The remarkable underwater adhesion strategy employed by mussels has inspired bioadhesives that have demonstrated promise in connective tissue repair, wound closure, and local delivery of therapeutic cells and drugs. While the pH of oxygenated blood and internal tissues is typically around 7.4, skin and tumor tissues are significantly more acidic. Additionally, blood loss during surgery and ischemia can lead to dysoxia, which lowers pH levels of internal tissues and organs. Using 4-armed PEG end-capped with dopamine (PEG-D) as a model adhesive polymer, the effect of pH on the rate of intermolecular cross-linking and adhesion to biological substrates of catechol-containing adhesives was determined. Adhesive formulated at an acidic pH (pH 5.7–6.7) demonstrated reduced curing rate, mechanical properties, and adhesive performance to pericardium tissues. Although a faster curing rate was observed at pH 8, these adhesives also demonstrated reduced mechanical and bioadhesive properties when compared to adhesives buffered at pH 7.4. Adhesives formulated at pH 7.4 demonstrated a good balance of fast curing rate, elevated mechanical properties and interfacial binding ability. UV–vis spectroscopy evaluation revealed that the stability of the transient oxidation intermediate of dopamine was increased under acidic conditions, which likely reduced the rate of intermolecular cross-linking and bulk cohesive properties for hydrogels formulated at these pH levels. At pH 8, competing cross-linking reaction mechanisms and reduced concentration of dopamine catechol due to auto-oxidation likely reduced the degree of dopamine polymerization and adhesive strength for these hydrogels. pH plays an important role in the adhesive performance of mussel-inspired bioadhesives and the pH of the adhesive formulation needs to be adjusted for the intended application.

Linear polyacrylamide (PAAm) is modified with dopamine or nitrodopamine (PAAm-D and PAAm-ND, respectively) to evaluate the effect of nitro-group modification on the interfacial binding properties of polymer-bound catechol. Nanocomposite hydrogels are prepared by mixing PAAm-based polymers with Laponite and the viscoelastic properties of these materials are determined using oscillatory rheometry. The incorporation of a small amount of catechol (≈0.1 wt% in swollen hydrogel) drastically increases the shear moduli by 1–2 orders of magnitude over those of the catechol-free control. Additionally, PAAm-ND exhibits higher shear moduli values than PAAm-D across the whole pH range tested (pH 3.0–9.0). Based on the calculated effective crosslinking density, effective functionality, and molecular weight between crosslinks, nitro-group functionalization of dopamine results in a polymer network with increased crosslinking density and crosslinking points with higher functionality. Nitro-functionalization enhances the interfacial binding property of dopamine and increases its resistant to oxidation, which results in nanocomposite hydrogels with enhanced stiffness and a viscous dissipation property.