CN113368312B - 一种可生物降解自粘附水凝胶的制备方法及其应用 - Google Patents
一种可生物降解自粘附水凝胶的制备方法及其应用 Download PDFInfo
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Abstract
一种可生物降解自粘附水凝胶制备方法及应用，涉及生物材料技术领域。步骤包括：先将天然高分子溶解在磷酸盐缓冲液(PH＝7.4)中，通过甲基丙烯酸酐修饰、透析、冻干得到甲基丙烯酸酐化天然高分子；其次将含酚羟基的天然化合物溶解在纯水中，加入碱性溶液调节溶液至碱性，搅拌反应一段时间得到含酚羟基的天然化合物预聚液；最后将甲基丙烯酸酐化天然高分子溶解在纯水中，待完全溶解得到甲基丙烯酸酐化天然高分子溶液，并加入含酚羟基天然化合物预聚液，通过自由基聚合得到可降解的自粘附水凝胶。本发明可自粘附在组织表面，起到止血、伤口闭合、细胞恢复的作用，具有良好的生物相容性降解性；适用于多种湿润软组织表面的粘附及皮肤损伤，肌肉损伤，神经损伤，心肌损伤等多种组织的修复。
Description
技术领域
本发明属于生物材料制备技术领域，具体涉及一种全天然可生物降解自粘附水凝胶的制备方法及其应用
背景技术
在世界医学范围内，每年都会进行很多外科手术和发生很多严重创伤治疗，所以伤口缝合与止血的问题都是必须解决的。当前的外科缝合技术涉及使用诸如缝合线，或夹子之类的侵入性技术，以及传统使用的止血剂，包括纱布，明胶海绵和绷带，他们通常存在着导致额外组织损伤，微生物感染，液体或空气泄漏的使用隐患。虽然商业粘合剂具有良好的粘附性，但其具有细胞毒性，不能用于伤口闭合或止血。因此，需要设计一种具有良好生物相容性的粘合剂。
随着生物医用材料的发展，已经开发出许多组织粘合剂作为伤口闭合或止血的替代方法。常见的组织粘合剂包括纤维蛋白胶，牛血清白蛋白/戊二醛，和氰基丙烯酸酯胶等。尽管这些组织粘合剂表现出良好的粘附性，并能够促进实现伤口的闭合。但是，氰基丙烯酸酯等粘合剂在体内的生物相容性差，对患者有害。因此，需要开发具有良好生物相容性的组织粘合剂。近年来，尽管基于水凝胶的新型组织粘合剂被广泛开发。但是，这些组织粘合剂有着复杂的制备过程和有限的生物降解性，存在着不能适时降解甚至阻碍伤口的完全愈合。因此，仍然需要更优异的组织粘合剂，使其具有优异的生物相容性和生物降解性，可靠的粘附性能，良好的抗炎症性能，以及简便、环境友好的制备方法。
本发明的目的是提供一种可生物降解自粘附水凝胶的制备方法及其应用，该方法制备的水凝胶以天然高分子聚合物为主体，具有良好的生物相容性，生物可降解性，且具有优异的组织粘附性及反复粘附性，能够牢固地粘附在生物组织表面且很容易剥离。
发明内容
针对传统合成高分子基水凝胶虽具有较好的组织粘附性，但生物降解性差的问题。本发明受植物抗氧化机理启发，设计了预聚没食子酸策略，以天然高分子明胶(天然高分子)作为水凝胶基底，在水凝胶中引入植物多酚没食子酸(含酚羟基的天然化合物)，制备得到了具有良好生物相容性和可生物降解性的没食子酸-明胶(天然高分子)复合水凝胶。
纯的甲基丙基酸酐明胶(GelMA)水凝胶存在易碎、柔性差、无粘附性等问题。本发明水凝胶中引入预聚没食子酸后，减弱了甲基丙基酸酐明胶链之间的缠结作用，赋予了没食子酸-明胶(天然高分子)复合水凝胶良好的力学柔韧性。此外，预聚没食子酸含有丰富的多酚基团，可以和机体组织上的氨基等基团发生反应，赋予了没食子酸-明胶(天然高分子)复合水凝胶优异的组织粘附性。
针对合成或天然水凝胶缺乏功能性的问题，利用某些天然植物具有抗氧化机理性质，设计并制备出了多功能的可生物降解的自粘附水凝胶。使其具有优异的抗氧化、抗炎性能以及促进细胞粘附、增殖的能力，能够抑制伤口炎症、清除伤口自由基、降低伤口氧化应激，并加速伤口愈合。
实现本发明之目的，所采用的技术方案是：一种可生物降解自粘附水凝胶的制备方法，其具体步骤如下：
步骤1：将天然高分子溶解在磷酸盐缓冲液(PH＝7.4)中，通过甲基丙烯酸酐修饰、透析、冻干得到甲基丙烯酸酐化天然高分子；
步骤2：将含酚羟基的天然化合物溶解在纯水中，通过加入碱性溶液调节溶液至碱性，搅拌反应一段时间得到含酚羟基的天然化合物预聚液；
步骤3：将步骤1得到的甲基丙烯酸酐化天然高分子溶解在纯水中，待完全溶解得到甲基丙烯酸酐化天然高分子溶液，并向甲基丙烯酸酐化天然高分子溶液中加入步骤2得到的含酚羟基天然化合物预聚液，然后通过自由基聚合得到可生物降解的自粘附水凝胶。
进一步的，所述步骤1中天然高分子包括明胶、胶原、丝素蛋白、壳聚糖、海藻酸钠、琼脂糖、葡聚糖。
进一步的，所述步骤2中含酚羟基的天然化合物包括单宁酸、咖啡酸、儿茶素、没食子酸、没食子醇、没食子酚、表没食子儿茶素、表儿茶素没食子酸酯、表没食子儿茶素没食子酸酯。
进一步的，所述步骤2具体过程如下：
S1：将含酚羟基的天然化合物溶解在纯水中，形成质量百分浓度为0.1～10.0％的溶液；
S2：向步骤S1中的溶液中加入碱性溶液，调节溶液至碱性；
S3：将步骤S2中的得到的混合液继续搅拌反应，得到酚羟基预聚液。
再进一步地，所述步骤S2中将S1得到的溶液调节至pH>7。
再进一步地，所述步骤S3中的反应温度为20～60℃，反应时间为10～180min。
进一步的，所述步骤3中的甲基丙烯酸酐化天然高分子溶液的制备方法为：将甲基丙烯酸酐化天然高分子溶解在纯水中，形成质量百分浓度为1.0～50.0％的溶液，然后向该溶液中加入引发剂和交联剂，充分混匀。
进一步地，所述交联剂为聚乙二醇PEG(二醇)二丙烯酸酯、N,N-亚甲基双丙烯酰胺中的任意一种。
进一步地，所述引发剂为过硫酸钾、过硫酸钠、过硫酸铵中的任意一种。
再进一步地，所述引发剂的质量百分浓度为0.5～10.0％。
再进一步地，所述交联剂的质量百分浓度为0.1～10.0％。
本发明中所述的纯水为去离子水或蒸馏水。
如所述的方法制备得到的水凝胶的应用，适用于皮肤损伤，肌肉损伤，神经损伤，心肌损伤等多种组织的修复。
如所述的方法制备得到的水凝胶的应用，适用于多种湿润软组织表面的粘附，可自粘附在组织表面，起到止血、伤口闭合、细胞恢复的作用。
本发明的有益效果是：
(1)本发明借鉴天然植物多酚的抗氧化活性，在水凝胶中引入具有酚羟基功能团，制备的全天然可降解自粘附水凝胶，既可以自粘附在组织表面，起到止血、伤口闭合的作用，又具有抗炎、抗氧化能力，无需额外负载生物活性因子，使其相比现有产品具有更强的功能性从而加速伤口修复。
(2)本发明制备的水凝胶与天然高分子结合，使其表现出良好的湿组织粘附性，且具有良好的生物相容性，对人体组织无刺激性，可应用于多种湿润软组织表面的粘附，从而应用于皮肤损伤，肌肉损伤，神经损伤，心肌损伤等多种组织的修复。
(3)本发明制备的水凝胶中富含具有紫外光吸收能力的酚羟基功能团，使得水凝胶具有良好的抗紫外线能力，作为皮肤伤口敷料时可保护皮肤免受紫外线照射，具有抗氧化的功能。
(4)本发明制备的水凝胶具有良好的可操作性，在使用时无需额外添加剂即可实现自粘附于机体组织表面，并能够长期保存条件下保持良好的粘附强度，且很容易剥离；可以降解后被组织吸收，加速伤口愈合。本发明制备方法操作简单，成本低，对环境友好。
附图说明
图1A图1B为本发明制备的所述水凝胶应用实施例黑白照片图。
图2A、2B、2C、2D、2E为本发明制备的水凝胶应用实施例黑白照片图。
图3为本发明制备的水凝胶溶解率曲线示意图。
图4为本发明制备的所述水凝胶紫外分光光度计测定的DPPH溶液的自由基清除效率示意图；。
图5为本发明制备的所述水凝胶采用激光共聚焦扫描显微镜(CLSM)观察水凝胶上L929细胞的形貌图。
图6为本发明制备所述水凝胶采用紫外可见分光光度计测定的吸光度与波长示意图。
具体实施方式
下面结合具体附图和实施例对本发明做进一步说明。
参见图1A、图1B本发明制备的水凝胶粘附在手指上，随着手指的弯曲并对皮肤进行局部用力拉伸，观察到水凝胶能很好的粘附在皮肤上，显示其具有优良的皮肤组织粘附性能。
图2A、图2B、图2C、图2D、图2E显示本发明水凝胶可以很好的粘附SD大鼠的新鲜的心、肝、脾、肺、肾。表明水凝胶具有良好的湿组织粘附性能。
图3：将本发明水凝胶制备成高2cm，直径8mm的圆柱状。首先，称量冷冻干燥后水凝胶的干重，并记为Mo；然后，将等重的水凝胶放到Ⅱ型胶原酶溶液中，在预定时间点取出水凝胶，然后冷冻干燥后称重，记为Mi，每组3个平行样。Ⅱ型胶原酶使用磷酸盐缓冲液(PH＝7.4)配制，浓度为2μg/mL。水凝胶的剩余质量百分数的计算公式：
剩余质量百分数＝(Mi/Mo)×100
效果：水凝胶在15天降解了50％，当30天的时候，水凝胶全部降解。显示其具有优良的降解性能。
图4：首先配制溶剂为甲醇溶液，浓度为0.04mg/mL的DPPH溶液。然后将3mL的DPPH溶液与3个直径10mm、厚度2mm的水凝胶样品混合，避光，放置在37℃的烘箱中。纯DPPH溶液作为对照组。在预定时间后吸取出反应后的DPPH溶液。以甲醇溶液为空白基线，通过紫外分光光度计测定DPPH溶液的吸光度，波长为516nm。
效果：使用经典的1,1-二苯基-2-三硝基苯肼(DPPH)自由基检测法进行了自由基清除实验。从UV-Vis光谱中可以看出，与纯的DPPH溶液相比，水凝胶处理后，在516nm处的吸光度会降低。结果表明，水凝胶具有良好的自由基清除能力。
图5：首先将L929细胞接种在水凝胶上，细胞密度为3×104细胞/孔，培养3天后，使用染色剂钙黄绿素-AM(A107，美国)对细胞进行染色，最后采用激光共聚焦扫描显微镜观察水凝胶上L929细胞的形貌。
效果：结果表明，接种在水凝胶上的细胞在3天后显示出高活力，表明水凝胶具有良好的生物相容性。此外，水凝胶组上的细胞形态更趋于梭形，有助于细胞铺展和生长。显示其具有良好的生物相容性及细胞亲和性。
图6：首先将水凝胶制备成长3cm，宽1cm，厚2mm的长方体片状。然后用紫外可见分光光度计(TU-1901，北京普析，中国)测试水凝胶的透光度，波长设置为200-800nm。
效果：水凝胶在紫外线区域的透射率几乎为零，这意味着水凝胶可以完全屏蔽紫外线。显示其具有优良的紫外线吸收能力。
实施例1
一种可生物降解自粘附水凝胶的制备方法，包括以下步骤：
步骤1：将来自猪皮的10g明胶在60℃的温度下溶解于200ml磷酸盐缓冲液(PH＝7.4)中，搅拌30min。然后以0.5ml/min缓慢加入8ml的甲基丙烯酸酐，并将混合物在50℃水浴锅中搅拌3h。为了终止甲基丙烯酰基改性反应，将溶液用200ml磷酸盐缓冲液稀释。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐明胶。
步骤2:将0.1g没食子酸溶于10ml去离子水，并在35℃水浴锅中搅拌10min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到没食子酸预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐明胶1.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的没食子酸预聚液，依次加入100μl聚乙二醇(二醇)二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
实施例2
步骤1：将来自猪皮的10g明胶在60℃的温度下溶解于200ml磷酸盐缓冲液(PH＝7.4)中，搅拌30min。然后以0.5ml/min缓慢加入8ml的甲基丙烯酸酐，并将混合物在50℃水浴锅中搅拌3h。为了终止甲基丙烯酰基改性反应，将溶液用200ml磷酸盐缓冲液稀释。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐明胶。
步骤2:将0.2g多巴胺溶于10ml去离子水，并在35℃水浴锅中搅拌10min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到多巴胺预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐明胶1.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的多巴胺预聚液，依次加入100μl聚乙二醇(二醇)二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
实施例3
步骤1：通过将1g壳聚糖溶解在99ml去离子水中来制备1wt％的壳聚糖溶液，然后将1ml乙酸以恒定的速度加入溶液中。将4ml的甲基丙烯酸酐添加到溶液中，并在室温下搅拌过夜。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐壳聚糖。
步骤2:将0.1g单宁酸溶于10ml去离子水，并在35℃水浴锅中搅拌10min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到单宁酸预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐壳聚糖0.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的单宁酸预聚液，依次加入100μl聚乙二醇(二醇)二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
实施例4
步骤1：将来自猪皮的10g明胶在60℃的温度下溶解于200ml磷酸盐缓冲液(PH＝7.4)中，搅拌30min。然后以0.5ml/min缓慢加入8ml的甲基丙烯酸酐，并将混合物在50℃水浴锅中搅拌3h。为了终止甲基丙烯酰基改性反应，将溶液用200ml磷酸盐缓冲液稀释。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐明胶。
步骤2:将0.1g表没食子儿茶素没食子酸酯溶于10ml去离子水，并在35℃水浴锅中搅拌10min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到表没食子儿茶素没食子酸酯预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐明胶1.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的表没食子儿茶素没食子酸酯预聚液，依次加入
100μl聚乙二醇(二醇)、二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
实施例5
步骤1：通过将1g壳聚糖溶解在99ml去离子水中来制备1wt％的壳聚糖溶液，然后将1ml乙酸以恒定的速度加入溶液中。将4ml的甲基丙烯酸酐添加到溶液中，并在室温下搅拌过夜。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐壳聚糖。
步骤2:将0.1g咖啡酸溶于10ml去离子水，并在35℃水浴锅中搅拌10min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到咖啡酸预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐壳聚糖0.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的咖啡酸预聚液，依次加入100μl聚乙二醇(二醇)二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
实施例6
步骤1：将5g海藻酸钠溶解于200ml磷酸盐缓冲液(PH＝7.4)中，搅拌30min。然后以0.5ml/min缓慢加入4ml的甲基丙烯酸酐，并将混合物在50℃水浴锅中搅拌3h。为了终止甲基丙烯酰基改性反应，将溶液用200ml磷酸盐缓冲液稀释。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐海藻酸钠。
步骤2:将0.1g没食子酸溶于10ml去离子水，并在35℃水浴锅中搅拌20min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到没食子酸预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐海藻酸钠0.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的没食子酸预聚液，依次加入100μl聚乙二醇(二醇)二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
实施例7
步骤1：将5g海藻酸钠溶解于200ml磷酸盐缓冲液(PH＝7.4)中，搅拌30min。然后以0.5ml/min缓慢加入4ml的甲基丙烯酸酐，并将混合物在50℃水浴锅中搅拌3h。为了终止甲基丙烯酰基改性反应，将溶液用200ml磷酸盐缓冲液稀释。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐海藻酸钠。
步骤2:将0.2g多巴胺溶于10ml去离子水，并在35℃水浴锅中搅拌20min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到多巴胺预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐海藻酸钠0.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的多巴胺预聚液，依次加入100μl聚乙二醇(二醇)二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
实施例8
步骤1：将5g葡聚糖溶解于200ml磷酸盐缓冲液(PH＝7.4)中，搅拌30min。然后以0.5ml/min缓慢加入4ml的甲基丙烯酸酐，并将混合物在50℃水浴锅中搅拌3h。为了终止甲基丙烯酰基改性反应，将溶液用200ml磷酸盐缓冲液稀释。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐葡聚糖。
步骤2:将0.1g单宁酸溶于10ml去离子水，并在35℃水浴锅中搅拌10min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到单宁酸预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐葡聚糖0.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的单宁酸预聚液，依次加入100μl聚乙二醇(二醇)二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
实施例9
步骤1：将5g海藻酸钠溶解于200ml磷酸盐缓冲液(PH＝7.4)中，搅拌30min。然后以0.5ml/min缓慢加入4ml的甲基丙烯酸酐，并将混合物在50℃水浴锅中搅拌3h。为了终止甲基丙烯酰基改性反应，将溶液用200ml磷酸盐缓冲液稀释。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐海藻酸钠。
步骤2:将0.1g表没食子儿茶素没食子酸酯溶于10ml去离子水，并在35℃水浴锅中搅拌10min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到表没食子儿茶素没食子酸酯预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐海藻酸钠0.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的表没食子儿茶素没食子酸酯预聚液，依次加入100μl聚乙二醇(二醇)二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
实施例10
步骤1：将5g葡聚糖溶解于200ml磷酸盐缓冲液(PH＝7.4)中，搅拌30min。然后以0.5ml/min缓慢加入4ml的甲基丙烯酸酐，并将混合物在50℃水浴锅中搅拌3h。为了终止甲基丙烯酰基改性反应，将溶液用200ml磷酸盐缓冲液稀释。之后，将溶液装入透析袋(MW＝14000)中，在37℃的环境下透析7天。将透析后的液体冻干得到甲基丙烯酸酐葡聚糖。
步骤2:将0.1g咖啡酸溶于10ml去离子水，并在35℃水浴锅中搅拌10min，之后，加入300μlNaOH(0.5g/ml)，继续搅拌20min，得到咖啡酸预聚液。
步骤3：取步骤1得到的甲基丙烯酸酐葡聚糖0.5g溶解于8ml水中，并向溶液中加入2ml步骤2得到的咖啡酸预聚液，依次加入100μl聚乙二醇(二醇)二丙烯酸酯、0.2g的过硫酸钠和20μl四甲基乙二胺，聚合形成所需的水凝胶。
本发明借鉴天然植物多酚的抗氧化活性，在水凝胶中引入具有酚羟基功能团，制备的可生物降解自粘附水凝胶，具有良好的生物相容性，对人体组织无刺激性，可应用于多种湿润软组织表面的粘附，从而应用于皮肤损伤，肌肉损伤，神经损伤，心肌损伤等多种组织的修复；比现有产品具有更强的功能性从而加速伤口修复；本发明制备的水凝胶中富含具有紫外光吸收能力的酚羟基功能团，使得水凝胶具有良好的抗紫外线能力，作为皮肤伤口敷料时可保护皮肤免受紫外线照射，具有抗氧化的功能。
Claims (6)
1.一种可生物降解自粘附水凝胶的制备方法，其特征在于，包括以下步骤：
步骤1：将天然高分子溶解在磷酸盐缓冲液PH=7.4中，通过甲基丙烯酸酐修饰、透析、冻干得到甲基丙烯酸酐化天然高分子；
步骤2：将含酚羟基的天然化合物溶解在去离子水或蒸馏水中，通过加入碱性溶液调节溶液至pH>7，搅拌反应温度为20~60℃，反应时间为10~180 min，得到含酚羟基的天然化合物预聚液；
步骤3：将步骤1得到的甲基丙烯酸酐化天然高分子溶解在纯水中，待完全溶解得到甲基丙烯酸酐化天然高分子溶液，并向甲基丙烯酸酐化天然高分子溶液中加入步骤2得到的含酚羟基天然化合物预聚液，然后依次加入质量百分浓度为0.1~10.0%的交联剂和质量百分浓度为0.5~10.0%的引发剂，通过自由基聚合得到可生物降解的自粘附水凝胶；所述步骤1中天然高分子包括明胶、海藻酸钠、琼脂糖、葡聚糖。
2.根据权利要求1所述的一种可生物降解自粘附水凝胶的制备方法，其特征在于，所述步骤2中含酚羟基的天然化合物包括单宁酸、咖啡酸、儿茶素、没食子酸、表没食子儿茶素、表儿茶素没食子酸酯、表没食子儿茶素没食子酸酯。
3.根据权利要求1所述的一种可生物降解自粘附水凝胶的制备方法，其特征在于，所述步骤2具体过程如下：
S1：将含酚羟基的天然化合物溶解在去离子水或蒸馏水中，形成质量百分浓度为0.1~10.0%的溶液；
S2：向步骤S1中的溶液中加入碱性溶液，调节溶液至碱性；
S3：将步骤S2中的得到的混合液继续搅拌反应，得到酚羟基预聚液。
4.根据权利要求1所述的一种可生物降解自粘附水凝胶的制备方法，其特征在于，所述步骤3中的甲基丙烯酸酐化天然高分子溶液的制备方法为：将甲基丙烯酸酐化天然高分子溶解在去离子水或蒸馏水中，形成质量百分浓度为1.0~50.0%的溶液，然后向该溶液中加入引发剂和交联剂，充分混匀。
5.根据权利要求1所述的一种可生物降解自粘附水凝胶的制备方法，其特征在于，所述步骤3中的交联剂为聚乙二醇（二醇）二丙烯酸酯、N,N-亚甲基双丙烯酰胺中的任意一种。
6.根据权利要求1所述的一种可生物降解自粘附水凝胶的制备方法，其特征在于，所述步骤3中的引发剂为过硫酸钾、过硫酸钠、过硫酸铵中的任意一种。
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