CN107312193A - 一种仿生的可注射黏附性水凝胶、制备方法及其在生物方面的应用 - Google Patents
一种仿生的可注射黏附性水凝胶、制备方法及其在生物方面的应用 Download PDFInfo
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Abstract
一种仿生的可注射黏附性水凝胶、制备方法及其在生物方面的应用,属于高分子材料技术领域。本发明首先用多巴胺对天然高分子透明质酸进行修饰,产物仍具有较高的水溶性,然后加入辣根过氧化物酶和过氧化氢,调节pH到弱碱性,通过振荡使其混合均匀后便会产生从溶胶到凝胶相转变的过程,伴随着颜色从无色到棕色的变化,赋予该水凝胶黏附的性质。除此之外,其原有的生物相容性好,无毒和可降解性等特征均保持了下来,我们也通过细胞毒性试验,体外降解试验等进一步证明了其性能的保存,结合以上特点,这种仿生的可注射黏附性水凝胶有潜力作为一种新型生物材料在细胞、组织工程等生物医学领域大展身手。
Description
技术领域
本发明属于高分子材料技术领域,具体涉及一种仿生的可注射黏附性水凝胶、制备方法及其在生物方面的应用。
背景技术
近年来,随着前沿学科的迅猛发展和科学技术的飞速发展,仿生材料被广泛应用到军事材料、生物医用材料、通讯材料等各个方面。仿生材料继承了天然生物材料的独特的结构和优越的性能,人们志在制备出具备不同功用的新型仿生材料。目前,对于仿生材料的研究无论在结构还是功能方面,都已经取得了较为显著的成果,而水凝胶也成为了受益者之一。水凝胶是一类具有三维立体的高分子网状结构的材料,亲疏水基团并存的结构使其既具有流动性,又具一定的力学强度。根据原料来源的不同,可以将水凝胶分为天然水凝胶和合成水凝胶。天然水凝胶由于其特有的生物学特性(生物相容性、生物可降解性等)和与细胞外基质的相似性而常被用于细胞和组织工程等方面,其中的一些天然生物高分子主要是胶原蛋白、纤维蛋白、透明质酸钠(HA)、明胶、壳聚糖、纤维素、藻酸盐和琼脂糖等物质,其与生物体的密切关系使其在人工组织、伤口敷料、药物缓释以及化学传感器等方面都具有广阔的应用前景。
随着人们生活质量和运动水平的不断提高,肌腱、神经等组织的损伤问题也越来越多,目前所存在的治疗手段主要有手术治疗和保守治疗,但都存在或大或小的风险,因此我们急需一种生物相容性好且具有黏附性的材料来帮助其修复并解决一些问题,于是仿生的黏附性水凝胶因其独特的生化功能与物理特性在众多的具有医用功能的聚合物材料中脱颖而出,在不损失材料本身特性的基础上仍能赋予其更多新型功能将使这种材料在生物医学等方面发挥重要作用。
发明内容
本发明的目的是提供一种仿生的可注射黏附性水凝胶、制备方法及其在生物方面的应用。
该方法首先用多巴胺对天然高分子透明质酸进行修饰,产物仍具有较高的水溶性,然后加入辣根过氧化物酶和过氧化氢,调节pH到弱碱性,通过振荡使其混合均匀后便会产生从溶胶到凝胶相转变的过程,伴随着颜色从无色到棕色的变化,赋予该水凝胶黏附的性质。除此之外,其原有的生物相容性好,无毒和可降解性等特征均保持了下来,我们也通过细胞毒性试验,体外降解试验等进一步证明了其性能的保存,结合以上特点,这种仿生的可注射黏附性水凝胶有潜力作为一种新型生物材料在细胞培养、伤口敷料、组织粘接、组织工程等生物医学领域大展身手。
本发明所述的具有可注射黏附性的智能聚多糖水凝胶的制备方法,其具体步骤如下:
1)1.0~4.0g聚多糖于室温下搅拌溶解在150~300mL去离子水中,依次加入1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)1.4260~5.7038g,N-羟基琥珀酰亚胺(NHS)0.8561~3.4244g,搅拌30~50分钟后加入多巴胺盐酸盐0.9404~3.7617g,用浓度为0.1~0.4mol/L的盐酸调节体系的pH为4.6~5.0之间,通氮气5~10分钟,密闭搅拌20~30小时,然后在通氮气的条件下用分子量为8000~14000的渗析袋渗析2~3天,换4~5次水,渗析后的聚合物水溶液用冻干机冻干2~3天后得到蓬松多孔的样品;
2)将步骤1)样品配成1.0~2.0wt%的水溶液,配置2~20mM的H2O2水溶液,20~200u/mL的氧化偶联剂水溶液,pH=5~8的磷酸缓冲溶液(PBS),分别取H2O2水溶液、氧化偶联剂水溶液和PBS溶液各400~800μL,混合均匀后,边振荡边向其中加入1~2mL步骤1)样品的水溶液,得到的无色透明的混合溶液在60~100s的时间内变为棕色,即得到本发明所述的仿生的可注射黏附性水凝胶。
上述方法中,聚多糖可以是透明质酸钠、海藻酸钠、果胶等天然聚多糖高分子。
上述方法中,聚多糖的分子量可以是200~700kDa。
上述方法中,氧化偶联剂可以是辣根过氧化物酶(HRP)、蘑菇多酚氧化酶、梨多酚氧化酶。
本发明优点如下:1.水凝胶原料来源广,生物相容性好,无毒,有利于产品的商品化;2.制备操作过程简便,绿色无污染。3.得到的水凝胶具有较强的黏附性的同时仍具有一定的力学强度,方便材料的塑形与固定;4.溶胶到凝胶的时间可调控,可满足不同情况下对成胶时间的要求;5.酶反应交联的方式取代化学交联剂交联,保持了原有的好的生物相容性和材料安全性;6.水凝胶含水量可以达到95%以上,冻干后的扫描电镜图显示其为疏松多孔结构,便于功能细胞的生存以及生物活性分子的储存与释放;7.可注射与黏附性的结合使其可用于微创治疗,使患者疼痛减轻,并且见效快。还可用于皮肤等外部创面的敷料、填充材料以及组织再生辅助材料等,具有广阔的发展前景。
附图说明
图1:为实施例1所制备的仿生水凝胶的相转变图。通过比较倾斜的试剂瓶中物质的前后变化我们可以看出,样品A和H2O2,HRP的混合溶液本为无色透明液体(图A),在加入PBS,振荡、静置80s后,变为凝胶固体(图B)。表明其具有可注射性质。
图2:为实施例1所制备的仿生水凝胶(HA-DA)的黏附力测试图(曲线1)。通过与同样以透明质酸作为高分子骨架的另一种水凝胶(HA-ALD)相比(曲线2)我们可以看出该水凝胶有较强的黏附力。
图3:为实施例1所制备的仿生水凝胶冻干后的扫描电镜图。从图中可以清楚的看到水凝胶冻干后疏松多孔的结构,利于细胞的增殖,药物的搭载与释放以及物质的交换。
具体实施方式
实施例1:
1)称取1.0g透明质酸钠(700kDa)于室温下搅拌溶解在150mL去离子水中,依次加入1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)1.4260g,N-羟基琥珀酰亚胺(NHS)0.8561g,快速搅拌30分钟后加入多巴胺盐酸盐0.9404g,完全溶解后得到无色透明的液体,之后用浓度为0.4mol/L的盐酸调节体系的pH到5.0,通氮气5分钟后,密闭搅拌20小时。然后在通氮气的条件下用分子量为14000的渗析袋在去离子水中渗析3天,换5次水,渗析后的聚合物水溶液用冻干机在-50℃条件下干燥3天后即可得到蓬松多孔的样品A。
2)称取样品A 0.10g于10mL玻璃瓶中,加入4.90mL去离子水,配成2.0wt%的水溶液,配置10mM的H2O2水溶液,100u/mL的辣根过氧化物酶(HRP)水溶液,pH为7.5的磷酸缓冲溶液(PBS),分别取H2O2水溶液、HRP水溶液和PBS各400μL,混合均匀后,边振荡边向其中加入1.0mL的样品A的水溶液,无色透明的混合溶液会在80s内变为棕色,即得到本发明所述的仿生的可注射黏附性水凝胶。
实施例2:
1)称取1.0g海藻酸钠于室温下搅拌溶解在200mL去离子水中,依次加入1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)2.852g,N-羟基琥珀酰亚胺(NHS)1.7122g,快速搅拌30分钟后加入多巴胺盐酸盐1.9124g,完全溶解后得到无色透明的液体,之后用浓度为0.4mol/L的盐酸调节体系的pH到4.7,通氮气5分钟后,密闭搅拌20小时。然后在通氮气的条件下用分子量为8000的渗析袋在去离子水中渗析3天,换5次水,渗析后的聚合物水溶液用冻干机在-50℃条件下干燥3天后即可得到蓬松多孔的样品B。
2)称取样品B 0.10g于10mL玻璃瓶中,加入4.90mL去离子水,配成2.0wt%的水溶液,配置20mM的H2O2水溶液,100u/mL的辣根过氧化物酶(HRP)水溶液,pH为7.5的磷酸缓冲溶液(PBS),分别取H2O2水溶液、HRP水溶液和PBS各400μL,混合均匀后,边振荡边向其中加入1.0mL的样品A的水溶液,无色透明的混合溶液会在100s内变为棕色,即得到本发明所述的仿生的可注射黏附性水凝胶。
实施例3:
1)称取1.0g果胶于室温下搅拌溶解在150mL去离子水中,依次加入1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)5.7038g,N-羟基琥珀酰亚胺(NHS)3.4244g,快速搅拌30分钟后加入多巴胺盐酸盐2.7112g,完全溶解后得到无色透明的液体,之后用浓度为0.4mol/L的盐酸调节体系的pH到5.0,通氮气5分钟后,密闭搅拌20小时。然后在通氮气的条件下用分子量为14000的渗析袋在去离子水中渗析2天,换4次水,渗析后的聚合物水溶液用冻干机在-50℃条件下干燥2天后即可得到蓬松多孔的样品C。
2)称取样品C 0.10g于10mL玻璃瓶中,加入4.90mL去离子水,配成2.0wt%的水溶液,配置10mM的H2O2水溶液,100u/mL的蘑菇多酚氧化酶水溶液,pH为8.0的磷酸缓冲溶液(PBS),分别取H2O2水溶液、蘑菇多酚氧化酶水溶液和PBS各400μL,混合均匀后,边振荡边向其中加入1.0mL的样品A的水溶液,无色透明的混合溶液会在90s内变为棕色,即得到本发明所述的仿生的可注射黏附性水凝胶。
Claims (6)
1.一种仿生的可注射黏附性水凝胶的制备方法,其步骤如下:
1)1.0~4.0g聚多糖于室温下搅拌溶解在150~300mL去离子水中,依次加入1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐1.4260~5.7038g,N-羟基琥珀酰亚胺0.8561~3.4244g,搅拌30~50分钟后加入多巴胺盐酸盐0.9404~3.7617g,用浓度为0.1~0.4mol/L的盐酸调节体系的pH为4.6~5.0之间,通氮气5~10分钟,密闭搅拌20~30小时,然后在通氮气的条件下用分子量为8000~14000的渗析袋渗析2~3天,换4~5次水,渗析后的聚合物溶液用冻干机冻干2~3天后得到蓬松多孔的样品;
2)将步骤1)样品配成1.0~2.0wt%的水溶液,配置2~20mM的H2O2水溶液,20~200u/mL的氧化偶联剂水溶液,pH=5~8的磷酸缓冲溶液,分别取H2O2水溶液、氧化偶联剂水溶液和磷酸缓冲溶液各400~800μL,混合均匀后,边振荡边向其中加入1~2mL步骤1)样品的水溶液,得到的无色透明的混合溶液在60~100s的时间内变为棕色,即得到仿生的可注射黏附性水凝胶。
2.如权利要求1所述的一种仿生的可注射黏附性水凝胶的制备方法,其特征在于:聚多糖是透明质酸钠、海藻酸钠或果胶。
3.如权利要求1所述的一种仿生的可注射黏附性水凝胶的制备方法,其特征在于:聚多糖的分子量是200~700kDa。
4.如权利要求1所述的一种仿生的可注射黏附性水凝胶的制备方法,其特征在于:氧化偶联剂是辣根过氧化物酶、蘑菇多酚氧化酶或梨多酚氧化酶。
5.一种仿生的可注射黏附性水凝胶,其特征在于:是由权利要求1~4任何一项所述的方法制备得到。
6.权利要求4所述的一种仿生的可注射黏附性水凝胶在生物方面的应用。
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CN113372585A (zh) * | 2021-07-26 | 2021-09-10 | 郑州大学 | 一种具有高粘附性复合功能水凝胶的制备方法及其应用 |
CN113577380A (zh) * | 2021-08-03 | 2021-11-02 | 曲阜师范大学 | 一种用于治疗和恢复肌肉损伤的新型生物医用材料及其制备方法 |
CN113559314A (zh) * | 2021-08-06 | 2021-10-29 | 西北大学 | 用于糖尿病足溃疡的仿细胞外基质水凝胶敷料及制备方法 |
CN113559314B (zh) * | 2021-08-06 | 2022-05-27 | 西北大学 | 用于糖尿病足溃疡的仿细胞外基质水凝胶敷料及制备方法 |
WO2023234747A1 (ko) * | 2022-06-02 | 2023-12-07 | 연세대학교 산학협력단 | 페놀기 유도체가 수식된 펙틴 및 그의 용도 |
CN115554460A (zh) * | 2022-09-26 | 2023-01-03 | 山东万容生物科技有限公司 | 一种多功能湿性敷料及其制备方法 |
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