Autoxidation-Induced Curing of 6-Hydroxycatechol-Containing Adhesive

Catechol is an oft-used crosslinking precursor and adhesive molecule for designing in-situ curable biomaterials and adhesives and the addition of chemical or enzymatic oxidants is required to initiate fast curing. Here, the feasibility for 6-hydroxydopamine (6-OHDA)-modified 8-armed polyethylene glycol (PEG) (8-arm PEG-DA-OH) to cure through autoxidation was evaluated. The modification of catechol side chain with an electron donating hydroxyl group at the 6-position drastically increased the rate of oxidation and the adhesive cured just over 1 minute through autoxidation. The cure time was decreased to under 40 seconds with the addition of branched polyethyleneimine (PEI). UV-vis spectra revealed that the deprotonated quinone of 6-OHDA is a key oxidation intermediate for chemical crosslinking between 6-OHDA and with primary amine. PEG functionalized with unmodified catechol did not solidify through autoxidation, which highlights the contribution of the electron-donating hydroxyl group in promoting fast oxidation and crosslinking. 8-arm PEG-DA-OH and PEI mixture also demonstrated significantly higher adhesion strength to pericardium tissues when compared to a commercial PEG-based adhesive, DuraSeal^®. This report highlights 6-OHDA as an effective crosslinking precursor and adhesive molecule for designing injectable adhesives that do not require externally added oxidants and the adhesive was activated by simple dissolution in an aqueous solution.