材料，总是希望具有良好的生物学活性，又具有一定的力学强度。目前，钙磷生物陶瓷的烧结多采用马弗炉烧结法，为提高材料的生物学活性，要适当地降低烧结温度，这样材料的强度往往较难保证；而为了提高材料的强度，常采用提高烧结温度和延长烧结时间的方法，而这将带来材料的晶粒尺寸变大，结晶度增高，使材料的生物降解性下降，高温长时间烧结还可能造成过烧现象，致使材料的理化性能下降。可见，采用常规的马弗炉烧结法，很难同时解决提高材料强度和增加材料生物学活性间的矛盾。 本文从提高磷酸钙生物活性陶瓷自身的性能出发，针对常规马弗炉烧结方法的不足，首次采用微波等离子体烧结了多孔β-TCP／HA生物活性陶瓷，并对其烧结工艺进行了研究，发现当用致密氧化铝样品台，工作气体流量75ml／min，烧结室压力1.3kPa，升温速率45℃／min，降温速率为40℃／min，烧结温度1050～1100℃，烧结15min，可制得具有较好力学强度，同时晶粒尺寸又较小的多孔β-TCP／HA生物活性陶瓷。经检测，其晶粒尺寸为200～400nm，明显小于常规马弗炉所烧结的600～800nm抗压强度明显高于相应温度下常规马弗炉烧结的制品(如1100℃，前者为2.31MPa，后者为2.00MPa)。通过对致密的HA和β-TCP／HA生物活性陶瓷的对比烧结研究，也得出类似的实验结果。 不同烧结方式所得多孔β-TCP／HA生物活性陶瓷的溶解实验结果表明，微波等离子体烧结的制品比常规马弗炉烧结的制品具有更高的溶解度，用Avrami的动力学模型方程拟合了溶解动力学速度，首次获得了微波等离子体烧结的多孔p一TCP/HA生物活性陶瓷的动力学溶解速度方程:一ln(1一x卜。.73t079，式中n小于1，表示其有较大的溶解速率;马弗炉烧结的多孔p一TCP/HA生物活性陶瓷的溶解动力学速度方程为:一ln(卜x卜0.37t’·”，n略大于1，显示出有较小的溶解速率。另外，实验结果还显示不同烧结温度对制品的溶解度也有较大影响，随着烧结温度的升高，制品的溶解度降低。 通过模拟生理微循环、生理大循环和模拟炎性历程的类骨磷灰石形成情况的研究表明，微波等离子体烧结的多孔p一TCP/HA生物活性陶瓷，其类骨磷灰石的形成量都明显多于用常规马弗烧结的制品，这预示微波等离子体烧结多孔p一TCP/HA生物活性陶瓷不仅能提高材料的强度，也可能提高材料的生物学性能，这为钙磷材料的烧结提供了一种全新的烧结方法。 通过对模拟体液的类骨磷灰石的形成情况的研究还预示，生理微循环可以促使类骨磷灰石在多孔钙磷材料表面的形成，但生理微循环不足以促进多孔钙磷材料内部的类骨磷灰石的形成:生理大循环不仅有利于多孔钙磷材料表面的类骨磷灰石形成，也有利于多孔钙磷材料内部的类骨磷灰石的形成;炎性历程的微酸性对钙磷材料表面的类骨磷灰石的形成有较大影响，先行的微酸性会使钙磷材料表面凹凸部分先行溶解，使材料变得光滑，破坏了成核的局部环境，从而生成类骨磷灰石的能力减弱。 针对常规Ca(NO3)2一(NH;):HPO;一NH3HZO一HZO共沉淀法制备双相钙磷生物陶瓷粉体的反应时间长，重复性不好等不足，本文较系统地分析了pH值，温度、反应物Ca/P比和反应时间等对沉淀物的影响，首次获得了固定初始反应物的Ca/P比略小于1.5，通过加热和调节反应的pH值来制备具有不同Ca/P比双相粉体的新工艺，新工艺和传统工艺相比，其优点是反应时间大大缩短，工艺重现性好。用新工艺合成的粉体，通过马弗炉烧结所得的多孔双相陶瓷，经细胞学实验观察，具有良好的生物相容性。另外，本文还从生成磷酸钙沉淀的热力学和控基磷灰石独特吸附性能出发，提出了该体系生成的沉淀为缺钙轻基磷灰石，并提出了缺钙经基磷灰石形成的可能解吸一吸附机理。 针对微波等离子体烧结腔加热区域和样品温度较难准确测定的问题，本论文首次将标准测温锥引入微波等离子体中，根据标准测温锥中的碳化痕迹快速测定了烧结腔的加热区域;用自制的多种不同标准物质对高温红外测温仪进行了校正，并对其精确度进行了讨论，显示其误差小于IOOC，为样品的实时测温提供了可能。另外本文还较系统地研究了微波功率、烧结室压力、工作气体流量等对烧结样品的温度影响等，开辟了一种测定和控制微波等离子体烧结温度的新方法。 本文对多孔p一TCP/队生物活性陶瓷的成型工艺也进行了研究，得出的较好成型工艺为:4%聚乙烯醇作为粘接剂，粉料和粘接剂的重量比为1:0.3，粉料和造孔剂的重量比为1:0.5，大孔造孔剂和微孔造孔剂的重量比为0.2:0.3，选择大孔造孔剂为硬酷酸，微孔造孔剂为硬酷酸或聚乙烯醇缩丁醛，混合时采用粘接剂先和造孔剂混匀，再和钙磷粉末混合，成型压力为60入4卫a，保压3min，成型后的坯体先在空气中风干2一3天，再在烘箱中缓慢升温至80℃烘烤。在该成型工艺下所制得的生物活性陶瓷结构均匀，具有较好的孔隙率和强度。关键词:p一TCP/HA合成微波等离子体烧结温度测定溶解性模拟体液细胞培养更多还原

【Abstract】 Synthetically produced porous -TCP/HA biphasic bioceramics have an important role among other biomaterials, because they are considered to be osteoconduction and osteoinduction, and the rate of biodegradation can be controlled by varying HA/TCP ratio. But there are some problems on them with conventional sintering, such as long holding time, high sintering temperature, large grain size and great difficulty to enhance the bioactivity and the mechanical strength simultaneously.In this paper, microwave plasma sintering was introduced to prepare the porous -TCP/HA biphasic bioceramics. Scanning electron microscopy, X-ray diffraction, Material test machine and Atomic absorption spectrophotometer were used to characterize sintered samples. The results show that when samples were placed on a dense Al2O3 substrate, sintering with a constant heating rate of 45C/min, the rate of O2 flowing 75ml/min, the pressure of plasma 1.3kPa, holding 15min at 1100C, the plasma-sintered samples exhibit a higher densification rate, smaller grain size and higher compressive strength compared to those of conventional sintered samples. Porous -TCP/HA biphasic bioceramics with average grain size of 400nm and compressive strength of 2.31MPa were obtained compared to those sintered by a conventional furnace with average grain size of 600nm and compressive strength of 2.00 MPa.. The [Ca2+] concentration and the dissolution rate of plasma-sintered samples are higher than those of conventional sintered samples in physiological saline. After immersed in swaying or dynamic simulated body fluid (SBF) and insimulated inflammation body fluid, the plasma-sintered samples are formed on more bone-like apatite than that conventional sintered samples formed on. The results indicate that plasma-sintered porous -TCP/HA biphasic bioceramics have better mechanical properties and may also have better biological properties.On the other hand, bone-like apatite was found formed on the edge of samples in swaying SBF, but the center area of samples was not discovered, which may mean that physiological micro-circulation benefits to form bone-like apatite on the edge of implanted porous Ca-P materials, but not benefits in the center area of implanted porous Ca-P materials. There was some bone-like apatite formed on the center area of samples besides the edge area in dynamic SBF, which may mean that the physiological through circulation benefits to form bone-like apatite not only on the edge area, but also in the center area of implanted porous Ca-P materials.The surface of samples that underwent a simulated inflammation procedure is smoother and the amount of bone-like apatite formed on them is less than that formed on the samples immersed in normal SBF all the duration, which may indicate that the light acid in an inflammation response would affect the bone reconstruction when Ca-P bioceramics implanted in living body.The dense HA and -TCP/HA biphasic bioceramics prepared by microwave plasma also exhibit a higher densification rate, smaller grain size and higher indentation hardness compared to those of conventional sintered samples. But the sintering behaviors of dense material are significantly different from those of porous -TCP/HA biphasic bioceramics. The sintering efficiency of dense HA and -TCP/HA biphasic bioceramics is lower than that of porous ones.In addition, aimed at solving some problems on a conventional co-precipitation method of preparing biphasic bioceramic powders, a modified co-precipitation method was introduced. The effect of reacting temperature, pH value, reacting time and the initial ratio of Ca/P on final precipitates were discussed. The results indicate that the final precipitates are calcium deficient hydroxyapatite. The biphasic bioceramic powders with different Ca/P ratios can been synthesized by fixing the initial ratio of Ca/P less than 1.5, heating the reacting solution and adjusting the pH.The modified co-precipitation method has a good repetition and requires a shorter ageing time. In this paper, the crystallization mechanism更多还原