用于钛合金表面改性的新型聚合物涂层的制备及性能研究

【作者】 黄涛；

【导师】 刘平生； 李利；

【作者基本信息】 南京师范大学 ， 高分子化学与物理， 2017， 硕士

【摘要】 钛合金因具有高比强度、低密度、优异生物相容性以及与天然骨组织相匹配的弹性模量等诸多优点而被作为人工关节、牙种植体等硬组织替代或修复材料广泛使用。然而,其固有的生物惰性以及缺乏抗炎症、抗菌、抗凝血等生物功能性决定了原始的钛合金难以引导再生组织生长,易引起术后感染以及导致血栓的形成,最终极大地降低钛合金植入器件的成功率。因此,如何改善钛合金植入器件的生物活性、提高其生物功能性,一直是临床医学中亟待解决的难题之一。生物材料的表面改性是一种提高其生物功能性非常有效的途径。它能够在保持基底材料性能不变的情况下,仅通过简单的表面形貌变化、表面构建生物活性分子或功能性材料在表面的构建等方式显著地提高基底材料的生物功能性。本论文基于膦酸(酯)化合物能与金属材料形成稳定配位作用,制备了两类四种新型的两性离子/膦酸(酯)共聚物,并研究了所制备的共聚物涂层钛合金表面的抗生物粘附性能。同时,制备了含膦酸基团的原子转移自由基聚合(ATRP)引发剂,进一步将其化学固定在钛合金表面并构建功能性含活性酯聚合物刷,具体的研究内容如下:(1)首先制备了高纯度的(甲基丙烯酰氧基)甲基膦酸二乙酯(DEMMP)单体,通过单体的核磁共振图谱对三种提纯方法的效果进行了比较;进一步通过DEMMP单体在ATRP以及可逆加成-断裂链转移(RAFT)条件下的聚合反应动力学的比较,考察并优化了可控制备DEMMP聚合物的工艺条件。(2)将DEMMP进一步脱酯基,制备高纯度(甲基丙烯酰氧基)甲基膦酸(MMPA)单体,并以过硫酸铵(APS)为引发剂、四甲基乙二胺(TEMED)为催化剂,成功制备了三种不同摩尔比的磺胺两性离子/膦酸无规共聚物(pSBMA-co-pMMPA);同时,采用RAFT制备了磺胺两性离子/膦酸酯嵌段共聚物(pDEMMP-b-pSBMA)。进一步将四种新型的共聚物对钛合金进行修饰。静态水接触角(SWCA)与X-射线电子能谱(XPS)证实了磺胺两性离子/膦酸(酯)成功地构建在钛合金表面;蛋白吸附和血小板粘附实验结果表明磺胺两性离子/膦酸(酯)共聚物作为一类新型的钛合金涂层材料,显著提高钛合金的抗生物粘附性能。同时,初步试验结果表明嵌段共聚物在提高抗生物粘附性能上优于无规共聚物。(3)制备了高纯度的甲基丙烯酸(N-羟基琥珀酰亚胺)活性酯单体(NHSMA);通过不同条件下的ATRP聚合反应动力学研究,考察并优化了其可控聚合行为。制备出窄分子量分布(Mn=59200,PDI=1.07)的pNHSMA活性酯聚合物;基于优化的条件,通过表面引发的原子转移自由基聚合(SI-ATRP)在钛合金表面构建了 pNHSMA活性酯聚合物。进一步采用小分子苄胺验证了所制备的pNHSMA活性酯聚合物及构建在钛合金表面的聚合物刷中活性酯基团的活性。更多还原

【Abstract】 Due to numerous merits such as high toughness,low density,excellent biocompatibility and comparable elastic modulus with human native bone tissues.titanium based alloys have been widely used for biomedical applications including artificial joints,dental implants,and other hard tissue regenerative materials.However,the intrinsic bioinert,as well as the lacking of anti-bacterial and blood compatibility,titanium alloy based implants cannot guid the regeneration of new tissues,and be apt to cause infections and form thrombus after the implantation,resulting in the final falure of the implantation.Therefore,the improvement of the bioactivity and the bio-functionalility of the titanium-based implants is one of the remaining challenges in the clinical medicine,and the R&D of new titanium based biomaterials to meet specific requirements is the hot research area in the biomedical engineering field.Surface modification is a promising strategy to improve the bioactivity and bio-functionality of the biomaterials.Through facile modification either changing the surface morphology or binding bioactive molecules or functional mateirals on the surface could significant enhances the bioactivity of the substrates without compromising the bulk propertiesIn the current study,four types of novel metal tetherable zwitterionic-phosphonate(or phosphonic)copolymers.mainly beased on the strong coordination between the phosphonate or phosphonic motif and the metal surface,have been prepared for improving the anti-biofouling ability of the titanium substrate.In the meantime,through a phosphonic type of tatherable initiator that immobilized on the titanium surface,active-ester containing polymeric brushes has been grafted on the surface of titanium alloy.The research contents are listed as follows:(1)A diethyl(methacryloyloxyl)phosphonate monomer was synthesized.Based on the NMR characterizations,the effects of three purification processes on the purity of the monomer were compared.The ATRP and RAFT of DEMMP monomers were performed.The kinetic studies of these two controlled radical polymerizations revealed that RAFT polymerization exhibited a better-controlled manner.(2)A(methacryloyloxyl)phosphonic acid monomer(MMPA)was synthesized through the hydrolysis of DEMMP monomer.Combined with zwitteironic SBMA monomer,three types of novel copolymers with varied mol.ratios(SBMA v.s.MMPA.9:1,8:2,6:4)between the two monomers were prepared by using APS and TEMED as the initiator and catalyst,respectively.In the meantime.a novel block polymer,pDEMMP-b-pSBMA,was prepared by RAFT process based on the previously optimized conditions.Furthermore,the four types of copolymers were coated onto the surface of titanium alloy.Static contact angle measurements and XPS revealed the succsful fabrication of zwitterionic/phosphonate(phosphonic)copolymer on the metal surface.Protein adsorption test and platelet adhesion measurements indicated that all four types of zwitterionic/phosphonate(phosphonic)copolymers generally significantly improved the anti-biofouling ability of the titanium substrates.The prelimilary comparison between the three random copolymers and the block copolymer showed that the later copolymer is superior to the three random copolymers in improving the anti-biofouling ability.(3)A mathacrylic acid N-hydroxysuccinimide ester monomer(NHSMA)was synthesized.Through the kinetic studies of the ATRP of NHSMA under different temperatures,the polymerization parameters were optimized,and well controlled pNHSMA polymers(Mn=59200,PDI=1.07)were prepared.In the meantime,take advantage of SI-ATRP,pNHSMA brushes were succeefully fabricated on the surface of titanium.Furthermore,the activity of the active ester pendant on both the pNHSMA polymers and the pNHSMA brushes were verified by the coupling reaction with benzylamine.更多还原