Oxygen Initiated Crosslinking of Electronically Optimized Catechols

Abstract

Catechol grafted macromolecules have attributes that overlap what's needed within non-toxic bioadhesives. However, decades of research have failed to make commercial progress as a general tissue adhesive. The major impediments include reliance on harmful crosslinking additives, long-term shelf-stability, and variability in preparation (e.g. two component mixing). This can arguably be assigned to the over-reliance on just one catechol crosslinker based on L-dopamine. Herein, we evaluate catechol scaffolds and oxidation processes that side-step these limitations and provide one-component (1C) bioadhesive designs. These 1C designs hypothesize activation via surface contact and oxygen exposure. The branched polyethylenimine (PEI) dendrimer serves as a model macromolecule, easily grafted via Schiff-base click chemistry. One of the optimized formulations, PEI-(5-OMe-3,4-DBA)₂₀, in which 20% of the primary amine groups of PEI are grafted with 5-methoxy-3,4-dihydroxybenzaldehyde (5-OMe-3,4-DBA) through Schiff-base linkages, initiates crosslinking immediately after air/O₂ exposure, but remains stable in anaerobic environments. Structural evaluation confirms PEI-(5-OMe-3,4-DBA)₂₀ undergoes spontaneous conversion to quinones, supported by aromatic CH integration (¹H-NMR) and first order decay of 5-OMe catechol Schiff-base (UV–vis). Gelation time occurs in 〈 1 min with shear strengths of 26 kPa on wetted collagen substrates.