CN115177783B - 一种双载智能水凝胶 - Google Patents
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Abstract
本发明公开了双载智能水凝胶，由以下成分组成：原料：Ag/PEG/CNT‑M+E，添加料为：SH‑4armPEG、AgNO3、CNTs、Metformin、Exosome，本发明通过糖尿病小鼠全层皮肤损伤模型结果表明，该双载智能水凝胶可以改善创周炎症水平，促进细胞增殖和血管生成来加速伤口愈合。HE和Masson染色证实愈合的创面胶原排列整齐，皮肤附件完整，具有减少疤痕的潜质。体外实验证实，该双载智能水凝胶能显著增强高糖环境下血管内皮细胞的增殖、迁移和管形成。
Description
技术领域
本发明涉及伤口生长恢复领域，尤其涉及双载智能水凝胶。
背景技术
目前已经提出各种通过水凝胶作为载体及保护手段来应对糖尿病创面慢性不愈的挑战，包括添加外源性细胞或细胞因子，如间充质干细胞，成纤维细胞生长因子 (FGF)等。然而，许多因素限制了水凝胶在这种临床环境中的使用。一方面，水凝胶负载的外源性细胞免疫介导的排斥风险较大，同时体积过大可能无法可靠的通过毛细血管发挥作用。另一方面生物材料不同的交联方式或多或少会对这些细胞或因子造成不同程度损害，降低治疗效果。
间充质干细胞 (MSCs) 作为再生医学领域中极具前途的工具，在增强上皮再生、促进血管生成等方面发挥独特优势。然而，MSC 存在如安全问题和高经济成本等限制了其发展。外泌体已被确定为其发挥治疗作用的主要贡献者，直接注射是最常用的外泌体给药方法，但由于其快速清除特性和较短的体内半衰期，会限制其治疗功能，因此，将外泌体与生物相容性材料相结合的智能设计使其在创面发挥持续稳定的生物活性，最大限度地减少了外泌体直接注射引起的快速清除问题。具有巨大的应用前景。
同时，二甲双胍是一种众所周知的治疗糖尿病的药物，可以通过激活血管内皮细胞AMPK 通路，抑制 NF-κB 活性，从而抑制细胞促炎和粘附分子基因的表达，发挥血管保护作用，负载二甲双胍的水凝胶材料已被证明可以通过促进血管生成加速糖尿病足创面愈合。并且，电活性材料的加入已被证明可以传递生物电信号促进角质形成细胞和成纤维细胞增殖、迁移和黏附活动，从而加速愈合过程，尤其适用于慢性创面。现代生物材料结合电活性物质是新型敷料的理想选择。我们将多壁碳纳米管这一导电材料加入水凝胶中，旨在合成一种智能凝胶敷料治疗糖尿病慢性创面。基于此，本发明设计了一种双载智能水凝胶，以解决上述问题。
发明内容
本发明的目的在于提供一种双载智能水凝胶 ，以解决上述背景技术提出的问题。
为实现上述目的，本发明提供如下技术方案：双载智能水凝胶，由以下成分组成：原料：Ag/PEG/CNT-M+E，添加料为：SH-4 arm PEG、AgNO3、CNTs、Metformin、Exosome。
进一步的，所述SH-4 arm PEG添加量为：60 mg/mL。
进一步的，所述AgNO3添加量为：8 mmol/L。
进一步的，所述CNTs添加量为2 mg/mL。
进一步的，所述Metformin添加量为1 mg / mL。
进一步的，所述Exosome添加量为100ug/mL。
进一步的：制备方法为：
（1）、首先将60 mg的SH-PEG与8 mmol/LAgNO3水溶液常温搅拌混合成Ag/PEG水凝胶，
（2）、然后掺入2 mgCNTs，混匀后，加入100 μL的ADSC-exo和1mg Metformin，搅拌后4度冰箱保存。
与现有技术相比，本发明的有益效果是：
本发明通过糖尿病小鼠全层皮肤损伤模型结果表明，该双载智能水凝胶可以改善创周炎症水平，促进细胞增殖和血管生成来加速伤口愈合。HE和Masson染色证实愈合的创面胶原排列整齐，皮肤附件完整，具有减少疤痕的潜质。体外实验证实，该双载智能水凝胶能显著增强高糖环境下血管内皮细胞的增殖、迁移和管形成。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对实施例描述所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为本发明双载智能水凝胶的示意图1；
图2为本发明双载智能水凝胶的示意图2；
图3为本发明外泌体释放曲线示意图；
图4为本发明小鼠使用实验图。
实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其它实施例，都属于本发明保护的范围。
实施例
本发明提供一种技术方案:一种双载智能水凝胶 ，如图1-图4所示，双载智能水凝胶，由以下成分组成：原料：Ag/PEG/CNT-M+E，添加料为：SH-4 arm PEG、AgNO3、CNTs、Metformin、Exosome，SH-4 arm PEG添加量为：60 mg/mL，AgNO3添加量为：8 mmol/L，CNTs添加量为2 mg/mL，Metformin添加量为1 mg / mL，Exosome添加量为100ug/mL。
该双载智能水凝胶可以改善创周炎症水平，促进细胞增殖和血管生成来加速伤口愈合。HE和Masson染色证实愈合的创面胶原排列整齐，皮肤附件完整，具有减少疤痕的潜质。体外实验证实，该双载智能水凝胶能显著增强高糖环境下血管内皮细胞的增殖、迁移和管形成。
实施例
双载智能水凝胶，制备方法为：首先将60 mg的SH-PEG与8 mmol/LAgNO3水溶液常温搅拌混合成Ag/PEG水凝胶，然后掺入2 mgCNTs，混匀后，加入100 μL的ADSC-exo和1mgMetformin，搅拌后4度冰箱保存。
该双载智能水凝胶具有持续释放外泌体及二甲双胍的作用，可用于糖尿病等慢性创面愈合。该智能水凝胶，将 4 臂 SH-PEG 与 Ag +交联，Ag-S 配位生成动态的 PEG 水凝胶，同时添加多壁碳纳米管这一导电活性材料与之形成氢键铰链，最终形成稳定的三维立体结构。与其他交联方式相比，这种基于温和的配位交联方法所形成的高度互连的多孔网络，有利于生物活性物质更好移动和释放，减少对所装载的货物的损害，随着水凝胶缓慢降解，所装载货物持续释放发挥生物学功效。
在本说明书的描述中，参考术语“一个实施例”、“示例”、“具体示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或示例中。在本说明书中，对上述术语的示意性表述不一定指的是相同的实施例或示例。而且，描述的具体特征、结构、材料或者特点可以在任何的一个或多个实施例或示例中以合适的方式结合。
以上公开的本发明优选实施例只是用于帮助阐述本发明。优选实施例并没有详尽叙述所有的细节，也不限制该发明仅为所述的具体实施方式。显然，根据本说明书的内容，可作很多的修改和变化。本说明书选取并具体描述这些实施例，是为了更好地解释本发明的原理和实际应用，从而使所属技术领域技术人员能很好地理解和利用本发明。本发明仅受权利要求书及其全部范围和等效物的限制。
Claims (3)
1.一种用于治疗糖尿病慢性创面的双载智能水凝胶，其特征在于由以下成分组成：原料：Ag/PEG/CNT-M+E，添加料为：SH-4arm PEG、AgNO3、CNTs、Metformin、Exosome；
所述SH-4arm PEG添加量为：60mg/mL；所述CNTs添加量为：2mg/mL；
所述的双载智能水凝胶，制备方法为：
(1)首先将60mg的SH-4arm PEG与8mmol/LAgNO3水溶液常温搅拌混合成Ag/PEG水凝胶；
(2)然后掺入2mgCNTs，混匀后，加入100μL的Exosome和1mgMetformin，搅拌后4度冰箱保存；所述CNTs为多壁碳纳米管；
该智能水凝胶，将SH-4arm PEG与Ag+交联，Ag-S配位生成动态的PEG水凝胶，同时添加多壁碳纳米管这一导电活性材料与之形成氢键交联，最终形成稳定的三维立体结构，所形成的高度互连的多孔网络，有利于生物活性物质更好移动和释放，减少对所装载的货物的损害，随着水凝胶缓慢降解，所装载货物持续释放发挥生物学功效。
2.根据权利要求1所述的用于治疗糖尿病慢性创面的双载智能水凝胶，其特征在于所述Metformin添加量为1mg/mL。
3.根据权利要求1所述的用于治疗糖尿病慢性创面的双载智能水凝胶，其特征在于所述Exosome添加量为100ug/mL。
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| CN111234267A (zh) * | 2020-03-25 | 2020-06-05 | 西安交通大学第二附属医院 | 一种导电光热自愈合复合水凝胶敷料及制备方法和应用 |
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| CN113289054A (zh) * | 2021-06-16 | 2021-08-24 | 四川大学 | 一种能够快速吸热的创伤敷料及其制备方法和应用 |
| WO2022123169A1 (fr) * | 2020-12-07 | 2022-06-16 | Urgo Recherche Innovation Et Developpement | Utilisation de la metformine pour diminuer l'inflammation dans la peau |
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| WO2008133918A1 (en) * | 2007-04-24 | 2008-11-06 | Rutgers, The State University Of New Jersey | Dressing compositions and methods |
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| CN114656657A (zh) * | 2022-04-06 | 2022-06-24 | 合肥工业大学 | 一种高导电性、自愈合纳米复合有机水凝胶的制备方法 |
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