A paintable ophthalmic adhesive with customizable properties based on symmetrical/asymmetrical cross-linking

In situ and efficient incision sealing for ophthalmic surgery remains unresolved. Current commercially available gel adhesives often suffer from unsuitable gelation time, difficulty in micro-delivery, and mismatched degradation period, leading to difficulties for application in ocular tissue areas. Herein, a novel hydrogel adhesive was developed based on the simultaneous crosslinking of poly(lysine) (PLL) and lysine (Lys) with an end-modified active ester multi-arm polyethylene glycol (PEG) via the amidation reaction, where the residual terminal active ester of PEG can also bond to amino groups on tissue to provide strong adhesion. Due to the different molecular structures around their amino groups, PLL and Lys can crosslink with 4-arm-PEG-NHS (active ester) respectively, to form symmetrical and asymmetrical crosslinking networks, which exhibit various mechanical properties. Therefore, just by adjusting PLL/Lys ratios, the PEG-PLL-Lys hydrogel can easily possess a suitable gelation time, appropriate mechanical properties and matched degradation rate. As a result, a paintable, readily accessible and biocompatible ophthalmic tissue adhesive (sealant) is prepared for sealing ocular tissue incision. Considering the simple strategy and outstanding performance, the PEG-PLL-Lys hydrogel is promising for clinical transformation.