Elsevier

Acta Biomaterialia

Volume 103, February 2020, Pages 92-101
Acta Biomaterialia

Full length article
Catechol-thiol-based dental adhesive inspired by underwater mussel adhesion

https://doi.org/10.1016/j.actbio.2019.12.002Get rights and content

Abstract

The critical problem associated with the underwater mussel adhesive catechol-based 3,4-dihydroxy-L-phenylalanine (DOPA) is its sensitivity to oxidation. To overcome this problem, mussels underwent etching in the presence of acidic pH conditions (<3.0), and thiol chemistry was used to control the propensity of DOPA for oxidation. Similar strategies deployed by mussels are also actively utilized in dental adhesives which undergo etching in the presence of phosphoric acid derivatives to maximize the bonding strength and adapt thiol chemistries to minimize shrinkage stress. In view of the similarities between dental and underwater mussel adhesives, we employ in this study the strategy of mussel adhesion—the combination of DOPA and thiol chemistry with acid etching—to one of the most critical issues in dental adhesives, namely, the dentin bonding with zirconia. As a result, the adhesion bonding between zirconia and dentin, one of the most elusive problems in dentistry, has improved compared to the commercially available adhesive resin formulation. In addition, in view of the similar human oral and mussel adhesive environments, our findings will considerably contribute to the translation of the adhesive system inspired by mussels.

Statement of significance

Mussels are effectively operated by creating an acidic environment when adhering with 3,4-dihydroxy-l-phenylalanine (DOPA)–thiol redox chemistry for underwater bonding. Similarly, in dental adhesives, phosphoric acid-based etching is used for dentin-bonding materials. In view of the similarity between dental adhesives and underwater mussel adhesives, the combination of DOPA and thiol chemistry with acid etching can be used to overcome one of the most critical issues in dentin medical adhesives. The proposed adhesion method produces high adhesion strengths compared to those currently used in dentin and zirconia adhesives. Here, we extend and evaluate dentin and zirconia dental adhesives by mixing with mussel (DOPA)–thiol redox chemistry and acid etching.

Introduction

The adhesive system of mussels possesses many intriguing properties that can be studied to engineer superior multifunctional devices and materials that would be useful and beneficial to man [1]. Mussels can be attached tightly to wet and rough surfaces owing to their specialized holdfast called byssus in adverse and turbulent environments which include saline conditions, variations of fluid flow, dynamic changes in temperature and pH, and the exposure of the effects from other microbes and enzymatic activities [2,3].The human oral environment possesses many similarities compared to the mussel living environment. The oral environment has natural salinity, and generates mechanical stresses from chewing food and the flow of saliva, stresses induced at varying temperatures and pH values, as well as biological stresses from the effect of plague by microbes [4]. While the tissues in the oral environment have slowly evolved from the biological functional point-of-view to better adapt to the aforementioned environments manifested at various levels of adversity compared to marine organisms, additional time is required for adaptation given the longer history of the marine organisms. Thus, the knowledge of numerous biological mechanisms in marine organisms provides useful information for emulating dental and other biomedical technologies.

The byssus of the mussels are composed mainly of a variety of adhesive proteins that play important roles in their adhesiveness to endure all the aforementioned conditions [3]. As these proteins are mainly secreted from the foot of the mussel, they are also known as mussel foot proteins (mfps) [2,3]. The key chemical functionality present in the mfps is the postranslationally modified amino acid 3,4-dihydroxy-l-phenylalanine (DOPA) [4]. The catecholic moiety of DOPA forms strong and reversible coordination complexes with metal ions and metal oxides, or undergoes covalent crosslinking with neighboring chemical moieties [5]. Given the aforementioned similarities of the underwater and the human oral environments, it is logical to assume that DOPA can potentially serve as a good candidate that can be used for dental adhesives. However, there are several difficulties in introducing DOPA directly in more practical application fields. One of them is the poor oxidation stability of DOPA. Given that the two hydroxyl groups on its benzene ring can be easily oxidized, the molecule is prone to change to dopaquinone [6,7]. Although dopaquinone has a crosslinking role in nature, it causes DOPA to lose its own adhesiveness. To circumvent this, two strategies have been adopted by mussels, i.e., applying a) adhesives in acidic pH and b) thiol-rich reducing environments [8,9].

Mussels create a local acidic environment (pH~2) by using their foot proteins when they secrete adhesive proteins [10]. The acidic pH is beneficial in protecting DOPA in the adhesives from being oxidized and allows the extinction and removal of microbes from the adhesive surface. At the same time, the thiol-rich antioxidant proteins mfp-6s, are co-secreted with DOPA to minimize the DOPA oxidation. With these two strategies, the underwater adhesives of mussels can yield the best underwater-adhesion performance in the marine environment [11].

Interestingly, the aforementioned two strategies adopted to minimize DOPA from oxidation—acid etching and thiol chemistry—are applied in dental adhesive technologies [12,13]. Firstly, dental adhesives in the clinical treatments for dental caries are generally applied after acid etching of the teeth with phosphoric acid derivatives, such as phenyl hydrogen phosphate (phenol-P), and 10-methacryloyloxy decyldihydrogen phosphate (10 MDP) [14]. The introduction of thiol-rich crosslinkers has been used as the strategy to minimize shrinkage stress in the dental adhesive during the photopolymerization of the dental resin and adhesives [15]. Indeed, pentaerythritol tetra(3-mercaptopropionate) (PETMP), which is a tetra-functional crosslinker with four thiol groups, dramatically reduced shrinkage stress, volume shrinkage, leachable species when it was used as a component in acyrl-based dental resin [16]. The acidic condition in the dental adhesive technology not only provides an ideal environment for DOPA-containing adhesives and their easy incorporation in the conventional dental adhesives, but also minimizes DOPA oxidation which causes DOPA lose its own adhesiveness. In addition, the poly thiols used for the reduction of shrinkage stress in the dental resin formulation ensure that the DOPA remains in its reduced state without losing its adhesiveness.

Therefore, in view of the similarities between dental adhesion and mussel adhesion environments, we applied the strategy of mussel adhesion—the combination of DOPA and thiol chemistry with acid etching—to the design of dental adhesive formulation. We synthesized a crosslinker containing both DOPA and thiol moieties, and observed that the addition of the crosslinker to the currently used dental formulation yields an enhanced adhesion between dentin and Zircornia, compared to the currently used dental formation.

Section snippets

Synthesis of silyl-protected catechol (SPC)

Eugenol (1.64 g, 1.0 equivalent) and triethylsilane (2.56 g, 2.2 equivalents) were placed into a 100 ml round bottomed flask and were stirred for 5 min to ensure a uniform environment with the condenser. The flask was immersed in tap water at room temperature (25 °C) to eliminate the influences of temperature changes. The catalyst, tris(pentafluorophenyl)borane (10.2 mg, 0.002 equivalents) was added to the mixture and stirred. After the vigorous formation of gas was observed, the reaction

Syntheses of catechol-functionalized adhesive compounds

Recently, cheap and efficient chemical mechanisms have been invented to protect the hydroxyl groups in DOPA with silane groups (SPC) [17]. Previous studies in which SPCs were used to combine acrylic groups at the ends showed that the adhesive strength increased even in the presence of saliva or water [18]. Additionally, acrylic and methacryl-conjugated catechols—used for silyl protection—have been shown to act as dental primers [19]. This has been suggested as a protection strategy to prevent

Conclusions

In the view of the similar dental adhesion and mussel adhesion strategies, we applied the wet-adhesion strategy found in mussel—the combination catechol and thiol moieties—to dental adhesive formulation. We synthesized the PETMP catechols, crosslinker molecules with catechol and thiol moieties, and evaluated the potential of the PETMP catechols as a component in the dental adhesive formulation. As a result, the adhesion bonding between zirconia and dentin, one of the most elusive problems in

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work was supported by the Marine Biotechnology Program (Marine BioMaterials Research Center) funded by the Ministry of Oceans and Fisheries, Korea (D11013214H480000110) and the National Research Foundation of Korea Grant funded by the Korean Government (NRF–2016M1A5A1027592 & NRF–2019M3C1B7025093).

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