【作者】 田野；

【导师】 王兴； 任鲁风；

【作者基本信息】 北京化工大学 ， 生物工程（专业学位）， 2020， 硕士

【摘要】 自愈性水凝胶是一类在受到外部创伤后,经过一定时间,可以自身修复成与之前形态、功能、性能相近的智能水凝胶。大部分的自愈性水凝胶与生物组织高度相似,具有非常良好的生物相容性,因此受到了大量科研工作者的关注。但是,由于需要引入具有自愈性的官能团,自愈性水凝胶往往需要经过较为复杂的制备过程。同时,成胶的pH、温度、压强以及使用时的生理毒性等问题也制约了自愈性水凝胶在生物医用材料方面的应用。近年来,研究者们将目光聚焦到开发一种合成简便、自愈条件温和可控、无毒无害且具有一定特殊性能的自愈性水凝胶。多组分反应因其特殊的优势(原子经济、反应高效、产物性状独特等)逐渐引起高分子化学家和材料学家的研究兴趣。多组分反应可通过一步反应,同时连接多个底物,合成新的具有多个官能团的单一分子,在大大提高合成的效率的同时,赋予分子独特的特性。因此,多组分反应在制备新的多功能分子方面具有天然的优势。将多组分反应引入高分子合成中,与自由基聚合反应相结合,采用“一锅煮”策略,在聚合的同时引入多个功能基团,可以一步合成新的多功能聚合物。本工作结合Kabachnik-Fields多组分反应(K-F反应)和自由基聚合反应,通过“一锅法”简便合成了前体高分子,再进行有效的水解反应,制备了含苯硼酸基团和带有负电荷的α-氨基膦酸基团的多功能聚合物。该聚合物侧链上的苯硼酸基团可在温和条件下通过动态硼酸酯键与聚乙烯醇生成聚阴离子自愈性水凝胶。经细胞实验测定,该水凝胶具有较低的细胞毒性,可用于三维细胞培养。在本文中,我们挑选了带有正电荷的顺铂作为模型药物,研究了该水凝胶的缓释放能力。该水凝胶中带负电荷的α-氨基膦酸基团与带正电的顺铂有效结合,降低了药物的释放速率,并显著提高了顺铂细胞安全性。这说明,该水凝胶可用于临床治疗中的药物递送体系。除此之外,由于关于α-氨基膦酸基团的研究较少,我们还通过模型分子,设计实验证明了 α-氨基膦酸基团和顺铂的结合。更多还原

【Abstract】 Self healing hydrogel is a kind of intelligent hydrogel which can be repaired by itself in a certain period of time after being subjected to external trauma.Most of the self-healing hydrogels have excellent biocompatibility because of their high similarity with biological tissues.However,due to the need to introduce self-healing functional group to hydrogel,self-healing hydrogels often require complex preparation processes.At the same time,pH,temperature,pressure and physiological toxicity also restrict the applications of self healing hydrogels in biomedical materials.In recent years,the researchers focused their attention on developing a self-healing hydrogel with simple synthesis process,mild self-healing condition,low cytotoxicity and other special properties.Multicomponent reactions have attracted the interest of polymer chemists and material scientists because of their special advantages(atomic economy,high efficiency,unique product properties,etc.).Multicomponent reactions can be used to synthesize new single molecules with multiple functional groups by connecting multiple substrates in one step,which greatly improves the efficiency of synthesis and endows the molecules with unique characteristics.Therefore,multicomponent reactions have advantages in the preparation of new multifunctional molecules.The introduction of multicomponent reaction into polymer synthesis,combined with free radical polymerization,and using the"one pot" strategy,the polymerization could introduce multifunctional groups at the same time,and obtain new multi-functional polymers via one-step synthesis.In this work,the precursor polymer was synthesized by "one pot" method,combining Kabachnik-Fields multicomponent reaction(K-F reaction)and free radical polymerization,and then the multifunctional polymer containing phenylboric acid group and a-aminophosphoric acid group with negative charge was prepared by a effective hydrolysis method.The boronic acid group on the side chain of the polymer can form poly anion self healing hydrogels through a dynamic borate ester bond with polyvinyl alcohol under mild conditions.The results showed that the hydrogel had low cytotoxicity and the hydrogel could be used for three-dimensional cell culture.In this paper,we selected positive-charged-cisplatin as a model drug,and studied the cumulative release from the hydrogel.The negatively charged α-aminophosphoric acid group in the hydrogel effectively combined with positively charged cisplatin,which reduced the release rate of the drug and significantly improved the cell safety of cisplatin.This indicates that the hydrogel can be used as a drug delivery system for clinical treatment.In addition,due to the lack of research on α-aminophosphoric acid group,we also designed a model molecule experiment and proved the binding between α-aminophosphoric acid group and cisplatin.更多还原