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Biomineralization: The Next Step in Restorative Dentistry

John C. Comisi, DDS, MAGD

April 28, 2017 Course - Expires Thursday, April 30th, 2020

Updates in Clinical Dentistry


While significant advances in resin-based sciences have occurred over a number of decades, problems with composite restorations, such as recurrent decay and fracture, have continued to materialize. Bioactive materials are those that deliver minerals beneficial to tooth structure, stimulating mineralization and formation of chemical bonds that help seal the tooth and prevent microleakage. Use of such materials, which are capable of apatite creation at the restorative–tooth interface, is an approach that can potentially enhance the longevity and durability of composite restorations. In dentistry’s efforts to overcome the challenges of resin-bonded adhesives, a change in methodology toward use of biomineralization may be warranted.

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For more than a century the dental profession has endeavored to successfully achieve the restoration of tooth structure after it has been damaged by dental caries or trauma. Many solutions have been proposed and used, yet there remains a constant yearning to find something better. During his time at the Eastman Dental Dispensary (now the Eastman Institute for Oral Health) in Rochester, New York, Dr. Michael Buonocore published a paper in 1955 titled, “A Simple Method of Increasing the Adhesion of Acrylic Filling Materials to Enamel Surfaces,”1 in which he proposed the use of an acid-etch technique to enable the adherence of acrylic fillings to the tooth surface. His paper emphasized that “A filling material capable of forming strong bonds to tooth structures would offer many advantages over present ones. With such a material, there would be no need for retention and resistance form in cavity preparation, and effective sealing of pits, fissures, and beginning carious lesions could be realized.” Thus, the dawn of adhesive dentistry was ushered in.

Hybridization and Composite Restorations

Several years later, Dr. Ray Bowen noted that there was a need to improve the restorative materials of that time so that they would have less solubility and sensitivity to desiccation and brittleness and provide greater dimensional stability.2 His proposal gave rise to what are now known as composites. The ability to effectively coat silica and bind it to bisphenol A-glycidyl methacrylate (bis-GMA) opened up new possibilities for durable long-lasting restorations. Later, Nakabayashi3 advanced this idea by proposing that a mechanism was available for enhancing adhesion by infiltrating resin monomers into dentinal tubules and thereby creating what is now known as the hybrid layer. This process of “tissue engineering” was a breakthrough and a tremendous advancement of the foundational work of Buonocore and Bowen. However, as Pashley pointed out, the relatively low bond strengths of early dentin bonding agents obtained on acid-etched dentin led to the development of dentin bonding systems that were applied directly on smear layers.4

As the years passed, new generations of resin bonding adhesion systems were developed to attempt to overcome the shortcomings of each previous generation. Different particle fillers were added to the resins of the composite materials and simpler forms of dental adhesives were developed. However, even as advances in resin-based sciences have occurred, problems have continued to compound. With the failure rate of composite restorations being double that of amalgam5 combined with the increasing trend to replace amalgam with composite, the overall effect could be detrimental to patients.6 The dental literature strongly urges a “call to action” regarding this trend from amalgam to composite, and it is imperative that clinicians understand fully why change is needed in the way restorative care is currently being provided to patients.7

Ferracane has identified some of the fundamental reasons for this failure; he illustrated that current research and development in the arena of resin-bonded composites has primarily focused on resin and filler modification. The principle reason for failure, he noted, is recurrent decay, with a secondary reason being fracture of composite restorations. The “most popular” formulations, he also indicated, are significantly weaker and less fracture-resistant than those produced in the 1970s and 1980s, before the push to minimize particle size occurred.”5

One reason why secondary decay is the primary source of composite restoration failure is that the adhesive–dentin interface is a weak link in these restorations. Bacterial enzymes, oral fluids, and the bacteria themselves penetrate the crevices created between the tooth and the composite, undermining the restoration and leading to recurrent decay and premature failure.8 Second, the traditional composite restoration is passive and typically does not provide any type of protection for the tooth. The concept of a passive restoration may at one time have been postulated to be essential so as not to cause interactions with the oral environment. However, this passiveness has been shown to lead to a higher susceptibility of composites to secondary caries.9 This passiveness allows for the accumulation of a high concentration of biofilm on the composite surfaces.6 Lastly, recent studies have indicated that the acids in oral biofilm affect the bond strength of adhesive materials.10 Additionally, when considering the current preponderant promotion and use of universal bonding agents it must be noted that though these newer adhesives feature increased versatility, they do not necessarily possess the technological advances for overcoming the challenges associated with the previous generations of adhesives. Therapeutic adhesives with bioprotective and biopromoting effects are still lacking in commercialized adhesives.11

Moisture, of course, is ubiquitous in the oral cavity, and yet restorative materials require clinicians to “dry” the tooth prior to restoring it with resin-bonded composites. This task is never really achievable, because, as Chow and Vogel explained in 2001, the enamel of the tooth is a “semipermeable membrane” with a constant flow of fluids coming outwards from the pulp.12 The odontoblasts have been shown to be dentin-secreting cells that survive the whole life of a healthy tooth and are critically involved in transmission of sensory stimuli from the dentin–pulp complex and the cellular defense against pathogens.13

Chaussin-Miller et al further reiterated this in 200614 in a paper on matrix metalloproteinases (MMPs), in which the authors explained how the role of these enzymes found in dentin and secreted by odontoblasts is to protect the tooth against the advancing acid attack of dental decay. However, since acids are used in bonding procedures, these same MMPs become activated and attack and degrade the hybrid layer formed by traditional bonding agents in the restorative process due to the presence of water. Among the many articles over the years that have reiterated this fact, it has been suggested that “if all exposed collagen fibrils were enveloped by resin then MMPs would not have free access to water, an obligatory requirement for these enzymes” to activate.15 However, in the hybridization process of dentin bonding, there is no realistic way to make this happen. Water is always present in the oral cavity and the teeth. Even when a tooth is desiccated, moisture will soon return, coming from the dental pulp–odontoblast complex.

Hence, the goal of achieving an ideal collagen network–infused hybrid layer that will provide a durable and continuous link between the dental adhesive and the dentin is never fully reached. Subsequently, the major mechanisms involved in deterioration of the water-rich, resin-sparse collagen fibrils in the hybrid layer lead to hydrolysis of the adhesive and, ultimately, failure of the restoration.6

In Mazzoni et al’s article titled, “Role of Dentin MMPs in Caries Progression and Bond Stability,”16 the authors state, “These endogenous enzymes also remain entrapped within the hybrid layer during the resin infiltration process, and the acidic bonding agents themselves (irrespective of whether they are etch and rinse or self etch) can activate these endogenous protease proforms.” Because impregnation of resin into dentin is frequently incomplete,17 these exposed and denuded dentin collagen matrices become exposed to free water, are enzymatically disrupted, and ultimately contribute to degradation of the hybrid layer and resin restoration failure.

Discussion on the use of anti-MMP agents and cross-linking agents to help overcome degradation of the hybrid layer is ongoing. A 2015 review18 found that although many possible agents are available there are disadvantages in their use, because each agent requires an extra step in its application, each has varying degrees of effectiveness, and, finally, they can lose the ability to stop enzymatic degradation over time.

Bioactivity and Biomineralization

The concept of bioactive materials was first introduced in 1969 and later defined as: “a bioactive material that elicits a specific biological response at the interface of the material which results in the formation of a bond between tissues and the material.”19 Jefferies developed this further, defining a bioactive material as one that forms a surface layer of an apatite-like material in the presence of saliva or a saliva substitute.20 Bioactive materials deliver minerals that are beneficial to the tooth structure, stimulating mineralization and formation of chemical bonds that help to seal the tooth and prevent microleakage.21 They are active materials, not passive, play a dynamic role, and perform favorably in the oral environment. They can reduce sensitivity,22 marginal leakage, and marginal caries23 and can be less technique sensitive.24

Glass-ionomer cements (GICs) have been used in dentistry because of their ability to form an ionic bond to tooth structure and for their fluoride-releasing and recharging properties. The calcium fluouroalumino silicate glass and polyacrylic acid mixture enables the chemical fusion and adhesion to tooth structure via the transfer of the ions contained in the glass. ten Cate25 proposed that the caries-preventive effects of fluoride released from GIC materials is mainly attributed to the effects of demineralization/remineralization at the tooth–oral fluids interface, and that sub part-per-million levels of fluoride are effective in shifting the balance from a demineralization to a remineralization process. However, he also stated that low levels of fluoride are ineffective in interfering with the growth and metabolism of bacteria and do not significantly reduce dissolution of tooth mineral as a result of fluoride incorporation.

Numerous other indirect reports of artificial caries remineralization can be found in the literature. However, a 2010 study by Kim et al challenges this issue. They examined strontium-based GIC to determine if demineralized dentin could be completely remineralized by nucleation of new apatite crystallites within an apatite-free dentin matrix.26 The study assessed specimens processed by transmission electron microscopy (TEM) and found that no apatite deposition could be identified in completely demineralized dentin that was immersed in three types of remineralization media, even with TEM/energy-dispersive x-ray (EDX) evidence of diffusion ions specific to the GIC material tested.

Jefferies et al21 also showed that GICs cannot close the gap between tooth and restorative material nor form apatite. Their research did, however, illustrate that materials such as calcium aluminate and calcium silicate have the ability to close the artificial gap created in their study and form apatite. The 50-µm control gap used in the study showed that calcium-based bioactive dental cements could seal or reseal artificially created gaps in simulated aqueous physiological conditions. This is clinically significant and suggests that these types of calcium-containing bioactive materials are capable of significantly improving the marginal stability of the tooth–restorative material interface and could significantly improve the long-term survival and serviceability of dental restorations.

Biomineralization is defined as how living organisms secrete inorganic materials in an organized manner.27 It is how the formation, structure, and properties of inorganic solids are deposited in biological systems. This occurs via the selective extraction and uptake of elements from the local environment and their incorporation into functional structures under strict biologic control. The formation of biologic apatite is also a biologically controlled process that entails precise ionic properties and appropriate crystalline size to enable this biomineralization process to occur.

In a study of the interaction between bioactive glass and collagen, Hench and Greenspan noted 40-nm gaps between the ends of tropocollagen subunits (approximately equal to the gap region), which they postulated serve as nucleation sites for the deposition of the hydroxyapatite mineral components.28 To further expand on this, Sauro and Pashley’s paper in 2016 states that, “if any Ca/P crystals are larger then 40 nm they may not ‘fit’ into demineralized collagen…the most recent research suggests that amorphous (non-crystalline) calcium phosphate (ACP) enters collagen fibril in a biomimetically stabilized ‘fluidic’ state.”29

Zhang et al determined that it is possible to prefabricate intermediate precursors of calcium phosphate (poly[acrylic] acid stabilized ACP solution [Pa-ACP])–loaded amine functionalized mesoporous silica nanoparticles (AF-MSNs) and enable intrafibrillar remineralization. This proof of concept study represented an important advance in the translation of biomineralization concepts into regimes for in situ remineralization of bone and teeth.30

Abuna et al illustrated that the use of biomimetic analogs of dentin phosphoproteins (poly[acrylic] acid) and/or sodium trimetaphosphate, in combination with resin-based materials that can release ionized calcium and phosphate ions in a neutral to alkaline water-rich environment, could induce intrafibrillar collagen remineralization.31 Their research illustrated that if demineralized dentin is covered with a flowable resin composite containing ACP, and immersed in biomimetic polyanions that can slowly diffuse through any water-filled porosities within adhesives and hybrid layers (ie, residual water in uninfiltrated dentin), it would be possible to “back-fill” such defects with apatite crystals and fossilize all dentin proteases as the matrix collagen remineralizes. This approach decreased nanoleakage and showed phosphate uptake and deposition of needle-like crystallites at the intrafibrillar level.


Thus, how can practitioners translate this science into clinical applications? Currently, there are actually several bioactive materials for use in clinical dentistry that act as the Jefferies definition stipulates,20 materials that in the presence of saliva or saliva substitutes demonstrate the creation of apatite at the restorative–tooth interface. This requires the material to be hydrophilic to allow water to pass through it while simultaneously maintaining its physical properties. If there is no apatite formation, then the material is not bioactive. This, the author believes, is the approach that has the best chance of enhancing longevity and durability in the restorative process.

Hybridization and conventional composite restorations, as described here and in the literature as discussed throughout, show shorter durability than intended or desired. The preponderance of multiple generations of resin adhesives and the various additives proposed to overcome the challenges of resin-bonded adhesives lead to conclusions that a change in methodology and direction is presently warranted.


The formation of a crystalline structure at the restorative–dentin interface is highly attractive as a means of overcoming the challenges manifested in dentistry’s current resin-bonded adhesives and composite restorations. Materials for restoration of the dentition must possess appropriate physical properties to withstand the hostile forces of the oral cavity and the essential ability to enable the tooth to “breath” in the oral environment so that a so-called “heal and seal” effect can be created. This would be the creation of a bioactive–biomineralizing interface that is able to allow Ca/P ion release to “feed” the mineral-starved tooth structure and enable and create appropriate biologic biomimetic remineralization processes, so that the elastic modulus, structure, and hardness of collagen fibrils can be completely recovered.


John C. Comisi, DDS, MAGD
Private Practice, Ithaca, New York


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2. Bowen RL. Properties of silica-reinforced polymer for dental restorations. J Am Dent Assoc. 1963;66:57-64.

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21. Jefferies SR, Fuller AE, Boston DW. Preliminary evidence that bioactive cements occlude artificial marginal gaps. J Esthet Restor Dent. 2015;27(3):155-166.

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31. Abuna G, Feitosa VP, Correra AB, et al. Bonding performance of experimental bioactive/biomimetic self-etch adhesives doped with calcium-phosphate fillers and biomimetic analogs of phosphoproteins. J Dent. 2016;52:79-86.

COST: $0
PROVIDER: Dental Learning Systems, LLC
SOURCE: Updates in Clinical Dentistry | April 2017

Learning Objectives:

  • Discuss the history and development of composite restorations and adhesive bonding agents.
  • Explain reasons for composite restoration failures and why changes are needed in the way restorative care is provided.
  • Describe the concept of bioactive materials and how their development and usage can enhance longevity and durability in the restorative process.


The author had no disclosures to report.

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