Tooth remineralization using catechol compounds

Abstract

This disclosure provides compositions and methods for remineralizing tooth dentin in a subject using one or more catechol-containing materials. This disclosure also provides compositions and methods for treating tooth hypersensitivity in a subject, comprising contacting exposed dentinal tubules with a catechol-containing material. This disclosure also provides compositions and methods for restoring acid-etched tooth dentin in a subject, comprising contacting tooth dentin with a catechol-containing material.

Description

Technical Field

[0001] The present invention relates to the field of treatment of teeth and hard tissues. More specifically, the present invention relates to the remineralization of dental dentin and catechol-containing materials used for such remineralization.

[0002] (Cross-reference to related applications) This application claims the priority and benefit of U.S. Provisional Patent Application No. 63 / 491,297, filed on March 21, 2023, which is hereby incorporated by reference in its entirety for all purposes.

Background Art

[0003] Tooth structure Human teeth perform several functions, including chewing, assisting in conversation, and the perception of beauty and facial harmony. Human teeth consist of three successive tissue layers: (1) "enamel" which is a hard and highly mineralized tissue (which is supported by an important connective tissue that is less mineralized), (2) "dentin" (which is formed from and supported by a soft connective tissue), and (3) "pulp" or "pulp". The pulp consists of a sensitive tissue containing blood vessels, nerve fibers, special cells, and pulp fluid. The dentin surrounding the pulp forms the main part of the tooth. It is a high-density bone-like tissue consisting of 70% by weight of inorganic substances, 20% by weight of organic substances, and 10% by weight of water.

[0004] Dentin Dentin is the calcified tissue of the body and, along with enamel, cementum, and pulp, is one of the four main components of a tooth. It is usually covered by enamel on the crown and cementum on the root, and surrounds the entire pulp. By volume, dentin consists of 45% inorganic hydroxyapatite, 33% organic matter, and 22% water. Its yellow appearance is greatly influenced by the translucency of enamel, which affects the color of the tooth. Less calcified and less brittle than enamel, dentin is necessary to support enamel. There are two main characteristics that distinguish dentin from enamel. First, dentin is formed throughout life. Second, dentin is sensitive, and can become hypersensitive to temperature changes, especially when enamel recedes and dentin channels are exposed, due to the sensory function of odontoblasts.

[0005] Dentin can be demineralized and stained for histological study. Dentin consists of microscopic channels called dentinal tubules, which radiate outward through the dentin from the pulp to the outer cementum or enamel boundary. Dentinal tubules extend from the dentinoenamel junction (DEJ) in the coronal region or the dentinocemental junction (DCJ) in the root region to the outer wall of the pulp. From the outer surface of the dentin to the region closest to the pulp, these tubules follow an S-shaped pathway. Within the tubules are odontoblastic processes, which are extensions of odontoblasts, as well as dental fluid containing a mixture of albumin, transferrin, tenascin, and proteoglycans. Furthermore, there is a branched tubular system that connects to one another. The main branches are the terminals of the tubules. Dentinal tubules contain cytoplasmic extensions of odontoblasts that maintain the dentin once it is formed. Due to the presence of dentinal tubules, dentin has a certain degree of permeability, which can increase pain sensation and the rate of tooth decay.

[0006] Dentin is a porous, yellowish, bone-like matrix. It is composed of 70-72% inorganic material (primarily hydroxyapatite and some amorphous calcium phosphate) by weight, 20% organic material (90% of which is type I collagen, with the remaining 10% being a matrix containing dentin-specific proteins), and 8-10% water (adsorbed on the surface or between crystals of minerals). Because it is softer than enamel, caries progresses more rapidly in dentin, leading to severe cavities if not properly treated; however, due to its elastic properties, it is a good support for enamel. Its flexibility prevents the breakdown of brittle enamel.

[0007] Remineralization and demineralization of hard tissues The process of enamel dissolution is called demineralization. It is the result of the interaction of enamel and dentin components with acids, caused by the bacterial action of plaque and various foods, as well as by the consumption of acidic beverages (e.g., fruit juices, wine, and some sports drinks and carbonated beverages). A decrease in pH leads to the dissolution of Ca and P ions into saliva. The solubility of different types of apatite found in dentin and enamel in acids differs significantly. For example, the solubility of carbonate apatite in an acid at a given pH is approximately an order of magnitude greater than that of hydroxyapatite, and the solubility of hydroxyapatite is an order of magnitude greater than that of fluoroapatite. Demineralization leads to common dental diseases, including the development of caries, the appearance of white spots, and the development of dentin hypersensitivity. Caries affects more than 90% of all adults in the United States. Caries is the result of bacterial acid-induced demineralization damage to the dentin of teeth. White spot lesions (WSLs) affect approximately 50% of orthodontic patients. WSLs result from localized demineralization caused by the accumulation of biofilm around orthodontic brackets. Dentin hypersensitivity (DH) affects approximately 11.5% of adults. DH is caused by the exposure of dentinal tubules due to dentin loss (shown in Figure 2), and can also be caused by the receding of gingival tissue around the base of the tooth.

[0008] The reverse process, called remineralization, is facilitated by some or all of the following mechanisms. Human saliva contains calcium and phosphate in a supersaturated state, which can remineralize hydroxyapatite crystals lost during demineralization. This is a fundamental process in preventing dentin loss. Under normal conditions, a balance is maintained between demineralization and remineralization. The remineralizing capacity of saliva is a classic example of a natural tooth rejuvenation mechanism. The remineralization process can also be initiated by controlling oral fluids. This can increase the resistance of teeth to acid attack, and methods such as using fluoride in toothpaste and local tap water have been known for many years. Fluoride ions from compounds such as NaF and SnF2 contribute to the remineralization process, including the OH in apatite. - It replaces some of the ions. Amorphous calcium phosphate (CaPO4), or ACP, is another compound used to promote remineralization. As the pH decreases, ACP dissociates to form calcium and phosphate ions, thereby minimizing the decrease in pH and limiting demineralization. Because ACP acts as a reservoir for calcium and phosphate ions and can maintain these ions in a supersaturated state, ACP inhibits the demineralization process and promotes remineralization. Remineralization complexes consisting of Ca and F have been proposed as additives to strips and packing materials.

[0009] Given the shortcomings of conventional fluoride-based and calcium phosphate systems, there is a need for methods and materials to aid in the regeneration, renewal, and / or repair of lost or damaged hard tissue.

[0010] Acid etching Acid etching or tooth conditioning is widely used in clinical practice. It is most frequently used for bonding resin materials. Different types and concentrations of acids may be used. Among these, 30-40% phosphoric acid with an application time of up to 60 seconds is the most frequently used. Another, less frequent application of acid is the removal of surface stains resulting from enamel or dentin developmental abnormalities (e.g., excessive fluoride intake). Reported uses include 18% and 37% hydrochloric acid, applied for up to 25 seconds.

[0011] Acid etching and partial demineralization of apatite crystals increase the porosity of the exposed surface. Such surfaces are well-suited for bonding of restorative and adhesive materials. Three distinct acid etching patterns can be distinguished. Type I patterns preferentially remove the core of the enamel rods. In Type II patterns, most of the prism sheath is removed, while the core of the rods remains intact. Type III patterns are characterized by irregular and indiscriminate etching.

[0012] Acid etching of hard tissues can lead to enamel or dentin loss, as well as a decrease in mechanical hardness and wear resistance. Furthermore, acid etching of the tooth surface, which is most resistant to acid attack, can accelerate the growth of caries lesions. For this reason, acids are used in dentistry primarily for treating hard tissues and to facilitate the adhesion of stained tooth restorative materials to such hard tissues. At low concentrations, acids are used as peroxide bleaching agents and additives in some rinses and toothpastes to stabilize various components. Dentists recommend limiting the use of acidic beverages and foods. The pH of most foods and beverages is above 2.5, usually between 4 and 7.

[0013] Teeth rejuvenation Tooth rejuvenation is one of the most important aspects of preventive and cosmetic dentistry. As explained above, it can be part of a natural process facilitated by saliva. However, in many cases, the natural role of saliva is not sufficient to protect teeth from deterioration. Several methods exist that aim to promote tooth rejuvenation. Most focus on improving one of the components of tooth rejuvenation and do not offer a complete solution. Such methods include fluoride addition to drinking water, mouthwash, gels and strips, toothpaste, professional oral cleaning, teeth whitening, tooth coating, and laser modification of tooth surfaces. These methods are described in more detail below.

[0014] Adding fluoride to drinking water contributes to the formation of fluoroapatite in the outer layer of teeth. Fluoride in water inhibits acid production in dental plaque, enhances remineralization of caries lesions, and promotes the formation of fluoroapatite (Ca 10 Fluoride plays multiple roles in preventing dental caries, including strengthening teeth against acid attack through the formation of (PO4)6F2. This effect occurs at low fluoride concentrations. High concentrations of fluoride can cause the formation of CaF2 and the destruction of tooth structure.

[0015] Mouse rinses are primarily used to reduce bacteria. Several additives, such as casein phosphopeptide amorphous calcium phosphate nanocomplexes, have proven effective in the remineralization process.

[0016] Different types of gels and strips have been shown to provide antimicrobial effects. Gels containing fluoride ions, calcium ions, and phosphate ions have been shown to be effective in the remineralization process. Preliminary treatment of teeth with low acid concentrations enhances the effects of fluoride treatment. Gels or strips may also contain peroxides for teeth whitening.

[0017] Brushing and flossing are daily regimens and therefore the most important forms of preventing tooth plaque buildup and tooth decay. Mechanical cleaning of teeth removes biofilm, prevents / reduces tartar buildup, and reduces acid production by bacteria. It also improves saliva's access to the tooth surface in a process that enhances the opportunity for remineralization. Furthermore, toothpaste often contains antibacterial, remineralizing, and whitening ingredients.

[0018] Professional oral hygiene in a dental clinic offers further benefits to brushing and flossing techniques, including the removal of supragingival and subgingival plaque and calculus, plaque detection, and the application of cariogenic agents. This procedure typically includes scaling and polishing of teeth, as well as subgingival currettage, resulting in a more effective method of preventing periodontal disease or other tooth loss, and an overall aesthetic improvement in the appearance of teeth and gums. Plaque detection and the application of cariogenic agents can also be performed by healthcare professionals as an aid to home care and remineralization. However, this procedure cannot remove intrinsic and deep extrinsic plaque.

[0019] Teeth function under mechanical, chemical, and thermal stress. Normal chewing places a moderate stress of 20 MPa on teeth over 1000 times a day. Occasionally, stress can reach 100 MPa. This cyclical load occurs in an aqueous fluid environment, which can have pH levels of 0.5–8 and temperature fluctuations of up to 50°C. Many different restorative materials have been developed to maintain strength and properties under harsh conditions (e.g., porous ceramic alumina impregnated with lanthanum aluminosilicate glass, or porous zirconia later impregnated with glass). Porcelain, the most common material, has excellent color properties but is brittle and relatively easily fractured unless reinforced or strengthened. Porcelain restorative treatment also destroys tooth structure, usually requiring tooth preparation, being expensive and time-consuming. These restorative materials, used in crowns or veneers, provide excellent aesthetic appearance and prevent caries when properly applied. However, the risk of recurrent caries remains. Since any destruction of tooth structure is harmful, clinicians have attempted to develop non-destructive or minimally destructive methods for restoring teeth. [Overview of the project]

[0020] In certain embodiments, the Disclosure relates to a method for remineralizing tooth dentin, comprising contacting tooth dentin with a catechol-containing material comprising one or more of catechol, semiquinone, or quinone. The catechol-containing material may comprise monomers, oligomers, or polymers of catechol or catechol-containing material, wherein the catechol exists as catechol and / or semiquinone and / or quinone in the absence of an amine, and the polymer layer optionally comprises at least one of a) a reactive species separate from catechol or the catechol-containing material, and b) a catalyst, co-catalyst, or accelerator.

[0021] In certain embodiments, the disclosure relates to a method for treating tooth hypersensitivity in a subject, comprising contacting exposed dentin tubules with catechol, semiquinone, or a catechol-containing material containing quinone.

[0022] In certain embodiments, the present disclosure provides a method for repairing acid-etched dentin in a subject, the method comprising contacting the dentin with a catechol-containing material.

Brief Description of the Drawings

[0023] In the drawings, they are not necessarily drawn to scale, and like numerals may represent similar components in different figures. Like numerals with different suffixes of letters may represent different instances of similar components. These drawings generally illustrate, by way of example and not limitation, various aspects discussed in this document. [Figure 1] A schematic diagram showing the transition between demineralization and remineralization of teeth in normal saliva under an acidic environment is shown. This illustration (193069566 (copyright)) was obtained with permission from Yomogi1 Dreamstime.com. [Figure 2] A schematic diagram of a tooth having exposed dentinal tubules, which are the cause of dentin hypersensitivity, is shown. [Figure 3] 3A - 3D show the formation of calcium phosphate (CaP) on PCS-coated aluminum. Figures 3A and 3B show SEM micrographs of either (A, C) untreated (Figure 3A) or (B, D) with 10% PCS coating (Figure 3B) aluminum surfaces. Figures 3C and 3D show EDX analyses of either untreated (Figure 3C) or with 10% PCS coating (Figure 3D) aluminum surfaces. The EDX analysis revealed that this material is the main CaP having an average Ca / P molar ratio of 1.24 ± 0.05 (n = 10). The scale bar on the SEM image is 10 microns. [Figure 4]Figures 4A-4F show PCS-induced remineralization of dentin. Molar samples were ground to expose smooth dentin, demineralized by limited acid etching, coated with 5% poly(catechol-styrene), and incubated in distilled water or 1.5× simulated body fluid (SBF) at 37°C for 72 hours. The samples were then analyzed by SEM. A 10-micron bar is shown as the scale. Figure 4A shows the distilled water control. Normal dentin is shown. Figure 4B shows the 1.5× SBF control. Some CaP is shown on the dentin surface. Figure 4C shows the 5% PCS sample. Formation of a sheet-like, solid CaP is shown inside the tubules and on the dentin. Figures 4D, 4E, and 4F show energy-dispersive X-ray spectroscopy data confirming ACP formation in the samples shown in Figures 4A, 4B, and 4C. The scale bars in Figures 4A, 4B, and 4C represent 10 microns. [Figure 5] This is a SEM micrograph of dentin tubules treated with a thin film layer of 1% poly(catechol-styrene) (PCS), showing calcification of individual tubules. Nucleation of individual tubules is observed. This nucleation growth emerges from and enters individual tubules, ultimately leading to complete occlusion. The magnification is 12,000x, and the scale bar is 2.5 microns. The sample was acid-etched with 40% phosphate gel for 2 minutes, PCS was applied, and then immersed in 1.5× simulated body fluid (SBF) at 37°C for 72 hours. [Figure 6]Figures 6A and 6B are SEM micrographs of the dentin surface untreated and treated with a thin film layer of 0.1% poly(catechol-styrene) (PCS), indicating that 0.1% PCS is sufficient for calcification. In Figure 6A, the dentin remains untreated, and the micrograph shows very small patches of CaP growth. Figure 6B is an enlarged view of the growth area, showing mild CaP bound sporadically to the dentin surface. Figure 6A has a magnification of 40 times, and the scale bar is 1 millimeter. Figure 8B has a magnification of 800 times, and the scale bar is 50 microns. The samples were acid-etched with 40% phosphoric acid gel for 2 minutes, PCS was applied to the corresponding groups, and then the samples were immersed in 1.5× simulated body fluid (SBF) at 37 °C for 72 hours. [Figure 7] Figures 7A - 7D are SEM micrographs of the dentin surface untreated and treated with a thin film layer of 1% poly(catechol-styrene) (PCS), showing the growth pattern of amorphous calcium phosphate after re-acid etching. In Figures 7A and 7C, the samples were acid-etched, immersed in 1.5× SBF for 72 hours, and then re-acid-etched. Figure 7A shows the SEM of the sample without PCS application. Figure 7C shows a sample where a 1% PCS thin film was applied, and after re-acid etching, some residual CaP remained on the surface, but the tubules were exposed and part of the polymer coating was destroyed by acid etching (not shown). In Figures 7B and 7D, the dentin surface was acid-etched, immersed in 1.5× SBF for 72 hours, re-acid-etched, and then immersed in 1.5× SBF for 72 hours. As shown in Figure 7B, growth of a CaP sheet was observed on the untreated surface. Figure 7D shows that even though part of the PCS coating was destroyed by acid etching, more extensive growth of CaP sheets was observed on the 1% PCS-treated surface. All acid etching was performed for 2 minutes using 40% phosphoric acid gel. The scale bars for panels A, B, C, and D are 1 millimeter. [Figure 8]Figures 8A and 8B are SEM micrographs of untreated and treated dentin surfaces with a 1% poly(catechol-styrene) (PCS) thin film layer, showing the growth of amorphous calcium phosphate on an un-acid-etched dentin surface. Figure 8A shows the untreated dentin surface. Exposed tubules are shown (inset). Figure 8B shows the entire dentin surface covered with amorphous calcium phosphate (ACP) sheet formations. For each panel, the magnification is 80x and the scale bar is 500 microns. Figures 8A and 8B have 80x magnified views and the scale bar is 500 microns. The samples were kept at 37°C and immersed in 1.5× simulated body fluid (SBF) for 72 hours. [Figure 9] Figures 9A-9C are SEM micrographs of dentin surfaces treated with a thin film layer of 5% poly(catechol-styrene) (PCS), showing that removal of the CaP sheet reveals occluded tubules beneath. The samples were incubated in 1.5× simulated body fluid (SBF) at 37°C for 72 hours, followed by immersion in a cola bath for 60 seconds. Figure 9A shows that a portion of the CaP sheet covering the dentin tubules was removed by the cola bath. Figure 9B shows occluded tubules observed in the area where the CaP sheet was removed. The 5% PCS layer remained intact. Figure 9A has a magnification of 80x, and the scale bar is 500 microns. Figure 9B has a magnification of 800x, and the scale bar is 50 microns. Figure 9C has a magnification of 2,500x, and the scale bar is 20 microns. Figure 9C shows occluded tubules observed in the area where the CaP sheet was removed. 5% of the PCS layer remained intact. Figure 9A has a magnification of 80x, and the scale bar is 500 microns. Figure 9B has a magnification of 800x, and the scale bar is 50 microns. Figure 9C has a magnification of 2,500x, and the scale bar is 20 microns. [Figure 10]Figures 10A–10D are SEM micrographs showing PCS-induced calcification of dentin, with enhanced calcification appearing in the dentinal tubules. Molar samples were polished to expose smooth dentin, demineralized by limited acid etching, coated with 5% PCS, and incubated in distilled water or 1.5× simulated body fluid (SBF) at 37°C for 72 hours. The samples were then analyzed by SEM. A 10-micron bar is shown as a scale. Representative images were obtained from areas with low remineralization (Figure 10A), moderate remineralization (Figures 10B and 10C), and high remineralization (Figure 10D). The results suggest that remineralization appears to begin within the dentinal tubules. [Modes for carrying out the invention]

[0024] This disclosure provides a method for tooth rejuvenation, including the remineralization of tooth structure, such as the dentin. The method also provides protection of the tooth from environmental conditions that may cause damage or demineralization of the dentin. The method provided herein also provides improved mechanical and chemical resistance of the tooth structure and improved aesthetic appearance. Tooth rejuvenation is defined as a change in tooth structure that results in an increase in some or all of the following parameters: wear resistance (mechanical resistance), resistance to chemical and / or bacterial attack, and restoration and improvement of the appearance of the tooth and other improvements of the tooth. One embodiment of this disclosure is a method for tooth rejuvenation, including the application of a layer of catechol-styrene composition to the tooth. In one embodiment, the dentin of the tooth can be remineralized using a catechol-containing compound such as poly(catechol-styrene).

[0025] definition In this disclosure, the singular forms “a,” “an,” and “the” include multiple references, and references to specific numerical values ​​include at least that specific value unless otherwise explicitly indicated by the context. Thus, for example, a reference to “material” is a reference to at least one such material and their equivalents known to those skilled in the art.

[0026] In this disclosure, the term “Subject” includes any human or non-human animal. In certain embodiments, the Subject is a human or a non-human mammal. In certain embodiments, the Subject is a human.

[0027] When a value is expressed as an approximate value using the descriptors “approximately” or “substantially,” that particular value will be understood to form another embodiment. In general, the use of the terms “approximately” or “substantially” refers to an approximate value that may vary depending on the desired characteristic that the disclosed subject aims to achieve and should be interpreted on its function within the specific context in which it is used. Those skilled in the art will be able to interpret this as a matter of course. In some cases, the number of significant figures used for a particular value may be one non-limiting way of determining the degree of the words “approximately” or “substantially.” In other cases, the gradual change used in a set of values ​​may determine the intended range available for the terms “approximately” or “substantially” for each value. If any range exists, all ranges are inclusive and combinable; that is, a reference to a value stated in a range includes all values ​​within that range.

[0028] Where a list is presented, please understand that, unless otherwise stated, each individual element of that list and any combination of that list should be interpreted as a separate embodiment. For example, a list of embodiments presented as "A, B, or C" should be interpreted as including embodiments "A", "B", "C", "A or B", "A or C", "B or C", or "A, B, or C".

[0029] For clarity, it will be understood that certain features of the Disclosure described herein in the context of separate embodiments may be provided in combination in a single embodiment. That is, unless otherwise apparent and inconsistent, each individual embodiment is considered combinable with any other embodiment, and such combination is considered a separate embodiment. Conversely, various features of the Disclosure described in the context of a single embodiment for brevity may be provided separately or in any partial combination. It should be further noted that claims may be drafted to exclude any optional elements. Therefore, this passage is intended to serve as an antecedent for the use of exclusive terms such as “simply,” “only,” or “negative” limitations with respect to the detail of the claim components. Finally, embodiments may be described as part of a series of steps or as part of a more general structure, but each such step may also be considered an independent embodiment in itself.

[0030] Catechols can form a wide range of reversible bonds with surfaces, including hydrogen bonds, cation-π interactions, and metal ion complex formation. Catechols can also form covalent bonds with certain binding surfaces (e.g., protein surfaces) and can crosslink with themselves.

[0031] Catechol groups are readily oxidized to semiquinones or quinones. Several studies have demonstrated that oxidation significantly reduces their binding to inorganic surfaces. During the oxidation of catechol to quinone, reactive oxygen species (ROS) are generated as byproducts.

[0032] Strong bonding to inorganic surfaces requires catechol (reduced form), while quinone (oxidized form) can covalently bond to organic materials via Schiff base addition or Michael reaction. A biomimetic adhesive inspired by mussels can be considered a bifunctional "catechol-quinone" mixture.

[0033] The catechol-containing material of the present invention is used for remineralization of dentin.

[0034] In one embodiment, the present disclosure relates to a dentin remineralization process in which a catechol-containing material comprises a catechol-containing monomer, polymer, or oligomer, wherein the catechol exists as catechol and / or as semiquinone and / or quinone in the presence or absence of a primary or secondary amine, and the polymer layer also comprises a reactive material that does not react with catechol or quinone.

[0035] In one embodiment, the disclosure relates to a polymer layer comprising a catechol-containing monomer, polymer, or oligomer, wherein the catechol exists as catechol and / or as semiquinone and / or quinone in the absence of a primary or secondary amine, and the polymer layer optionally comprises a reactive material that does not react with catechol or quinone.

[0036] In some embodiments, the catechol-containing monomer, polymer, or oligomer in the polymer layer is a monomer. In some embodiments, the catechol-containing monomer, polymer, or oligomer in the polymer layer is an oligomer. In some embodiments, the catechol-containing monomer, polymer, or oligomer in the polymer layer is a polymer.

[0037] In some embodiments, the catechol-containing material comprises catechol or a reactive species separate from the catechol-containing material, the reactive species being acrylics such as 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BisGMA), ethoxylated bisphenol-A dimethacrylate (EBPADMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), tert-butylphenoxy BisGMA (MtBDMA), modified urethane dimethacrylate, amide-modified bisphenol-A, CH3BisGMA, acidic bisphenol-A dimethacrylate, alicyclic epoxide-derived dimethacrylate, aromatic urethane dimethacrylate, urethane-modified BisGMA, acidic aromatic dimethacrylate, oxydiphthalic acid dimethacrylate, phenyl dihydroxymethacrylate diphosphonate, acidic bisphenol-A dimethacrylate, morpholine carbonyl methacrylate, and phenyl carbonate methacrylate.

[0038] In some embodiments, the catechol-containing material includes a free radical polymerization initiator such as an acrylate polymerization initiator, which may be photoactivated, including benzoyl peroxide (BPO), 2,3-bornanedione (camphorquinone), ethyl-4-(dimethylamino)benzoate (EDMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (ODMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (TPO), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, or a combination thereof.

[0039] In some embodiments, the acrylate is an acrylate monomer comprising a vinyl group and at least one of a carboxylic acid ester and a carboxylic acid nitrile, and the acrylate is linear or branched. In some embodiments, the acrylate is ethyl acrylate, ethylene-methyl acrylate, methyl methacrylate, 2-chloroethyl vinyl ether, 2-hydroxyethyl acrylate, hydroxyethyl methacrylate, butyl acrylate, trimethylolpropane triacrylate (TMPTA), or a combination thereof.

[0040] In one embodiment, the catechol-containing material has a thickness of about 10 nanometers to about 100 microns. In some embodiments, the catechol-containing material has a thickness of about 15 nanometers to about 50 microns. In some embodiments, the remineralizing polymer layer has a thickness of about 15 nanometers to about 15 microns. In some embodiments, the remineralizing polymer layer has a thickness of about 150 nanometers to less than about 15 microns. In some embodiments, the remineralizing polymer layer has a thickness of about 150 nanometers to about 1.5 microns.

[0041] In some embodiments, the remineralizing polymer layer is approximately 10 nanometers to approximately 100 microns, or approximately 10 nanometers to approximately 100 nanometers, or approximately 100 nanometers to approximately 150 nanometers, or approximately 150 nanometers to approximately 200 nanometers, or approximately 200 nanometers to approximately 250 nanometers, or approximately 250 nanometers to approximately 300 nanometers, or approximately 300 nanometers to approximately 350 nanometers, or approximately 350 nanometers to approximately 400 nanometers, or approximately 400 nanometers to approximately 450 nanometers, or approximately 450 nanometers to approximately 500 nanometers. It has a thickness of meter, or approximately 500 nanometers to approximately 550 nanometers, or approximately 550 nanometers to approximately 600 nanometers, or approximately 600 nanometers to approximately 650 nanometers, or approximately 650 nanometers to approximately 700 nanometers, or approximately 700 nanometers to approximately 750 nanometers, or approximately 750 nanometers to approximately 800 nanometers, or approximately 800 nanometers to approximately 850 nanometers, or approximately 850 nanometers to approximately 900 nanometers, or approximately 900 nanometers to approximately 950 nanometers, or approximately 950 nanometers to approximately 1000 nanometers.

[0042] In some embodiments, the remineralizing polymer layer has a thickness of approximately 1 micron to approximately 1.5 microns, or approximately 1.5 microns to approximately 5 microns, or approximately 5 microns to approximately 10 microns, or approximately 10 microns to approximately 15 microns, or approximately 15 microns to approximately 20 microns, or approximately 20 microns to approximately 25 microns, or approximately 25 microns to approximately 30 microns, or approximately 30 microns to approximately 35 microns, or approximately 35 microns to approximately 40 microns, or approximately 40 microns to approximately 45 microns, or approximately 45 microns to approximately 50 microns, or approximately 50 microns to approximately 55 microns, or approximately 55 microns to approximately 60 microns, or approximately 60 microns to approximately 65 microns, or approximately 65 microns to approximately 70 microns, or approximately 70 microns to approximately 75 microns, or approximately 75 microns to approximately 80 microns, or approximately 80 microns to approximately 85 microns, or approximately 85 microns to approximately 90 microns, or approximately 90 microns to approximately 95 microns, or approximately 95 microns to approximately 100 microns.

[0043] In one embodiment, the catechol-containing monomer, polymer, or oligomer in the remineralizing polymer layer includes polycatecholstyrene (PCS).

[0044] In some embodiments, PCS is prepared in one or more suitable solvents. For example, PCS may be prepared as a solution in acetone, tert-butyl alcohol, ethanol, isopropyl alcohol, or a combination thereof, or one or more other suitable solvents understood in the art. In some embodiments, PCS is prepared as a solution in acetone. In some embodiments, PCS is prepared as a solution in tert-butyl alcohol. In some embodiments, PCS is prepared as a solution in isopropyl alcohol. In some embodiments, PCS is prepared as a solution in ethanol.

[0045] In some embodiments, the PCS comprises a solution containing approximately 0.001% to 10% PCS, approximately 0.05% to 5% PCS, approximately 0.01% to 2% PCS, approximately 0.5% to 1% PCS, approximately 0.1% to 0.5% PCS, and any and all increments in between. In some embodiments, the PCS comprises approximately 0.1% catechol.

[0046] In some embodiments, the PCS includes approximately 20% to approximately 22% catechol, or approximately 22% to approximately 24% catechol, or approximately 24% to approximately 26% catechol, or approximately 26% to approximately 28% catechol, or approximately 28% to approximately 30% catechol, or approximately 30% to approximately 32% catechol, or approximately 32% to approximately 34% catechol, or approximately 34% to approximately 36% catechol, or approximately 36% to approximately 38% catechol, or approximately 38% to approximately 40% catechol.

[0047] In some embodiments, the remineralizing polymer layer includes a reactive material that does not react with catechol or quinone. In some embodiments, the reactive material does not react with catechol or quinone at ambient temperature. In some embodiments, the reactive material does not react with catechol or quinone at low temperatures.

[0048] In some embodiments, the reactive material that does not react with catechol or quinone is a resin, oligomer, polymer, or monomer. In some embodiments, the reactive material is an oligomer. In some embodiments, the reactive material is a polymer. In some embodiments, the reactive material is a monomer.

[0049] In one embodiment, the remineralizing polymer layer is a continuous layer. In another embodiment, the remineralizing polymer layer is a discontinuous layer. In another embodiment, the remineralizing polymer layer is a patterned layer or a textured layer.

[0050] In some embodiments, the remineralizing polymer layer comprises one or more additives. In some embodiments, the one or more additives comprises one or more catalysts, for example, one or more photoinitiators. The one or more photoinitiators may include one or more of camphorquinone (CQ), azobisisobutyronitrile (AIBN), benzoyl peroxide, 2,2-dimethoxy-2-phenylacetophenone, and one or more combinations thereof. In some embodiments, the photoinitiator may include one or more additional photosensitizers or coinitiators, for example, one or more peroxides, aliphatic azo compounds, etc. In some embodiments, the catalyst, cocatalyst, or accelerator, and the catalyst, cocatalyst, or accelerator are acrylate catalysts or combinations thereof that promote the acrylate polymerization reaction.

[0051] In some embodiments, the photoinitiator is CQ. CQ can be used at concentrations of about 0.01% to about 1%, about 0.05% to about 0.75%, about 0.1% to about 0.5%, and any and all increments in between. In some embodiments, CQ is used at a concentration of 0.1%.

[0052] In some embodiments, the catechol-containing monomer, oligomer, or polymer includes PCS.

[0053] In some embodiments, the polymer layer on the dentin is applied as a solution. In some embodiments, the solution contains about 0.001% to about 10% by weight of a catechol-containing monomer, polymer, or oligomer. In some embodiments, the solution contains about 0.01% to about 5% by weight of a catechol-containing monomer, polymer, or oligomer. In some embodiments, the solution contains about 0.01% to about 1% by weight of a catechol-containing monomer, polymer, or oligomer. In some embodiments, the solution contains about 0.1% to about 1% by weight of a catechol-containing monomer, polymer, or oligomer.

[0054] In some embodiments, the solution contains about 0.001% to about 0.005% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.005% to about 0.01% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.01% to about 0.02% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.02% to about 0.03% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.03% to about 0.04% by weight of catechol-containing monomers, polymers, or oligomers. or oligomers, or about 0.04% to about 0.05% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.05% to about 0.06% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.06% to about 0.07% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.07% to about 0.08% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.08% to about 0.09% by weight of catechol-containing monomers, polymers, or oligomers Ligomers, or catechol-containing monomers, polymers, or oligomers in an amount of approximately 0.09% to approximately 0.1% by weight, or catechol-containing monomers, polymers, or oligomers in an amount of approximately 0.1% to approximately 0.11% by weight, or catechol-containing monomers, polymers, or oligomers in an amount of approximately 0.11% to approximately 0.12% by weight, or catechol-containing monomers, polymers, or oligomers in an amount of approximately 0.12% to approximately 0.13% by weight, or catechol-containing monomers, polymers, or oligomers in an amount of approximately 0.13% to approximately 0.14% by weight, or approximately 0.14% to approximately 0.15% by weight of catechol-containing monomers, polymers, or oligomers, or approximately 0.15% to approximately 0.2% by weight of catechol-containing monomers, polymers, or oligomers, or approximately 0.2% to approximately 0.25% by weight of catechol-containing monomers, polymers, or oligomers, or approximately 0.25% to approximately 0.3% by weight of catechol-containing monomers, polymers, or oligomers, or approximately 0.3% to approximately 0.35% by weight of catechol-containing monomers, polymers, or oligomers, or approximately 0.35% to approximately 0.It contains 4% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.4% to about 0.45% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.45% to about 0.5% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.5% to about 0.75% by weight of catechol-containing monomers, polymers, or oligomers, or about 0.75% to about 1% by weight of catechol-containing monomers, polymers, or oligomers, or about 1.25% to about 1.5% by weight of catechol-containing monomers, polymers, or oligomers, or about 1.5% to about 1.75% by weight of catechol-containing monomers, polymers, or oligomers, or about 1.75% to about 2% by weight of catechol-containing monomers, polymers, or oligomers.

[0055] In some embodiments, the catechol-containing monomer, polymer, or oligomer used in the solution is polycatecholstyrene (PCS). In some embodiments, the solution contains about 0.001% to about 10% by weight of PCS. In some embodiments, the solution contains about 0.01% to about 5% by weight of PCS. In some embodiments, the solution contains about 0.01% to about 1% by weight of PCS. In some embodiments, the solution contains about 0.1% to about 1% by weight of PCS.

[0056] In some embodiments, the solution contains approximately 0.001% to approximately 0.005% PCS by weight, or approximately 0.005% to approximately 0.01% PCS by weight, or approximately 0.01% to approximately 0.02% PCS by weight, or approximately 0.02% to approximately 0.03% PCS by weight, or approximately 0.03% to approximately 0.04% PCS by weight, or approximately 0.04% to approximately 0.05% PCS by weight, or approximately 0.05 PCS of weight % to approximately 0.06 weight %, or approximately 0.06 weight % to approximately 0.07 weight %, or approximately 0.07 weight % to approximately 0.08 weight %, or approximately 0.08 weight % to approximately 0.09 weight %, or approximately 0.09 weight % to approximately 0.1 weight %, or approximately 0.1 weight % to approximately 0.11 weight %, or approximately 0.11 weight % to approximately 0.12 weight %, or approximately 0.12 weight % PCS of approximately 0.13% by weight, or approximately 0.13% to approximately 0.14% by weight, or approximately 0.14% to approximately 0.15% by weight, or approximately 0.15% to approximately 0.2% by weight, or approximately 0.2% to approximately 0.25% by weight, or approximately 0.25% to approximately 0.3% by weight, or approximately 0.3% to approximately 0.35% by weight, or approximately 0.35% to approximately 0. Includes 4% by weight PCS, or approximately 0.4% to approximately 0.45% by weight PCS, or approximately 0.45% to approximately 0.5% by weight PCS, or approximately 0.5% to approximately 0.75% by weight PCS, or approximately 0.75% to approximately 1% by weight PCS, or approximately 1.25% to approximately 1.5% by weight PCS, or approximately 1.5% to approximately 1.75% by weight PCS, or approximately 1.75% to approximately 2% by weight PCS.

[0057] In some embodiments, the solution also includes an aqueous solvent or organic solvent for dissolving the catechol-containing monomer, polymer, or oligomer. In some embodiments, the organic solvent is acetone, tert-butyl alcohol, ethanol, isopropyl alcohol, or a combination thereof.

[0058] In some embodiments, the organic solvent is acetone. In some embodiments, the organic solvent is tert-butyl alcohol. In some embodiments, the organic solvent is ethanol. In some embodiments, the organic solvent is isopropyl alcohol. In some embodiments, the organic solvent is a combination of one or more of acetone, tert-butyl alcohol, ethanol, and isopropyl alcohol. In some embodiments, the organic solvent is acetone, and catechol or catechol-containing material is PCS. In some embodiments, the organic solvent is tert-butyl alcohol, and catechol or catechol-containing material is PCS. In some embodiments, the organic solvent is ethanol, and catechol or catechol-containing material is PCS. In some embodiments, the organic solvent is isopropyl alcohol, and catechol or catechol-containing material is PCS. In some embodiments, the organic solvent is a combination of one or more of acetone, tert-butyl alcohol, ethanol, and isopropyl alcohol, and catechol or catechol-containing material is PCS. In some embodiments, the organic solvent further comprises one or more oxidizing or acidifying agents. For example, in some embodiments, the organic solvent further comprises acetic acid.

[0059] The pH of the solution is not particularly limited. In some embodiments, the pH of the solution is about 3, or about 3.5, or about 4, or about 4.5, or about 5, or about 5.5, or about 6, or about 6.5, or about 7, or about 7.5, or about 8, or about 8.5, or about 9, or about 9.5, or about 10, or about 10.5, or about 11.

[0060] In some embodiments, the pH of the solution is approximately 3–3.5, or approximately 3.5–4, or approximately 4–4.5, or approximately 4.5–5, or approximately 5–5.5, or approximately 5.5–6, or approximately 6–6.5, or approximately 6.5–7, or approximately 7–7.5, or approximately 7.5–8, or approximately 8–8.5, or approximately 8.5–9, or approximately 9–9.5, or approximately 9.5–10, or approximately 10–10.5, or approximately 10.5–11.

[0061] method In certain embodiments, the Disclosure provides a method for remineralizing the dentin of a tooth by contacting one or more surfaces of the tooth with one or more catechol-containing materials as intended herein. One or more surfaces of the tooth may include the dentin of the tooth. The catechol-containing material may include one or more of catechol, semiquinone, or quinone. In some embodiments, the catechol or catechol-containing material is a PCS. The PCS can be applied in a solution containing about 0.001% to about 10% by weight of PCS. In some embodiments, the solution contains about 0.01% to about 5% by weight of PCS. In some embodiments, the solution contains about 0.01% to about 1% by weight of PCS. In some embodiments, the solution contains about 0.1% to about 1% by weight of PCS.In some embodiments, the solution is approximately 0.001% to approximately 0.005% by weight of PCS, or approximately 0.005% to approximately 0.01% by weight of PCS, or approximately 0.01% to approximately 0.02% by weight of PCS, or approximately 0.02% to approximately 0.03% by weight of PCS, or approximately 0.03% to approximately 0.04% by weight of PCS, or approximately 0.04% to approximately 0.05% by weight of PCS, or approximately 0.05% to approximately PCS of 0.06% by weight, or PCS of approximately 0.06% to approximately 0.07% by weight, or PCS of approximately 0.07% to approximately 0.08% by weight, or PCS of approximately 0.08% to approximately 0.09% by weight, or PCS of approximately 0.09% to approximately 0.1% by weight, or PCS of approximately 0.1% to approximately 0.11% by weight, or PCS of approximately 0.11% to approximately 0.12% by weight, or PCS of approximately 0.12% to approximately 0.13% by weight PCS, or PCS of approximately 0.13% to approximately 0.14% by weight, or PCS of approximately 0.14% to approximately 0.15% by weight, or PCS of approximately 0.15% to approximately 0.2% by weight, or PCS of approximately 0.2% to approximately 0.25% by weight, or PCS of approximately 0.25% to approximately 0.3% by weight, or PCS of approximately 0.3% to approximately 0.35% by weight, or PCS of approximately 0.35% to approximately 0.4% by weight, or approximately 0.4 PCS in amounts of % to approximately 0.45 wt%, or approximately 0.45 wt% to approximately 0.5 wt%, or approximately 0.5 wt% to approximately 0.75 wt%, or approximately 0.75 wt% to approximately 1 wt%, or approximately 1.25 wt% to approximately 1.5 wt%, or approximately 1.5 wt% to approximately 1.75 wt%, or approximately 1.75 wt% to approximately 2 wt% (including any and all increments between these). PCS can be applied in solutions containing approximately 1 wt% to approximately 3 wt%, approximately 2 wt% to approximately 5 wt%, approximately 3 wt% to approximately 7 wt%, approximately 4 wt% to approximately 10 wt%, and any and all increments between these.

[0062] The tooth surface may include tooth surfaces that have undergone acid etching. The tooth surface may also include tooth surfaces that have not undergone acid etching. Acid etching may include acid etching using an acid such as phosphoric acid. Acid etching may include acid etching using an acid weaker than phosphoric acid, such as maleic acid or polyacrylic acid.

[0063] In certain embodiments, the Disclosure provides a method for treating tooth hypersensitivity in a subject, comprising contacting exposed dentin tubules with a catechol-containing material comprising catechol, semiquinone, or quinone. The catechol-containing material may include PCS. The PCS may be applied in a solution containing about 0.001% to about 10% by weight of PCS. In some embodiments, the solution contains about 0.01% to about 5% by weight of PCS. In some embodiments, the solution contains about 0.01% to about 1% by weight of PCS. In some embodiments, the solution contains about 0.1% to about 1% by weight of PCS. In some embodiments, the solution contains approximately 0.001% to approximately 0.005% PCS by weight, or approximately 0.005% to approximately 0.01% PCS by weight, or approximately 0.01% to approximately 0.02% PCS by weight, or approximately 0.02% to approximately 0.03% PCS by weight, or approximately 0.03% to approximately 0.04% PCS by weight, or approximately 0.04% to approximately 0.05% PCS by weight, or approximately 0.05 PCS of weight % to approximately 0.06 weight %, or approximately 0.06 weight % to approximately 0.07 weight %, or approximately 0.07 weight % to approximately 0.08 weight %, or approximately 0.08 weight % to approximately 0.09 weight %, or approximately 0.09 weight % to approximately 0.1 weight %, or approximately 0.1 weight % to approximately 0.11 weight %, or approximately 0.11 weight % to approximately 0.12 weight %, or approximately 0.12 weight % PCS of approximately 0.13% by weight, or approximately 0.13% to approximately 0.14% by weight, or approximately 0.14% to approximately 0.15% by weight, or approximately 0.15% to approximately 0.2% by weight, or approximately 0.2% to approximately 0.25% by weight, or approximately 0.25% to approximately 0.3% by weight, or approximately 0.3% to approximately 0.35% by weight, or approximately 0.35% to approximately 0. Includes 4% by weight PCS, or approximately 0.4% to approximately 0.45% by weight PCS, or approximately 0.45% to approximately 0.5% by weight PCS, or approximately 0.5% to approximately 0.75% by weight PCS, or approximately 0.75% to approximately 1% by weight PCS, or approximately 1.25% to approximately 1.5% by weight PCS, or approximately 1.5% to approximately 1.75% by weight PCS, or approximately 1.75% to approximately 2% by weight PCS.

[0064] manner The following embodiments are illustrative and not intended to limit the scope of the present disclosure or the appended claims. Any part(s) of any one or more embodiments may be combined with any part(s) of any one or more other embodiments.

[0065] Embodiment 1: A method for remineralizing the dentin of a tooth, comprising contacting the dentin of the tooth with a catechol-containing material containing one or more of catechol, semiquinone, or quinone.

[0066] Embodiment 2: The method according to Embodiment 1, wherein the catechol-containing material comprises monomer, oligomer, or polymer catechol or catechol-containing material, wherein the catechol exists as catechol and / or as semiquinone and / or quinone in the absence of an amine, and the polymer layer optionally comprises at least one of a) a reactive species separate from the catechol or catechol-containing material, and b) a catalyst, co-catalyst, or accelerator.

[0067] Embodiment 3: The method according to Embodiment 2, wherein the catechol-containing material comprises the catechol or a reactive species separate from the catechol-containing material, and the reactive species comprises acrylic, silane, silicone, methacrylate, polyvinyl alcohol (PVA), urethane, or a combination thereof.

[0068] Embodiment 4: The catechol-containing material contains the catechol or a reactive species separate from the catechol-containing material, wherein the reactive species is 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BisGMA), ethoxylated bisphenol-A dimethacrylate (EBPADMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), tert-butylphenoxyBisGMA (MtBDMA), modified urethane dimethacrylate The method according to embodiment 3, wherein the acrylic is relate, amide-modified bisphenol-A, CH3BisGMA, acidic bisphenol-A dimethacrylate, alicyclic epoxide-derived dimethacrylate, aromatic urethane dimethacrylate, urethane-modified BisGMA, acidic aromatic dimethacrylate, oxydiphthalic acid dimethacrylate, phenyl dihydroxymethacrylate diphosphonate, acidic bisphenol-A dimethacrylate, morpholine carbonyl methacrylate, phenyl carbonate methacrylate, and other acrylics.

[0069] Embodiment 5: The method according to Embodiment 1, further comprising a free radical polymerization initiator such as an acrylate polymerization initiator, which includes photoactivatable substances such as benzoyl peroxide (BPO), 2,3-bornanedione (camphorquinone), ethyl-4-(dimethylamino)benzoate (EDMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (ODMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (TPO), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, or a combination thereof.

[0070] Embodiment 6: The method according to Embodiment 3, wherein the reactive species is the acrylate.

[0071] Embodiment 7: The method according to Embodiment 1, wherein the catechol-containing material is placed on the dentin of a tooth.

[0072] Embodiment 8: The method according to Embodiment 1, wherein the catechol-containing material has a thickness of about 10 nanometers to about 500 microns.

[0073] Embodiment 9: The method according to Embodiment 1, wherein the catechol-containing material comprises about 0.1% poly(catechol-styrene) (PCS).

[0074] Embodiment 10: The method according to Embodiment 1, wherein the catechol-containing material contains PCS in an amount ranging from about 0.1% to about 10%.

[0075] Embodiment 11: The method according to Embodiment 1, wherein the catechol-containing material comprises at least partially oxidized PCS.

[0076] Embodiment 12: The method according to Embodiment 1, wherein the catechol-containing material comprises at least partially reduced PCS.

[0077] Embodiment 13: The method according to Embodiment 1, wherein the catechol-containing material comprises at least one material having a partially intermediate oxidation state.

[0078] Embodiment 14: A method for treating tooth hypersensitivity in a subject, comprising contacting exposed dentinal tubules with catechol, semiquinone, or a catechol-containing material containing quinone.

[0079] Embodiment 15: The method according to Embodiment 14, wherein the catechol-containing material comprises monomer, oligomer, or polymer catechol or catechol-containing material, wherein the catechol exists as catechol and / or as semiquinone and / or quinone in the absence of an amine, and the polymer layer optionally comprises at least one of a) a reactive species separate from the catechol or catechol-containing material, and b) a catalyst, co-catalyst, or accelerator.

[0080] Embodiment 16: The method according to Embodiment 15, wherein the catechol-containing material comprises the catechol or a reactive species separate from the catechol-containing material, and the reactive species comprises acrylic, silane, silicone, methacrylate, polyvinyl alcohol (PVA), or a combination thereof.

[0081] Embodiment 17: The catechol-containing material contains the catechol or a reactive species separate from the catechol-containing material, wherein the reactive species is 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BisGMA), ethoxylated bisphenol-A dimethacrylate (EBPADMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), tert-butylphenoxyBisGMA (MtBDMA), modified urethane dimethacrylate The method according to embodiment 16, wherein the acrylic is rilate, amide-modified bisphenol-A, CH3BisGMA, acidic bisphenol-A dimethacrylate, alicyclic epoxide-derived dimethacrylate, aromatic urethane dimethacrylate, urethane-modified BisGMA, acidic aromatic dimethacrylate, oxydiphthalic acid dimethacrylate, phenyl dihydroxymethacrylate diphosphonate, acidic bisphenol-A dimethacrylate, morpholine carbonyl methacrylate, phenyl carbonate methacrylate, etc.

[0082] Embodiment 18: The method according to Embodiment 14, further comprising a free radical polymerization initiator such as an acrylate polymerization initiator, which includes photoactivatable substances such as benzoyl peroxide (BPO), 2,3-bornanedione (camphorquinone), ethyl-4-(dimethylamino)benzoate (EDMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (ODMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (TPO), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, or a combination thereof.

[0083] Embodiment 19: The method according to Embodiment 16, wherein the reactive species is the acrylate.

[0084] Embodiment 20: The method according to Embodiment 14, wherein the catechol-containing material is placed on the dentin of a tooth.

[0085] Embodiment 21: The method according to Embodiment 14, wherein the catechol-containing material has a thickness of about 10 nanometers to about 500 microns.

[0086] Embodiment 22: The method according to Embodiment 14, wherein the catechol-containing material contains about 0.1% poly(catechol-styrene) (PCS).

[0087] Embodiment 23: The method according to Embodiment 14, wherein the catechol-containing material contains PCS in an amount ranging from about 0.1% to about 10%.

[0088] Embodiment 24: The method according to Embodiment 14, wherein the catechol-containing material comprises at least partially oxidized PCS.

[0089] Embodiment 25: The method according to Embodiment 14, wherein the catechol-containing material comprises at least partially reduced PCS.

[0090] Embodiment 26: The method according to Embodiment 14, wherein the catechol-containing material comprises at least one material having a partially intermediate oxidation state.

[0091] Embodiment 27: A method for restoring acid-etched tooth dentin in a subject, comprising contacting the tooth dentin with catechol, semiquinone, or a catechol-containing material containing quinone.

[0092] Embodiment 28: The method according to Embodiment 27, wherein the catechol-containing material comprises monomer, oligomer, or polymer catechol or catechol-containing material, wherein the catechol exists as catechol and / or as semiquinone and / or quinone in the absence of an amine, and the polymer layer optionally comprises at least one of a) a reactive species separate from the catechol or catechol-containing material, and b) a catalyst, co-catalyst, or accelerator.

[0093] Embodiment 29: The method according to Embodiment 28, wherein the catechol-containing material comprises the catechol or a reactive species separate from the catechol-containing material, and the reactive species comprises acrylic, silane, silicone, methacrylate, polyvinyl alcohol (PVA), or a combination thereof.

[0094] Embodiment 30: The catechol-containing material contains the catechol or a reactive species separate from the catechol-containing material, wherein the reactive species is 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BisGMA), ethoxylated bisphenol-A dimethacrylate (EBPADMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), tert-butylphenoxyBisGMA (MtBDMA), modified urethane dimethacrylate The method according to embodiment 29, wherein the acrylic is rilate, amide-modified bisphenol-A, CH3BisGMA, acidic bisphenol-A dimethacrylate, alicyclic epoxide-derived dimethacrylate, aromatic urethane dimethacrylate, urethane-modified BisGMA, acidic aromatic dimethacrylate, oxydiphthalic acid dimethacrylate, phenyl dihydroxymethacrylate diphosphonate, acidic bisphenol-A dimethacrylate, morpholine carbonyl methacrylate, phenyl carbonate methacrylate, and other acrylics.

[0095] Embodiment 31: The method according to Embodiment 27, further comprising a free radical polymerization initiator such as an acrylate polymerization initiator, which includes photoactivatable substances such as benzoyl peroxide (BPO), 2,3-bornanedione (camphorquinone), ethyl-4-(dimethylamino)benzoate (EDMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (ODMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (TPO), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, or combinations thereof.

[0096] Embodiment 32: The method according to Embodiment 29, wherein the reactive species is the acrylate.

[0097] Embodiment 33: The method according to Embodiment 27, wherein the catechol-containing material is placed on the dentin of a tooth.

[0098] Embodiment 34: The method according to Embodiment 27, wherein the catechol-containing material has a thickness of about 10 nanometers to about 500 microns.

[0099] Embodiment 35: The method according to Embodiment 27, wherein the catechol-containing material contains about 0.1% poly(catechol-styrene) (PCS).

[0100] Embodiment 36: The method according to Embodiment 27, wherein the catechol-containing material contains PCS in an amount ranging from about 0.1% to about 10%.

[0101] Embodiment 37: The method according to Embodiment 27, wherein the catechol-containing material comprises at least partially oxidized PCS.

[0102] Embodiment 38: The method according to Embodiment 27, wherein the catechol-containing material comprises at least partially reduced PCS.

[0103] Embodiment 39: The method according to Embodiment 27, wherein the catechol-containing material comprises at least one material having a partially intermediate oxidation state. [Examples]

[0104] Example 1: PCS-induced calcification on aluminum A simple aluminum substrate was used to determine whether poly(catechol-styrene) promotes CaP formation under physiological conditions. The aluminum was cleaned, coated with a thin layer of 10% PCS(w / v), immersed in 1.5× simulated body fluid (SBF), and incubated at 37°C for 14 days. A white crystalline substance was observed on the aluminum within 24 hours (data not shown). Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) (Figures 3A-3D) revealed that the induction layer was calcium phosphate (CaP).

[0105] Example 2: PCS-induced calcification of dentin To determine whether PCS can induce CaP formation on demineralized dentin, extracted molars were obtained from dental clinics, cleaned, and stored in chloramine T at 4°C. The teeth were embedded in resin and polished with 600-grit silicon carbide paper to obtain smooth dentin. They were then acid-etched with 40% phosphate gel for 2 minutes, rinsed in diH2O, coated with PCS (5% in acetone), and incubated in 1.5×SBF at 37°C for 3 days. The samples were dried, sputter-coated, and analyzed by SEM and EDS (Figures 4A-4F). The results showed PCS-induced formation of a CaP sheet covering the exposed dentin. This sheet had a Ca / P ratio of 1.63, close to the expected value for hydroxyapatite (HA). High-magnification SEM showed the crystalline morphology (Figure 5). While not constrained by theory, endogenous HA may have acted as a template for calcification. Dentinal tubules were observed to contain nucleation sites from which CaP grew outward in uniform layers, coalescing to form sheets. Interestingly, stripes (linear patterns in Figure 4C) were observed. PCS may selectively adhere to proteins distributed in this striped pattern. These proteins may be rich in Cys (free-SH) and / or Lys (free-NH2), in which case oxidized PCS covalently binds to them.

[0106] Meanwhile, earlier studies were conducted using 5% or 10% PCS in acetone. We decided to determine whether calcification could be achieved with a smaller amount of PCS. Therefore, we performed similar experiments using 0.1% PCS in acetone. The results shown in Figures 6A and 6B show that when treated with a 0.1% PCS thin film, we can see the growth of large CaP sheets on the dentin surface. The CaP fuses together to form large sheets. These micrographs show that even 0.1% PCS is sufficient to generate large calcified CaP sheets on the dentin surface.

[0107] Example 3: Resistance of PSC to chemical and physical attack Remineralization after re-acid etching To determine whether PCS provides protection against chemical attack, the growth pattern of calcium phosphate (CaP) after a second acid etching of dentin samples was evaluated. Briefly, samples were acid-etched, a 1% PCS thin film was applied, and immersed in 1.5 × SBF for 72 hours. As shown in Figure 7B, CaP sheet growth was observed. The samples were then re-acid-etched. After re-acid etching, some residual CaP remained on the surface (Figure 7C). However, the tubules were exposed, indicating that the acid etching had partially destroyed the polymer coating. The samples were then re-immersed in 1.5 × SBF for 72 hours. As shown in Figure 7D, even though some of the PCS coating had been destroyed by acid etching, a larger amount of CaP sheet growth was observed on the 1% PCS-treated surface. All acid etching was performed using 40% phosphate gel for 2 minutes.

[0108] Furthermore, even if a portion of the CaP sheet is destroyed by acid treatment, the results shown in Figures 9A-9C confirm that the dentinal tubules are indeed occluded by the CaP sheet. This result provides strong evidence for the use of PCS for the treatment of dentin hypersensitivity caused by exposure of dentinal tubules.

[0109] Remineralization without acid etching It is standard practice to acid-wash or acid-etch the tooth surface before dental procedures in order to prepare and / or clean the surface. Often, the acid-wash or acid-preparation step is necessary for certain detail adhesives or dental procedures to interact properly with the tooth surface. Phosphoric acid is often used as the first-choice acid. However, patients with tooth hypersensitivity may not be able to tolerate acids as strong as phosphoric acid, in which case weaker acids such as maleic acid or polyacrylic acid may be used. The above experiment was performed following acid etching with a strong acid, which is a standard practice. However, to determine whether remineralization by PCS requires acid etching, CaP formation was evaluated in the absence of acid etching. Thus, SEM images of the dentin surface were obtained without acid etching. The results shown in Figures 8A and 8B show that the entire dentin surface was covered with a CaP sheet without the need for acid etching.

[0110] Example 4: Remineralization Pattern Localization of remineralization To evaluate the calcification pattern, different regions of CaP sheets formed after treatment with 5% PCS were assessed at 1,250x magnification. The resulting images, shown in Figures 10A–10D, indicate remineralization, which appears to begin within the dentinal tubules and continue to spread from these sites to form the sheet. These results provide support for the use of PCS in the treatment of dentin hypersensitivity.

Claims

1. A method for remineralizing tooth dentin, comprising contacting the tooth dentin with a catechol-containing material comprising one or more of catechol, semiquinone, or quinone.

2. The method according to claim 1, wherein the catechol-containing material comprises monomer, oligomer, or polymer catechol or catechol-containing material, wherein the catechol exists as catechol and / or as semiquinone and / or quinone in the absence of an amine, and the polymer layer optionally comprises at least one of a) a reactive species separate from the catechol or catechol-containing material, and b) a catalyst, co-catalyst, or accelerator.

3. The method according to claim 2, wherein the catechol-containing material comprises the catechol or a reactive species separate from the catechol-containing material, and the reactive species comprises acrylic, silane, silicone, methacrylate, polyvinyl alcohol (PVA), urethane, or a combination thereof.

4. The catechol-containing material comprises the catechol or a reactive species separate from the catechol-containing material, wherein the reactive species is 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BisGMA), ethoxylated bisphenol-A dimethacrylate (EBPADMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDDMA), tert-butylphenoxyBisGMA (MtBDMA), modified urethane dimethacrylate The method according to claim 3, wherein the acrylic is such as amide-modified bisphenol-A, CH3BisGMA, acidic bisphenol-A dimethacrylate, alicyclic epoxide-derived dimethacrylate, aromatic urethane dimethacrylate, urethane-modified BisGMA, acidic aromatic dimethacrylate, oxydiphthalic acid dimethacrylate, phenyl dihydroxymethacrylate diphosphonate, acidic bisphenol-A dimethacrylate, morpholine carbonyl methacrylate, or phenyl carbonate methacrylate.

5. The method according to claim 1, further comprising a free radical polymerization initiator such as an acrylate polymerization initiator, which includes photoactivatable substances such as benzoyl peroxide (BPO), 2,3-bornanedione (camphorquinone), ethyl-4-(dimethylamino)benzoate (EDMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (ODMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (TPO), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, or a combination thereof.

6. The method according to claim 3, wherein the reactive species is an acrylate.

7. The method according to claim 1, wherein the catechol-containing material is placed on the dentin of a tooth.

8. The method according to claim 1, wherein the catechol-containing material has a thickness of about 10 nanometers to about 500 microns.

9. The method according to claim 1, wherein the catechol-containing material comprises about 0.1% poly(catechol-styrene) (PCS).

10. The method according to claim 1, wherein the catechol-containing material contains PCS in an amount ranging from about 0.1% to about 10%.

11. The method according to claim 1, wherein the catechol-containing material comprises at least partially oxidized PCS.

12. The method according to claim 1, wherein the catechol-containing material comprises at least partially reduced PCS.

13. The method according to claim 1, wherein the catechol-containing material comprises at least one material having a partially intermediate oxidation state.

14. A method for treating tooth hypersensitivity in a subject, comprising contacting exposed dentinal tubules with catechol, semiquinone, or a catechol-containing material containing quinone.

15. The method according to claim 14, wherein the catechol-containing material comprises monomer, oligomer, or polymer catechol or catechol-containing material, wherein the catechol exists as catechol and / or as semiquinone and / or quinone in the absence of an amine, and the polymer layer optionally comprises at least one of a) a reactive species separate from the catechol or catechol-containing material, and b) a catalyst, co-catalyst, or accelerator.

16. The method according to claim 15, wherein the catechol-containing material comprises the catechol or a reactive species separate from the catechol-containing material, and the reactive species comprises acrylic, silane, silicone, methacrylate, polyvinyl alcohol (PVA), or a combination thereof.

17. The catechol-containing material comprises the catechol or a reactive species separate from the catechol-containing material, wherein the reactive species is 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BisGMA), ethoxylated bisphenol-A dimethacrylate (EBPADMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), tert-butylphenoxyBisGMA (MtBDMA), modified urethane dimethacrylate The method according to claim 16, wherein the acrylic is an amide-modified bisphenol-A, CH3BisGMA, acidic bisphenol-A dimethacrylate, alicyclic epoxide-derived dimethacrylate, aromatic urethane dimethacrylate, urethane-modified BisGMA, acidic aromatic dimethacrylate, oxydiphthalic acid dimethacrylate, phenyl dihydroxymethacrylate diphosphonate, acidic bisphenol-A dimethacrylate, morpholine carbonyl methacrylate, phenyl carbonate methacrylate, etc.

18. The method according to claim 14, further comprising a free radical polymerization initiator such as an acrylate polymerization initiator, which includes photoactivatable substances such as benzoyl peroxide (BPO), 2,3-bornanedione (camphorquinone), ethyl-4-(dimethylamino)benzoate (EDMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (ODMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (TPO), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, or a combination thereof.

19. The method according to claim 16, wherein the reactive species is an acrylate.

20. The method according to claim 14, wherein the catechol-containing material is placed on the dentin of a tooth.

21. The method according to claim 14, wherein the catechol-containing material has a thickness of about 10 nanometers to about 500 microns.

22. The method according to claim 14, wherein the catechol-containing material comprises about 0.1% poly(catechol-styrene) (PCS).

23. The method according to claim 14, wherein the catechol-containing material contains PCS in an amount ranging from about 0.1% to about 10%.

24. The method according to claim 14, wherein the catechol-containing material comprises at least partially oxidized PCS.

25. The method according to claim 14, wherein the catechol-containing material comprises at least partially reduced PCS.

26. The method according to claim 14, wherein the catechol-containing material comprises at least one material having a partially intermediate oxidation state.

27. A method for restoring acid-etched tooth dentin in a subject, comprising contacting the tooth dentin with catechol, semiquinone, or a catechol-containing material containing quinone.

28. The method according to claim 27, wherein the catechol-containing material comprises monomer, oligomer, or polymer catechol or catechol-containing material, wherein the catechol exists as catechol and / or as semiquinone and / or quinone in the absence of an amine, and the polymer layer optionally comprises at least one of a) a reactive species separate from the catechol or catechol-containing material, and b) a catalyst, co-catalyst, or accelerator.

29. The method according to claim 28, wherein the catechol-containing material comprises the catechol or a reactive species separate from the catechol-containing material, and the reactive species comprises acrylic, silane, silicone, methacrylate, polyvinyl alcohol (PVA), or a combination thereof.

30. The catechol-containing material comprises the catechol or a reactive species separate from the catechol-containing material, wherein the reactive species is 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BisGMA), ethoxylated bisphenol-A dimethacrylate (EBPADMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), tert-butylphenoxyBisGMA (MtBDMA), modified urethane dimethacrylate The method according to claim 29, wherein the acrylic is an amide-modified bisphenol-A, CH3BisGMA, acidic bisphenol-A dimethacrylate, alicyclic epoxide-derived dimethacrylate, aromatic urethane dimethacrylate, urethane-modified BisGMA, acidic aromatic dimethacrylate, oxydiphthalic acid dimethacrylate, phenyl dihydroxymethacrylate diphosphonate, acidic bisphenol-A dimethacrylate, morpholine carbonyl methacrylate, phenyl carbonate methacrylate, etc.

31. The method according to claim 27, further comprising a free radical polymerization initiator such as an acrylate polymerization initiator, which includes photoactivatable substances such as benzoyl peroxide (BPO), 2,3-bornanedione (camphorquinone), ethyl-4-(dimethylamino)benzoate (EDMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (ODMAB), 2-(ethylhexyl)-4-(dimethylamino)benzoate (TPO), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, or a combination thereof.

32. The method according to claim 29, wherein the reactive species is an acrylate.

33. The method according to claim 27, wherein the catechol-containing material is placed on the dentin of a tooth.

34. The method according to claim 27, wherein the catechol-containing material has a thickness of about 10 nanometers to about 500 microns.

35. The method according to claim 27, wherein the catechol-containing material comprises about 0.1% poly(catechol-styrene) (PCS).

36. The method according to claim 27, wherein the catechol-containing material contains PCS in an amount ranging from about 0.1% to about 10%.

37. The method according to claim 27, wherein the catechol-containing material comprises at least partially oxidized PCS.

38. The method according to claim 27, wherein the catechol-containing material comprises at least partially reduced PCS.

39. The method according to claim 27, wherein the catechol-containing material comprises at least one material having a partially intermediate oxidation state.

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