Japanese Dental Science Review: Jorge Perdigão
Japanese Dental Science Review: Jorge Perdigão
Japanese Dental Science Review: Jorge Perdigão
Review Article
a r t i c l e i n f o a b s t r a c t
Article history: The essential goal of any adhesive restoration is to achieve a tight and long-lasting adaptation of the
Received 5 June 2020 restorative material to enamel and dentin. The key challenge for new dental adhesives is to be simul-
Accepted 24 August 2020 taneously effective on two dental substrates of conflicting nature. Some barriers must be overcome to
accomplish this objective. While bonding to enamel by micromechanical interlocking of resin tags within
the array of microporosities in acid-etched enamel can be reliably achieved and can effectively seal the
restoration margins against leakage, bonding effectively and durably to organic and humid dentin is the
most puzzling task in adhesive dentistry.
Much of the research and development of dental adhesives has focused on making the clinical procedure
more user-friendly by reducing the number of bottles and/or steps. Although clinicians certainly prefer
less complicated and more versatile adhesive materials, there is a trade-off between simplification of
dental adhesives and clinical outcomes. Likewise, new materials are launched with claims of being novel
and having special properties without much supporting evidence.
This review article discusses dental adhesion acknowledging pioneer work in the field, highlights the
substrate as a major challenge to obtain durable adhesive restorations, as well as analyzes the three
adhesion strategies and their shortcomings. It also reviews the potential of chemical/ionic dental adhe-
sion, discusses the issue of extensively published laboratory research that does not translate to clinical
relevance, and leaves a few thoughts in regard to recent research that may have implications for future
adhesive materials.
© 2020 The Author. Published by Elsevier Ltd on behalf of The Japanese Association for Dental
Science. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).
1. Introduction When clinical studies are completed, often a new version of the
same material has already been made available on the market. In
Dental adhesion was responsible for a paradigm shift in den- fact, dental adhesives can be launched without proof of clinical
tistry (Table 1). Dental adhesives have become one of the most efficacy, as the FDA usually reviews “the Section 510(k) premar-
intriguing biomaterials in Health Sciences. Research efforts in the ket notification of intent to market the device and determines the
last 20 years have shifted from clinically-proven multi-step den- device to be substantially equivalent to legally marketed predicate
tal adhesives to simplified versions that do not perform adequately devices” used for the same indications [3–5].
in laboratory and clinical studies [1,2]. The ideal goals for clinical It is extremely difficult for practicing dentists to keep updated
effectiveness and durability of the restorations have been fre- as so many dental adhesives are constantly launched on the market
quently neglected in favor of fewer number of bottles and quicker and updated or relaunched within short periods of time. In addition,
application of newer dental adhesives. dentists do not have access to the latest evidence-based informa-
Several obstacles must be overcome to accomplish the objective tion. As a result, dentists rely on the information provided by the
of developing a dental adhesive that bonds effectively to enamel industry representatives or information disseminated in contin-
and dentin, and achieves durable restorations that seal the margins uing education courses and dental meetings, often without solid
and provide some form of resistance to recurrent caries lesions. evidence to support the claims [6].
The continuous development and frequent introduction of den- The objective of this review article is to summarize the current
tal adhesives render existing materials outdated within a few years. evidence on dental adhesion, from the challenging substrate to the
latest trends, many of which do not extrapolate to sound evidence
pertinent to clinical practice.
https://doi.org/10.1016/j.jdsr.2020.08.004
1882-7616/© 2020 The Author. Published by Elsevier Ltd on behalf of The Japanese Association for Dental Science. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
J. Perdigão / Japanese Dental Science Review 56 (2020) 190–207 191
Table 1
Changes that resulted from the introduction of adhesives in Dentistry.
Positive Negative
The use of dental adhesives has expanded across different dental disciplines Clinicians tend to rely solely on adhesion as the source of primary retention in
(Operative Dentistry, Orthodontics, Pediatric Dentistry, Periodontology, clinical situations without enamel margins or without enough residual tooth
Prosthodontics, Endodontics) structure, as in core build-up composite resin restorations
Dental adhesives are used to retain a wide range of restorative materials – Potential for marginal bacterial leakage when the cavo-surface margin is in
glass-matrix ceramics, oxide ceramics, pre-polymerized composite resins, dentin/cementum
direct composite resins, metal-based restorations, fiber posts, fiber splinting
materials
More conservative tooth preparations (lesion-specific preparations) Post-operative sensitivity in posterior adhesive restorations related to
polymerization shrinkage stress
Reliable micromechanical retention to etched enamel without Enamel cracks in posterior adhesive restorations related to polymerization
macro-retention features shrinkage stress
Reinforcement of residual tooth structure; undermined enamel does not need Moisture contamination of the operatory field may be more detrimental for
to be always removed adhesive than for non-adhesive restorations
Increased resistance to recurrent caries lesions when dentin is impregnated Small monomers, such as HEMA, may easily seep into the pulp space and cause
with dental adhesive pulp inflammation
Increased resistance to caries lesions in sealed fissure systems of posterior Frequent open contacts in posterior composite resin restorations (compared to
teeth amalgam restorations)
High efficacy to treat root sensitivity Adhesives may cause pulp necrosis if applied in preparations close to the pulp
Some adhesives have antibacterial properties, which may prevent recurrent Some of the monomers in dental adhesives may cause contact dermatitis
caries lesions
Stronger retention of glass-matrix ceramics restorations; adhesives increase
the resistance to fracture of glass-matrix ceramics
Stable chemical adhesion to hydroxyapatite for some adhesive materials when
dentin is not etched with phosphoric acid
2. Milestones in dental adhesion Etching enamel with phosphoric acid (Fig. 1) is still considered,
sixty-five years later, as the gold standard for bonding resin-based
In 1952, a manuscript published in the British Dental Jour- materials to tooth structure. The interlocking of resin tags (Fig. 1)
nal by Kramer and McLean described an in-situ study that was within the microsized porosities left by enamel chemical etch-
carried out in 124 preparations of 118 teeth scheduled to be ing can effectively seal the restoration margins in the long-term
extracted for orthodontic reasons [7]. The authors used 15 com- [13]. There is clinical evidence that dental adhesives result in more
binations of restorative materials. Tooth sections were stained reliable clinical behavior when enamel is etched prior to the appli-
with hematoxylin/eosin upon extraction, and observed blindly cation of the adhesive [14]. Nonetheless, new adhesives are still
under the optical microscope. The authors then matched the being launched without recommendations for etching enamel with
data with the experimental groups. Some of the sections dis- phosphoric acid.
played “an altered reaction observed as a narrow zone of material Another milestone in adhesive dentistry occurred in 1960.
staining deeply with hæmatoxylin immediately bordering the cav- Rafael Bowen (who retired from the ADA Foundation Research
ity. This zone averaged about 3 m in thickness and was seen to Center in 2018 after 62 years of continuous service) and Mario
be composed of dentine having an intense affinity for hæmatoxylin. Rodriguez presented a paper [15] at the IADR meeting in Chicago
This change was present in all of the 28 teeth filled with Sevriton- that reported the tensile strength of several materials, including
adhesive. Similar changes were absent from all of the 96 teeth filled a new silica-resin material that contained “about 70 per cent vinyl
with other materials.” The specific chemically-cured adhesive used silane-treated clear fused silica combined with about 30 per cent of an
in this study had been developed in 1949 by Oskar Hagger, a adduct of glycidyl methacrylate and bisphenol A”. It is worth under-
chemist who worked for DeTrey/Amalgamated Dental Company lining here the inclusion of a silane to bond the inorganic filler to the
[8]. The adhesive contained a phosphate monomer, later identi- new Bis-GMA resin. By 1963, the full composition of the new mate-
fied by Dr. Buonocore’s research group as glycerol phosphoric acid rial had been finalized [16]. Based on Bowen’s research with the
dimethacrylate [9], which is still used in a few dental adhesives Bis-GMA molecule, the first commercial composite resin (Addent,
as GPDM [10]. Remarkably, the findings of the 1952 manuscript 3 M) was introduced in 1964 as a chemically-cured paste-paste
[7] were the first reference to the concept currently known as material. Interestingly, since that time most changes in composite
the hybrid layer, elegantly illustrated with an image of dentin resin technology have been in the filler particle size and distribu-
altered by the adhesive [7]. In addition, the use of the phosphate tion rather than in the resin matrix, which is still based on Bis-GMA,
monomer GPDM as a dentin adhesive may now be part of history also known as Bowen’s resin.
as the first research report of a self-etch adhesive in the litera- Alan Wilson and Brian Kent, working at the Laboratory of the
ture. Government Chemist in the UK, invented in 1968 one the most
In 1955, a major advance for the history of dental adhesion was groundbreaking materials in dentistry, for which the patent was
published in the Journal of Dental Research [11]. Michael Buono- applied for in 1969 [17]. This self-adhesive material was widely
core used 85% phosphoric acid to change enamel surfaces and make known as glass-ionomer cement (GIC), although the correct ter-
them more suitable for mechanical adhesion, using an industrial minology is glass polyalkenoate cement [18]. The first report of
technique that improved the adhesion of paints to metal surfaces. their findings in the literature appeared in 1971 [19]. The commer-
Buonocore later expanded his acid-etch technique to clinical den- cial version was subsequently launched in Europe in 1975 under
tistry to seal pits and fissures, as reported in 1967 [12]. The authors the commercial name ASPA by Amalgamated Dental International,
used 50% phosphoric to etch pits and fissures, followed by the appli- DeTrey Division.
cation of a silica-filled methacrylate adhesive. This novel technique, Takao Fusayama, defying the general belief that etching dentin
which was not standard of care in 1967, resulted in a reduction of caused irreversible pulp damage, in 1979 reported that etching
caries incidence in pits and fissures by as much as 86.3% at 1 year dentin and enamel with 40% phosphoric acid for 60 sec substan-
[12]. tially improved the adhesion of Clearfil Bond System-F (Kuraray)
192 J. Perdigão / Japanese Dental Science Review 56 (2020) 190–207
Fig. 1. (a) SEM micrograph of human enamel etched with 35% phosphoric acid for 15 s. Original magnification = 5,000X. (b) SEM micrograph of a replica of an interface of
etched enamel with a dental adhesive. After curing the adhesive, the specimen was left in 6N HCl for 12 h to dissolve the enamel. The enamel prisms at the interface were
not dissolved because the etched enamel was impregnated with polymerized adhesive, creating a hybrid layer. H – hybrid layer; Ad – adhesive; E – residual enamel. Original
magnification = 5,000X.
[20]. For the first time, the concept of “total-etch” was associated interlocking of resin monomers into the array of microporosities
with improved dentin adhesion. left by the acid chemical dissolution of enamel (Fig. 1). Bonding to
Nobuo Nakabayashi’s research team was responsible for another enamel after etching with phosphoric acid is certainly the founda-
breakthrough in 1982, when they reported for the first time tion for the durability of adhesive restorative procedures.
a “demineralization-resistant zone” [21] in dentin after etching Dentin is a complex biocomposite structure, defined by some
dentin with 10% citric acid-3% ferric chloride (10:3 solution) for authors as a puzzle of different types of dentin and by other authors
30 sec and applying 4-META (methacryloxyethyltrimellitate anhy- as a bone-like nanocomposite built of carbonated hydroxyapatite
dride) cured with tri-n-butyl borane. This concept of hybrid layer mineral particles, protein, and water [24,25]. As opposed to enamel,
in etched dentin was identified using the scanning electron micro- dentin is a humid and more organic substrate. Dentin adhesion
scope (SEM). The same authors also highlighted the importance of has been one of the most challenging and less predictable tasks
monomers with both hydrophobic and hydrophilic groups to pro- in adhesive dentistry due to the dynamic compositional differences
mote adhesion with tooth substrates by penetration and infiltration and complex histology of dentin. The ability of adhering restorative
dentin as a new concept in biocompatible materials for dental use materials intimately to dentin is affected by many factors, includ-
[21]. ing biological and clinical factors. These factors include the patient’s
The most recent milestone was associated with the adhesion- age, location of the tooth in the mouth, dentin depth and perme-
decalcification concept (AD-concept) for adhesion to dentin ability, pulpal fluid flow, presence of sclerotic and/or carious dentin,
[22,23]. This concept was originally described for carboxylic acids. radicular versus coronal dentin, type of restorative material and
When these acids are applied on hydroxyapatite they first form procedure, isolation, parafunctional habits, dentist’s experience,
ionic bonds to calcium, which may be dependent on the pKa of among others [26–31].
each acid. While some of the carboxylic acids, such as oxalic acid, The mineral phase (hydroxyapatite) of dentin is on average
stay attached to calcium on the hydroxyapatite surface resulting 45 vol%, while the organic matrix is 33 vol%, the remainder being
in insignificant decalcification, other carboxylic acids result in a water [32]. Type I collagen is the most abundant protein in the
significant decalcification of hydroxyapatite with minimal or no organic phase. Dentin encloses a maze of inverted-cone shaped
chemical attachment. This adhesion-decalcification (AD) concept is tubules that traverse dentin, radially oriented with the larger diam-
still relevant. Etch-and-rinse (ER) adhesives follow the decalcifica- eter facing the pulp [26]. Garberoglio and Brännström in 1976 [33]
tion pathway derived from phosphoric acid etching, whereas mild measured the area occupied by the tubules and the tubular diam-
self-etch (SE) adhesives (pH ≈ 2), such as those that contain 10- eter in 30 extracted teeth. The number of tubules near the pulp
methacryloyloxydecyl dihydrogen phosphate or 10-MDP (MDP), was 45,000 per square millimeter and their diameter 2.5 m. In
tend to follow the adhesion pathway. Nevertheless, mild SE adhe- middle dentin, the number of tubules was 29,500/mm2 and the
sives still cause minimal decalcification, which is still required for average diameter was 1.2 m. In superficial dentin, the area occu-
calcium release and subsequent formation of stable MDP-Ca salts pied by tubules was 20,000/mm2 and the average tubule diameter
and respective nanolayering, as discussed later in this article. was 0.9 m [33]. The contents of water increase 20-fold from super-
ficial to deep dentin. The mean tubule volume in coronal dentin is
10% of the entire dentin volume, while near the DEJ it is 4% and
3. The substrate increases to 28% near the pulp [33] (Fig. 2).
Dentin tubules are permeated with fluid under constant out-
Enamel and dentin are the dental substrates to which we bond ward pulpal pressure estimated to be 25 to 30 mm Hg [34]. In
our restorative materials. Cementum may also be involved when addition, there is fluid present within the intertubular dentin
the cavo-surface margin is located apically to the cementum- area, making dentin an intrinsically moist hard tissue throughout
enamel junction. its internal structure. Dentin contains extensions of the odonto-
Enamel is a dry substrate without vital structures containing blast (odontoblastic processes) and intra-tubular collagen fibers
92 vol% of mineral phase (hydroxyapatite), which makes enamel in deeper areas (Fig. 3), less frequently in middle and superficial
almost the ideal substrate to form a tight adhesive joint. The dentin. These characteristics, which we sometimes overlook as clin-
acid-etch technique [11] is still the gold standard for bonding icians, attest the greater challenge when an adhesive restoration is
resin-based materials to tooth structure. The micromechanical inserted in deep dentin compared to restorations placed in more
interaction of adhesives with enamel is a result of the diffusion and superficial dentin.
J. Perdigão / Japanese Dental Science Review 56 (2020) 190–207 193
Fig. 2. (a) SEM micrograph of fractured superficial dentin. Int – intertubular dentin; P – peritubular dentin; T – dentin tubule; Arrows – bacteria in the tubule lumen. Original
magnification = 10,000X. (b) SEM micrograph of fractured deep dentin 75 m from the pulp of the same tooth in Fig. 2a. Original magnification = 10,000X.
Fig. 3. (a) SEM micrograph of fractured middle dentin showing an odontoblastic process extending from the tubule Int – intertubular dentin; P – peritubular dentin; T –
dentine tubule. Original magnification = 10,000X. (b) SEM micrograph of fractured deep dentin showing intratubular collagen (asterisk) with the characteristic 64 nm collagen
banding pattern. Int – intertubular dentin; P – peritubular dentin; T – dentin tubule. Original magnification = 25,000X.
Fig. 6. Sequence of SEM micrographs to illustrate the morphological characteristics of the bonding substrate in a NCCL of a recently extracted mandibular canine. (a) SEM
micrograph depicting a general view of the NCCL. The incisal aspect is on the right side (E-enamel), with the cervical aspect on the left side (R-root). The white arrows point
to the natural incisal cavo-surface margin. The dark arrows point to the natural cervical cavo-surface margin. Original magnification = 30X. (b) SEM micrograph of the area
included in the rectangle in Fig. 6a. The horizontal dotted line separates the unetched area (upper half) from the area that was etched with 35% phosphoric acid for 15 s
(lower half). Original magnification = 100X. (c) SEM micrograph of the area included in the rectangle of Fig. 6b (etched area). Note the sclerotic casts in the tubules (circles)
and, overall, hypermineralized dentin. Original magnification = 1,000X. (d) SEM micrograph of a sclerotic cast (asterisk) obliterating the tubule (T). Note how intertubular
dentin (Int) is densely mineralized. Original magnification = 15,000X. (e) SEM micrograph of bacteria (arrows) ‘fossilized’ into the mineralized area of intertubular dentin
(Int). Original magnification = 15,000X. (f) SEM micrograph of a longitudinal fracture of dentin in a NCCL. Note how the tubule is obliterated with rhombohedral mineral
crystals, which were elegantly described in 1989 [173]. Int – intertubular dentin; P – peritubular dentin; T – dentin tubule. Original magnification = 15,000X.
Since the early 1990s, the concept of wet or moist dentin for ER ter retention rate for ER adhesives when compared to dry dentin
adhesives [60,61] has been widely advocated and taught in den- [64,65].
tal schools. The collagen left in the area of demineralized dentin Leaving the dentin moist after etching and rinsing may not be so
collapses when dentin is air-dried after rinsing off the etchant. crucial with current simplified adhesives, as agitation of the adhe-
This collapse results in incomplete infiltration of the adhesive into sive during application improves infiltration of the monomers into
demineralized intertubular dentin [62] and lower bond strengths etched dentin. In fact, a clinical study in non-carious cervical lesions
[63]. For this reason, keeping the dentin substrate moist (glis- (NCCLs) found that passive application of the adhesive resulted in
tening) after rinsing off the etching gel has been recommended 82.5% retention rate after 2 years compared to 92.5% retention rate
based on in vitro testing. However, in vitro tests are carried out in of the restorations in which the adhesive was scrubbed vigorously
“laboratory-type” or unaffected dentin, as discussed above. When [66]. Furthermore, leaving dentin moist has been shown to cause
the degree of dentin moisture was tested in clinical trials with degradation of the resin dentin interfaces at 6 months [67]. Den-
the same or similar ER adhesives, including a recent study with tists are advised to gently dry dentin after rinsing off the gel without
a universal adhesive, moist dentin was not associated with bet- inducing desiccation.
196 J. Perdigão / Japanese Dental Science Review 56 (2020) 190–207
Table 2
Classification of dental adhesives by adhesion strategy.
Ac – Phosphoric acid; Pr – Hydrophilic primer; BR – Non-solvated bonding resin; GIC– glass ionomer cement; PAA -
polyacrylic acid.
Fig. 7. (a) SEM micrograph of a fractured human dentin specimen with smear layer and a smear plug created with diamond bur. Int – intertubular dentin; P – peritubular
dentin; T – dentin tubule; Sp – smear plug; Oc –occlusal surface; Dotted circle – another tubule plugged with smear layer. Original magnification = 10,000X. (b) SEM
micrograph of human dentin etched with liquid phosphoric acid for 15 sec. Int – intertubular dentin; P – peritubular dentin; T – dentin tubule; Oc – occlusal surface; Pc –
exposed peritubular collagen from dissolution of the peritubular dentin; Dd – dentin demineralized by the etching agent; arrows – other tubules. Original magnification =
10,000X. (c) SEM micrograph of human dentin treated with the Clearfil SE primer (Kuraray) from the 2-step SE adhesive Clearfil SE Bond. The asterisk marks the area of dentin
partially decalcified by the primer (pH = 1.8–2.0). Upon application of the respective hydrophobic bonding resin, this 0.5 m deep area will become the hybrid layer. Int –
intertubular dentin; T – dentin tubule; Oc – occlusal surface; Sp – primer-infiltrated smear plug. Original magnification = 15,000X. (d) SEM micrograph of occlusal view of
human dentin treated with GC Cavity Conditioner (20% polyacrylic acid with 3% aluminum chloride hexahydrate) for 10 sec, and rinsed with water for 15 sec. Note residual
smear layer (ovals) and some patent tubules (T). The intertubular dentin does not have morphological characteristics of demineralization (no visible collagen fibers). Original
magnification = 5,000X.
J. Perdigão / Japanese Dental Science Review 56 (2020) 190–207 197
Table 3
Etch-and-rinse adhesives.
Advantages Disadvantages
Three-step ER adhesives have been available since the 1990s, therefore they Acetone-based adhesives need more applications than those recommended by
have a long-track record. the respective manufacturers [51].
High immediate dentin and enamel bond strengths in laboratory studies Over-etching decreases bond strengths [52].
Excellent bonding to enamel in vitro and durable restorations in clinical More technique sensitive than SE adhesives, as the potential for incomplete
studies. However, retention rates for 2-step ER adhesives are lower than for infiltration of the adhesive into the etched dentin depends on several
3-step ER adhesives [49]. contributing factors occurring simultaneously in a very short time.
Clinical studies over 5 years with excellent results for specific 3-step ER Hydrolytic degradation of the bonds occurs when margins are located in
adhesives. Optibond FL (Kerr) resulted in excellent retention at 13 years in dentin.
NCCLs [50]. Optibond FL is still the reference against which all ER adhesives
are compared.
As these adhesives contain organic solvents such as ethanol or acetone, minor The clinical and in vitro performance of 2-step ER adhesives undergo
dentin contamination with saliva does not always decrease bond strengths degradation faster than that of 3-step ER adhesives.
in vitro.
As opposed to 2-step ER adhesives, 3-step ER adhesives contain a hydrophobic Bond strengths may vary with the degree of moisture, depending on the
bonding resin that prevents or delays the degradation of the resin-dentin specific adhesive.
interface by making the interface impermeable and increasing the film
thickness. The lack of solvent increases the degree of conversion.
ER adhesives may result in mechanical interlocking with etched dentin Although clinical evidence demonstrates that ER adhesives do not cause more
provided that the dentin in not overetched, the primer/adhesive for 2-step post-operative sensitivity than SE adhesives [53,54], some clinicians claim that
ER adhesives is applied in an active scrubbing mode, and that there is not ER adhesives cause higher incidence of post-operative sensitivity with
excessive water within the interfibrillar spaces. posterior composite restorations.
Ability to bond composite, porcelain, fiber posts, etched or sandblasted metals, Solvent air-drying time recommended by the manufacturers is insufficient
or amalgam. [55] and must be extended.
Table 4
Median intertubular dentin demineralization of current phosphoric acid gels [56].
Fig. 9. (a) SEM micrograph of human dentin etched with 32% phosphoric acid (Scotchbond Universal Etchant, 3M). Original magnification = 7,000X. (b) SEM micrograph
of human dentin etched with 35% phosphoric acid (Scotchbond Etchant, 3M). Original magnification = 7,000X. Int – intertubular dentin; P –peritubular dentin; T – dentin
tubule; Oc – Occlusal surface; Pc – exposed peritubular collagen from dissolution of the peritubular dentin; Dd – dentin demineralized by the etching agent; Circles – silica
thickening agent; Arrows – intertubular anastomoses.