Anti-fatigue adhesive non-swelling hydrogel constructed by covalent topological structure and micro-nano gel for stretchable bioelectronics

Hydrogel adhesives are rapidly emerging as a promising candidate toward flexible bioelectronics due to their adhesive characteristics and tissue-like mechanical properties. However, current hydrogel adhesives manifest weak anti-fatigue adhesion and an inability to ensure long-term integration of bio...

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Main Authors: Gongwei Tian, Ming Zhu, Jianhui Chen, Cuiyuan Liang, Qinyi Zhao, Dan Yang, Yan Liu, Shuanglong Tang, Jianping Huang, Zhiyuan Liu, Weihong Lu, Meifang Zhu, Wei Yan, Dianpeng Qi
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Language:English
Published: KeAi Communications Co., Ltd. 2025-11-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25002828
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author Gongwei Tian
Ming Zhu
Jianhui Chen
Cuiyuan Liang
Qinyi Zhao
Dan Yang
Yan Liu
Shuanglong Tang
Jianping Huang
Zhiyuan Liu
Weihong Lu
Meifang Zhu
Wei Yan
Dianpeng Qi
author_facet Gongwei Tian
Ming Zhu
Jianhui Chen
Cuiyuan Liang
Qinyi Zhao
Dan Yang
Yan Liu
Shuanglong Tang
Jianping Huang
Zhiyuan Liu
Weihong Lu
Meifang Zhu
Wei Yan
Dianpeng Qi
author_sort Gongwei Tian
collection DOAJ
description Hydrogel adhesives are rapidly emerging as a promising candidate toward flexible bioelectronics due to their adhesive characteristics and tissue-like mechanical properties. However, current hydrogel adhesives manifest weak anti-fatigue adhesion and an inability to ensure long-term integration of bioelectrodes on wet and dynamic tissue surfaces because they are constrained by their high swelling ratio and exclusive formation of covalent bonds at the tissue interface and its own weak cohesion. Here, we for the first time develop covalent bond topological adhesion paired with double covalent bond cross-linking in hydrogel to enhance cohesive force and adhesive force, achieving excellent anti-fatigue tissue adhesion and adhesive's capacity to follow significant tissue deformation. The adhesive strength of our hydrogel (Sodium alginate-polyacrylamide-acrylic acid N-hydroxysuccinimide ester hydrogel (SPAN) as the substrate and liquid adhesive containing chitosan (LC) as the adhesive layer) reaches impressive 290 kPa, surpassing that of the reported hydrogels (∼130 kPa). Additionally, fatigue threshold of SPAN/LC adhesion (240 J m−2) far exceeds SPAN (48.6 J m−2) and SPAN/LC (without NHS ester) (71.6 J m−2). Simultaneously, micro-nano gel and pre-swelling strategy enhance the elongation at break (1330 %) and limit swelling of SPAN in vivo (V/V0 = 1) by storing SPAN chains and acting as physical cross-linking points, thereby increasing adhesion stability and biocompatibility. The adhesion strength of SPAN/LC to the tissue consistently remains above 125 kPa after 70 days of immersion in a buffer solution. Employing the hydrogel as the soft interfacing material, we further demonstrate stretchable micro-electrode arrays (MEAs) for long-term electrophysiological recording and stimulation in rat models. Thanks to the superior anti-fatigue performance of the hydrogel adhesives, this MEAs adheres tightly to the wet and continuously moving subcutaneous muscle of a living rat, enabling the stable collection of electrophysiological signals with high signal-to-noise ratios for 35 days. These excellent performances pave the way for establishing a new paradigm in long-term stable and highly efficient signal transmission at the dynamic electrodes–tissue interface.
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spelling doaj-art-b182a259152d41a3bc736abce7c1e7302025-08-20T03:50:26ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-11-015317818710.1016/j.bioactmat.2025.06.045Anti-fatigue adhesive non-swelling hydrogel constructed by covalent topological structure and micro-nano gel for stretchable bioelectronicsGongwei Tian0Ming Zhu1Jianhui Chen2Cuiyuan Liang3Qinyi Zhao4Dan Yang5Yan Liu6Shuanglong Tang7Jianping Huang8Zhiyuan Liu9Weihong Lu10Meifang Zhu11Wei Yan12Dianpeng Qi13MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR China; School of Medicine and Health, Harbin Institute of Technology, Harbin, 150001, PR ChinaMIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR ChinaMIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR ChinaMIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR ChinaMIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR ChinaMIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR ChinaMIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR ChinaMIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR ChinaBiomedical Microdevices Research Laboratory, Shenzhen Institutes of Advanced Technology, The Chinese Academy of Sciences, 1068 Xueyuan Avenue, Shenzhen, 518055, PR ChinaBiomedical Microdevices Research Laboratory, Shenzhen Institutes of Advanced Technology, The Chinese Academy of Sciences, 1068 Xueyuan Avenue, Shenzhen, 518055, PR ChinaMIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR China; School of Medicine and Health, Harbin Institute of Technology, Harbin, 150001, PR ChinaState Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, PR ChinaState Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, PR China; Corresponding author.MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, Zhengzhou Research Institute of Harbin Institute of Technology, Zhengzhou, 450000, PR China; Corresponding author. MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China.Hydrogel adhesives are rapidly emerging as a promising candidate toward flexible bioelectronics due to their adhesive characteristics and tissue-like mechanical properties. However, current hydrogel adhesives manifest weak anti-fatigue adhesion and an inability to ensure long-term integration of bioelectrodes on wet and dynamic tissue surfaces because they are constrained by their high swelling ratio and exclusive formation of covalent bonds at the tissue interface and its own weak cohesion. Here, we for the first time develop covalent bond topological adhesion paired with double covalent bond cross-linking in hydrogel to enhance cohesive force and adhesive force, achieving excellent anti-fatigue tissue adhesion and adhesive's capacity to follow significant tissue deformation. The adhesive strength of our hydrogel (Sodium alginate-polyacrylamide-acrylic acid N-hydroxysuccinimide ester hydrogel (SPAN) as the substrate and liquid adhesive containing chitosan (LC) as the adhesive layer) reaches impressive 290 kPa, surpassing that of the reported hydrogels (∼130 kPa). Additionally, fatigue threshold of SPAN/LC adhesion (240 J m−2) far exceeds SPAN (48.6 J m−2) and SPAN/LC (without NHS ester) (71.6 J m−2). Simultaneously, micro-nano gel and pre-swelling strategy enhance the elongation at break (1330 %) and limit swelling of SPAN in vivo (V/V0 = 1) by storing SPAN chains and acting as physical cross-linking points, thereby increasing adhesion stability and biocompatibility. The adhesion strength of SPAN/LC to the tissue consistently remains above 125 kPa after 70 days of immersion in a buffer solution. Employing the hydrogel as the soft interfacing material, we further demonstrate stretchable micro-electrode arrays (MEAs) for long-term electrophysiological recording and stimulation in rat models. Thanks to the superior anti-fatigue performance of the hydrogel adhesives, this MEAs adheres tightly to the wet and continuously moving subcutaneous muscle of a living rat, enabling the stable collection of electrophysiological signals with high signal-to-noise ratios for 35 days. These excellent performances pave the way for establishing a new paradigm in long-term stable and highly efficient signal transmission at the dynamic electrodes–tissue interface.http://www.sciencedirect.com/science/article/pii/S2452199X25002828Hydrogel adhesivesCovalent bond topologyAnti-fatigue adhesionLong-term integrationFlexible bioelectronics
spellingShingle Gongwei Tian
Ming Zhu
Jianhui Chen
Cuiyuan Liang
Qinyi Zhao
Dan Yang
Yan Liu
Shuanglong Tang
Jianping Huang
Zhiyuan Liu
Weihong Lu
Meifang Zhu
Wei Yan
Dianpeng Qi
Anti-fatigue adhesive non-swelling hydrogel constructed by covalent topological structure and micro-nano gel for stretchable bioelectronics
Bioactive Materials
Hydrogel adhesives
Covalent bond topology
Anti-fatigue adhesion
Long-term integration
Flexible bioelectronics
title Anti-fatigue adhesive non-swelling hydrogel constructed by covalent topological structure and micro-nano gel for stretchable bioelectronics
title_full Anti-fatigue adhesive non-swelling hydrogel constructed by covalent topological structure and micro-nano gel for stretchable bioelectronics
title_fullStr Anti-fatigue adhesive non-swelling hydrogel constructed by covalent topological structure and micro-nano gel for stretchable bioelectronics
title_full_unstemmed Anti-fatigue adhesive non-swelling hydrogel constructed by covalent topological structure and micro-nano gel for stretchable bioelectronics
title_short Anti-fatigue adhesive non-swelling hydrogel constructed by covalent topological structure and micro-nano gel for stretchable bioelectronics
title_sort anti fatigue adhesive non swelling hydrogel constructed by covalent topological structure and micro nano gel for stretchable bioelectronics
topic Hydrogel adhesives
Covalent bond topology
Anti-fatigue adhesion
Long-term integration
Flexible bioelectronics
url http://www.sciencedirect.com/science/article/pii/S2452199X25002828
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