Dual-network hydrogel based on ionic nano-reservoir for gastric perforation sealing  

基于纳米离子储层的双网络胃穿孔封堵水凝胶

作　　者：Yuehui Yuan Hao Wu Xueyang Ren Jianwu Wang Ruiqing Liu Benhui Hu Ning Gu 袁月辉;吴昊;任雪洋;王建武;刘瑞清;胡本慧;顾宁(School of Biomedical Engineering and Informatics,Nanjing Medical University,Nanjing 211166,China;State Key Laboratory of Bioelectronics,Jiangsu Key Laboratory for Biomaterials and Devices,School of Biological Science and Medical Engineering,Southeast University,Nanjing 210009,China;School of Materials Science and Engineering,Nanyang Technological University,Singapore 639798,Singapore;Jiangsu Key Laboratory of Xenotransplantation,Nanjing Medical University,Nanjing 211166,China)

机构地区：[1]School of Biomedical Engineering and Informatics,Nanjing Medical University,Nanjing 211166,China [2]State Key Laboratory of Bioelectronics,Jiangsu Key Laboratory for Biomaterials and Devices,School of Biological Science and Medical Engineering,Southeast University,Nanjing 210009,China [3]School of Materials Science and Engineering,Nanyang Technological University,Singapore 639798,Singapore [4]Jiangsu Key Laboratory of Xenotransplantation,Nanjing Medical University,Nanjing 211166,China

出　　处：《Science China Materials》2022年第3期827-835,共9页中国科学（材料科学（英文版）

基　　金：supported by the National Natural Science Foundation of China(81971701,51832001,and 81901873);the Natural Science Foundation of Jiangsu Province(BK20201352);the Program of Jiangsu Specially-Appointed Professor。

摘　　要：In recent years,remarkable progress has been made in the research of injectable hydrogel for internal tissue healing.However,the therapeutic outcome is usually limited when the hydrogel is used for the treatment of gastric perforation due to the high acidic gastric juice and violent deformation of the gastric wall.Regarding these challenges,we proposed an ionic nano-reservoir(INR)-based dual-network hydrogel,which has excellent adhesion and mechanical properties,and can be easily applied to the perforation site to block the perforation while promoting tissue repairing.The results showed that the first network made of polyacrylamide had cross-linked on the stomach tissue within 5 s under blue light,and enhanced the adhesion performance through mechanical interlock.The nano-hydroxyapatite acted as ionic INR,which can gradually release Ca^(2+) under acid environments to form the second network with sodium alginate and inhibit the swelling of hydrogel in gastric juice.Meanwhile,the adhesion was further enhanced through amide covalent bonds at the hydrogel-tissue interface with the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide(EDC/NHS).The dual network hydrogels obtained by the INR strategy could be employed as a potential therapeutic option for gastric perforation and other similar biomedical prolems.近年来,对于可注射水凝胶用于内部组织损伤修复的研究取得了一定进展,但将此类水凝胶用于胃穿孔治疗时,依然面临强酸性胃液及胃壁的剧烈形变带来的严峻问题.鉴于此,我们提出了一种基于纳米离子储库(INR)的双网络水凝胶策略,该水凝胶具有优异的黏附和机械性能,可以简便地涂覆于穿孔部位,在封堵穿孔的同时促进组织修复.结果显示,在蓝光条件下,聚丙烯酰胺(PAM)可以于5 s内在胃组织上交联形成第一重网络,并通过机械互锁增强黏附性能;此外,纳米羟基磷灰石作为纳米离子储库可在酸性环境下释放Ca^(2+),与海藻酸钠(SA)形成第二重网络,抑制水凝胶在胃液中的溶胀.同时,通过在体系中引入碳二亚胺/N-羟基琥珀酰亚胺(EDC/NHS),可以促进水凝胶-组织界面上酯酰胺共价键的形成,从而进一步增强黏附力.因此我们认为,这种通过纳米离子储库策略获得的双网络水凝胶有望用于解决胃穿孔乃至其他类似的生物医学问题.

关 键 词：injectable hydrogel ionic cross-linking adhesion TOUGHNESS wound dressing 

分 类 号：R318.08[医药卫生—生物医学工程] TQ427.26[医药卫生—基础医学]