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/O ₂ 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 ( ¹ H‐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.