SVOA Dentistry

ISSN:2753-9172

Review Article

Bioactive Materials in Restorative Dentistry: A Literature Review

Luis Gabriel Ladino1*, Alejandra Bernal2, Daniel Calderón3 and Diego Cortés4

Affiliation:

1Associate Professor, Postgraduate Program in Prosthodontics, Institución Universitaria Colegios de Colombia (UNICOC). Bogotá, Colombia
2Department of Prosthodontics, Institución Universitaria Colegios de Colombia (UNICOC), Bogotá, Colombia
3Department of Prosthodontics, Institución Universitaria Colegios de Colombia (UNICOC), Bogotá, Colombia
4Department of Prosthodontics, Institución Universitaria Colegios de Colombia (UNICOC), Bogotá, Colombia
*Corresponding Author: Luis Gabriel Ladino, Department of Prosthodontics, Institución Universitaria Colegios de Colombia (UNICOC), Bogotá, Colombia.
orcid.org/0000-0002-1849-8594

Received: February 25, 2021 Published: March 10, 2021

Abstract:
Bioactive materials have had a great impact on restorative dentistry, favoring the longevity of restorations, cell stimula-
tion for dentin repair, increasing adhesive resistance, and reducing the recurrence of cavities and bacterial microfiltra-
tion. Treatment with bioactive materials has covered various fields in restorative dentistry, generating direct interac-
tions are the substrate and remineralization by initiating precipitation and ion exchange that allow the development of a
hydroxyapatite layer favoring the dental remineralization process. Its antimicrobial action has an impact on the protec-
tion of recurrent cavities and bacterial microfiltration. Besides, interdigitation with the collagen mesh and apatite crys-
tallization in the dentinal tubules favors the treatment of tooth sensitivity. This article provides a review of the charac-
teristics of bioactive materials used in restorative dentistry.

Keywords: Dental Materials, Bioceramics, Bioactive Materials, Remineralization

Introduction
Currently, there is a change in the behavior of dental materials, going from being passive biomaterials without having a
positive or negative reaction in the body to having constant bioactivity with a positive and expected reaction, causing
cellular stimulation or antimicrobial activity1. With the advances established in the late 1960s in the second generation
of biomaterials and the research of Dr. Hench in bone regeneration and the introduction of bioactive glasses, various
compounds that generate bioactivity have been implemented in various areas of dentistry 2. Bioactivity in dentistry de-
pends on its clinical applicability, they can be defined as “a material that forms a surface layer of a material similar to
apatite in the presence of an inorganic phosphate solution” 3. They can also be defined as those materials capable of
inducing a desired tissue response of the host 4. Bioactive materials have evolved in their composition and have been
used in various fields of medicine and dentistry (in bone regeneration, coating of implants, bactericidal and bacterio-
static in caries processes, cavity bases, dental sensitivity, remineralization of enamel and dentin, dental adhesives, en-
dodontic perforation repair, pulp capping, root canal disinfection, endodontic sealants) 5.

1. Evolution of Bioactive Materials

The purpose of tissue bioengineering is to accelerate the regeneration and repair of affected tissues, in this way science
produces and increases new therapies and/or develops new biomaterials that restore, improve, or prevent the deterio-
ration of the function of compromised tissues6.

Dental materials have a passive or active interaction with the surrounding tissues 7. Bioactive materials have recently
appeared, which are all those that promote a biological response at the interface of the material and the tissue, generat-
ing a union between them8. In general, bioactive materials have been shown to promote the release of calcium, sodium,
silica, and phosphate ions, which produce an effect such as angiogenesis and antimicrobial activity 6.

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Osteogenic properties in bone defects have been reported since the 1920s with the use of calcium phosphate or
“tricalcium phosphate”, being one of the first biominerals used in the field of medicine; in the same decade, calcium hy-
droxide was used as a bioactive agent as a promoter in the formation of a dentinal bridge on the exposed pulp tissue,
since then it has been the “gold standard” of pulp capping9.

In 1950 the word biomimetic was cited by the biomedical and biophysical engineer Otto Schmitt referring to the study
of multidisciplinary and biological mechanisms of products that imitate nature; the word biomimetic derives from the
Latin "Bio" which means life and "mimetic" which is related to the imitation of the biomechanical process inspired by
nature. Understanding the biomimetic approach involves the concept of multiple ideas from biochemistry, materials
science, and bioengineering. In clinical dentistry, the term refers to the repair of the affected dentition by imitating the
characteristics of a natural tooth in terms of appearance, biomechanics, and function 10.

The first generation of biomaterials had the characteristic of being bio-inert, they did not generate any or little response
to the tissue where they are used, they were limited to simulating the mechanical characteristics of the surrounding tis-
sue11.

In the 1960s, Wilson and Kent, seeking to improve the properties of zinc polyalkeonate cement, introduced glass iono-
mer (GI), with anticariogenic properties because of the release of fluoride, direct bonding to the tooth structure, low
coefficient of thermal expansion, similar to the tooth structure and low cytotoxicity, with “active” and biomimetic char-
acteristics 7,10. Since then, several modifications have been introduced in order to improve its mechanical properties.
The introduction of resin-modified glass ionomers (RMGI) with superior mechanical strength, were used for posterior
restorations. Besides, the new generations of glass ionomers maintain the desirable characteristics of conventional ones
such as fluoride release, ion exchange, adhesion enamel, and dentin, and low filtration 12.

Larry L. Hench in 1969 developed a material that precipitates hydroxyapatite in aqueous solutions with the ability to
bind to hard and soft tissues that, unlike bio-inert materials, was not encapsulated in fibrous tissue10. Thus, he intro-
duced the term bioactive glass composed of silicate glasses which he called “Bioglass 45S5” acting on the surrounding
tissues without generating a response such as foreign body, toxicity, or inflammation 13.

The second generation of bioactive materials sought to provoke a specific and controlled action in a biological environ-
ment11.

The third generation started in the 1990s, it focused on the processes of tissue regeneration including cell adhesion,
proliferation, differentiation through the activation of specific genes. At the University of Melbourne in Australia, a com-
pound was developed that mixes casein phosphopeptides in a solution of phosphate and calcium salts (CPP-ACP) capa-
ble of forming an amorphous crystal of calcium phosphate, having anti-cariogenic properties by adhering to the biofilm
and release ions under acidic conditions6.

In the late 1990s, the Mineral Trioxide Aggregate (MTA) developed by Lee in association with Loma Linda University
became commercially available. Septodont in 2008, developed a material based on the purification of calcium silicate
(Biodentine®), with better setting time, mechanical properties, and handling. In 2010, the Bisco company launched the
resin-modified calcium silicate known as (RMCS) or by its trade name TheraCal LC® 14.

This is how in recent years biomimetic approaches have been generated to develop dental materials with nanoparticles
that have remineralizing, regenerative, and antimicrobial capacities such as mouth rinses, toothpaste, composites, bioc-
eramics, bonding materials (adhesives), dentin substitute materials, and dental cement 15.

2. Mechanisms of action of bioactive materials.

Hench classifies bioactive materials into two groups: a) in which bioactivity leads to induction and production as a con-
sequence of the rapid surface reaction of the material; Furthermore, it induces an intracellular and extracellular re-
sponse, generating the binding of the material to hard tissue and soft tissue b) in which only conduction occurs due to a
slower surface reaction that only induces extracellular response16.

The oral cavity has a dynamic and complex environment in which restorative materials and dental tissues are exposed
to a wide range of variations in terms of pH, temperature, microorganisms, and nutrients; dental tissues are in constant
ionic exchange of fluorine, calcium, phosphate, generating a balance thanks to the regulatory role of saliva 17.

3. Classification

We can then classify the action of bioactive materials in dentistry depending on their intervention with the tissues.

Restorative

The incorporation of bioactive agents induces the mineralization of the collagen mesh and the fossilization of metallo-
proteinases, playing a protective therapeutic role from dental restorations 18.

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The hydrolysis of the adhesive interface between dental tissue and the bonding agent of the restorative material is a
predominant factor in longevity in restorative dentistry; with the exposure of the collagen mesh during demineraliza-
tion, interdigitation is favored and the bond strength between the dental substrate and the restorative material increas-
es, but captesin k proteases are activated, which are matrix metalloproteinases (MMPs) that degrade the adhesive inter-
face19. The remineralization process can induce a reduction in the enzymatic degradation given by proteases. To do this,
bioactive glasses have the potential to release silicon and fluorine that generate a structural change by having a chelat-
ing action with Ca2 + and Zn2 +, capable of inhibiting the action of metalloproteinases (MMPs) cathepsin K, preserving
the integrity of the mesh collagen within the hybrid layer 20.

The incorporation of bioactive fillers in the restorative materials induces the formation of apatite crystals, thus generat-
ing a bond by interdigitation directly proportional to the exposure time between the bioactive glasses and the collagen
mesh of demineralized dentin, and saliva plays an important role in the release of phosphate, calcium and silica ions
showing a direct correlation between the ability to form apatite induced by bioactive glass and adhesion to dentin, pene-
trating deep into the dentinal tubules, generating an entanglement that increases adhesive strength 10,16. The interfacial
layer of apatite, due to the deposition and formation within the dentin tubules that are at a depth of 270 µm, allows the
presence of bioactive glass to be beneficial in the interfaces of adhesive restorations, improving the interface between
dentin and the restorative substrate, reducing the microgaps21.

Remineralize

Remineralization is defined as the gain of calcified material in the dental structure that replaces that previously lost by
demineralization and that is generated by acids and a decrease in the pH of bacterial metabolism that generate the exit
of ions from the dental tissue22.

Bioactive materials play a fundamental role in remineralization processes thanks to ionic exchange, generating super-
saturation of the fluids that lead to ionic precipitation in demineralized tissues and the formation of amorphous calcium
phosphate with the growth of hydroxyapatite crystals, not only of the extra fibrillar collagen mesh but also improves the
mechanical properties of the intra fibrillar network, besides, emulating the histomorphology of the dental substrate 13.

Khoroushi et al. compared the flexural strength of demineralized and non-demineralized dentin bars in interaction with
resin-modified glass ionomer and with resin-modified glass ionomer with a composition of 20% bioactive glass, im-
mersed in a saliva solution artificial, demonstrating that demineralization and immersion conditions have an effect on
the biomechanical behavior of demineralized dentin. In this same condition, it was also observed that the flexural re-
sistance values were higher for ionomers modified with resin with bioactive glasses compared to ionomers without the
addition of bioactive components7. The high concentration of calcium ions close to the interface of the material favors
the precipitation and nucleation of calcium phosphate, improving the remineralizing capacity of the ionomers, but af-
fecting the microhardness of the material by acting as fillers that united to the ionomer matrix 23.

There is a similar behavior with the addition of bioactive to composites; Although it does not affect the degree of poly-
meric conversion, a reduction in mechanical properties has been observed with increasing content by volume; present-
ing a lack of cohesion between the composite conglomerate and the bioactive filler 24.

New bioactive glass compositions have been developed to promote and improve bioactivity, the addition of calcium ox-
ide is essential in the first step of the formation of hydroxyapatite due to an exchange of hydrogen ions, bioactive glass
compositions created with calcium and silica oxide were shown to improve mechanical resistance and better minerali-
zation ability and lower surface roughness1. The addition of fluorine to the bioactive glass maintains the polymerization
of the silicate network, the connectivity of the structure, and the bioactivity of the bioactive glass, resulting in the for-
mation of fluorapatite (FAP), important due to the resistance of the substrate in acidic media, lower solubility compared
to hydroxyapatite, and it is more chemically stable than hydroxyapatite or carbonated hydroxyapatite, favoring enamel
remineralization in initial caries lesions; It increases the mechanical properties, the mineral content, the recovery of
mineral volume, It presents a covering with a layer of crystals and produces ultra-structural changes20,25. At the dentin
level, the formation of an apatite layer achieves a decrease in the degree of decalcification during the mineralization pro-
cess, promoting an increase in the mineral matrix and the appearance of a new interface indicating a chemical interac-
tion, significantly decreasing the values of the roughness of the tissue, the deposition in the tubules with obliteration by
the apatite precipitation increasing the percentage of tubular occlusion, reducing the permeability of the dentin and gen-
erating a barrier against bacterial microfiltration and, therefore, preventing pulpal inflammation 1,25.

Desensitizing

Bioactive glasses have been accepted as mineralizing agents as well as desensitizing agents in the treatment of dental
hypersensitivity caused by the opening of the dentinal tubules8. Bioactive glass reacts with artificial saliva to form apa-
tite hydroxycarbonate crystals within collagen fibers that are equivalent to the mineral phase of human hard tissues 14.

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These deposits occlude the dentinal tubules, due to its physical-chemical behavior, which makes it a candidate material
for dental remineralization and desensitization processes, causing an increase in calcium and phosphate on the surface
of dental enamel; The term “remineralization” should be used when the mineral components come from the exterior of
the enamel, that is, from the calcium and phosphate contained in saliva 7,8.

The remineralization process induced by bioactive glasses is probably due to a simultaneous bioactive phenomenon
characterized by the release of silica and a subsequent polycondensation reaction induced by the precipitation of calci-
um and phosphate on the organic matrix creating a base for the formation of calcium phosphate 26.

A study by Ubaldini et al. devalued the effects of bioglass45S5 and biosilicate in the remineralization process after a den-
tal whitening process, found an increase in the mineral content of the samples, and additionally the adhesion strength
was increased after treatment with bioglass27.

Antibacterial

The components of these materials have the ability to generate an alkaline medium, with a pH between 8 and 9 that fa-
vors bacterial inhibition, reducing the formation of secondary caries thanks to the Zn ions that bind to the proteins of
the microorganisms generating structural changes in the membrane inducing cell lysis 18.

The incorporation of Methacryloxydodecylpyridinium (MDPB) monomers creates a long-lasting antibacterial effect and
does not compromise mechanical properties such as strength and biocompatibility; These monomers depend on quater-
nary ammonium to show antibacterial activities and have a bactericidal effect on a wide range of microorganisms pro-
duced by the breakdown of the bilipid layer and subsequent death of these microorganisms. 28

The MDPB monomer can be copolymerized and covalently bound in the resin matrix, becoming a long-lasting immobi-
lized agent and in contact against oral bacteria, it has antibacterial activity against S. Mutans, Lactobacillus Casei, and
Actinomyces Naeslundi, it is capable of eradicating residual bacteria from the interior of dentinal tubules of prepared
dental cavities29.

4. Bioactive materials in restorative dentistry.

A bioactive material must be biocompatible, sterile, not soluble or resorbable, Bactericidal, bacteriostatic, maintain pulp
vitality, stimulate reparative dentin, with adhesive properties, radiopaque, resistant to compression and traction, inter-
act with a moist environment, and easy to handle14. Ideally, restorative materials should mimic the tissues, facilitate the
distribution of forces during the masticatory function, emulate the hardness of the tissues, not generate allergic or cyto-
toxic reactions, and generate a positive response in the surrounding tissues10. Bioactive materials cover a great variety
within preventive and restorative dentistry30,31.

Composite Resin

Composite resins can generate bioactivity by modifying their organic phase by adhering antibacterial monomers or by
adding bioactive fillers, generating an antibacterial and remineralizing mechanism. The incorporation of bioactive glass-
es in the inorganic matrix of the resin generates a significant bacterial reduction (E. Coli, S. Aureus, S. Mutans), without
altering the mechanical properties; This reaction can be explained due to the alkalinization of the medium promoting
the precipitation of ions, Silicate, Calcium, Sodium and phosphate, generating tissue damage and inhibition of bacterial
enzymes and finally lysis32.

To avoid degradation of the adhesive interface, quaternary ammonium methacrylates (QAM) composite resins such as
12-methacryloxydodecypyridiumbromide (MDPB) with protease inhibitory and antibacterial activities have been inte-
grated, reducing bacterial microfiltration and the prevalence of secondary caries 33.

The addition of bioactive glasses generates more mineral precipitation between the collagen fibers and with the pres-
ence of zinc ions, cell proliferation and differentiation are stimulated; zinc intervenes in the mineralization mechanism
and interferes in the collagen degradation process mediated by metal proteinases34. The incorporation of amorphous
calcium phosphate ACP fillers generates Hydroxyapatite (HA) precursors, favoring the remineralization process through
a process of dissolution of calcium and phosphate ions, generating a supersaturation of the medium and subsequently
ionic precipitation for the crystallization of HA favoring biomimetic mineralization and in turn decreasing the micro gap
of the adhesive interface35.

Glass ionomer

The glass ionomer was one of the first so-called "smart" materials, given the characteristics that allow it to release fluo-
ride ions, favoring dentinal repair; the release of fluorine increases acids, carrying out a buffer effect in the medium
where it is found, due to the presence of aluminum fluoride and hydrogen fluoride ions that are concentrated in their
dissolution and gelation stage, but they decrease in their hardening and maturation 36.

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The incorporation of bioactive agents such as Bioglass in glass ionomers decreases the mechanical properties by in-
creasing their percentage by weight of filler but increases the bioactive properties 37.

The bioactive glasses together with the ionomers favor the formation of hydroxyapatite in the collagen mesh exposed in
an acidic environment, improving the mechanical properties of the dentin in its remineralization process; This ionic pre-
cipitation occludes the dentinal tubules, decreasing the hydrodynamic flow, playing an important role as a desensitiz-
er38.

Hydroxyapatite Precursors

Amorphous Calcium Phosphate (ACP) is stable calcium and fluorine ion precipitator, which promotes the formation of
Hydroxyapatite. Due to its high solubility in aqueous media and its rapid conversion into HA, it has been stabilized with
casein phosphopeptide (CPP) forming an amorphous calcium casein phosphate complex (CPP-ACP) favoring the satura-
tion of fluorine and phosphate ions in saliva and bacterial plaque, generating anti-cariogenic and remineralizing bene-
fits15. In initial caries lesions, it increases the surface hardness values in tissues demineralized by the acidic environment
generated by the bacterial attack, significantly reducing the roughness of the enamel, decreasing the surface energy, and
disfavoring the adhesion of biofilm5,39.

Bioceramics

Bioceramics are bio-inert or bioactive compounds, with a crystalline phase embedded in a residual amorphous matrix
with a wide variety of indications due to their biocompatibility, dimensional stability, and biomineralization ability, in
which we can find silicates, aluminates, hydroxyapatite, zirconia, phosphates calcium, and bioactive glasses 4. They can
be synthesized by different methods: Fusion, vapor deposition, sol-gel synthesis, changing the physico-mechanical prop-
erties, and favoring biometry with the surrounding tissues 40. The bioactivity of bioceramics is given by their adhesive
properties to tissues and ionic precipitation that favors biomineralization and alkalinization of the medium that pro-
vides antimicrobial activity, 41.

Bioactive Glass

Although its first application given by Dr. Hench was in bone regeneration, bioactive glasses have had great applicability
in different clinical settings. The principle of bioactivity is given by the formation of an apatite layer on the surface of the
tissues that are capable of emulating their characteristics, although it retains less mechanical properties 1,17. The incor-
poration of bioactive glasses to restorative materials facilitates the degradation of proteases, favoring the bond strength,
and decreases the hydrolytic degradation of the adhesive interface 20. The use of monomers with mixtures of bioactive
glasses and monomers derived from quaternary ammonium generate antibacterial environments that decrease microfil-
tration and recurrent caries42,43. In addition, the interdigitation of the bioactive glass with the collagen mesh allows
greater adhesive strength and facilitates the growth of apatite crystals, which consequently will lead to the continuous
reduction of the micro gap between the restorative material and the dental tissue 44.

Silicate-based cements

They are hydrophilic compounds with a basic composition of calcium oxide (CaO), silicon dioxide (SiO 2), and calcium
aluminate derived from Portland cement. One of the first materials to be evaluated was the Mineral Trioxide Aggregate
(MTA), which has antimicrobial properties thanks to its alkaline pH and favors the formation of dentin bridges in pulp
repair3,45. Biodentine is a tricalcium silicate-based cement with greater compressive and flexural strength, shorter set-
ting time, and lower solubility. Its pH exerts a bacterial lethal effect, due to protein denaturation and damage to DNA and
cell cytoplasm46. In 2018, Mahmoud et al. In their systematic review confirmed the bacteriostatic properties of Bio-
dentine® and MTA, the induction of enamel bridges, promoting odontoblastic proliferation, reparative dentin, and
preservation of pulp vitality47. Theracal® is a cement-based on calcium silicate modified with a hydrophilic resin that
allows it to interact in humid environments and have sustained precipitation of calcium and hydroxide over time48. The
interaction with the resinous compounds implies an inflammatory response in the pulp cells, being the one that offers
the lowest therapeutic response compared to other cement based on calcium silicate 49.

Conclusion
Bioactive materials have evolved rapidly in recent years, their application includes different areas of dentistry. Particu-
larly in restorative dentistry, bioactive materials are used mainly as pulp capping, and liner, thanks to the fact that they
release products that help integration with tissues. Additionally, they are used to dentin adhesion systems are used for
core building. There is a lack of literature on long-term follow-up on some of the materials, so their effectiveness should
be interpreted with caution.

Conflict of Interest
The authors declare no conflict of interest.
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Citation: Luis Gabriel Ladino, Alejandra Bernal, Daniel Calderon and Diego Cortes. “Bioactive Materials in Restorative
Dentistry: A Literature Review”. SVOA Dentistry 2:2 (2021) pages 74-81.

Copyright: © 2021 All rights reserved by Luis Gabriel Ladino et al. This is an open access article distributed under the
Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.

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