Effect of Nitro-Functionalization on the Cross-Linking and Bioadhesion of Biomimetic Adhesive Moiety

Abstract

Dopamine mimics the exceptional moisture-resistant adhesive properties of the amino acid, DOPA, found in adhesive proteins secreted by marine mussels. The catechol side chain of dopamine was functionalized with a nitro-group, and the effect of the electron withdrawing group modification on the cross-linking chemistry and bioadhesive properties of the adhesive moiety was evaluated. Both nitrodopamine and dopamine were covalently attached as a terminal group onto an inert, 4-armed poly(ethylene glygol) (PEG-ND and PEG-D, respectively). PEG-ND and PEG-D exhibited different dependence on the concentration of NaIO4 and pH, which affected the curing rate, mechanical properties, and adhesive performance of these biomimetic adhesives differently. PEG-ND cured instantly and its bioadhesive properties were minimally affected by the change in pH (5.7–8) within the physiological range. Under mildly acidic conditions (pH 5.7 and 6.7), PEG-ND outperformed PEG-D in lap shear adhesion testing using wetted pericardium tissues. However, nitrodopamine only formed dimers, which resulted in the formation of loosely cross-linked network and adhesive with reduced cohesive properties. UV–vis spectroscopy further confirmed nitrodopamine’s ability for rapid dimer formation. The ability for nitrodopamine to rapidly cure and adhere to biological substrates in an acidic pH make it suitable for designing adhesive biomaterials targeted at tissues that are more acidic (i.e., subcutaneous, dysoxic, or tumor tissues).

Model polymer system for investigating the generation of hydrogen peroxide and its biological responses during the crosslinking of mussel adhesive moiety

“…Due to the inert and highly predictable characteristics of PEG [26, 34], the observed changes in the physical and mechanical properties as well as biological responses can be fully attributed to the reactivity of the catechol side chain. When catechol is oxidized with the addition of NaIO 4 , PEG-D4 cured rapidly (under 30 seconds) as the branched architecture of PEG-D4 provides a junction point for rapid network formation when catechol moieties dimerize [26].…”

Hydrogen peroxide generation and biocompatibility of hydrogel-bound mussel adhesive moiety

“…Specifically, our data indicated that significantly higher amount of H 2 O 2 was produced during the process of polydopamine formation (Figure S4). Most importantly, catechol-containing bioadhesives typically require the addition of strong oxidants (i.e., NaIO 4 ) to initiate rapid cohesive and interfacial crosslinking [6, 36, 62, 63]. Additional study is require to evaluate the production of ROS and the biocompatibility of mussel-mimetic bioadhesives during the process of in situ curing.…”

Recent approaches in designing bioadhesive materials inspired by mussel adhesive protein

“…Similarly, catechol side chain modified with an electron withdrawing nitro‐groups significantly increased the reactivity and interfacial binding strength of the catechols [Fig. 7(B)] 121. Nitro‐catechol bound to an inorganic surface exhibited increased resistance to elevated temperature and oxidation when compared to an unsubstituted catechol 122, 123, 124.…”