Enhancing Robustness of Adhesive Hydrogels through PEG-NHS Incorporation

[Image: see text] Tissue wounds are a significant challenge for the healthcare system, affecting millions globally. Current methods like suturing and stapling have limitations as they inadequately cover the wound, fail to prevent fluid leakage, and increase the risk of infection. Effective solutions for diverse wound conditions are still lacking. Adhesive hydrogels, on the other hand, can be a potential alternative for wound care. They offer benefits such as firm sealing without leakage, easy and rapid application, and the provision of mechanical support and flexibility. However, the in vivo durability of hydrogels is often compromised by excessive swelling and unforeseen degradation, which limits their widespread use. In this study, we addressed the durability issues of the adhesive hydrogels by incorporating acrylamide polyethylene glycol N-hydroxysuccinimide (PEG-NHS) moieties (max. 2 wt %) into hydrogels based on hydroxy ethyl acrylamide (HEAam). The results showed that the addition of PEG-NHS significantly enhanced the adhesion performance, achieving up to 2-fold improvement on various soft tissues including skin, trachea, heart, lung, liver, and kidney. We further observed that the addition of PEG-NHS into the adhesive hydrogel network improved their intrinsic mechanical properties. The tensile modulus of these hydrogels increased up to 5-fold, while the swelling ratio decreased up to 2-fold in various media. These hydrogels also exhibited improved durability under the enzymatic and oxidative biodegradation induced conditions without causing any toxicity to the cells. To evaluate its potential for clinical applications, we used PEG-NHS based hydrogels to address tracheomalacia, a condition characterized by inadequate mechanical support of the airway due to weak/malacic cartilage rings. Ex vivo study confirmed that the addition of PEG-NHS to the hydrogel network prevented approximately 90% of airway collapse compared to the case without PEG-NHS. Overall, this study offers a promising approach to enhance the durability of adhesive hydrogels by the addition of PEG-NHS, thereby improving their overall performances for various biomedical applications.