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 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.