The limited durability of resin-dentin bonds severely compromises the lifetime of tooth-colored restorations Bond degradation occurs via hydrolysis of suboptimally polymerized hydrophilic resin components and degradation of water-rich, resin-sparse collagen matrices by matrix metalloproteinases (MMPs) and cysteine cathepsins This review examined data generated over the past three years on five experimental strategies developed by different research groups for extending the longevity of resin-dentin bonds They include: (1) increasing the degree of conversion and esterase resistance of hydrophilic adhesives; (2) the use of broad-spectrum inhibitors of collagenolytic enzymes, including novel inhibitor functional groups grafted to methacrylate resins monomers to produce anti-MMP adhesives; (3) the use of cross-linking agents for silencing the activities of MMP and cathepsins that irreversibly alter the 3-D structures of their catalytic/allosteric domains; (4) ethanol wet-bonding with hydrophobic resins to completely replace water from the extrafibrillar and intrafibrillar collagen compartments and immobilize the collagenolytic enzymes; and (5) biomimetic remineralization of the water-filled collagen matrix using analogs of matrix proteins to progressively replace water with intrafibrillar and extrafibrillar apatites to exclude exogenous collagenolytic enzymes and fossilize endogenous collagenolytic enzymes A combination of several of these strategies should result in overcoming the critical barriers to progress currently encountered in dentin bonding

Limitations in Bonding to Dentin and Experimental Strategies to Prevent Bond Degradation

Periodontal diseases (PD) are chronic infectious inflammatory diseases characterized by the destruction of tooth-supporting structures, being the presence of periodontopathogens required, but not sufficient, for disease development. As a general rule, host inflammatory mediators have been associated with tissue destruction, while anti-inflammatory mediators counteract and attenuate disease progression. With the discovery of several T-cell subsets bearing distinct immunoregulatory properties, this pro- vs. anti-inflammatory scenario became more complex, and a series of studies has hypothesized protective or destructive roles for Th1, Th2, Th17, and Treg subpopulations of polarized lymphocytes. Interestingly, the “protective vs. destructive” archetype is usually considered in a framework related to tissue destruction and disease progression. However, it is important to remember that periodontal diseases are infectious inflammatory conditions, and recent studies have demonstrated that cytokines (TNF-α and IF...

Destructive and Protective Roles of Cytokines in Periodontitis: A Re-appraisal from Host Defense and Tissue Destruction Viewpoints

Dentin organic matrix, with type I collagen as the main component, is exposed after demineralization in dentinal caries, erosion or acidic conditioning during adhesive composite restorative treatment. This exposed matrix is prone to slow hydrolytic degradation by host collagenolytic enzymes, matrix metalloproteinases (MMPs) and cysteine cathepsins. Here we review the recent findings demonstrating that inhibition of salivary or dentin endogenous collagenolytic enzymes may provide preventive means against progression of caries or erosion, just as they have been shown to retain the integrity and improve the longevity of resin composite filling bonding to dentin. This paper also presents the case that the organic matrix in caries-affected dentin may not be preserved as intact as previously considered. In partially demineralized dentin, MMPs and cysteine cathepsins with the ability to cleave off the terminal non-helical ends of collagen molecules (telopeptides) may lead to the gradual loss of intramolecular gap areas. This would seriously compromise the matrix ability for intrafibrillar remineralization, which is considered essential in restoring the dentin's mechanical properties. More detailed data of the enzymes responsible and their detailed function in dentin-destructive conditions may not only help to find new and better preventive means, but better preservation of demineralized dentin collagenous matrix may also facilitate true biological remineralization for the better restoration of tooth structural and mechanical integrity and mechanical properties.

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Matrix Metalloproteinases and Other Matrix Proteinases in Relation to Cariology: The Era of ‘Dentin Degradomics'

Optimizing dentin bond durability: Control of collagen degradation by matrix metalloproteinases and cysteine cathepsins

Fluoride was introduced into dentistry over 70 years ago, and it is now recognized as the main factor responsible for the dramatic decline in caries prevalence that has been observed worldwide. However, excessive fluoride intake during the period of tooth development can cause dental fluorosis. In order that the maximum benefits of fluoride for caries control can be achieved with the minimum risk of side effects, it is necessary to have a profound understanding of the mechanisms by which fluoride promotes caries control. In the 1980s, it was established that fluoride controls caries mainly through its topical effect. Fluoride present in low, sustained concentrations (sub-ppm range) in the oral fluids during an acidic challenge is able to absorb to the surface of the apatite crystals, inhibiting demineralization. When the pH is re-established, traces of fluoride in solution will make it highly supersaturated with respect to fluorhydroxyapatite, which will speed up the process of remineralization. The mineral formed under the nucleating action of the partially dissolved minerals will then preferentially include fluoride and exclude carbonate, rendering the enamel more resistant to future acidic challenges. Topical fluoride can also provide antimicrobial action. Fluoride concentrations as found in dental plaque have biological activity on critical virulence factors of S. mutans in vitro, such as acid production and glucan synthesis, but the in vivo implications of this are still not clear. Evidence also supports fluoride’s systemic mechanism of caries inhibition in pit and fissure surfaces of permanent first molars when it is incorporated into these teeth pre-eruptively.

Mechanisms of action of fluoride for caries control.

This review focuses specifically on matrix metalloproteinases (MMPs) and their role in physiological and pathological extracellular matrix (ECM) remodeling and degradation processes in the oral environment. A group of enzymes capable of degrading almost all ECM proteins, MMPs contribute to both normal and pathological tissue remodeling. The expression of different MMPs may be upregulated in pathological conditions such as inflammation and tumor invasion. The balance between activated MMPs and tissue inhibitors of metalloproteinases (TIMPs) controls the extent of ECM remodeling. Prior to mineralization, MMPs may participate in the organization of enamel and dentin organic matrix, or they may regulate mineralization by controlling the proteoglycan turnover. There is evidence indicating that MMPs could be involved in the etiology of enamel fluorosis and amelogenesis imperfecta. They seem to play a part in dentinal caries progression, since they have a crucial role in dentin collagen breakdown in caries lesions. MMPs have been identified in pulpal and periapical inflammation and are strongly correlated with periodontal diseases, since they are the major players in collagen breakdown during periodontal tissue destruction. The use of MMP inhibitors could help the prevention and treatment of many MMP-related oral diseases.

The role of matrix metalloproteinases in the oral environment.

Despite a plethora of in situ studies and clinical trials evaluating the efficacy of fluoridated dentifrices on caries control, in vitro pH cycling models are still broadly used because they mimic the dynamics of mineral loss and gain involved in caries formation. This paper critically reviews the current literature on existing pH-cycling models for the in vitro evaluation of the efficacy of fluoridated dentifrices for caries control, focusing on their strengths and limitations. A search was undertaken in the MEDLINE electronic journal database using the keywords "pH-cycling", "demineralization", "remineralization", "in vitro", "fluoride", "dentifrice". The primary outcome was the decrease of demineralization or the increase of remineralization as measured by different methods (e.g.: transverse microradiography) or tooth fluoride uptake. Inclusion of studies, data extraction and quality assessment were undertaken independently and in duplicate by two members of the review team. Disagreements were solved by discussion and consensus or by a third party. One hundred and sixteen studies were included, of which 42 addressed specifically the comparison of dentifrices using different pH-cycling models. The other studies included meta-analysis or reviews, data about the effect of different fluoride sources on de-remineralization, different methods for analysis de-remineralization and chemical variables and characteristics of dental hard tissues that might have influence on de-remineralization processes. Generally, the studies presented ability to detect known results established by clinical trials, to demonstrate dose-related responses in the fluoride content of the dentifrices, and to provide repeatability and reproducibility between tests. In order to accomplish these features satisfactorily, it is mandatory to take into account the type of substrate and baseline artificial lesion, as well as the adequate response variables and statistical approaches to be used. This critical review of literature showed that the currently available pH-cycling models are appropriate to detect dose-response and pH-response of fluoride dentifrices, and to evaluate the impact of new active principles on the effect of fluoridated dentifrices, as well as their association with other anti-caries treatments.

/pdf/ph-cycling-models-for-in-vitro-evaluation-of-the-efficacy-of-uxstqku29m.pdf

pH-cycling models for in vitro evaluation of the efficacy of fluoridated dentifrices for caries control: strengths and limitations.

https://www.zora.uzh.ch/id/eprint/27369/1/Magalhaes_Dentin_Erosion_JDent_2009.pdf

Chlorhexidine and green tea extract reduce dentin erosion and abrasion in situ.

This proof-of-concept study assessed whether the reduction of the degradation of the demineralized organic matrix (DOM) by pre-treatment with protease inhibitors (PI) is effective against dentin matrix loss. Bovine dentin slices were demineralized with 0.87 M citric acid, pH 2.3, for 36 hrs. In sequence, specimens were treated or not (UT, untreated) for 1 min with gels containing epigallocatechin 3-gallate (EGCG, 400 µM), chlorhexidine (CHX, 0.012%), FeSO4 (1 mM), NaF (1.23%), or no active compound (P, placebo). Specimens were then stored in artificial saliva (5 days, 37°C) with the addition of collagenase (Clostridium histolyticum, 100 U/mL). We analyzed collagen degradation by assaying hydroxyproline (HYP) in the incubation solutions (n = 5) and evaluated the dentin matrix loss by profilometry (n = 12). Data were analyzed by ANOVA and Tukey’s test (p < 0.05). Treatment with gels containing EGCG, CHX, or FeSO4 led to significantly lower HYP concentrations in solution and dentin matrix loss when compared ...

https://journals.sagepub.com/doi/pdf/10.1177/0022034512455801

Impact of Protease Inhibitors on Dentin Matrix Degradation by Collagenase

Matrix metalloproteinase (MMP) inhibition has been shown to reduce dentin caries progression, but its role in dental erosion has not yet been assessed. This study tested the hypothesis that gels containing MMP inhibitors (epigallocatechin gallate-EGCG and chlorhexidine) can prevent dental erosion. Volunteers (n = 10) wore palatal devices containing bovine dentin blocks (n = 10/group) treated for 1 min with EGCG at 10 (EGCG10) or 400 microM (EGCG400), chlorhexidine at 0.012%, F at 1.23% (NaF), and no vehicle (placebo). Erosion was performed with Coca-Cola (5 min) 4X/day during 5 days. The wear, assessed by profilometry (mean +/- SD, microm), was significantly reduced by the gels containing MMP inhibitors (0.05 +/- 0.02(a), 0.04 +/- 0.02(a), and 0.05 +/- 0.02(a) for EGCG10, EGCG400, and chlorhexidine, respectively) when compared with NaF (0.79 +/- 0.35(b)) and placebo gels (1.77 +/- 0.35(b)) (Friedman and Dunn's tests, p < 0.01). The use of gels delivering MMP inhibitors was shown to prevent erosion and opens a new perspective for protection against dental erosion.

A. R. Hannas

Papers

The role of matrix metalloproteinases in the oral environment.

pH-cycling models for in vitro evaluation of the efficacy of fluoridated dentifrices for caries control: strengths and limitations.

Chlorhexidine and green tea extract reduce dentin erosion and abrasion in situ.

Impact of Protease Inhibitors on Dentin Matrix Degradation by Collagenase

Gels Containing MMP Inhibitors Prevent Dental Erosion in situ