【作者】 邓迟；

【导师】 翁杰；

【作者基本信息】 西南交通大学 ， 材料学， 2010， 博士

【摘要】 面对临床上骨缺损增多的现实问题,生物医用复合骨修复材料的研究日益深入和广泛。随着纳米技术的发展,研究人员期待利用纳米材料的特殊效应,提高骨修复材料的综合性能,以满足骨科临床应用的需要。目前广泛研究的一类骨修复材料是磷灰石／聚合物复合材料,尤以纳米磷灰石(n-HA)与聚合物的复合材料为热点,其目的是模拟自然骨n-HA与胶原的纳米复合结构。然而,人们在制备n-HA／聚合物复合材料时,由于纳米颗粒易于团聚为大颗粒,不利于其在聚合物基体中均匀分散,且整体上将减少纳米颗粒与基体的接触面积,降低填充相与基体的界面结合强度,成为提高该类复合材料性能特别是力学性能的难点。因此,对n-HA颗粒采用物理吸附和化学结合等表面修饰手段改性成为防止或降低其在聚合物中团聚,以期有效地改善该类复合材料的综合性能特别是力学性能,是纳米生物复合材料领域的重要研究方向。本论文着重点就在于系统地研究不同特性的表面修饰改性剂对n-HA表面的修饰效果及其在纳米颗粒／聚合物复合生物材料修饰改性中的作用。整个论文一方面选用生物相容性好的聚乙二醇(PEG)系聚合物如PEG以及在PEG分子中分别引入疏水链段丙交酯的PEG-b-PLA共聚物(PELA)以及疏水链段聚氧乙烯的PPO-PEG-PPO共聚物(F127)对n-HA颗粒表面分别进行物理吸附修饰处理,采用溶液共混-热压成型技术将三种表面修饰的n-HA颗粒与降解速率适当的外消旋聚乳酸(PDLLA)复合制备成PEG系表面修饰n-HA/PDLLA复合材料,研究了表面修饰对该类复合材料的力学性能、亲水性与生物相容性的影响。论文另一方面选用三种硅烷偶联剂如γ-缩水甘油醚氧丙基三甲氧基硅烷(KH560)、γ-甲基丙烯酰氧基丙基三甲氧基硅烷((KH570)及N-β-(氨乙基)-γ-氨丙基三甲氧基硅烷(KH792)对n-HA颗粒表面分别进行化学结合修饰处理,采用溶液／热双共混-热压成型技术将硅烷表面修饰的n-HA颗粒与生物相容性好的聚己内酯(PCL)复合制备成硅烷表面修饰的n-HA/PCL复合材料,研究了硅烷修饰对该类复合材料的力学性能、亲水性、生物活性与生物相容性的作用。论文第二章首先将PEG分别溶于尺度为0.45μm-1.32μm和50nm-200nm范围的HA水溶胶中进行表面修饰,考察PEG对不同尺度HA颗粒的修饰效果。结果表明,50nm-200nm尺度范围的HA比0.45μm-1.32μm的HA表面活性大,与水分子结合更紧密,在水溶胶中形成的网络结构更牢固,使水溶胶中PEG与50nm-200nm尺度范围的HA形成的氢键较弱,PEG对该尺度范围HA表面修饰作用比0.45μm-1.32μm尺度范围的HA差。随后,为考察PEG表面修饰对HA纳米晶粒形成的影响,在化学沉淀法合成HA前后分别加入PEG对n-HA颗粒进行表面修饰。结果表明,两个不同阶段的表面修饰均使PEG吸附在HA表面,低温烧结后晶粒结构趋同。HA合成前加入PEG妨碍了HA晶粒的生长、减小其晶粒。HA合成后加入PEG不影响HA晶粒的生长发育。论文第三章研究了PEG系物理吸附和硅烷系化学结合表面修饰对聚合物纳米复合材料力学性能的影响。首先用三种表面活性剂PEG.PELA及F127分别对n-HA颗粒进行表面修饰处理,然后采用溶液共混-热压成型技术与PDLLA复合成n-HA/PDLLA新材料。研究发现,PEG表面修饰的n-HA/PDLLA复合材料具有1293%的高延伸性。表面能高n-HA颗粒与线形PDLLA分子链段形成了新的吸附点而使二者更加牢固连接,使得PDLLA结构交联化,在外力的拉伸作用下,交联化的PDLLA与n-HA吸附交叉点依次解吸而使复合材料具有高的延伸率。随后,采用溶液／热双共混-热压成型法制备了KH560.KH570及KH792化学结合表面修饰的n-HA/PCL复合材料,研究了该类复合材料的力学性能和结晶温度。结果表明,硅烷化学结合表面修饰有效提高了该类复合材料力学强度、杨氏模量和结晶化温度。论文第四章研究了PEG系表面修饰对n-HA/PDLLA复合材料的亲水性的作用。结果表明,PEG系表面修饰改善了聚合物纳米材料的亲水性。同时,也研究了硅烷化学结合表面修饰对n-HA/PCL复合材料的亲水性的影响。研究发现,含量为2%KH560硅烷偶联剂表面修饰改善了n-HA/PCL复合材料的亲水性。含量为5%KH792硅烷偶联剂表面修饰减低了n-HA/PCL复合材料的亲水性。其它含量的硅烷偶联剂表面修饰对n-HA/PCL复合材料的亲水性没有显著影响。论文第五章研究了PEG系表面修饰对n-HA/PDLLA复合材料的细胞相容性的影响。结果表明,PEG系表面修饰的复合材料与骨髓瘤细胞相互作用的alamar blue和ALP活性值均大于相应地对照组复合材料与骨髓瘤细胞相互作用值,PEG表面修饰提高了n-HA/PCL复合材料的细胞相容性。同时,也研究了硅烷化学结合表面修饰对n-HA/PCL复合材料的生物活性和细胞相容性的作用。结果发现,含量为2%的三种硅烷偶联剂表面修饰的HA/PCL复合材料在2倍的模拟体液中能够沉积出类骨磷灰石,具有良好的生物活性,但沉积出类骨磷灰石时间相对较长。硅烷表面修饰一定程度地降低了n-HA/PCL复合材料的细胞相容性。更多还原

【Abstract】 Great attention is paid to nano-apatite/polymer composite biomaterials for bone repair, as a result of an increasing number of patients suffered from bone defects in clinic practice. It is of vital importance to improve properties such as mechanical characteristics and biological property of apatite/polymer biocomposites. Some special effects brought by apatite nano-particles are introduced to composite biomaterials by imitating chemical composition and structure of organic bone and expected to explore new applications in bone repair. However, nano-apatite (n-HA) particles tend to become bigger aggregates, and thus the aggregates of n-HA particles can not be equably dispersed in polymer matrix in fabricating functional composites and interfacial bonding strength between aggregate and polymer matrix is lessened, which result in weakening mechanical and biological properties of biocomposites. Surface modifications in physical, chemical or engineering ways have been suggested to weaken the aggregates of n-HA particles, therefore, it is necessary to innovate traditional ways in surface modifications to weak aggregates of n-HA particles and improve compositive properties nano-apatite/polymer composites.This dissertation stresses two hands about surface modification of n-HA partices and effects of physical or chemical modification on improving properties of polymeric composite biomaterials. On the one hand, it focused on inpact of physical adsorption modification of surface coating agents with n-HA particles in mechnical strength, elongation rate,hydrophile and cell compatibility of n-HA/poly (D,L-lactide) (PDLLA) composite biomaterials. On the other hand, it emphasized influence of chemical reaction modification of silane coupling agents to n-HA particles on mechnical strength, elasticity modulus, hydrophile, bioactivity and cell compatibility of n-HA/poly (ε-polycaprolacton) (PCL) composites.Polyethylene Glycol (PEG) was firstly selected to coat n-HA and micro-sized apatite(m-HA) particles to understand effects of PEG on surface modification of different size HA. Results showed that with scale of HA rising, Hydrogen bonding between two molecules of PEG and HA would change stronger, and therefore bonding strength between them was weaker than between m-HA and PEG. in aqueous slurry. Secondly, PEG was coated on the surface of n-HA particles by two physical adsorption technical routes to discuss the formation of HA nano-crystals. Results showed that morphology of the HA particles exhibited acicular shape and the same size as without coating HA. PEG appeared on the surface of HA crystals and crystallization of HA particles sintered up to 800℃was not evidently different by two methods. PEG as a medium reagent could inhibit their growth in some directions, and reduced size of HA crystals. However, HA crystals in the second route were not influenced by the modifier.Three kinds of surface coating agents like Polyethylene glycol (PEG), poly (propyl oxide)-poly (ethyl oxide)-co-poly(propyl oxide)(Pluronic F127) and poly(D, L-lactide)-co-poly (ethylene glycol) (PELA) were firstly employed to modify the surfaces of n-HA particles, respectively, and then modified n-HA/PDLL A composites were prepared by combining solvent-blend with hot-pressing method. The results showed that PEG-modified n-HA/PDLLA composite displayed 1242.93 % ultrahigh elongation rate.Mechanism of ultrahigh elongation rate of modified n-HA/PDLLA composite was firstly suggested.The linear structure of molecular chain of PDLLA polymer matrix was changed into cross-linked one by interaction with molecules of the modifiers and nano-apatite, and this cross-liked structure of PDLLA molecular chain led to the high elastic and plastic deformation.On the other hand,3-Methylacryloxy propyl-trimethoxy silane (KH560),γ-Methacryloxy propyltrimethoxy silane (KH570) and N-(β-aminoethyl)-γ-aminopropyltrimethoxy silane (KH792) were emloyed to modi- fy the surfaces of n-HA particles, respect-ively, and then the silane modified n-HA/ PCL composites were prepared by combining solvent dispersion, melting-blend and hot-pressing methods. Results showed that three silane coupling agents successfully graft to the surfaces of HA nano-particles. Crystalline temperatures of KH560, KH570 and KH792 modified n-HA/PCL composites were heightened. Measurements of mechanical properties proved that ultimate tensile strength of the silane modified composite was higher than one of the contrastive group.Three silane modifications improve interfacial quality between nano-fillers and PCL polymers. In addition, n-HA particles present uniformly and de-agglomerative dispersion in PCL composites, which resulted from our fabrication technique. Two major factors discussed above lead to an enhanced mechanical properties of PCL matrix composite biomaterials.Hydrophile, Alamar Blue and ALP activity of PEG, PELA and F127 modified n-HA/ PDLLA composites were carefully examined. Results showed that good hydrophile was found on three kinds of PEG polymer modified n-HA/PDLLA composite biomaterials and it suggested that PEG modification of n-HA had positive effects on enhancing hydrophile of PDLL-matrix composites. Besides, PEG surface modification of n-HA particles could elevate values of Alamar Blue and ALP activity and this hinted that PEG modification promoted cell compatibility of n-HA/PDLLA composite with cancer of bone.Hydrophile, bioactivity, Alamar Blue and ALP activity of the KH560、KH570 and KH792 modified n-HA/PCL composite were carefully mearsured. Results showed that three silane modified n-HA/PCL composites was bioactive materials, through there are longer time to induced like-bone apatite on the surfaces of the silane modified composites. Besides, contents of three kinds of the silane coating agents had the important effects on hydrophile of modified composites. For examples, 2% contents of KH560 in the modified materials were propitious to improve hydrophile, while 5% contents of KH79 were prone to counterwork hydrophile. On the whole, three kinds of of the silane coating agents baffled to improve the cell compatibility of n-HA/PCL composite with cancer of bone.更多还原