Probing the neutralization behavior of zwitterionic monomer-containing dental adhesive

Graphical abstract


  • Dental adhesive containing zwitterionic monomer shows tuning neutralization rate.

  • Resin exhibits faster photo-polymerization rate and higher conversion simultaneously.

  • Polymer shows improved neutralization rate without compromised mechanical properties.



To investigate the polymerization kinetics, neutralization behavior, and mechanical properties of amine-functionalized dental adhesive cured in the presence of zwitterionic monomer, methacryloyloxyethyl phosphorylcholine (MPC).


The control adhesive was a mixture based on HEMA/BisGMA/2- N -morpholinoethyl methacrylate (MEMA) (40/30/30, w/w/w). The control and experimental formulations containing MPC were characterized with regard to water miscibility of liquid resins, photopolymerization kinetics, water sorption and solubility, dynamic mechanical properties and leachables from the polymers (aged in ethanol). The neutralization behavior of the adhesives was determined by monitoring the pH of lactic acid (LA) solution.


The water miscibility decreased with increasing MPC amount. The water sorption of experimental copolymer specimen was greater than the control. The addition of 8 wt% water led to improved photo-polymerization efficiency for experimental formulations at MPC of 2.5 and 5 wt%, and significant reduction in the cumulative amounts of leached HEMA, BisGMA, and MEMA, i.e. 90, 60 and 50% reduction, respectively. The neutralization rate of MPC-containing adhesive was faster than control. The optimal MPC concentration in the formulations was 5 wt%.


Incompatibility between MEMA and MPC led to a decrease in water miscibility of the liquid resins. Water (at 8 wt%) in the MPC-containing formulations (2.5–5 wt% MPC) led to higher DC, faster <SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='RPmax’>RmaxPRPmax
R P max
and significant reduction in leached HEMA, BisGMA, and MEMA. The neutralization rate was enhanced with the addition of MPC in the amine-containing formulation. Promoting the neutralization capability of dentin adhesives could play an important role in reducing recurrent decay at the composite/tooth interface.


Resin-based composite is rapidly becoming the most popular dental restorative material and with the global emphasis on the elimination of dental amalgam, it is anticipated that the popularity of composite will continue to increase . In spite of its popularity, clinical studies report a failure rate for composite restorations that is double to triple that of amalgam . NIDCR points to an average lifespan of 6–7 years for dental composites and patients at highest risk for decay are particularly susceptible to early failure .

Since composite is too viscous to bond directly to the tooth, a low viscosity adhesive is used to form the bond between the tooth and composite. Acid-etching provides effective mechanical bonding between enamel and adhesive, but bonding to dentin has been fraught with problems. There are a variety of intrinsic and extrinsic factors that lead to acute and chronic degradation of the adhesive bond to dentin . These factors include host-derived enzymes, e.g. matrix metalloproteinases (MMPs) that degrade exposed collagen at the adhesive/dentin (a/d) interface ; oral fluids, bacterial and salivary enzymes degrade the adhesive ; cariogenic and aciduric bacteria demineralize the tooth structure and the inability of the material to increase the local pH facilitates the outgrowth of more aciduric and cariogenic bacteria . It is anticipated that the outgrowth of more aciduric and cariogenic bacteria would lead to increased acid production at the adhesive/dentin (a/d) interface. The acid could infiltrate the a/d interface―provoking demineralization of the tooth structure and potentially, degradation of the adhesive.

The primary reason that amalgam and composite restorations fail is recurrent caries, i.e. carious lesions on the margins of existing restorations, but the risk of recurrent caries is 3.5 times greater for composite . Recurrent decay is most often localized at the gingival margin of Class II composite restorations and is linked to failure of the bond between the tooth and composite and increased levels of the cariogenic bacterium, Streptococcus mutans , at the perimeter of these materials . At the vulnerable gingival margin, the adhesive is often the primary barrier between the prepared tooth and surrounding environment . Degradation of the adhesive at the gingival margin leads to gaps at the composite/tooth interface―these gaps will be infiltrated by oral fluids, enzymes and bacteria. The infiltration of these noxious agents at the interface between the composite material and tooth structure will ultimately lead to failure of the restoration.

A dentin adhesive that is capable of neutralizing the acid in this local environment could mitigate the damage associated with oral fluid infiltration. It could play an important role in maintaining the integrity of the a/d bond and the seal at the composite/tooth interface. Reports of increased levels of the cariogenic bacterium, S. mutans and the observation that the inability of the material to increase the local pH facilitates the outgrowth of more aciduric and cariogenic bacteria highlight the need for materials that could buffer the pH at the microenvironment of the composite/tooth interface . Thus, a dental adhesive that is capable of neutralizing the acid could play an important role in reducing recurrent decay at the vulnerable gingival margin.

The potential of amine-containing dental adhesives to provide buffering as well as the required physical and mechanical properties has been investigated recently . Due to the highly crosslinked network structures, the neutralization rate for the bulk polymer was relatively slow, i.e. 4–8 weeks were required to reach neutral pH . While these results are promising, the slow rate of neutralization may offer limited benefit under in vivo conditions.

The biocompatible, hydrophilic zwitterionic monomer, e.g. 2-methacryloyloxyethyl phosphorylcholine (MPC), has been used to create protein-repellent surfaces . To date, there has been limited investigation of MPC as a co-monomer for dental adhesive development . The lack of attention may be related, in part, to the limitations of the zwitterionic functional groups―these groups can bind water molecules more strongly than other hydrophilic monomers via electrostatically induced hydration . The addition of zwitterionic monomer led to adhesive materials with remarkably improved hydrophilicity and strong protein-repellent capability. The bond strength between adhesive and dentin was not compromised with lower MPC concentration in the adhesive formulations .

In previous studies from our group , tertiary amine-functionalized dental adhesive copolymers showed neutralization capabilities in lactic acid solution but, due to the highly crosslinked network structures, the neutralization rate was relatively slow. Understanding the relationship between neutralization kinetics and the crosslinked network is necessary for the development of dental adhesives that can offer buffering of the interfacial micro-environment while also providing the required physicochemical and mechanical properties. The objectives of this study were to investigate the neutralization behavior of dental adhesive incorporating both amine monomer and zwitterionic monomer, MPC. The study tested the hypotheses that incorporating MPC into the amine-containing dental adhesive would: (1) improve the water compatibility; (2) accelerate the rate of neutralization; and (3) not significantly decrease the mechanical properties under wet conditions.

Materials and methods


2,2-Bis[4-(2-hydroxy-3-methacryloxypropoxy) phenyl]propane (BisGMA), 2-hydroxyethyl methacrylate (HEMA), 2- N -morpholinoethyl methacrylate (MEMA), and 2-methacryloyloxyethyl phosphorylcholine (MPC) were obtained from Sigma-Aldrich (St. Louis, MO) and used as received without further purification as monomers. Camphoroquinone (CQ), ethyl-4-(dimethylamino) benzoate (EDMAB), diphenyliodonium hexafluorophosphate (DPIHP), and l (+)-lactic acid (LA) were obtained from Sigma-Aldrich (St. Louis, MO). All other chemicals were reagent grade and used without further purification.

Preparation of adhesive formulations

HEMA/BisGMA/MEMA (40/30/30, w/w/w) was used as the control (HBM). The formulations consisting of HEMA, BisGMA, MEMA, and MPC are noted as experimental and listed in Table 1 . CQ (0.5 wt%), EDMAB (0.5 wt%), and DPIHP (0.5 wt%) were used as a three-component photoinitiator system, with respect to the total amount of monomers. Mixtures of monomers/photoinitiators are prepared in a brown glass vial under amber light as reported previously .

Table 1
Formulations of the neat resin and water-containing adhesives, and evaluation of their photo-polymerization behaviors.
Run HEMA (%) BisGMA (%) MEMA (%) MPC (%) D 2 O (%) DC of C C (%) <SPAN role=presentation tabIndex=0 id=MathJax-Element-2-Frame class=MathJax style="POSITION: relative" data-mathml='Rpmax[M]’>Rmaxp[M]Rpmax[M]
R p max [ M ]
× 100 (1/s)
Neat resin HBM 40 30 30 77.3 (0.1) 12.07 (0.64)
MPC-2.5 37.5 30 30 2.5 75.9 * (0.2) 13.39 (0.88)
MPC-5 35 30 30 5 74.3 * (0.2) 14.32 * (0.01)
MPC-10 30 30 30 10 72.6 * (0.1) 16.93 * (0.42)
Water-containing HBM-W 36.8 27.6 27.6 8 80.0 (0.6) 11.34 (0.08)
MPC-2.5-W 34.5 27.6 27.6 2.3 8 81.1 (0.6) 16.70 # (0.36)
MPC-5-W 32.2 27.6 27.6 4.6 8 83.5 # (0.3) 17.40 # (0.69)
MPC-10-W 27.6 27.6 27.6 9.2 8 79.9 (0.9) 15.14 # (0.81)

* Significantly ( p < 0.05) different from the HBM formulation.

# Significantly ( p < 0.05) different from the HBM-W formulation. The value in the () is the standard deviation.

Water miscibility and viscosity of adhesive formulations

The procedure for determining water miscibility of adhesive formulations has been reported . In brief, about 0.5 g neat resin was weighed into a brown vial and water was added in increments of ∼0.005 g until the mixture was visually observed to be turbid. The percentage of water in the mixture was noted (w 1 ). The mixture was then back-titrated using the neat resin until the turbidity disappeared and the percentage of water in the mixture was noted (w 2 ). The water miscibility (W wm , %) of the liquid formulation was calculated as the average of w 1 and w 2 . Three specimens of each formulation were measured. The viscosities of the liquid resin formulated with or without water were carried out in a Brookfield DV-II+Pro viscometer (Brookfield Engineering Laboratories, Middleborough, MA) at varying shear rate from 112.5 to 165 s −1 . The sample volume was 0.5 mL and each formulation was measured three times.

Real-time conversion and maximum polymerization rate

The degree of conversion (DC) and polymerization kinetic behavior were determined by real-time FTIR as described previously . The spectra were obtained by an infrared spectrometer (Spectrum 400 Fourier transform infrared spectrophotometer, Perkin-Elmer, Waltham, MA), equipped with an attenuated total reflectance (ATR) accessory (PIKE Technologies Gladi-ATR, Madison, WI) at a resolution of 4 cm −1 . A time-based spectrum collector (Spectrum TimeBase, Perkin-Elmer) was used for continuous and automatic collection of spectra during polymerization. A minimum of three measurements (n = 3) were carried out for each adhesive formulation. Methacrylic double bond conversion was monitored by the band ratio profile-1637 cm −1 (C C)/1608 cm −1 (phenyl). The average of the last 50 values of the time-based spectra is reported as the DC value. The maximum polymerization rate ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-3-Frame class=MathJax style="POSITION: relative" data-mathml='Rpmax/[M]’>Rmaxp/[M]Rpmax/[M]
R p max / [ M ]
) was determined using the maximum slope of the linear region of the DC vs. time plots .

Specimens preparation

The rectangular beam specimens were prepared by injecting the prepared resin into a glass-tubing mold (Fiber Optic Center, Inc., part no.: ST8100, New Bedford, MA). Disc specimens were prepared by injecting the resin into a standard aluminum hermetic lid (Tzero ® , P/N:901600.901) and covering them with a mylar film to prevent oxygen exposure. The specimens were light-cured for 40 s at 23 ± 2 °C with an LED light curing unit (LED Curebox, 100 mW/cm 2 irradiance, Proto-tech, Portland, OR). The polymerized rectangular and disc specimens were stored in the dark at 23 ± 2 °C for at least 48 h before testing. The resultant rectangular beam specimens of cross section 1 mm × 1 mm and length 15 mm were used to determine water sorption and dynamic mechanical analysis. The disc specimens were used to study the neutralization behavior.

Water sorption and solubility of copolymer

The experimental protocol for the water sorption analyses has been reported . In brief, water sorption and solubility were measured using rectangular beam specimens (1 mm × 1 mm × 15 mm). Five specimens were prepared for each adhesive formulation. Samples were weighed (m 1 ) with a calibrated electronic balance (resolution of 0.01 mg, Mettler Toledo, XS 205 Dual range, Columbus, OH) and immersed in distilled water to prewash for 7 days at 37 °C. Following the 7-day prewash, the specimens were dried in a vacuum oven in the presence of freshly dried silica gel at 37 °C; the specimens were removed every 24 h to determine the weight. This process was continued until a constant mass (m 2 ) was recorded for each beam specimen. After prewashing, the dried specimens were immersed in distilled water and at fixed time intervals, they were removed, blotted to remove excess water, weighed (m 3 ) and returned to the water until a constant weight was obtained. The values (%) for water sorption (W sp ) and solubility (W su ) were calculated by the following equations:

<SPAN role=presentation tabIndex=0 id=MathJax-Element-4-Frame class=MathJax style="POSITION: relative" data-mathml='Wsp=m3−m2m2×100%’>Wsp=m3m2m2×100%Wsp=m3−m2m2×100%
W s p = m 3 − m 2 m 2 × 100 %
<SPAN role=presentation tabIndex=0 id=MathJax-Element-5-Frame class=MathJax style="POSITION: relative" data-mathml='Wsu=m1−m2m1×100%’>Wsu=m1m2m1×100%Wsu=m1−m2m1×100%
W s u = m 1 − m 2 m 1 × 100 %
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Nov 22, 2017 | Posted by in Dental Materials | Comments Off on Probing the neutralization behavior of zwitterionic monomer-containing dental adhesive
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