【作者】 陈松；

【导师】 季金苟；

【作者基本信息】 重庆大学 ， 药物化学， 2008， 硕士

【摘要】 骨缺损修复材料一直是生物材料领域的研究热点之一。十多年来,由于组织工程修复材料的诸多优点使得其已逐渐成为骨修复材料发展的方向。组织工程支架材料的发展走过了由单一的生物高分子材料、无机生物陶瓷材料等向复合多孔材料发展的道路。羟基磷灰石(HA)/有机聚合物复合材料是当前硬组织修复材料研究中的重点之一。HA是构成人骨无机质的主要成分,具有优异的生物相容性和生物活性,能与骨组织形成牢固的键合,一直是近二、三十年骨修复和替代材料研究的热点。但其脆性大,在生理条件下抗疲劳性不强,从而限制了其临床应用。将HA与一些韧性较好、弹性模量与人骨接近的聚合物复合,可以将二者的优良性能充分结合起来,有望得到高强、柔韧、易加工塑形、力学相容性好且具有良好生物相容性和生物活性的新一代骨修复材料。本文以Ca(NO3)2·4H2O, (NH4)2HPO4和NH4HCO3为原料,采用化学沉淀法辅以微波辐射制备了含碳酸根的纳米缺钙羟基磷灰石(d-CHA),讨论了溶液pH值、微波辐射时间、微波功率等工艺条件对所制得的d-CHA粉体钙磷摩尔比的影响。用XRD、IR、SEM对所制得的粉体进行了分析。研究结果表明:在pH为8～9的范围内,以一个适中的微波功率辐射处理反应溶液1小时,能够在较短时间内合成d-CHA粉体。本文采用改进的溶液共混-模压成型-沥滤法来制备d-CHA/PLA多孔复合材料,希望得到具有良好生物相容性、力学性能及生物降解性,能符合骨细胞生长需要的组织工程支架材料,通过对d-CHA/PLA用量比及孔隙率等参数的控制,来调节材料的机械性能与生物降解速率。并利用XRD、IR、SEM等现代化分析手段,以及化学物理分析方法,对复合材料的成分、微观结构、孔隙率、吸水率、抗压强度等性能进行了分析和表征。研究结果表明,采用化学沉淀法辅以微波辐射所制备的d-CHA是制备复合材料的理想原料。在制备d-CHA/PLA多孔复合材料时,当致孔剂含量为60%~70%时,复合材料的孔隙率可达60%~70%,能满足细胞生长的要求。材料的抗压强度可以达到3MPa,符合骨组织工程的要求。实验还发现,当PLA/d-CHA用量比相同时,致孔剂加入量越大,复合材料孔隙率越高,力学强度越低。PLA与d-CHA用量不同对支架材料力学性能有明显的影响,其它条件相同时,d-CHA/PLA用量比为2:8的情况下支架材料具有相对较好的成型性及抗压强度。将上述制得的d-CHA/PLA多孔复合材料,浸泡在模拟体液(SBF)中,置于37℃恒温水浴里,进行体外降解,通过X-射线衍射(XRD)、红外光谱仪(FTIR)及SEM分析,发现有少量的d-CHA转化为类骨磷灰石。由材料的降解试验结果还可以看出,PLA用量越多,或d-CHA用量越少,复合材料的降解速率越快。且降解试验结果显示,d-CHA/PLA比例为2:8的材料降解速率适中,具有较好的生物降解性。更多还原

【Abstract】 Bone default repairing material is one of the hotspots of Biomaterial research. During the last ten years, Bone tissue engineering had been becoming the developing direction of this field for many of its merits. Biologic matrix has been developed from bio-poly-materials or bioceramics only to bio-composites. Now, the bio-composites have been confirmed to be one of the developing directions of bone tissue engineering matrix materials.Hydroxyapatite/organic polymer biomedical composite is a hot topic of hard tissue biomaterials research. Hydroxyapatite (HA), the main mineral composition of bone, can form strong bone-bonding with natural bone and has been used extensively for biomedical applications and bone regeneration based on its high biocompatible, bioactive and osteoconductive properties, which has been the research focus of bone repair and substitute materials in resent 20-30 years. However, due to the brittleness, high modulus and fatigue failure in vivo, it is restricted in clinic for un-load bearing bone repair. In order to improve the mechanical property of HA material for hard tissue replacement, study on HA and polymer composite is highlighted. The combination of (HA) bioactivity and (polymer) toughness may result in a new load-bearing bioactive material with good mechanical property, excellent bioactivity and biocompatibility.In this paper, Ca(NO3)2·4H2O, (NH4)2HPO4 and NH4HCO3 were used as starting materials. Calcium-deficient carbonated HA (d-CHA) nanoparticles were synthesized using a precipitation method assisted with microwave irradiation. The influence of different technical parameters such as pH value of the solution, time and power of microwave irradiation on the Ca/P molar rations of HA powders were discussed. XRD, IR and SEM were used to analyze the HA powders. The results showed that calcium-deficient carbonated HA nanoparticles with high performance could be quickly synthesized by irradiating the reaction solution for 1 h at a moderate microwave power. The pH value of solution ranged from 8～10.In order to make a kind of bone tissue engineering matrix material with favorable biocompatibility, mechanical properties and biodegradability, a process which consists of a solvent casting stage, a compression molding stage and a leaching stage had been used to fabricate macroporous composites of PLA and d-CHA. The mechanical properties and degradable characteristics of this material could be controlled by adjusting the components ratio and the porosity. The characters of composites, such as composition, microstructure, porosity, water absorption, compressive strength were analyzed with IR, XRD, SEM and some chemistry methods.The results show that: d-CHA powders synthesized using a precipitation method assisted with microwave irradiation were the best materials to fibracate macroporous composites. The porosity of composites could be different from 60% to 70% when poregen dosage addition was from 60% to 70%, and this porosity was suited cell fostering. The compressive strength of composites was 3MPa, and this compressive strength was suited the demands of bone tissue engineering. When the ratio of PLA and d-CHA was determined, with the increasing of the porogen dosage, the porosity would be increased, and the mechanical properties would be dropped down. Different dosage of PLA andβ-TCP could affect the composites properties. With the same other conditions, d-CHA/PLA=2:8, the composites possessed better advantages for molding and better mechanical properties. The composite samples were immersed in stimulated body fluid(SBF) at 37℃, the samples were characterized by XRD, IR and SEM. The results showed that bone-like apatite was formed on the surface of composites. From the results of degradation experiments, it could be seen that with more PLA given, or amount d-CHA powder reduced, the speed of degrading increased. And the results showed that when d-CHA/PLA was 2:8, the composites possessed mezzo degrading speed and best biodegradability.更多还原