Contemporary restorative ion-releasing materials: current status, interfacial properties and operative approaches

ABSTRACT Minimally invasive (MI) concepts in restorative dentistry in the year 2020 request from the practitioner not only a scientifically supported rationale for carious tissue

removal/excavation and defect-oriented, biological cavity preparation, but also a deep understanding of how to ensure a biomechanically stable and durable restoration in different clinical

situations by applying different restorative options. Bio-interactive materials play an increasingly relevant role, as they not only replace diseased or lost tissue, but also optimise tissue

mineral recovery (among other properties) when used in restorative and preventive dentistry. Indeed, this is of certain interest in MI restorative dentistry, especially in those cases where

gap formation jeopardises the integrity of the margins along resin composite restorations, causing penetration of bacteria and eventually promoting the formation of secondary caries.

Recently, the interest in whether ion-releasing materials may reduce such biofilm penetration into margin gaps and reduce such a risk for development and propagation of secondary caries is

growing significantly among clinicians and scientists. The aim of this article was to explore mechanisms involved in the process that allow mineral deposition at the interface between such

materials and dentine, and to describe how conventional 'bioactive' restorative materials currently available on the market may benefit treatments in MI dentistry. KEY POINTS *

Explores the mechanisms involved in the process that allows mineral deposition at the interface between such materials and dentine, and describes how conventional 'bioactive'

restorative materials currently available on the market may be beneficial for treatments in minimally invasive (MI) dentistry. * Different carious tissue removal methods are currently

available. However, chemo-mechanical methods reach a compromise between MI tissue removal to protect the pulp and an 'adhesion-friendly' substrate to enable successful restoration

placement and interfacial longevity. * Contemporary 'therapeutic' bio-interactive materials should now be used for tissue replacement, as they may be able to reduce the

susceptibility of tooth mineral to dissolution and/or to recover its mechanical properties via remineralisation. You have full access to this article via your institution. Download PDF

SIMILAR CONTENT BEING VIEWED BY OTHERS 3-YEAR RANDOMIZED CLINICAL TRIAL TO EVALUATE THE PERFORMANCE OF POSTERIOR COMPOSITE RESTORATIONS LINED WITH ION-RELEASING MATERIALS Article Open access

28 February 2024 GLASS IONOMER POLYALKENOATE CEMENTS AND RELATED MATERIALS: PAST, PRESENT AND FUTURE Article 13 May 2022 SECONDARY CARIES AND MARGINAL ADAPTATION OF ION-RELEASING VERSUS

RESIN COMPOSITE RESTORATIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS Article Open access 10 November 2022 INTRODUCTION Teeth are formed through a highly

organised mineralisation process resulting in hierarchically arranged tissues, each one with specific properties.1,2 They are composed of a combination of tissues with different embryologic

origin and precise genetic regulation to result in a unique composition, size, shape and spatial distribution of minerals and organic components, comprising enamel, dentine, cementum and

pulp.3 During a lifetime, teeth are exposed continuously to changing oral micro-environments with harsh conditions characterised by the presence of extrinsic and bacterial metabolic acids,

while being required to perform optimally under variable and high masticatory loads. In combination, these are the fatigue-exposure factors that lead eventually to enamel and dentine

breakdown.4 In enamel, demineralisation induced by low pH can be counterbalanced when the biofilm fluid/acquired pellicle/saliva is super-saturated with calcium and phosphate ions.5 In

dentine, however, the higher organic content of this tissue and its complexity, including the collagen network, makes the process of mineral repair more complicated.6 Minimally invasive (MI)

operative intervention approaches are focused on the sole removal of the diseased tissues and replacement by a biocompatible material. Contemporary interventions, driven by the advent of

'therapeutic' bio-interactive materials should now be used to broaden the application of this concept, resulting in tissue replacement which is able to reduce the susceptibility of

tooth mineral to dissolution and/or able to recover its mechanical properties via remineralisation. LOSS AND GAIN OF MINERAL IN ENAMEL AND DENTINE The dental caries process is initiated by

a drop in pH within the biofilm induced by specific metabolic activities of the organised bacteria.7 Tooth remineralisation may be expected to occur to a certain extent in the presence of

calcium-saturated saliva, and fluoride upregulates this process. Although a complete full-lesion remineralisation is unlikely, it is often also not required for arresting the caries

process.8 Hence, most advances in bio-interactive dental restorative material technology have focused on dentine remineralisation or dentine protection/replacement, also because the overall

longevity of restorations is still of some concern in cavity margin sites located on dentine. As previously stated, dentine is a complex tissue composed of mineral and organic phases.

Dentine remineralisation is an intricate and dynamic process that entails highly orchestrated interactions of several cellular and matrix components.9 Essentially, it involves the renovation

of an organic phase (type I collagen) and inorganic apatite, leading to intrafibrillar mineralisation of collagen.10 However, both stages must be in synergistic connection in order to allow

precise mineral precipitation, both within the collagen intrafibrillar and interfibrillar spaces, and a recovery of the mechanical properties of the dentine tissue.11 For many years, the

role of collagen in dentine was underestimated; it had been first considered only a passive organic scaffold.12,13 However, recent evidence suggests that both the structure and assembly of

type I collagen are essential in order to act as an active template for mineralisation, guiding the crystal deposition in parallel arrays, with preferential growth in the axial direction in

the spaces between fibrils.14 MI dentistry aims to minimise the amount of tissue removal and the maximal preservation of non-denatured collagen, which can still be protected by a

hydroxyapatite coating.15 BACKGROUND ON THE CURRENT GUIDELINES FOR CARIOUS TISSUE REMOVAL An updated approach to carious tissue removal has been recently reviewed and discussed.16 Clinicians

are still prompted to excavate lesions when a mechanically resistant tooth-restoration complex is needed to restore the patient's function and/or aesthetics. However, the traditional

management for many years has been the complete or near-complete removal of the entire carious tissue biomass, in the belief that this would stop the caries process (non-selective removal).

More recently, an improved understanding of the pathophysiology of the caries process and clinical trial evidence on carious tissue removal methods have supported the contemporary

alternatives of 'prevention of extension' as opposed to 'extension for prevention'.17 In selective carious tissue removal, for instance, carious issue is only completely

removed in the periphery of a cavity, ensuring the stability and longevity of the restoration, while close to the pulp, affected and, in some cases, infected carious tissue may well be

retained and sealed under the restoration if this prevents pulp exposure. As a result, the sealed dentine beneath restorations placed following such carious tissue removal will be a

combination of sound/translucent dentine at the cavity periphery and affected/demineralised dentine at the base, adjacent to the pulp.18 Although conventional dental adhesives may achieve

statistically lower bond strengths when applied to such affected dentine as compared to a sound dentine substrate,19 the real values are still within the clinically safe standards for dental

adhesion.20 Importantly, the surface area of the cavity affected in that way is usually small compared with the overall surface of the whole cavity. Moreover, different carious tissue

removal methods result in different histological dentine substrates and morphology of the residual dentine.21,22 In general, chemo-mechanical methods reach a compromise between MI tissue

removal to protect the pulp23,24 and an 'adhesion-friendly' substrate to enable successful restoration placement and interfacial longevity.25 Figure 1 shows the morphology of

residual dentine surfaces after different carious tissue removal techniques. The use of conventional ion-releasing dental materials such as glass-ionomer cements (GICs) seems to provide a

net mineral gain in carious dentine.26 Using experimental biomimetic remineralising adhesive materials, it is possible to induce intrafibrillar mineralisation of collagen (Fig. 2). Indeed,

it has been demonstrated that such a biomimetic strategy for remineralisation may reinstate the mechanical properties of the demineralised dentine, as specific Ca/P compounds, such as

amorphous calcium phosphate (ACP), can fill the nanometre-sized spaces within the collagen fibrils.26,27 This mineral exchange results in remineralisation, protecting the collagen against

further proteolytic degradation. At the clinical level, it results in increased restoration longevity and less incidence of secondary caries. Furthermore, they are biocompatible,

acid-resistant and have thermal expansion coefficients similar to that of dentine. THE ROLE OF NEW MATERIALS IN ENGINEERING DEMINERALISED DENTINE Polymer, ceramics or resin composite

biomaterials can be used to repair or replace damaged organs or tissues in the human body. Research currently has focused on developing nanoscale materials with biomimetic properties. In

dentistry, the effect of these dentine-replacement materials is clinically relevant and represented by ion leaching/releasing from the bulk material and interaction with the underlying

tissue. Furthermore, the application of such materials may provide feasible means to extend the longevity of material-dentine interface. For example, experimental adhesives containing

calcium silicate-based, bio-interactive micro-fillers have been found promising to preserve the bond strength against ageing.28 Ultraconservative interventions aim to preserve the sound

structure of the tooth as much as possible. However, the preparation of MI cavities must also be supported by therapeutic restorative techniques that induce protection of the

material-dentine interface against hydrolytic or enzymatic degradation processes, avoiding deterioration of the bond and failure of the restoration over time.29 This concept of removal is

accomplished by leaving partial or demineralised caries-affected dentine as a residual substrate. As mentioned before, it is known that adhesion to this type of substrate is compromised

compared to sound dentine. This is probably due to a combination of the reduced biomechanical properties of caries-affected tissue (for example, its modulus of elasticity), and the fact that

the chemistry and structure of caries-affected dentine can affect the depth of dentine demineralisation and degree of adhesive infiltration.30 Furthermore, irregular distribution and

shallow penetration of adhesive monomers into demineralised collagen result in poor infiltration and adhesive phase separation. This hinders hybrid layer formation and results in a reduced

bond strength.31 In order to improve the durability of the bond between adhesives and caries-affected dentine, alternative restorative procedures are necessary, most of them involving

biomimetic (phosphoprotein) analogues.32 The strategy of these materials to improve the durability of restorations relies on its ability to inhibit the activity of the collagenolytic enzymes

present in dentine and cause mineral deposition.33 The dentine collagenolytic enzymes, including matrix metalloproteinases (MMPs) and cysteine cathepsins, are responsible for the

degradation of collagen fibrils exposed at the bonded interface. They are produced by odontoblasts and remain as inactive zymogens until a change in chemical morphology, resulting from

application of adhesive systems or the biological caries process, results in its activation.34 Since restorations are (most of the time) placed over/on carious tissue, it is possible that

they are present in the residual dentine in the activated form under the restoration. Their activity is downregulated by the presence of calcium and zinc, chelating or replacing the active

site or by 'coating' the substrate.35 Ionic dissolution products released from these materials have also been shown to reduce the degradation of exposed collagen and enhance the

deposition of minerals.36,37 It still remains unclear how this healing process occurs.38 However, it seems that the Si concentration and the Ca/P ratio are critical. ACP is a precursor of

hydroxyapatite and it has been reported that they can inactivate some MMPs.39 The mechanisms involved in inhibition of proteolytic degradation of dentine-material interfaces are a key issue,

which may be accomplished by ion-releasing materials to improve the dentine bonding durability and the therapeutic applications of these materials in caries prevention. With improved

understanding of the interaction between dentine and such bio-interactive 'smart' materials, it may be possible to develop routes for the synthesis of new functional materials with

structural precision at different dimensional levels. The ultimate goal is to produce materials to replace or protect the exposed collagen, mimicking as best as possible the original sound

tissue. Moreover, it would be interesting to investigate the possibility of extending their bio-interactivity by combining calcium phosphate (CaP) phases with different solubilities and/or

developing controlled release approaches to expand their use in caries prevention. CONVENTIONAL 'BIO-INTERACTIVE' ION-RELEASING MATERIALS MI operative dentistry concepts require,

as part of restorative therapy, materials which are able to: 1) deliver mineral ions; 2) bind to collagen (acting as template of calcium and phosphorus and stimulating nucleation of apatite

crystallisation); 3) protect collagen from degradation; 4) provide an adequate pH to favour new mineral formation; and 5) repel or constrain bacteria.40 Ionic dissolution from ion-releasing

materials may be the key factor in understanding their remineralisation potential. Calcium and phosphorous are the main components of the biological apatite. Other inorganic ions, such as

fluoride, zinc, magnesium and silanol groups, may also act as substitutes in apatite crystal formation. One description of 'bioactive/bio-interactive' materials postulates that

these materials should be able to elicit a specific biological response at the interface, resulting in the formation of a bond between the tissue and the material.41 Part of the interaction

mechanism is due to ion release and, in this regard, some attention will be given to its laboratory and clinical properties applied to MI operative dentistry. There are several materials

already present on the market, which are able to release specific ions at the interface (Table 1). However, new 'smart' materials are being developed to facilitate dentine

remineralisation, incorporating inorganic fillers (bioglass, CaP, hydroxyapatite/calcium silicate particles and silicon nanoparticles) in order to promote remineralisation at the bonded

interface.19,40 Although few of them cause full remineralisation, they play an important therapeutic role at the interface. Table 1 offers an overview of current commercially available

bio-interactive restorative materials. ZINC POLYCARBOXYLATE CEMENTS Zinc polycarboxylate cements (ZPCs) were the first dental cements showing some chemical adhesion to tooth structure. They

were often used for luting restorations, intra-canal posts or orthodontic bands. It soon became clear that the use of zinc polycarboxylate resulted in more retention and less

demineralisation in enamel under the bands compared to zinc phosphate cements.42 The powder contains oxides of zinc, magnesium, tin, bismuth and/or alumina. Zinc and magnesium may act as a

direct activator of the enzyme alkaline phosphatase and has been shown to inhibit osteoclast activity, thus inducing the precipitation of poorly crystallised apatite.43,44 Zinc is also known

to induce collagen cross-link formation and may help to prevent enzymatic degradation.45 The liquid is an aqueous solution of polyacrylic acid (PAA), a known non-collagenous protein

surrogate for biomimetic intrafibrillar mineralisation of collagen fibrils32 able to regulate the growth of the mineral crystallites during remineralisation processes. Indeed, this polymer

has acidic characteristics and a predisposition to bind cations and stabilised ACP nanoprecursors.46 A recent study has shown the potential of these 'traditional' cements in

increasing the mineral density in artificially induced carious dentine produced by a microbial protocol up to similar values achieved by GICs and calcium silicate cements.47 ZPCs, in fact,

have indeed slightly outperformed GICs in this regard (Fig. 3). Figure 4 illustrates the high contrast outer layer formed over the ZPC restored samples after 45 days of intra-pulpal pressure

with simulated body fluid (SBF). In modern dentistry, such materials would be useful as pulp protection materials and/or as dentine replacement materials after deep selective carious tissue

removal. GICS ZPCs were clinically replaced by GICs, which also contain PAA but, in addition, also exhibit fluoride release. They are water-based restorative materials composed of

fluoro-alumino silicate powder which, by acid attack, forms polyalkenoate salts that interact with the subjacent dentine, forming an ion-interchange layer or diffusion zone. The formation of

calcium polycarboxylate not only facilitates tissue remineralisation but also allows chemical bonding48 at the interface. At the clinical level, this is a significant factor in the

long-term adhesion and mineralisation ability, upgrading GICs as one of the most used restorative materials in paediatric dentistry, for example. Modified forms of GICs, such as Glass

Carbomers, have appeared on the market, with a similar composition and setting reaction to conventional GICs.49 They are claimed to contain nanocrystals of calcium fluorapatite (FAp) and

hydroxyapatite, which can act as nuclei for the remineralisation process and initiate the formation of FAp.50 While they show reduced clinical success as a restorative material,45 its use as

a sealant or as pulp protection could be promising. Resin-modified glass-ionomer cements (RMGICs) possess improved clinical properties. They are also considered self-adhesive materials and

contain methacrylate-based monomers (HEMA, TEGDMA, UDMA), vinyl-modified polyalkenoic acid (VPA), photo-activators (such as camphorquinone) and tertiary amines (co-initiators), in order to

allow photopolymerisation.51,52 RMGICs can bond micromechanically to dentine due to the resin infiltration of exposed collagen after PAA conditioning. They are also able to bond chemically

to dentine by ionic interaction of carboxyl groups from the acid with calcium ions of the remaining hydroxyapatite crystals in the tooth substrate.53 The longevity of resin-dentine bonds may

also be improved by using materials or clinical measures that may reduce the stress concentration at the interface between resin and dentine during light-curing procedures.54 RMGICs can be

used in deeper cavities in order to provide a 'stress absorption' layer that will absorb part of the shrinkage of the resin composite used for the restoration.55,56 This has been

advocated to prevent stress development at the dentine-bonded interface,57,58 thus decreasing the risk for gap formation and microleakage. One more factor to consider as a source of

degradation is the occlusal stress during mastication and in cases of parafunctional habits; all these factors can affect the integrity of the bond interface.59 It has been shown that the

use of RMGICs can provide a more stable bond to dentine, as well as provide a longer-lasting marginal sealing compared to resin composites. This seems to be correlated to the ability of such

materials to dissipate the occlusal stress and to the beneficial result of the ions released over time. Indeed, it is of particular interest in modern MI therapeutic restorative dentistry,

since it has been demonstrated that cyclic mechanical stress can promote gap formation at the margins of resin composite restorations. Bacterial penetration into narrow margin gaps might

ultimately promote secondary caries formation.60 From RMGICs, other material classes have been developed. Giomers, for example, are resin composite materials where a pre-reacted

glass-ionomer (PRG) filler technology has been incorporated.61 The main advantage of this material would be its improved fluoride release, but otherwise their clinical performance can be

compared to conventional resin composites.62 More recently, a new type of bioactive flowable resin-based restorative GIC, containing fluoro-alumino silicate particles and polyacid components

along with a bioactive ionic resin matrix, has been developed (Activa, Pulpdent, USA). One study63 has demonstrated that the use of a conventional RMGIC or the Activa restorative

GIC/resin-based material can reduce the degradation during load cycling and/or prolonged storage in artificial saliva of the hybrid layer created with modern universal adhesive applied in

etch and rinse mode (Fig. 5). BIOACTIVE GLASSES Among other known bioactive and ion-releasing materials are bioactive glasses (also known as bioglass, often shortened to BAG).64 The basic

components of bioactive glasses are calcium oxide, sodium, phosphorous and silica.65 The surface reaction is a complex, multistage process derived from their reactions with tissue fluids,

which results in the formation of a biologically active hydroxy-carbonate apatite layer.66 It has been found that this reaction releases critical concentrations of soluble Si, Ca, P and N

ions, which induce intracellular and extracellular responses.67 Although most information about this material has been acquired through bone research, this material has been used in

dentistry especially for dentine mineralisation68 and for the treatment of dentine hypersensitivity.69 However, the most common way to use bioactive glasses in dentistry is via

air-abrasion/polishing procedures. Indeed, the pre-treatment of dental substrates using Bioglass 45S5 (Sylc, Velopex, London UK) in air-abrasion devices is currently used in restorative

dentistry to create a 'bioactive smear layer' within the interface, which can be incorporated into the hybrid layer during application of RMGICs and self-etch adhesives. This

bioactive smear layer remains available at the bonding interface, and induces remineralisation and protection of the dentine-bonded interface.19 Moreover, it has been demonstrated that CaP

has the ability to mediate MMP-2 and MMP-9 by forming a high-molecular-weight aggregate, CaP-MMP, which immobilises MMPs by binding to fibrin.70 The binding capacity can also be influenced

by the alkaline pH generated by the bioactive glasses during water immersion. A reduction in this activity is expected at around pH 10, since the ideal activity of MMP occurs at neutral pH.

In addition, the surface created by Bioglass 45S5 is a SiO2-rich gel layer.43,71 The sequestration of calcium and phosphate ions from the glass and their diffusion through the SiO2-rich

layer can induce their transformation into ACPs. After that, hydroxyapatite can be formed and it is well known that they may inhibit MMP activity.72 The interactions between CaP complexes

and amino acids indicates an involvement in bone mineralisation regulation. Although few studies focus on amino acids bound to surfaces, this appears to be due to an affinity of exposed

collagen for the glass surface and chemical interaction between the dentine and glass, likewise in bone regeneration, leading to apatite formation at the interface.73 CALCIUM SILICATE

CEMENTS The first calcium silicate dental cement, mineral trioxide aggregate (MTA), was developed in the 1990s as a repair material for endodontic perforations and root-end fillings due its

biocompatibility and ability to induce mineralised tissue formation.74 This cement is primarily composed of di- and tri-calcium silicate, tri-calcium aluminate, tetra-calcium aluminoferrite

and bismuth oxide. Calcium silicate cements are hydrophilic materials that can tolerate humidity and release calcium and hydroxyl ions into surrounding fluids (saliva, blood, dentinal

fluid). These materials set by a hydration and precipitation mechanism, the remineralisation mechanism differing due to the alkaline nature of these materials. Degradation of collagen

fibrils occurs and leads to the formation of a porous structure, which facilitates the penetration of high concentrations of calcium and carbonate ions, leading to increased mineralisation

in this zone.75 It is important to note that they cannot induce biomimetic remineralisation by re-establishing functional properties. Their ability is to induce mineral precipitation and

induce formation of a reparative/osteo-dentine. Its clinical indications have been expanded to include pulp-capping procedures, pulpotomies or root apical barrier formation.76 Due to its

biocompatibility and sealing ability, they have become an important material in supporting the concept of MI dentistry. As mentioned before, the alkaline setting reaction of these cements

can reduce MMP activity and also has beneficial antibacterial effects on caries-affected (and infected) dentine.77,78 Studies also demonstrated optimal healing responses, with dentine bridge

formation in the pulp space79,80,81 confirming the biocompatibility of calcium silicate cements. They also exhibit expansion and contraction properties similar to dentine, which results in

higher resistance to margin leakage and subsequent bacterial migration.78 Despite some of these materials potentially being affected by colour change or staining, all these properties

together facilitate its successful clinical use. SILVER DIAMINE FLUORIDE Silver diamine fluoride (SDF) was first approved for dentistry use in Japan in the 1960s82 and, since then, has been

used in China, Brazil, Argentina and Australia. In 2014, USA licensed an SDF product for therapeutic use in tooth sensitivity.83 Its main application is, however, directly related to MI

dentistry concepts to arrest carious lesion progression or prevent lesion establishment.84 Nevertheless, SDF has a major adverse effect regarding the black stained appearance left after its

use, raising aesthetic concerns from patients and/or parents. SDF has a very alkaline pH (around 10) and the solution contains diamine-silver and fluoride ions. The interaction of silver and

fluoride has a synergistic effect on the tooth structure, favouring the synthesis of fluorohydroxyapatite,85 which is chemically more stable than hydroxyapatite in acid environments, with

important implications in remineralisation/re-hardening of the carious lesion.86 Another _in vitro_ study found that SDF increases the mineral density of artificial carious lesions;87

however, the mechanism behind it is still not completely clear. It has been proposed that it would rather occur due to a reaction between silver and dentine minerals, rather than the classic

fluoride-mediated remineralisation,88 and some recent micro-CT investigations (unpublished data) may support this assumption, since a high-density superficial layer has been found in

carious dentine after SDF application, which may even be extended into deeper dentine parts (Fig. 6). Furthermore, fluoride and silver also inhibit MMP and cathepsin activity and, therefore,

may also inhibit dentine/collagen degradation.88 Finally, SDF also has a well-known antibacterial effect, with inhibition of cariogenic biofilm formation.89 Limited data is still available

regarding advanced characterisation of SDF-tooth interactions. At present, more attention is being given to trying to mitigate the staining problem.90 A saturated potassium iodide solution

has been used to minimise this side effect and/or restoration with GICs over SDF-stained dentine to mask the stained tissue. Some SDF solutions are already commercially available in

combination with self-cured GICs. FUTURE PROSPECTS - DENTINE INTERFACE BIOMINERALISATION Two different models of _in vitro_ remineralisation can be found in the literature, classified as the

top-down/classical and bottom-up/non-classical approaches. A major criticism in the classical approach is that it results in extrafibrillar remineralisation without remineralisation of the

intrafibrillar components.32 Therefore, in this approach, conventional remineralisation does not occur by spontaneous nucleation of mineral matrix, but rather by the growth of residual

apatite crystals in demineralised dentine. If there are only a few residual crystals, there is no remineralisation.10 On the other hand, the bottom-up approach was suggested as an

alternative and is independent from apatite crystallites that may have remained. This biomimetic remineralisation is driven by analogues, leading to hierarchical remineralisation of

dentine,32,91 resulting in a highly ordered intrafibrillar nanoapatite assembly. Dentine biomineralisation occurring within the restorative interface could be accomplished following the

bottom-up strategy, where the crystals and structures formed can incorporate organic macromolecules.6,14 It is known that, in demineralised dentine, the collagen intrafibrillar gap regions

are spaces which hydroxyapatite mineral precursors occupy; eventually nucleate and hydroxyapatite crystal plates grow.32 It is therefore important to have mineral re-incorporation when the

dentine is exposed to demineralisation (from erosion, caries or restorative procedures). A mineral crystal is formed through a nucleation event in which a cation and anion pair bond and

create nuclei for crystal growth. Many biominerals are formed by an amorphous precursor pathway mediated by a non-collagenous protein. Several inorganic materials have been shown to be

bio-interactive and able to deliver remineralising ions. Once such biomineralisation processes are better understood and their place in the MI operative approach is recognised, the

interaction between materials and tooth surfaces, namely 'bio-interactivity', should also be considered in the longevity of the tooth-restoration complex.6,92 Development of

biomaterials able to catalyse remineralisation of incompletely resin-infiltrated collagen matrices created by resin adhesives will represent a great advance in dental care. CONCLUSIONS There

are different methods available to perform carious tissue removal. The first important concept to consider is the type of substrate that these methods leave to be further treated. Thereby,

a good diagnosis and the planned treatment could act together with the 'smart' materials to heal the tissue left behind. Hence, in MI dentistry, the 'bio-interactivity'

is important to create a therapeutic surface for adhesive procedures. As current commercially aesthetic resin composite materials have no ability to remineralise the collagen network after

acid demineralisation, ion-releasing materials need to be used in association. Unfortunately, they are also not able to immediately remineralise the remaining caries-affected dentine.

However, they have specific therapeutic benefits that could improve the protection of collagen fibrils until the remineralisation process occurs. Zinc polycarboxylate was the first cement to

show chemical ability to bond chemically to dental hard tissues. They are nowadays used quite rarely, as GICs and RMGICs have a wider range of applications along with an ability to release

fluoride in the micro-environment. However, both have the ability to induce mineral precipitation at the interface in specific ways. Quick-setting calcium silicate-based cements may be

indicated for deeper cavities due to their ability to stimulate the pulp cells to produce a reparative dentine bridge and create calcium carbonate and/or apatite-like crystallisation layers

along the interface. Moreover, they also possess antibacterial properties against eventual remaining microorganisms left after selective carious tissue removal, reducing the risk for

secondary caries and improving the longevity of restorations. As opposed to dentine-replacement materials, SDF can be applied without caries removal as it is able to simultaneously prevent

and arrest lesion progression by a synergistic interaction between released ions and tooth tissue. Using this association of different materials to restore the cavity, it is possible to

reduce the stain effect and keep the therapeutic benefit of the hardened carious lesion. Application of modern adhesive systems in combination with ion-releasing dentine-replacement

materials may offer to practitioners the possibility to perform adhesive restorations with long-lasting performance. Furthermore, understanding the ion-releasing process of materials may be

the key factor for the development of a therapeutic bonding system, being a promising alternative way to reduce the degradation of the resin-dentine interface. REFERENCES * He L H, Yin ZH,

van Vuuren L J, Carter E A, Liang X W. A natural functionally graded biocomposite coating: Human enamel. _Acta Biomater_ 2013; 9: 6330-6337. * Bertassoni L E. Dentin on the nanoscale:

Hierarchical organisation, mechanical behaviour and bioinspired engineering. _Dent Mater_ 2017; 33: 637-649. * Giacaman R, Perez V A, Carrera A. Mineralisation processes in hard tissues:

Teeth. _In_ Aparicio C, Ginebra M P (eds) _Biomineralisation and biomaterials: Fundamentals and applications_. pp 147-185. Waltham: Woodhead Publishing, 2016. * Neves A A, Coutinho E, Alves

H D, Assis J T. Stress and strain distribution in demineralized enamel: A micro-CT based finite element study. _Microsc Res Tech_ 2015; 78: 865-872. * Larsen M J, Pearce E I. Saturation of

human saliva with respect to calcium salts. _Arch Oral Biol_ 2003; 48: 317-322. * Niu L N, Zhang W, Pashley D H _et al._ Biomimetic remineralization of dentin. _Dent Mater_ 2014; 30: 77-96.

* Kidd E A, Fejerskov O. What constitutes dental caries? Histopathology of carious enamel and dentin related to the action of cariogenic biofilms. _J Dent Res_ 2004; DOI:

10.1177/154405910408301s07. * Fernandez-Ferrer L, Vicente-Ruiz M, Garcia-Sanz V _et al._ Enamel remineralization therapies for treating postorthodontic white-spot lesions: A systematic

review. _J Am Dent Assoc_ 2018; 149: 778-786. * Goldberg M, Kulkarni A B, Young M, Boskey A. Dentin: Structure, composition and mineralization. _Front Biosci (Elite Ed)_ 2011; 3: 711-735. *

Bertassoni L E, Habelitz S, Kinney J H, Marshall S J, Marshall-Jr G W. Biomechanical perspective on the remineralization of dentin. _Caries Res_ 2009; 43: 70-77. * Sauro S, Osorio R, Watson

T F, Toledano M. Influence of phosphoproteins' biomimetic analogues on remineralization of mineral-depleted resin-dentin interfaces created with ion-releasing resin-based systems. _Dent

Mater_ 2015; 31: 759-777. * Hunter G K, Poitras M S, Underhill T M, Grynpas M D, Goldberg H A. Induction of collagen mineralization by a bone sialoprotein-decorin chimeric protein. _J

Biomed Mater Res_ 2001; 55: 496-502. * Saito T, Arsenault A L, Yamauchi M, Kuboki Y, Crenshaw M A. Mineral induction by immobilized phosphoproteins. _Bone_ 1997; 21: 305-311. * Gower L B.

Biomimetic mineralization of collagen. _In _Aparicio C, Ginebra M P (eds) _Biomineralisation and biomaterials: Fundamentals and applications_. pp 187-232. Waltham: Woodhead Publishing, 2016.

* Banerjee A. Minimal intervention dentistry: Part 7. Minimally invasive operative caries management: Rationale and techniques. _Br Dent J_ 2013; 214: 107-111. * Schwendicke F, Frencken J

E, Bjorndal L _et al._ Managing carious lesions: Consensus recommendations on carious tissue removal. _Adv Dent Res_ 2016; 28: 58-67. * FDI World Dental Federation. FDI policy statement on

minimal intervention dentistry (MID) for managing dental caries: Adopted by the general assembly: September 2016, Poznan, Poland. _Int Dent J_ 2017; 67: 6-7. * Schwendicke F, Frencken J,

Innes N. Clinical recommendations on carious tissue removal in cavitated lesions. _Monogr Oral Sci_ 2018; 27: 162-166. * Sauro S, Pashley D H. Strategies to stabilise dentine-bonded

interfaces through remineralising operative approaches: State of the art. _Int J Adhes Adhes_ 2016; 69: 39-57. * Neves A, Coutinho E, Cardoso M, de Munck J, Van Meerbeek B. Micro-tensile

bond strength and interfacial characterization of an adhesive bonded to dentin prepared by contemporary caries-excavation techniques. _Dent Mater_ 2011; 27: 552-562. * Neves A A, Coutinho E,

Cardoso M V, Lambrechts P, Van Meerbeek B. Current concepts and techniques for caries excavation and adhesion to residual dentin. _J Adhes Dent_ 2011; 13: 7-22. * Banerjee A, Kidd E A M,

Watson T F. Scanning electron microscopic observations of human dentine after mechanical caries excavation. _J Dent_ 2000; 28: 179-186. * Neves A A, Coutinho E, De Munck J, Van Meerbeek B.

Caries-removal effectiveness and minimal-invasiveness potential of caries-excavation techniques: A micro-CT investigation. _J Dent_ 2011; 39: 154-162. * Banerjee A, Kidd E A M, Watson T F.

In vitro evaluation of five alternative methods of carious dentine excavation. _Caries Res_ 2000; 34: 144-510. * Neves A A, Coutinho E, Cardoso M V, de Munck J, Van Meerbeek B. Micro-tensile

bond strength and interfacial characterization of an adhesive bonded to dentin prepared by contemporary caries-excavation techniques. _Dent Mater_ 2011; 27: 552-562. * Schwendicke F,

Al-Abdi A, Pascual Moscardo A, Ferrando Cascales A, Sauro S. Remineralization effects of conventional and experimental ion-releasing materials in chemically or bacterially-induced dentin

caries lesions. _Dent Mater_ 2019; 35: 772-779. * Liu Y, Mai S, Li N _et al._ Differences between top-down and bottom-up approaches in mineralizing thick, partially demineralized collagen

scaffolds. _Acta Biomater_ 2011; 7: 1742-1751. * Profeta A C, Mannocci F, Foxton R _et al._ Experimental etchandrinse adhesives doped with bioactive calcium silicate-based micro-fillers to

generate therapeutic resin-dentin interfaces. _Dent Mater_ 2013; 29: 729-741. * Tjaderhane L, Nascimento F D, Breschi L _et al._ Strategies to prevent hydrolytic degradation of the hybrid

layer: A review. _Dent Mater_ 2013; 29: 999-1011. * Erhardt M C G, Toledano M, Osorio R, Pimenta L A. Histomorphologic characterization and bond strength evaluation of caries-affected

dentin/resin interfaces: Effects of long-term water exposure. _Dent Mater_ 2008; 24: 786-798. * Wang Y, Spencer P, Walker M P. Chemical profile of adhesive/caries-affected dentin interfaces

using raman microspectroscopy. _J Biomed Mater Res A_ 2007; 81: 279-286. * Liu Y, Kim Y K, Dai L _et al._ Hierarchical and non-hierarchical mineralisation of collagen. _Biomaterials_ 2011;

32: 1291-1300. * Tjaderhane L, Nascimento F D, Breschi L _et al_. Optimizing dentin bond durability: control of collagen degradation by matrix metalloproteinases and cysteine cathepsins.

_Dent Mater _2013; 29: 116-135. * Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. _Circ Res_ 2003; 92:

827-839. * Tezvergil-Mutluay A, Agee K A, Hoshika T _et al._ The requirement of zinc and calcium ions for functional MMP activity in demineralized dentin matrices. _Dent Mater_ 2010; 26:

1059-1067. * Boelen G J, Boute L, d'Hoop J, EzEldeen M, Lambrichts I, Opdenakker G. Matrix metalloproteinases and inhibitors in dentistry. _Clin Oral Investig_ 2019; 23:2823-2835. *

Osorio R, Yamauti M, Sauro S, Watson T F, Toledano M. Experimental resin cements containing bioactive fillers reduce matrix metalloproteinase-mediated dentin collagen degradation. _J Endod_

2012; 38: 1227-1232. * Page-McCaw A, Ewald A J, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. _Nat Rev Mol Cell Biol _2007; 8: 221-233. * Fu H, Rahaman M N, Day

D E, Huang W. Effect of pyrophosphate ions on the conversion of calciumlithiumborate glass to hydroxyapatite in aqueous phosphate Solution_. J Mater Sci Mater Med_ 2010; 21: 2733-2741. *

Osorio R, Toledano M. Biomaterials for catalysed mineralization of dental hard tissues. _In_ Aparicio C, Ginebra M P (eds) _Biomineralisation and biomaterials: Fundamentals and

applications_. pp 365-376. Waltham: Woodhead Publishing, 2016. * Jones J R. Reprint of: Review of bioactive glass: From Hench to hybrids. _Acta Biomater_ 2015; DOI:

10.1016/j.actbio.2015.07.019. * Anusavice K J, Shen C, Rawls H R. Dental cements. _In_ Anusavice K J, Shen C, Rawls H R (eds) _Phillips' science of dental materials_. pp 418-473.

Philadelphia: Saunders, 2012. * Hoppe A, Guldal N S, Boccaccini A R. A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics.

_Biomaterials_ 2011; 32: 2757-2774. * Ma J, Wang J, Ai X, Zhang S. Biomimetic self-assembly of apatite hybrid materials: From a single molecular template to bi-/multi-molecular templates.

_Biotechnol Adv _2014; 32: 744-760. * Osorio R, Osorio E, Cabello I, Toledano M. Zinc induces apatite and scholzite formation during dentin remineralization. _Caries Res_ 2014; 48: 276-290.

* Qi Y P, Li N, Niu L N _et al._ Remineralization of artificial dentinal caries lesions by biomimetically modified mineral trioxide aggregate. _Acta Biomater_ 2012; 8: 836-842. * Pires P M,

Santos T P, Fonseca-Goncalves A, Pithon M M, Lopes R T, Neves A A. Mineral density in carious dentine after treatment with calcium silicates and polyacrylic acid based cements. _Int Endod J_

2018; 51: 1292-1300. * Falsafi A, Mitra S B, Oxman J D, Ton T T, Bui H T. Mechanisms of setting reactions and interfacial behaviour of a nano-filled resin-modified glass ionomer. _Dent

Mater_ 2014; 30: 632-643. * Koenraads H, Van der Kroon G, Frencken J E. Compressive strength of two newly developed glass-ionomer materials for use with the atraumatic restorative treatment

(art) approach in class ii cavities. _Dent Mater_ 2009; 25: 551-556. * Zainuddin N, Karpukhina N, Law R V, Hill R G. Characterisation of a remineralising glass carbomer ionomer cement by

MAS-NMR spectroscopy. _Dent Mater_ 2012; 28: 1051-1058. * Olegario I C, Hesse D, Mendes F M, Bonifacio C C, Raggio D P. Glass carbomer and compomer for art restorations: 3year results of a

randomized clinical trial. _Clin Oral Investig_ 2019; 23: 1761-1770. * Attin T, Vataschki M, Hellwig E. Properties of resin-modified glass-ionomer restorative materials and two

polyacid-modified resin composite materials. _Quintessence Int_ 1996; 27: 203-209. * Sidhu S K, Watson T F. Interfacial characteristics of resin-modified glass-ionomer materials: A study on

fluid permeability using confocal fluorescence microscopy. _J Dent Res_ 1998; 77: 1749-1759. * Nikolaenko S A, Lohbauer U, Roggendorf M, Petschelt A, Dasch W, Frankenberger R. Influence of

cfactor and layering technique on microtensile bond strength to dentin. _Dent Mater_ 2004; 20: 579-585. * Irie M, Suzuki K, Watts D C. Marginal gap formation of light-activated restorative

materials: Effects of immediate setting shrinkage and bond strength. _Dent Mater_ 2002; 18: 203-210. * Irie M, Suzuki K, Watts D C. Immediate performance of self-etching _versus_ system

adhesives with multiple light-activated restoratives. _Dent Mater_ 2004; 20: 873-880. * Sampaio PC, de Almeida Junior A A, Francisconi L F _et al._ Effect of conventional and resin-modified

glass-ionomer liner on dentin adhesive interface of class i cavity walls after thermocycling. _Oper Dent_ 2011; 36: 403-412. * Sauro S, Faus-Matoses V, Makeeva I _et al._ Effects of

polyacrylic acid pre-treatment on bonded-dentine interfaces created with a modern bioactive resin-modified glass ionomer cement and subjected to cycling mechanical stress. _Materials

(Basel)_ 2018; 11: 1884. * Toledano M, Cabello I, Aguilera F S, Osorio E, Osorio R. Effect of in vitro chewing and bruxism events on remineralization, at the resin-dentin interface. _J

Biomech_ 2015; 48: 14-21. * Khvostenko D, Salehi S, Naleway S E _et al._ Cyclic mechanical loading promotes bacterial penetration along composite restoration marginal gaps. _Dent Mater_

2015; 31: 702-710. * Ikemura K, Tay F R, Endo T, Pashley D H. A review of chemical-approach and ultramorphological studies on the development of fluoride-releasing dental adhesives

comprising new pre-reacted glass ionomer (PRG) fillers. _Dent Mater J_ 2008; 27: 315-339. * Gordan V V, Mondragon E, Watson R E, Garvan C, Mjor I A. A clinical evaluation of a self-etching

primer and a giomer restorative material: Results at eight years. _J Am Dent Assoc_ 2007; 138: 621-627. * Sauro S, Makeeva I, Faus-Matoses V _et al._ Effects of ions-releasing restorative

materials on the dentine bonding longevity of modern universal adhesives after load-cycle and prolonged artificial saliva aging. _Materials (Basel)_ 2019; 12: 722. * Hench L L. Biological

applications of bioactive glasses. _Life Chem Rep_ 1996; 13: 187-241. * Yli-Urpo H, Narhi M, Narhi T. Compound changes and tooth mineralization effects of glass ionomer cements containing

bioactive glass (s53p4): An in vivo study. _Biomaterials_ 2005; 26: 5934-5941. * Salonen J I, Arjasamaa M, Tuominen U, Behbehani M J, Zaatar E I. Bioactive glass in dentistry. _J Min Inv

Dent_ 2009; 2: 208-218. * Hench L L. Bioceramics. _J Amer Ceram Soc _1998; 74: 1487-1510. * Prabhakar A R, Paul M J, Basappa N. Comparative evaluation of the remineralizing effects and

surface micro hardness of glass ionomer cements containing bioactive glass (s53p4): An in vitro study. _Int J Clin Paediatr Dent_ 2010; 3: 69-77. * Sauro S, Watson T F, Thompson I. Dentine

desensitization induced by prophylactic and air-polishing procedures: An in vitro dentine permeability and confocal microscopy study. _J Dent_ 2010; 38: 411-422. * Makowski G S, Ramsby M L.

Differential effect of calcium phosphate and calcium pyrophosphate on binding of matrix metalloproteinases to fibrin: Comparison to a fibrin-binding protease from inflammatory joint fluids.

_Clin Exp Immunol_ 2004; 136: 176-187. * Hench L L, Jones J R. Bioactive glasses: Frontiers and challenges. _Front Bioeng Biotechnol_ 2015; 3: 194. * Kremer E A, Chen Y, Suzuki K, Nagase H,

Gorski J P. Hydroxyapatite induces autolytic degradation and inactivation of matrix metalloproteinase-1 and3. _J Bone Miner Res_ 1998; 13: 1890-1902. * Tavafoghi M, Cerruti M. The role of

amino acids in hydroxyapatite mineralization. _J Royal Soc Interface_ 2016; 13: 20160462. * Torabinejad M, Hong C U, McDonald F, Pitt Ford T R. Physical and chemical properties of a new

root-end filling material. _J Endod_ 1995; 21: 349-353. * Atmeh A R, Chong E Z, Richard G, Festy F, Watson T F. Dentin-cement interfacial interaction: Calcium silicates and polyalkenoates.

_J Dent Res_ 2012; 91: 454-459. * Camilleri J, Montesin F E, Papaioannou S, McDonald F, Pitt Ford T R. Biocompatibility of two commercial forms of mineral trioxide aggregate. _Int Endod J_

2004; 37: 699-704. * Ali A H, Koller G, Foschi F _et al._ Self-limiting versus conventional caries removal: A randomized clinical trial. _J Dent Res_ 2018; 97: 1207-1213. * Tawil P Z, Duggan

D J, Galicia J C. Mineral trioxide aggregate (MTA): Its history, composition, and clinical applications. _Compend Contin Educ Dent_ 2015; 36: 247-252; quiz 254, 264. * Fransson H. On the

repair of the dentine barrier. _Swed Dent J _2012; 226: 9-84. * Kim S G, Malek M, Sigurdsson A, Lin L M, Kahler B. Regenerative endodontics: A comprehensive review. _Int Endod J_ 2018; 51:

1367-1388. * Sanz J L, Rodriguez-Lozano F J, Llena C, Sauro S, Forner L. Bioactivity of bioceramic materials used in the dentin-pulp complex therapy: A systematic review. _Materials (Basel)_

2019; 12: 1015. * Yamaga R, Yokomizo I. Arrestment of caries of deciduous teeth with diamine silver fluoride. _Dent Outlook _1969; 33: 1007-1013. * Horst J A, Ellenikiotis H, Milgrom PL.

UCSF protocol for caries arrest using silver diamine fluoride: rationale, indications and consent. _J Calif Dent Assoc _2016; 44: 16-28. * Gao S S, Zhao I S, Hiraishi N _et al_. Clinical

trials of silver diamine fluoride in arresting caries among children: a systematic review. _JDR Clin Trans Res_ 2016; 1: 201-210. * Chen Y, Miao X. Thermal and chemical stability of

fluorohydroxyapatite ceramics with different fluorine contents. _Biomaterials_ 2005; 26: 1205-1210. * Mei M L, Nudelman F, Marzec B _et al_. Formation of fluorohydroxyapatite with silver

diamine fluoride. _J Dent_ Res 2017; 96: 1122-1128. * Mei M L, Ito L, Cao Y, Li Q L, Lo E C, Chu C H. Inhibitory effect of silver diamine fluoride on dentine demineralisation and collagen

degradation_. J Dent_ 2013; 41: 809-817. * Mei M L, Lo E C M, Chu C H. Arresting dentine caries with silver diamine fluoride: what's behind it? _J Dent_ _Res_ 2018; 97: 751-758. * Mei M

L, Li Q L, Chu C H, Lo E C M, Samaranayake L P. Antibacterial effects of silver diamine fluoride on multi-species cariogenic biofilm on caries. _Ann Clin Microbiol Antimicrob _2013; 12: 4.

* Zhao I S, Chu S, Yu O Y, Mei M L, Chu C H, Lo E C M. Effect of silver diamine fluoride and potassium iodide on shear bond strength of glass ionomer cements to caries-affected dentine. _Int

Dent J_ 2019; 69: 341-347. * Watson T F, Atmeh A R, Sajini S, Cook R J, Festy F. Present and future of glass-ionomers and calcium-silicate cements as bioactive materials in dentistry:

Biophotonics-based interfacial analyses in health and disease. _Dent Mater_ 2014; 30: 50-61. * Wang Z, Shen Y, Haapasalo M _et al._ Polycarboxylated microfillers incorporated into

light-curable resin-based dental adhesives evoke remineralization at the mineral-depleted dentin. _J Biomater Sci Polym Ed_ 2014; 25: 679-697. Download references ACKNOWLEDGEMENTS Dr Paula

Maciel Pires was undertaking a PhD exchange programme at Cardenal Herrera University during the writing up of this manuscript and that was supported by a CAPES grant from Brazil (grant

numbers 88882.424807/2018-01 and 88881.188518/2018-01). Unpublished data presented in this manuscript is part of a FAPERJ project granted to Dr Aline de Almeida Neves (E-26/203.185/2016) and

micro-CT images of SDF-treated teeth were kindly provided by Dr Andréa Fonseca-Gonçalves and Gabriella Fernandes Rodrigues from the Federal University of Rio de Janeiro. Part of this work

was also supported by 'Programa de Consolidación de Indicadores: Fomento Plan Estatal CEU-UCH 2018-2020' granted to Dr Salvatore Sauro. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS

* Department of Paediatric Dentistry and Orthodontics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Dental Biomaterials, Preventive & Minimally Invasive Dentistry,

Departamento de Odontologia, CEU Cardenal Herrera University, Alfara del Patriarca, Valencia, Spain Paula Maciel Pires * Department of Paediatric Dentistry and Orthodontics, Universidade

Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Conservative & MI Dentistry, Faculty of Dental, Oral & Craniofacial Sciences, King’s College London, UK Aline de Almeida Neves *

Department of Therapeutic Dentistry, Sechenov University of Moscow, 119435 Moscow, Russia Irina Mikhailovna Makeeva * Department of Oral Diagnostics, Digital Health and Health Services

Research Founding Chair, Berlin Institute for AI and Health Policy (BAIP) Specialist in Restorative and Preventive Dentistry Charité – Universitätsmedizin Berlin Aßmannshauser Str. 4-6

14197, Berlin, Germany Falk Schwendicke * Department of Stomatology, Medicine and Dental School, University of Valencia, 46010 Valencia, Spain Vicente Faus-Matoses * National Institute of

Advanced Industrial Science and Technology (AIST), Health Research Institute, 2217-14 Hayashi-cho, Takamatsu 761-0395, Japan; Okayama University, Graduate School of Medicine, Dentistry and

Pharmaceutical Sciences, Department of Pathology & Experimental Medicine, Japan Kumiko Yoshihara * Conservative & MI Dentistry, Faculty of Dental, Oral & Craniofacial Sciences,

King’s College London, UK Avijit Banerjee * Department of Therapeutic Dentistry, Sechenov University of Moscow, 119435 Moscow, Russia; Dental Biomaterials, Preventive & Minimally

Invasive Dentistry, Departamento de Odontologia, CEU Cardenal Herrera University, Alfara del Patriarca, Valencia, Spain Salvatore Sauro Authors * Paula Maciel Pires View author publications

You can also search for this author inPubMed Google Scholar * Aline de Almeida Neves View author publications You can also search for this author inPubMed Google Scholar * Irina Mikhailovna

Makeeva View author publications You can also search for this author inPubMed Google Scholar * Falk Schwendicke View author publications You can also search for this author inPubMed Google

Scholar * Vicente Faus-Matoses View author publications You can also search for this author inPubMed Google Scholar * Kumiko Yoshihara View author publications You can also search for this

author inPubMed Google Scholar * Avijit Banerjee View author publications You can also search for this author inPubMed Google Scholar * Salvatore Sauro View author publications You can also

search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Salvatore Sauro. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE

Pires, P., Neves, A., Makeeva, I. _et al._ Contemporary restorative ion-releasing materials: current status, interfacial properties and operative approaches. _Br Dent J_ 229, 450–458 (2020).

https://doi.org/10.1038/s41415-020-2169-3 Download citation * Received: 23 February 2020 * Accepted: 06 May 2020 * Published: 09 October 2020 * Issue Date: October 2020 * DOI:

https://doi.org/10.1038/s41415-020-2169-3 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative