Tian Gongwei, Zhu Ming, Chen Jianhui, Liang Cuiyuan, Zhao Qinyi, Yang Dan, Liu Yan, Tang Shuanglong, Huang Jianping, Liu Zhiyuan, Lu Weihong, Zhu Meifang, Yan Wei, Qi Dianpeng
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.
Bioact Mater. 2025 Jul 9;53:178-187. doi: 10.1016/j.bioactmat.2025.06.045. eCollection 2025 Nov.
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) far exceeds SPAN (48.6 J m) and SPAN/LC (without NHS ester) (71.6 J m). Simultaneously, micro-nano gel and pre-swelling strategy enhance the elongation at break (1330 %) and limit swelling of SPAN (V/V = 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.
水凝胶粘合剂因其粘附特性和类似组织的机械性能，正迅速成为柔性生物电子学领域的一个有前景的候选材料。然而，目前的水凝胶粘合剂表现出抗疲劳粘附力弱，且无法确保生物电极在潮湿和动态组织表面的长期整合，因为它们受到高溶胀率的限制，在组织界面仅形成共价键，且自身内聚力较弱。在此，我们首次在水凝胶中开发了共价键拓扑粘附与双共价键交联相结合的方法，以增强内聚力和粘附力，实现优异的抗疲劳组织粘附以及粘合剂跟随组织显著变形的能力。我们的水凝胶（以海藻酸钠-聚丙烯酰胺-丙烯酸N-羟基琥珀酰亚胺酯水凝胶（SPAN）为基底，含壳聚糖的液体粘合剂（LC）为粘附层）的粘附强度达到了令人印象深刻的290 kPa，超过了已报道的水凝胶（约130 kPa）。此外，SPAN/LC粘附的疲劳阈值（240 J/m²）远远超过SPAN（48.6 J/m²）和SPAN/LC（不含NHS酯）（71.6 J/m²）。同时，微纳米凝胶和预溶胀策略通过储存SPAN链并作为物理交联点，提高了SPAN（V/V = 1）的断裂伸长率（1330%）并限制了其溶胀，从而增加了粘附稳定性和生物相容性。在缓冲溶液中浸泡70天后，SPAN/LC对组织的粘附强度始终保持在125 kPa以上。以该水凝胶作为软界面材料，我们进一步展示了用于大鼠模型中长期电生理记录和刺激的可拉伸微电极阵列（MEA）。得益于水凝胶粘合剂卓越的抗疲劳性能，该MEA紧密粘附在活鼠潮湿且不断移动的皮下肌肉上，能够在35天内稳定收集高信噪比的电生理信号。这些优异的性能为在动态电极-组织界面建立长期稳定且高效的信号传输新范式铺平了道路。
