15(1):47-60 (2004) Crit Rev Oral Biol Med 47

(1) Introduction

Over the past 30 years, restorative dentistry has seen a rev-olution in techniques, materials available, prevalence of

disease, and patient priorities. Today's dentist is able to pre-vent damage from caries by using materials and techniquesthat were unknown in 1970. Furthermore, the dentist'sapproach to cavity preparation in the management of caries isradically different from what it was in the past. Whereas'extension for prevention' was the main philosophy then,today the ultraconservative preservation of tooth structure isthe primary goal (Staehle, 1999). A second major force chang-ing dentistry has been the attitude of patients. Patients nolonger seek dental treatment exclusively for pain. Rather, theyare interested in better esthetics, whiter teeth, and remodeled"smiles" (Lutz and Krejci, 2001). This restorative revolution hasbeen made possible with the development of new resin-basedmaterials that can be bonded to tooth structure (Roulet andDegrange, 2001).

Not all of these changes in the restorative revolution havebeen without controversy or concern. The use of new materialswith new chemistries, the etching of dentin, and the need toensure complete polymerization and sealing of the restorationto the tooth have raised questions about the biological safety ofnew materials and techniques. Research over the past 10 yearshas partially defined the mechanisms by which resin compos-ite materials integrate with the dentin-pulp complex. It is thepurpose of this review to present recent and relevant informa-tion about the biological risks and consequences of resin-toothbonding and how these risks are affected by the material, itsclinical properties, and its manipulation by the practitioner.These biological risks are complex and interactive, and are stillincompletely defined. In broad terms, these risks can be divid-ed into those stemming from the toxicological properties of the

materials themselves (direct biological risks) and those stem-ming from microbiological leakage (indirect biological risks).

(2) The Direct Biological Risks of Resin-based Materials

The low number of reported biological problems with resin-based materials, despite the placement of millions of restora-tions worldwide, is testimony to their apparent biocompatibil-ity. However, there are also reports of post-placement toothsensitivity (Unemori et al., 2001), local immunological effects(Jontell et al., 1995), apoptotic reactions (Goldberg et al., 1994),and long-term pulpal inflammation (Hebling et al., 1999). Thereare other reports, less well-documented, that resin-based mate-rials may have systemic estrogenic effects (Schafer et al., 1999),may elicit allergic reactions (Katsuno et al., 1996), or may possi-bly even act as carcinogens (Schweikl and Schmalz, 1999).Therefore, it is imperative that we reach a more precise defini-tion of the direct biological risks associated with the use ofresin-based materials.

(2.1) THE DENTIN-PULP COMPLEX

The primary focus for the definition of the direct biologicalrisks of resin-based materials is the dentin-pulp complex(Pashley, 1996). Despite the prevailing and accepted thoughtthat this complex acts anatomically and functionally as a unit,it is instructive for us to consider the unique properties of eachcomponent of the dentin-pulp complex, to understand howresin-based materials interact with it.

Dentin is a mineralized tissue that surrounds the dentalpulp and the processes of the odontoblasts. On average, dentincontains approximately 50 vol% mineral (hydroxyapatite crys-tals), 30 vol% organic components (mostly type I collagen),and 20 vol% fluid (Mjör et al., 2001). The collagen fibrils are

BIOLOGICAL RISKS OF RESIN-BASED MATERIALSTO THE DENTIN-PULP COMPLEX

Serge Bouillaguet

Department of Cariology and Endodontics, Departement of Dental Materials, School of Dental Medicine, University of Geneva, 19 Rue Barthélemy-Menn, CH-1205 Geneva, Switzerland; serge.bouillaguet@medecine.unige.ch

ABSTRACT: Over the past 30 years, restorative dentistry has seen a revolution in materials, restorative techniques, and patientpriorities. This revolution has been made possible with the development of new resin-based materials which can be bonded tothe tooth structure. Not all of these changes have been without controversy or concern, and some have raised questions aboutthe biological safety of these new materials and techniques. It is the purpose of this review to present recent and relevant infor-mation about the biological risks and consequences of resin-tooth bonding and how these risks are affected by the material, itsclinical properties, and its manipulation by the practitioner. These biological risks are complex and interactive, and are stillincompletely defined. In broad terms, these risks can be divided into those stemming from the toxicological properties of thematerials themselves (direct biological risks) and those stemming from microbiological leakage (indirect biological risks).

Key words. Biocompatibility, composites, bonding, acid-etching, microleakage, nanoleakage.

arranged in a network, forming a matrix for the hydroxy-apatite crystals. Spaces of 20-50 nm separate fibrils about 20-100 nm in diameter (Eick et al., 1997). This network is uni-formly mineralized and forms the bulk of the dentin (inter-tubular dentin). In dentin immediately adjacent to the tubules(peritubular dentin), the mineralized component predomi-nates, and the collagen network is sparse. The dentinal tubulesrun from the dentin-enamel junction and converge on oneanother toward the pulp of the tooth (Outhwaite et al., 1976).In cross-section, the density of the tubules is about15,000/mm2 near the DEJ to over 65,000/mm2 near the pulp

(Garberoglio andBrännström, 1976).Furthermore, thetubular diameterincreases from 0.5 �mnear the DEJ to over2.5 �m near the pulp.The convergence ofthe tubules and theirincreased diametertoward the pulp areresponsible for anincrease in dentin per-meability near thepulp (Fig. 1). The per-meability of thedentin allows for bothoutward pulpal fluidflow and inward dif-fusion of chemicaland bacterial prod-ucts. Pashley (1990)has used the Hagen-Poiseuille equation toshow that fluid filtra-tion varies with thefourth power of theradius of the dentintubule, and that thedriving force is the

fluid pressure gradient. The inward diffusion of bacterial orproducts of material degradation may cause deleterious reac-tions in the dental pulp. However, the dentin acts as a diluterof diffusing substances. According to the Fick equation, therate of diffusion is dependent on the applied concentration butis inversely proportional to the dentin thickness. The surfacearea available for diffusion, the temperature, and the chemicalcharacteristics of the diffusing molecules all affect diffusion(Pashley, 1985). Dentinal diffusion of bacterial or materialproducts is a critical factor in the assessment of material bio-logical or microbiological risks. It has been clearly established

from in vitro and in vivo studiesthat outward flow of dentinalfluid cannot completely com-pensate for the inward diffu-sion of chemicals or bacteria(Fig. 2), and that the thicknessof dentin remaining betweenprepared surfaces and the pulpis the critical variable in deter-mining whether dentin canprotect the pulp (Holz andBaume, 1973; Pashley andMatthews, 1993).

The dental pulp consists ofa loose connective tissue thatoccupies the central part of thetooth. At the periphery, theodontoblasts line the dentin,and their processes extend intothe dentinal tubules for at leastseveral hundred microns (Fig.

48 Crit Rev Oral Biol Med 15(1):47-60 (2004)

Figure 1. Schematic of convergence of tubules toward the pulp. (A) Periphery of the dentin. Most surface area is occu-pied by intertubular dentin (✰), with a few tubules surrounded by hypermineralized peritubular dentin (✪). (B) Nearthe pulp, the increase in tubule diameter has occurred largely at the expense of the peritubular dentin. This substratehas a high protein content. As the remaining dentin is made thinner (from A to B), the permeability of the dentinincreases, because both diameter and density of dentinal tubules are increased. Reprinted with permission fromElsevier.

Figure 2. In vivo diffusion through dentin of a solutionof silver nitrate. (A) Diffusion of silver particles(arrows) across dentinal tubules 35 min after theapplication of a silver nitrate solution (✺) inside thecavity (HE staining x 40). (B) Penetration of silver par-ticles (✺) into the pulp area and into the capillary sys-tem active at clearing the pulp (HE staining x 40).

3). Odontoblasts are connected to eachother by gap junctions, desmosomes,and tight junctions and are highly spe-cialized in the synthesis and the secre-tion of organic molecules and the min-eralization of the dentin. Turner et al.(1989) have shown that a functionalbarrier exists between the odonto-blasts that prevents the passage ofmacromolecules from the pulp into thepredentin and dentin. They alsodemonstrated that this functional bar-rier may become permeable duringcavity preparation. This barrier mayalso be important for the function ofthe odontoblasts as a perceptualorgan. According to the hydrodynam-ic theory, dentinal pain is induced byrapid fluid shifts across dentinaltubules (Brännström and Aström,1972). These shifts are caused by tem-perature, pressure, or mechanical per-turbation and result in a mechanicaldeformation of the odontoblasts andnearby nerves. The mechanical defor-mation of A-delta nerves is responsiblefor brief, sharp pain that characterizesdentin sensitivity (Närhi, 1990). Thecentral part of the dental pulp containscells, fibers, vessels, ground substance, and interstitial fluidquite similar to that of other connective tissues. Tissue pres-sure in the pulp (called pulpal pressure) is the result of vas-cular pressure, and recent research indicates that normal pul-pal pressure is about 15 cm H2O (Ciucchi et al., 1995). In thepresence of inflammation, the pulpal vascular beds becomemore permeable, leading to localized increases in tissue pres-sure and increased pain (Heyeraas and Berggreen, 1999). Theincreased permeability of pulpal blood vessels also promotesthe release of blood plasma proteins into the pulp, andinflamed pulpal fluid is therefore more protein-rich than nor-mal pulpal fluid. These plasma proteins (mostly albumin andglobulin) may bind or agglutinate inside the dentinal tubules(Hanks et al., 1994).

After tooth formation is complete, the odontoblastsmaintain the dentin and continuously and slowly depositand mineralize new secondary dentin. The secretion of sec-ondary dentin occurs rhythmically, with a daily rate ofapproximately 5 microns. If the odontoblasts are irritated bytrauma, bacterial infection, or material degradation products,the odontoblasts form tertiary dentin over 4-6 weeks. Theexact cellular source and induction mechanisms of the pro-duction of tertiary dentin are not fully understood, but if theinsult that caused the damage is removed before pulpalnecrosis occurs, then the formation of tertiary dentin re-establishes a barrier between the insult and the pulp (Baume,1980). Thus, tertiary dentin formation, which is much fasterthan secondary dentin formation, is regarded as an impor-tant defense mechanism of the pulp-dentin complex inresponse to either pathological or physiological insults (Fig.4). The long-term evolution and treatment of the dentin-pulpcomplex are central considerations of most dental restorativeprocedures, but are becoming especially important in older

patients, in whom pulpal insults are longstanding and repar-ative processes are much less effective (Burke andSamarawickrama, 1995).

(2.2) RESIN-BASED MATERIALSAND POLYMERIZATION

The BisGMA molecule is the basis for most current resin-based materials. Several reviews of the composition andproperties of current composite restorative materials havebeen recently published (Ferracane, 1995). Composites are amixture of a polymerized resin network reinforced by a glassyfiller. The polymer is formed by polymerization of monomerslike BisGMA, urethane dimethacrylate (UDMA), and triethyl-ene glycol dimethacrylate (TEGDMA), among others.Monomers may be slightly soluble in water, but are common-ly quite hydrophobic. Dentinal bonding agents used to bondcomposite resins to tooth substrates often contain monomerssimilar to those in the composite, but nearly all contain or usehydroxyethyl methacrylate (HEMA). HEMA is amphotericand displaces water in the dentin but is also miscible withmost of the monomers of the composite. The biocompatibilityof dentin-bonding agents is imperative, since they are placedon etched dentin near the pulp, where tubular density anddiameter are greatest. Bonding agents are also at greatest riskfor incomplete cure, since they are thin and oxygen inhibitionof polymerization is a significant factor (Rueggeberg andMargeson, 1990).

Light-activated polymerization for contemporary compos-ites and adhesives is accomplished with the use of blue lightbetween 450 and 500 nm in wavelength. Typically, 500-800mW/cm2 of light for 30-40 sec (15-24 Jcm-2) is necessary topolymerize an increment of composite, which must be suffi-ciently thin to receive the full power density of the curing light.

15(1):47-60 (2004) Crit Rev Oral Biol Med 49

Figure 3. The dentin-pulp complex. The dentinand pulp exist together as an integrated unit.The functional barrier that develops betweenthe odontoblasts prevents the passage ofmacromolecules from the pulp into the pre-dentin and dentin (HE staining x 40).

Figure 4. Tertiary dentin. Tertiary dentin for-mation (arrows) is regarded as an importantdefense mechanism of the pulp-dentin com-plex in response to either pathological orphysiological insults. The presence of tertiarydentin reduces dentin permeability.

Although increments of 1 to 3 mm thick are generally used, itis important to note that a complete polymerization is neverachieved. Theoretically, a 100% conversion of monomer topolymer is possible, but as much as 25 to 50% of the methacry-late monomer double-bonds actually remains unreacted in thepolymer (Asmussen, 1982; Imazato et al., 2001). Any unpoly-merized monomer in the composite is a potential biological lia-bility if it leaches from the composite toward the pulp of thetooth (Hume and Gerzina, 1996). More recent evidence alsosuggests that extracellular or salivary enzymes may degradepolymerized networks over time, making the hydrolyzedproducts available to tissues (Santerre et al., 2001).

The shrinkage that accompanies polymerization of con-temporary composites is a significant problem to the overallbiocompatibility of these materials. Nearly all compositesshrink linearly from 0.6-1.4%, depending on the type of com-posite, the rate of cure, and the amount and nature of the filler(De Gee et al., 1993; Davidson and De Gee, 2000). Althoughshrinkage has been substantially reduced in modern compositeformulations (Labella et al., 1999), shrinkage places stress onany bonds that have been formed between the restoration andthe tooth (Davidson et al., 1984). If these bonds are broken, thena gap will form that will allow for percolation of bacterial prod-ucts into the restoration.

The risk of biological harm from degraded or unpoly-merized monomers is dependent on several key factors.First, the component must be free of the polymer to diffuseinto the pulpal tissues. Second, the component must haveproperties, such as solubility, that encourage its diffusioninto the pulp. Third, the time and dose of the pulpal expo-sure must be sufficient to cause a biological reaction, andfinally, the component must have biological properties incells that cause problems.

(2.3) BIOCOMPATIBILITY CONCEPTS

Williams has defined biocompatibility as the ability of amaterial to perform with an appropriate host response in aspecific application (Williams, 1990). This definition assumesa risk-benefit balance that needs to be evaluated. The firststep in the assessment of risk is to determine the hazardposed by components of resin-based restorative materials.Dose-response assessment is a key step in hazard identifica-tion. This assessment is achieved with in vitro cytotoxicitytests, tests for inflammation, tests for immune response,genotoxic (mutagenicity), and, finally, gene expression inodontoblast-like cell lines (Hanks et al., 1996). TheADA/ANSI Doc. 41 (1982) and ISO 10993 (1993) describethese different tests. The second step in risk assessment is todetermine the doses of the chemicals that will be released bythe material. For adhesive resins, a "dentin-barrier test" hasbeen developed to determine the concentrations of compo-nents of dental materials that might reach pulpal tissues(Hanks et al., 1988). The second tier of tests also includesintracutaneous reactivity, skin sensitization, and dentalusage tests. Characterizing the risk constitutes the final stepof the process. The dose response is compared with the esti-mated dose exposure: If the dose to cause an adverseresponse is greater than the estimated exposure by a com-fortable safety margin, the likelihood of an adverse eventoccurring in an exposed population is small, and the materi-al may be deemed to have a low risk of biological problems.

Although a few in vivo studies have attempted to docu-ment the biological risks of resin-based materials, most infor-mation on the hazards posed by the components of resin-based restorative materials has been gained from in vitrostudies. As early as 1991, Hanks et al. reported the toxic con-centrations of 11 components of dental resins on mouse fibro-blasts. Later, Ratanasathien et al. (1995) evaluated the effectsof simultaneous exposures of cells to several resins. Theydemonstrated the additive cytotoxic effects produced byHEMA when used as a solvent for BisGMA. The synergismbetween these 2 molecules has been shown to affect theapparent toxicity of each individual resin component for thecultured cells. These unique experiments established thatresins or combinations of resins alter fibroblast mitochondri-al activity. Rakich et al. (1999) demonstrated that resinmonomers are also a hazard to inflammatory cells that arecommon in the pulpal tissue, and Noda et al. (2003) haveshown that resins alter the secretion of inflammatory media-tors from human macrophages. Other studies have shownthat HEMA is able to diffuse rapidly through dentin in vitroin sufficient concentrations to cause cytotoxicity (Bouillaguetet al., 1996), and that bonding agents, as used clinically, elutesufficient amounts of monomer through dentin to cause sig-nificant cellular toxicity after 1 wk (Bouillaguet et al., 1998).The persistent cytotoxicity observed after 1 wk reinforced theneed for evaluation of the long-term effects of the resinmonomers on cellular systems. Indeed, long-term studiesthat used sublethal concentrations of HEMA (Bouillaguet etal., 2000a), TEGDMA, or BisGMA (Lefebvre et al., 1999) for 5-6 wks showed that resins clearly altered cellular mitochond-rial activity and total protein content per cell, even at concen-trations of 1-10% of those used in short-term experiments.These results confirmed that risk assessment of dentin adhe-sives must also be considered with a long-term view.

(3) The Microbiological Risks of Resin-Tooth Restorations

Post-operative sensitivity, pulpitis, and secondary caries are thethree major post-operative problems known to occur after theplacement of resin-based restorations (Mjör et al., 2000). Post-operative sensitivity is presumably caused by minute fluidmovements through open or unsealed tubules which are acti-vated by temperature, osmotic changes, or by occlusal loads(Pashley et al., 1996; Paphangkorakit and Osborn, 2000).Pulpitis and pulpal necrosis can occur because of the chemicalrisks of the materials but are more likely to occur when micro-organisms penetrate the gap formed as a result of resin poly-merization shrinkage (Bergenholtz, 2000). Secondary cariesresults when bacterial colonization of marginal gaps allows forthe dissolution of tooth structure. All of these clinical problemsare eliminated or greatly reduced when the dentin or enamel isimpregnated with resins, thereby eliminating marginal gapsand leakage and effectively sealing the tooth (Nakabayashi andPashley, 1998).

(3.1) BONDING AND SEALING

Buonocore's acid-etch technique, introduced in 1955 andrefined later by Silverstone (1975), has been shown to providea good seal between resin-based materials and etched enamel.This seal is a result of the penetration of an adhesive intomicroporosities created by differential etching of enamel

50 Crit Rev Oral Biol Med 15(1):47-60 (2004)

prisms. The goals of enamel etching are to clean the enameland to remove the enamel smear layer. Etching results in ahigh-energy surface that allows for good wetting by thehydrophobic bonding resin and good penetration of the resininto the microporosities (Fig. 5).

Whereas bonding of resin-based materials to acid-etchedenamel has become routine and reliable, different, more com-plex procedures have been required for bonding to dentinbecause of the completely different nature of the dentin sub-strate. Bonding to dentin is further complicated by the forma-tion of a smear layer during cavity preparation (Pashley, 1989).However, good dentin bonding and sealing are possible withthe use of adhesives with complex chemistries. Use of theseadhesives requires multi-step and demanding attention toclinical details (Van Meerbeek et al., 1998a). Two categories ofadhesive systems are currently available: total-etching andself-etching adhesives.

Total-etching adhesives

These require relatively high concentrations of acids (32-37%phosphoric acid) applied to dentin in a separate etching step.After 15 sec of etching, a water rinse removes the acid and dis-solved mineral and leaves the acid-insoluble collagen fiberssuspended in the water. This collagen network is highlyhydrophilic and particularly sensitive to dehydration andshrinkage (Pashley et al., 1993). The next step in the bondingprocess is to embed these fibrils with resins. One approach isto use an aqueous solution of hydrophilic monomers such asHEMA in an intermediate step called priming (Nakabayashiand Takarada, 1992). When gently dried with air, the HEMA-water-collagen mixture will slowly dehydrate but will remainfully expanded to allow for the subsequent incorporation ofthe adhesive resin (Pashley et al., 2000). This bonding strategyis used by the so-called three-step total-etching adhesive sys-tems (Fig. 6).

Some manufacturers have developed "one-bottle" adhe-sives that contain mixtures of organic solvents and resins(HEMA, BisGMA, TEGDMA, UDMA) to impregnate the col-lagen-water network. These organic solvents (acetone oralcohol) quickly displace water in the collagen network,because the driving force for water removal is greater than

with the HEMA-water primers (Fig. 7). Therefore, these mix-tures achieve a dynamic dehydration, because the stiffeningof the collagen fibers and the incorporation of the bondingresin occur simultaneously (Maciel et al., 1996). However,recent research indicates that one-bottle adhesives increasethe shrinkage of wet-decalcified dentin, thereby reducinginfiltration of resin monomers (Nakajima et al., 2002). The

15(1):47-60 (2004) Crit Rev Oral Biol Med 51

Figure 5. Bonding resin-based materials to enamel. Acid-etching ofenamel prior to adhesive application allows for a good wetting ofthe surface by the hydrophobic resin and a good penetration into themicroporosities created by the acid (orig. mag. x 2400).

Figure 6. Modified SEM illustrationof bonding to dentin with conven-tional (three-step) total-etching adhe-sives. (A) Acid etching of the dentin.The smear layer has been removed,and both peritubular and intertubu-lar dentin is demineralized. Theexposed collagen fibers are highlyhydrophilic (blue) and particularlysensitive to dehydration. (B) Primingof the dentin. The water has beenreplaced by hydrophilic primers(orange) which have impregnated

the collagen fibers. Priming with water-based primers is a slow dif-fusing process. The evaporation of the water solvent will leave thecollagen fibers coated and stiffened by the resins. The substrate haschanged from hydrophilic to hydrophobic. (C) Application of theadhesive resin. The hydrophobic resin (red) diffuses into the denti-nal tubules and impregnates the entire depth of the demineralizeddentin before being polymerized.

Figure 7. Modified SEM image of bonding to dentin with one-bottle(two-step) total-etching adhesives. (A) Acid-etched dentin (blue). (B)Application of the primer/adhesive mixture. The organic solventsused in these mixtures (green) quickly displace water in the collagennetwork because of the diffusion gradient they create between thewater of the collagen and solvent in the bonding agent. Therefore, theincorporation of the primer and the bonding resin inside the collagennetwork can occur simultaneously.

advantage of these systems is the elimination of priming as aseparate step, simplification of the procedure, and savings inclinical time.

Whether a separate priming step is used or not, whenadhesive resins penetrate the intertubular demineralizeddentin and polymerize around the collagen fibrils, they formthe so-called 'hybrid layer' (Nakabayashi et al., 1982). Dentinhybridization also occurs at the periphery of dentin tubules,where the peritubular dentin was dissolved and resin plugs areformed. This process is referred to as the hybridization of theresin tag (Nakabayashi and Pashley, 1998). The intimatehybridization of both the intertubular and peritubular dentincontributes to the sealing and bonding of resin-based materialsto dentin.

Self-etching adhesives

These are an alternative clinical approach to total-etchingsystems. Self-etching adhesives contain acidic monomerscombined with hydrophilic monomers that simultaneouslyetch and prime the dentin. For most systems of this nature,the etch-prime step is followed by the application of theadhesive resin. Theoretically, the adhesive resin infiltrates tothe same depth as the acidic primer exposed the collagen indentin (Fig. 8). This hypothesis has been recently confirmedby laser Raman microscopy (Miyazaki et al., 2002). Becauseself-etching adhesives eliminate the rinsing of the etchantand the drying of the water necessary in the total-etching sys-tems, they are simpler to use and may provide more consis-tent clinical results. Hybrid layers formed by self-etchingadhesives on sound dentin are generally thinner than thoseproduced by total-etching systems. Further, the resin tags areshallower, and the sealing and bonding may rely mostly onintertubular hybridization in normal dentin (Inoue et al.,2000). Self-etching adhesives do not bond as well to enamelas do total-etching systems, and recent research indicates thatthe quality of the resin-dentin bonds formed by such adhe-sives is directly related to the aggressiveness of the system(Tay and Pashley, 2001). Manufacturers are currently tryingto perfect new adhesive systems that condense etching, prim-ing, and bonding into a single step. These 'all-in-one' adhe-sives are in their infancy and will likely undergo significantevolution in coming years.

There are differ-ent methods for mea-suring bonding andsealing of resins todentin. Ciucchi et al.(1997a) evaluated thesize and volume of thegap formed in vitrobetween resin-basedmaterials and dentinduring polymeriza-tion. Their resultsclearly showed thatresin-based materialsthat bond to dentinhad the smallest gaps.However, none of thematerials was withoutsome gaps, indicatingthat polymerization

shrinkage forces exceeded the dentin bond strengths in atleast some areas of the restoration. Other studies have direct-ly measured the ability of dentin adhesives to limit fluid flowthrough dentin and therefore seal the dentin tubules(Bouillaguet et al., 2000b). The results showed that no mater-ial completely sealed the dentin, but that most contemporaryadhesive systems significantly reduced fluid movement (by> 95% in many cases). Collectively, these studies indicate thatdentin-resin bonds are critical to maintain a seal and to resistpolymerization shrinkage stresses, thereby limiting themicrobiological risks. Another method for measuring theability of adhesives to resist polymerization shrinkage forcesassesses their microtensile bond strengths to dentin (Sano etal., 1994a). A microtensile bond test is used because it is themost accurate measure of composite-dentin bond strength(Pashley et al., 1999). Generally, for the comparison of mate-rials, dentin adhesives are applied on flat dentin to avoid theinfluence of cavity geometry on bonding. Recent research hasindicated that the conventional three-step total-etching adhe-sives were best able to bond composite to dentin under thesecircumstances. The two-step total-etching system and theself-etching system gave comparable bond strengths, but theone-step self-etching system was not as reliable as the othersystems (Bouillaguet et al., 2001a; Inoue et al., 2001). Almostall in vitro bonding studies are done on flat dentin surfaces,yet, clinically, such surfaces are seldom encountered. Otherstudies have evaluated the influence of cavity geometry onbonding, in Class I or Class II MOD cavities, and showed thatbond strengths to cavity walls were reduced by 20% com-pared with flat dentin, where no polymerization stress is pre-sent (Yoshikawa et al., 1999; Bouillaguet et al., 2001b). Theauthors cautioned in interpreting bond strengths obtained onflat surfaces, because these studies probably overestimatedentin bond strengths in most cases. This point is important,since the flat system is often used by manufacturers to pro-mote their products. The ability of the materials to bond todentin is further compromised by their often complex andtechnique-sensitive nature. The ability of an operator tonegotiate these complexities is therefore an important factorin the successful management of these materials. Few studieshave investigated the influence of the operator on the quali-ty of resin-dentin bonds. However, there is increasing evi-

52 Crit Rev Oral Biol Med 15(1):47-60 (2004)

Figure 8. Modified SEM image of bonding to dentin with (two-step) self-etching adhesives. (A) The smear-layercovering the dentin surface and the smear-plugs occluding the dentinal tubules are impregnated by the self-etch-ing primer (light blue). (B) Application of the acidic primer. The acidic resin (blue) has dissolved and impregnat-ed the smear layer. The resin has also penetrated the dentinal tubules. (C) Dentinal substrate after application ofthe adhesive resin. Theoretically, the adhesive resin (purple) infiltrates to the same extent as the acidic primerexposed the collagen.

dence that the influence of the operator is of paramountimportance in the performance of dentin-bonding agents(Ciucchi et al., 1997b; Finger and Balkenhol, 1999; Bouillaguetet al., 2002).

Studies show that contemporary dentin adhesives have thepotential to provide a good, but not complete, seal of thedentin. The type of product is important, as is the configurationof the cavity preparation with respect to the ultimate bondstrength and seal obtained. The clinical environment is com-plex and often compromises the conditions necessary to obtainthe best dentin seals and the lowest microbiological risks. Thus,the risk of microbiological contamination remains in the clini-cal situation.

(3.2) MICROLEAKAGE AND NANOLEAKAGE

Failure of dentin adhesives to seal the dentin and the enamelresults in microleakage or nanoleakage. Leakage has beenshown to occur at the margins of the restoration, but may alsobe limited to internal aspects of the restoration. Thus, both themarginal (peripheral) seal and the internal dentinal seal areimportant to the longevity of resin-based restorations.Although a few in vivo studies have attempted to documentthe presence of leakage (Ryge, 1981), most information onmicroleakage has been gained from in vitro studies. Asdefined by Kidd (1996), microleakage is the passage of bacte-ria, fluids, molecules, or ions between a cavity wall and therestorative material. Microleakage gaps are many microme-ters wide and result from either a lack of primary bonding orthe secondary loss of bonding. Primary bonding may be lostwith time because of occlusal forces or hydrolytic degrada-tion. However, the most likely cause of microleakage is fromthe volumetric shrinkage that occurs concurrently with poly-merization of the resin. If the resin-tooth bond is too weak,polymerization forces will debond the resin from the tooth,and microleakage will result. The ability of the resin-toothbond to resist polymerization shrinkage forces depends onmany complex and interacting factors. The nature of the resinshrinkage first depends on the shape of the cavity preparationand the ratio of bonded to unbonded (or free) surfaces (Feilzeret al., 1987; Davidson and Feilzer, 1997). This so-called C-fac-tor is a clinically relevant predictor of the risk of microleakagedevelopment. Restorations with high C-factors (> 3.0) are atgreatest risk for debonding and microleakage (Yoshikawa etal., 1999). The stress at the tooth-resin interface is also influ-enced by the kinetics of the polymerization reaction. A resin-based material will flow plastically to accommodate shrink-age until it reaches the so-called gel-point, after which flowcannot occur and the stress of polymerization contraction willbe directly transmitted to the tooth-resin interface. If the cur-ing is done rapidly, as with high-intensity curing units, thenthe gel-point is reached earlier and more shrinkage stress istransmitted to the interface. Therefore, high polymerizationrates are more likely to cause debonding and microleakage(Yoshikawa et al., 2001).

Unlike microleakage, nanoleakage may result even whenthe bond between the tooth and resin is intact. If the adhesiveresin does not completely infiltrate the demineralized dentin,some of the collagen network will contain small nanospacesbetween the hybrid layer and the mineralized dentin. Thesespaces have been verified by experiments with silver nitrateand scanning electron microscopy (Sano et al., 1994b). The

spaces appear to be contiguous because the silver nitrate candiffuse well into interface, even when no interfacial gap(microleakage) is present. Sano and co-workers coined theterm "nanoleakage" to distinguish this type of leakage frommicroleakage (Sano et al., 1995). All adhesive systems exhibitsome degree of nanoleakage, although some systems havemore nanoleakage than others.

In total-etching systems, the water used to rinse the acidmust be removed with air before priming occurs. If too littlewater is removed, then bonding is compromised, because theprimer and adhesive resin cannot penetrate the hydrophilicenvironment (Tay et al., 1996) and cannot polymerize. If toomuch water is removed, then the collagen network will col-lapse and will not be effectively infiltrated by the primer oradhesive resin. To a lesser degree, primers that use organic sol-vents such as acetone also cause a shrinkage of the network(Nakajima et al., 2002). Any factor that limits infiltration of thecollagen-water network by resin results in at least somenanoleakage. Nanoleakage may also result from the incom-plete diffusion of high-molecular-weight resin monomers intothe primed collagen network, simply because of inadequatetime for the diffusion to occur. If the resin adhesive containsfillers, then its ability to penetrate the network is further com-promised. Regions of demineralized dentin that have not beensuccessfully embedded with resin have been implicated asweak links in dentin-resin bonding. Furthermore, the exposedcollagen network may make the resin-collagen hybrid layermore susceptible to hydrolytic degradation over the long term(De Munck et al., 2003).

With self-etching systems, the risk of nanoleakage islower, because the acidic monomer that etches the dentin isalso the primer. Thus, the adhesive resin is more likely to infil-trate to the complete depth of the etching. However, traces ofacid or solvent may remain impregnated within the adhesiveand subsequently inhibit the polymerization of themonomers. Further, recent research indicates that the newerself-etching adhesives are semi-permeable membranesbecause of the high hydrophilicity of these resins (Tay et al.,2002, 2003). The existence of both microleakage and nanoleak-age has been well-documented. It is clear that microleakagehas deleterious consequences for resin-based restorations bygreatly increasing the microbiological risks (Bergenholtz,2000). However, the clinical consequences of nanoleakage areless clearly understood.

(4) Clinical Perspectives on Resins and Resin-bonding/sealing

Adhesive resins can be used safely for numerous clinical appli-cations if care is taken to control substrates, chemistry, andpolymerization. Further, adhesive systems have the potentialto seal restorations and consequently to offer an effective pro-tection to the dentin-pulp complex against microbiologicalrisks. This potential, however, is not realized because of thecomplexity of the bonding procedures, which are often poorlyunderstood by the average clinician.

(4.1) CLINICAL PERSPECTIVES ON RESIN TOXICITY(MINIMIZING DIRECT BIOLOGICAL RISKS)

Although factors (such as remaining dentin thickness, dentinpermeability, and dentin location) that alter the diffusion andinfluence the toxicity of resins have been identified, one funda-

15(1):47-60 (2004) Crit Rev Oral Biol Med 53

mental clinical problem is that a dentist has only a subjectiveidea of these factors when preparing a cavity for a resin-basedrestoration. Fortunately, some clinical recommendations can bemade to minimize direct biological risks.

Cavity preparation

Cavity preparations in vital teeth are usually performed underlocal anesthesia. Local anesthetics contain vasoconstrictors thatmay compromise pulpal blood clearance that is normally veryefficient (Kim and Dörscher-Kim, 1990). The dentinal fluidpressure, which is normally outward from the pulp and tendsto reduce ingress of substances, is therefore reduced. Thus,direct biological risks of resin-based materials may increase sig-nificantly during cavity preparation. Treatment of caries lesionsinvolves removal of infected tissues but requires the preserva-tion of the hypermineralized dentin (transparent layer) locatedat the front of the lesion. This layer is much less permeable thantubular dentin and therefore offers much more resistance to thediffusion of materials toward the pulp.

Selecting an adhesive

To minimize direct biological risks associated with the use ofresin-based materials, one should carefully evaluate the biolog-ical risks of each adhesive system under relevant clinical con-ditions. Shallow cavities located in superficial or scleroticdentin do not pose a major biological risk, because the perme-ability of the dentin is low and the thickness of the remainingdentin is adequate to prevent any adverse effects from diffus-ing materials (Mjör and Ferrari, 2002). Therefore, total-etchingadhesives that provide reliable bonding to enamel and dentinare recommended. On the other hand, deep cavities closer tothe pulp are more challenging for the clinician because of theintrinsic permeability and wetness of the dentinal substrate.Gwinnett and Tay (1998) observed a persistent inflammationand granulomatous reaction in human pulp in response to theapplication of a total-etching adhesive to deep dentin. Theyalso reported the presence of resin globules displaced into thedentin tubules and penetrating the pulp. In deep dentin, theetching as a preliminary step of the bonding process will makethe substrate even more permeable and hydrophilic. Increasedhydrophilicity limits the wetting of the tubule wall by theresins, may allow the dentin surface to be contaminated bydentinal fluid, or may interfere with the polymerizationprocess. Therefore, the use of self-etching adhesives systems isindicated for young, deep, permeable dentin, because self-etch-ing adhesives often leave some residual smear plug material inthe tubules which limits the diffusion of uncured monomerstoward the pulp (Tay et al., 2000).

Conversion of monomers

It is generally accepted that the better the polymerization, thelower the biological risks (Kaga et al., 2001). Clinically, thepolymerization of resin-based materials is achieved with lightenergy, and there is a great deal of interest in developing high-power curing units. With these units, the dentist can curefaster and the material may have better biological properties,because increased conversion rates of monomer to polymerare expected. However, the use of high-output energy lights iscontroversial, because it is not clear if the energy emitted bythe unit is totally absorbed by the photo-initiators (CQ orPPD) to initiate polymerization. Wavelengths outside those

necessary to activate these photo-initiators do not improvethe cure of the resin, but do increase the overall risk to thepulp from secondary generation of heat (Hannig and Bott,1999). Most recent developments in light-curing units arefocusing on blue-emitting diodes (LEDs), which do not gen-erate heat (Nomura et al., 2002). However, temperature risemay also occur because of the exothermic polymerization ofthe composite material.

Long-term degradation

The long-term clinical degradation of resin-based materialsand dental adhesives is not known in detail but has beenreported for some materials (Hashimoto et al., 2000). Clinically,the long-term toxic effects of resin-based materials are extreme-ly difficult to distinguish from the effects of microleakage andbacterial contamination. It is likely that both factors contributeto pulpal stress and disease. Furthermore, it is likely that, clin-ically, pulpal cells that have chronically suffered from exposureto toxic components of resins will respond differently to bacte-rial challenge compared with healthy cells. In vitro evidencesuggests that these interactions between resin components andbacterial products may increase or decrease the body's abilityto respond appropriately (Rakich et al., 1999). Such interactionsare critical to the biocompatibility of any material, and suchdata are not clinically available. Ideally, the dentist would liketo know the inflammatory status of the pulp and the history ofexposure to components of material or bacteria. These factorsare significant to the patient, because the death of an over-stressed pulp leads inevitably to pain and significant restora-tive preparation time and costs.

(4.2) CLINICAL PERSPECTIVES ON RESIN-TOOTHBONDING (MINIMIZING MICROBIOLOGICAL RISKS)

Clinically, the biggest problem with bonding resin-based mate-rials to teeth is that the clinician will have no indication of howsuccessful the bond is until many years later. There is no wayfor the clinician to measure the strength of the bond, the seal ofthe dentin, or the presence of bacteria beneath the restoration.Yet each of these factors is critical to the longevity and overallsuccess of the restoration. This section will focus on the clinicalstrategies used to minimize the microbiological risks withresin-based restorations.

Complete removal of micro-organisms

A preliminary step in the placement of resin-based restora-tions is the complete removal of micro-organisms inside thecavity. This requirement is based on the concept that bacterialinfection or re-infection from residual micro-organismsbeneath the restoration induces pulpal inflammation andnecrosis (Bergenholtz, 2000). Bacterial removal has to be bal-anced with the conservation of the inner part of the carieslesion (transparent layer). Caries-disclosing solutions are usedfor this purpose. However, these dyes cannot detect bacteriawithin the dentin tubules. Thus, caries-disclosing solutions areuseful but cannot guarantee the complete elimination of bac-teria from a cavity preparation. Current clinical practice alsoadvocates the use of dental rubber dam to avoid the bacterialcontamination of the cavity that may occur from outside thecavity preparation (e.g., saliva). Aside from a better control ofthe operating field, the use of a rubber dam has a positiveeffect on the quality of some adhesive systems (Hitmi et al.,

54 Crit Rev Oral Biol Med 15(1):47-60 (2004)

1999). However, the prevention of external contamination ofthe cavity preparation is often not straightforward, becausebacterial contamination may also come from water lines ofdental units (Tonetti-Eberle et al., 2001).

Using disinfectants

Previous studies have shown that rinsing cavity surfaces withsodium hypochlorite solutions (3-10%) or hydrogen peroxide(3%) reduces bacterial load. Sodium hypochlorite has proteo-lytic properties, hydrogen peroxide is oxidative, and both dif-fuse through dentin (Hanks et al., 1994). Thus, these agents maykill bacteria within dentin tubules, but may also carry a certainbiological risk of their own (Costa et al., 2001). Because there issome evidence that cavity disinfectants such as hypochloriteinterfere with bonding and polymerization of resins, the rou-tine use of these agents is not recommended (Lai et al., 2001;Osorio et al., 2002). Furthermore, acid-etching and self-etchingresins are probably bactericidal to some degree, because mostbacteria cannot survive in extremely low pH conditions(Murray et al., 2002). Therefore, cavity disinfection withhypochlorite or peroxide may be superfluous.

Embedding bacteria with resins

For many years, controversy has raged about the ability ofresidual bacteria to survive or multiply in a cavity prepara-tion sealed with resins. However, the work of Mertz-Fairhurstand co-workers (1995) clearly demonstrated that Class I cariescan be arrested by the placement of sealed posterior compos-ite restorations on top of the caries lesions without theremoval of the caries lesion. The results of this study serious-ly challenged the need for cavity disinfection if a sealedrestoration can be obtained. However, a complete seal of thecavity may be compromised by infected dentin, poor bond-ing, and polymerization shrinkage. Therefore, relying on theintegrity of the seal to limit bacterial growth may not alwaysbe wise in practical terms.

Selecting an adhesive system

Bacterial leakage and sealing of dentin are interdependent, andgood sealing always results in a lower microbiological risk.Many reports have confirmed the superiority of total-etchingadhesives over self-etching adhesives in terms of bond strengthto dentin (Van Meerbeek et al., 2001). This superiority has alsobeen confirmed for enamel bonding and resin bonding to scle-rotic and caries-affected dentin (Inoue et al., 2001). Therefore,total-etching adhesives are the material of choice for most clin-ical applications. However, inadequate bonding with total-etching systems can be observed when resin penetration isincomplete. Clinically, the biggest drawback of total-etchingsystems is the control of moisture. Achieving the appropriateamount of dentin wetness causes much of the clinical confu-sion. Overdrying or overwetting the tooth will significantlycompromise the quality of the resin bond to dentin (VanMeerbeek et al., 1998b). These decreased bond strengths arecaused primarily by a decreased intertubular permeability ofdentin to adhesives (Fig. 9). Adhesives have various abilities toaccommodate overwettness or overdryness. Water-ethanol sys-tems are favorable in this regard compared with acetone-basedsystems. Water-ethanol systems are therefore considered moreuser-friendly (Perdigão and Frankenberger, 2001).

Because they eliminate the need for a separate etching-

rinsing step, self-etching adhesives are less sensitive to mois-ture conditions than are total-etch systems. This fact has beenthe primary driving force for the development and clinical useof the self-etching systems. However, most current researchalso agrees that the quality of self-etching bonds to enamel,sclerotic dentin, and caries-affected dentin is inferior to thatobtained by a total-etching system (Yoshiyama et al., 2002).Although the cause of poorer bonding is not completelyknown, it is likely that the relatively weak acidity of the acidicprimer plays a role, because this weaker acid would not etchthese substrates as well as would phosphoric acid (Tay et al.,2000).

In addition to the wetness of the dentin, the thickness ofthe adhesive layer contributes to the strength and durability ofthe bonds (Abdalla and Davidson, 1993). The adhesive resinshould be spread uniformly onto surfaces, with an optimalthickness to provide sealing and to act as a stress absorber dur-ing composite shrinkage (Choi et al., 2000). Despite differencesamong materials, research supports the concept of thick adhe-sive layers acting as stress absorbers (Zheng et al., 2001).

Control for polymerization shrinkage stresses

The management of shrinkage stresses during polymerizationis a critical factor in the clinical performance of dental adhe-sives. Poor management of the shrinkage stresses that developduring the curing of the restorative material can cause the fail-ure of a restoration that is otherwise well-managed and well-placed. Among current adhesive materials, the shrinkage of theresin is unavoidable to some degree. However, proper clinicalmanagement can minimize the impact of polymerizationshrinkage on the clinical performance of the restoration. Twofactors in the management of polymerization shrinkage are themethod of curing and the manner in which composite is insert-ed into the cavity.

Early in the development of resin-based materials, theconcept of incremental addition of material to the cavity, com-bined with the use of the so-called "directed-cure", was pro-posed as a clinical solution to volumetric shrinkage (Lutz etal., 1992). In recent years, several new light-curing conceptshave been introduced with the goal of improving compositeproperties and reducing stress from polymerization shrinkage

15(1):47-60 (2004) Crit Rev Oral Biol Med 55

Figure 9. Defective bonding. SEM micrograph of a specimen thatwas overdried after the etching gel was rinsed off. In such cases, theadhesive resin cannot penetrate the demineralized dentin because ofthe collapse of the collagen network (arrows) (orig. mag. x 10,000).

(Versluis, 2000). Pulse-delay curing relies on the concept thatan initial, low-energy pulse of curing light will start, but notcomplete, the polymerization reaction. This slows polymer-ization and allows shrinkage stresses to be dissipated by flowof the material, before the gel point of the polymer has beenreached. After some time, a higher-energy light pulse isapplied to complete the polymerization (Sahafi et al., 2001).Exponential curing is conceptually similar to pulse-delay cur-ing, except that the application of light is continuous, withintensities that are exponentially modulated from low to high.There is some evidence that these strategies do reduce poly-merization stresses (Bouschlicher and Rueggeberg, 2000). Inan effort to cure larger increments of composite faster, inves-tigators have developed newer lights with high outputs.Plasma-arc-curing (PAC) lights may emit 2000-2500 mW/cm2

and therefore are purported to cure composites in muchshorter times (3-10 sec). However, the shrinkage stresses dur-ing curing are probably higher, because the composite reach-es its gel-point early in the polymerization process, and allsubsequent shrinkage stress is then transferred to the resin-tooth interface. Finally, one must remember that the self-cur-ing composites (also called chemical curing) offer the clinicaladvantages of a relatively slow cure rate (therefore limitingshrinkage stress) and a complete cure independent of cavitydimension, depth, or accessibility to light (Feilzer et al., 1993).Therefore, self-cure resins have been used by some practition-ers in combination with more superficial layers of light-curedresins.

A variety of restorative techniques has been used clinical-ly to control polymerization shrinkage stresses. These tech-niques can be divided into direct and indirect strategies. Thedirect method cures the composite in situ, whereas indirectmethods fabricate and cure most of the bulk of the restorationin a model or die of some type. The motivation for the indirecttechnique is that the composite can be cured with times,intensities of light, and temperatures that would not be possi-ble clinically. In this manner, it has been proposed that mostof the shrinkage occurs before the restoration is cemented.The problem with this technique is that a tremendous poly-merization stress occurs within the luting resin cement,because an extremely high C-factor may occur if the cavitydesign is not appropriate. Further, previous research indicatesthat, in a rigid situation (e.g., inlay cementation), the contrac-tion stresses that develop during cementation are stronglyrelated to the resin layer thickness and the compliance of thesubstrate (Alster et al., 1995, 1997). Thus, ironically, indirectstrategies may be worse than direct strategies in terms ofpolymerization stresses. The indirect method may be success-ful if the cavity can be designed to maximize free surfaces orthe inlay can be fabricated to allow for some free cementationspace. The dual-bonding technique has been used to cementindirect restorations. In this technique, the clinician must pro-tect the pulp of the tooth during the time the inlay is beingfabricated. The adhesive layer is applied to the cavity surfacesbefore an impression is taken for the fabrication of a laborato-ry-made restoration. Thus, the dentin is sealed and the pulp isprotected against bacterial leakage, thereby reducingmicrobiological risks (Paul and Schärer, 1997). The restorationis then luted with adhesive resins during the second visit. Theuse of slow-curing cements (dual-curing cements) will help toreduce the polymerization stresses during cementation,although some clinicians recommend only light-cured

cements for indirect restorations.In direct restorations, several techniques have been used

to limit polymerization stresses, thereby reducing microbio-logical risks. Generally, a total bonding strategy is used inthese types of restorations. For the total bonding concept, theentire cavity surface is covered with the adhesive, and the fill-ing material is incrementally polymerized onto it. The adhe-sive layer is thick enough to absorb polymerization shrinkagestresses. Choi and co-workers (2000) have reported that stresswas significantly absorbed and relieved by the application ofan increasing thickness of low-stiffness adhesive. Some clini-cians have also advocated the use of flowable materials at thebase of the restoration to absorb these stresses. In general, bycarefully curing the different increments of composites insidea low configuration factor cavity, the clinician can maintainstresses at a low level using this technique. When the configu-ration factor is higher (e.g., in Class 1 or 5 cavities), shrinkagestresses increase the risk that polymerization stresses will putthe integrity of the restoration at risk. Under such conditions,the use of the selective bonding concept may be indicated(Krejci and Stavridakis, 2000). The concept of selective bond-ing is to pre-determine the location of the failure in case ofexcessive stress. The goal is for the dentin to remain sealedeven if polymerization stresses become acute in an area of theinternal part of the restoration.

(5) Perspective on Bonding Resins to the Dentin-Pulp Complex

The various issues that influence the biocompatibility of adhe-sive materials are complex and interactive and not fully under-stood. However, there are several developments in evaluationmethods, clinical techniques, and materials that may help usbetter estimate these risks and improve the reliability of resin-based restorations. One significant problem with today's eval-uation of biological risks is the inability of current in vivo oranimal tests to adequately predict the long-term response ofthe human pulp. Improvements in in vitro tests, including testsfor leakage, could give them a greater potential to evaluate thebiological risks of new materials. The application of new mate-rials and techniques will be optimized only if the dentist canproperly and rapidly diagnose the problems. The future willprobably include much-improved diagnostic tools, like newtechniques to detect caries. Another likely diagnostic tool willprobably focus on the measurement of the remaining dentinthickness (RDT). The RDT is paramount to the selection andclinical success of an appropriate treatment (About et al., 2001;de Souza et al., 2003). In addition to new diagnostic methods,new materials and dental adhesives are likely to be devel-oped. Adhesives and adhesive strategies will likely be adapt-ed or even customized to deal with a variety of bonding sub-strates, including enamel, dentin, sclerotic dentin, and caries-affected dentin. Newer adhesives will probably have newchemistries, focus on both chemical and mechanical bonding,be more water-resistant, easier to manipulate, and less sus-ceptible to operator error. In addition to new adhesives, thefuture will likely bring new resin restorative materials withreduced polymerization shrinkage and shrinkage stress.Some recent developments in dental composite research havefocused on the use of resin-based materials containing a mix-ture of oxiranes and polyol that can polymerize by light acti-vation (Eick et al., 2002). With these new chemical structures,

56 Crit Rev Oral Biol Med 15(1):47-60 (2004)

suitable formulations can be designed for the development ofdental composites with acceptable mechanical and biologicalproperties.

SummaryOver the last decades, the development of resin-based materi-als has provided the clinician with many techniques and mate-rials with which to restore tooth structure, esthetics, and func-tion. The clinical success of these new restorative techniqueshas been attributed to the ability of resin-based materials to sealthe resin-tooth interface in the absence of any adverse biologi-cal effect. Although recent literature indicates that the risks ofacute pulpal toxicity to resins are unlikely, it is clear that today'stests are not adequate to predict long-term clinical biologicalrisks. The formation of a perfect seal around resin-basedrestorations is further required to offer an effective protectionto the dentin-pulp complex against microbiological risks.Although most adhesive systems have the potential to sealrestorations, research has shown that sealing of cavities withresin-based materials is not always predictable. Fortunately,there are several anticipated developments in evaluation meth-ods, clinical techniques, and materials that may help us betterestimate these risks and improve the reliability of resin-basedrestorations.

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