多孔凝胶与血红蛋白催化功能体系的构建及其初步的医学应用
发布时间：2018-11-01 14:24
【摘要】：水凝胶是一种可吸水膨胀并易于修饰的天然高分子聚合物。因其具备较高的生物相容性和可生物降解性被广泛应用于生物组织工程。本文以明胶(Gel)、对羟基苯丙酸(HPA)、酪胺酸(Tyr)为原料,合成三种多孔型水凝胶支架或基质材料,用以分别封装酶催化反应底物或酶,一方面借助血液中血红蛋白(Hgb)或葡萄糖氧化酶(GOD)的催化功能,实现对潜血或血糖目标物的快速传感分析;另一方面,利用酶催化反应引起水凝胶的物理化学性质变化,研制成兼具杀菌和止血功能的生物材料。由此设计的功能化多孔水凝胶可望在传感、止血材料和药物输送等领域具有广泛的应用前景。(1)通过引入交联剂将Gel和HPA连接形成多孔水凝胶支架,用以封装Hgb催化显色反应底物,并共价键合固定于氨基化的玻璃毛细管内壁,制得对潜血敏感的毛细管阵列比色分析平台。该平台借助毛细现象自动吸取样品,并利用血液中Hgb催化封装的底物显色反应,建立一种快速、灵敏、高通量的可视化检测潜血的分析方法,实现了对微量人体排泄物(如唾液、尿液、粪便)中潜血速测。(2)将含有酚羟基基团的Tyr与Gel共价键合,并引入过氧化氢,制得具有高抗菌性和药物缓释能力的可塑性止血水凝胶材料。借助血液中Hgb催化封装的过氧化氢氧化Tyr反应,在伤口出血处形成高强度水凝胶,达到迅速止血的效果。同时,水凝胶中过氧化氢可抑制伤口处细菌生长,其致密的多孔结构可为伤口提供防护屏障和温润的愈合环境,籍以减少组织的二次伤害;通过活体老鼠试验,验证了水凝胶的快速止血功能。这种具有快速止血、药物缓释、抑菌、可注射的止血水溶胶材料,在生物医学材料和组织工程领域具有巨大的应用价值。(3)将Gel、HPA、Tyr三者共价交联构建成网络复合材料,用以封装GOD,制得对血糖敏感的功能化水凝胶复合材料。将该材料置于石英晶体微天平(QCM)中,利用GOD催化血糖中葡萄糖产生过氧化氢,并借助血液中的Hgb催化过氧化氢氧化其中的HPA与Tyr反应,使复合材料由溶胶状态变为凝胶状态,进而导致QCM频率的规律性变化,实现对血糖的快速、简便、灵敏的速测。这种基于功能化水凝胶的QCM检测法可望广泛用于临床的血糖分析。
[Abstract]:Hydrogel is a kind of natural polymer which can expand and modify easily. Because of its high biocompatibility and biodegradability, it is widely used in tissue engineering. In this paper, three kinds of porous hydrogel scaffolds or matrix materials were synthesized from gelatin (Gel), p-hydroxyphenylalanate (HPA), tyramidine (Tyr), which were used to encapsulate the substrate or enzyme respectively. On the one hand, with the help of the catalytic function of hemoglobin (Hgb) or glucose oxidase (GOD) in blood, the fast sensing analysis of occult blood or blood glucose target was realized. On the other hand, the physical and chemical properties of hydrogels were changed by enzyme-catalyzed reaction, and a biological material with both bactericidal and hemostatic functions was developed. The functional porous hydrogel is expected to be widely used in the fields of sensing, hemostatic materials and drug delivery. (1) Gel and HPA are joined to form porous hydrogel scaffolds by introducing crosslinking agent. A capillary array colorimetric analysis platform sensitive to occult blood was prepared by encapsulating the substrate of Hgb catalytic chromogenic reaction and covalently bonding to the inner wall of the glass capillary tube. With the help of capillary phenomenon, a rapid, sensitive and high-throughput method for visual detection of occult blood was established by using the substrates color reaction catalyzed by Hgb in blood. Rapid detection of occult blood in trace human excreta (such as saliva, urine, feces) was achieved. (2) Tyr containing phenolic hydroxyl group was covalently bonded with Gel, and hydrogen peroxide was introduced. A plastic hemostatic hydrogel with high antimicrobial activity and drug release ability was prepared. A high strength hydrogel was formed in the wound bleeding area by oxidation of Tyr with hydrogen peroxide catalyzed by Hgb in blood and the effect of hemostasis was achieved quickly. At the same time, hydrogen peroxide in hydrogel can inhibit the growth of bacteria in the wound, its dense porous structure can provide a protective barrier and warm healing environment for the wound, so as to reduce the secondary injury of tissue. The rapid hemostasis function of hydrogel was verified by living mouse test. This kind of haemostatic hydrosol material with rapid hemostasis, drug release, bacteriostasis and injectable injection has great application value in biomedical materials and tissue engineering. (3) Gel,HPA, will be used in the field of tissue engineering. (3) Gel,HPA, is widely used in the field of biomedical materials and tissue engineering. The network composite was constructed by covalent crosslinking of Tyr, which was used to encapsulate GOD, to make functional hydrogel composite which was sensitive to blood sugar. The material was placed in quartz crystal microbalance (QCM) and GOD was used to catalyze glucose in blood glucose to produce hydrogen peroxide, and Hgb in blood to catalyze the oxidation of HPA to Tyr. The composite material changed from sol state to gel state, which resulted in the regular change of QCM frequency, and the rapid, simple and sensitive measurement of blood glucose was realized. This QCM method based on functional hydrogel is expected to be widely used in clinical blood glucose analysis.
【学位授予单位】：曲阜师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O648.17
本文编号：2304191
[Abstract]:Hydrogel is a kind of natural polymer which can expand and modify easily. Because of its high biocompatibility and biodegradability, it is widely used in tissue engineering. In this paper, three kinds of porous hydrogel scaffolds or matrix materials were synthesized from gelatin (Gel), p-hydroxyphenylalanate (HPA), tyramidine (Tyr), which were used to encapsulate the substrate or enzyme respectively. On the one hand, with the help of the catalytic function of hemoglobin (Hgb) or glucose oxidase (GOD) in blood, the fast sensing analysis of occult blood or blood glucose target was realized. On the other hand, the physical and chemical properties of hydrogels were changed by enzyme-catalyzed reaction, and a biological material with both bactericidal and hemostatic functions was developed. The functional porous hydrogel is expected to be widely used in the fields of sensing, hemostatic materials and drug delivery. (1) Gel and HPA are joined to form porous hydrogel scaffolds by introducing crosslinking agent. A capillary array colorimetric analysis platform sensitive to occult blood was prepared by encapsulating the substrate of Hgb catalytic chromogenic reaction and covalently bonding to the inner wall of the glass capillary tube. With the help of capillary phenomenon, a rapid, sensitive and high-throughput method for visual detection of occult blood was established by using the substrates color reaction catalyzed by Hgb in blood. Rapid detection of occult blood in trace human excreta (such as saliva, urine, feces) was achieved. (2) Tyr containing phenolic hydroxyl group was covalently bonded with Gel, and hydrogen peroxide was introduced. A plastic hemostatic hydrogel with high antimicrobial activity and drug release ability was prepared. A high strength hydrogel was formed in the wound bleeding area by oxidation of Tyr with hydrogen peroxide catalyzed by Hgb in blood and the effect of hemostasis was achieved quickly. At the same time, hydrogen peroxide in hydrogel can inhibit the growth of bacteria in the wound, its dense porous structure can provide a protective barrier and warm healing environment for the wound, so as to reduce the secondary injury of tissue. The rapid hemostasis function of hydrogel was verified by living mouse test. This kind of haemostatic hydrosol material with rapid hemostasis, drug release, bacteriostasis and injectable injection has great application value in biomedical materials and tissue engineering. (3) Gel,HPA, will be used in the field of tissue engineering. (3) Gel,HPA, is widely used in the field of biomedical materials and tissue engineering. The network composite was constructed by covalent crosslinking of Tyr, which was used to encapsulate GOD, to make functional hydrogel composite which was sensitive to blood sugar. The material was placed in quartz crystal microbalance (QCM) and GOD was used to catalyze glucose in blood glucose to produce hydrogen peroxide, and Hgb in blood to catalyze the oxidation of HPA to Tyr. The composite material changed from sol state to gel state, which resulted in the regular change of QCM frequency, and the rapid, simple and sensitive measurement of blood glucose was realized. This QCM method based on functional hydrogel is expected to be widely used in clinical blood glucose analysis.
【学位授予单位】：曲阜师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O648.17
【参考文献】
相关期刊论文 前1条
1 王全林,刘志洪,蔡汝秀,吕功煊;血红蛋白作为催化剂高灵敏测定过氧化[J];分析化学;2002年08期
，本文编号：2304191
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