Human dentine is chemically composed of minerals in the form of apatite crystals (about 70 vol%), organic matrix (20 vol%), and water (10 vol%). The volumetric percentage between these components varies according to tooth size, shape, location on the arch, and age‐related changes or dental diseases . Various morphological structures of dentine, such as dentinal tubules, incremental growth lines (Von Ebner and Owen), Tomes granular layer, and intratubular, intertubular, and interglobular dentine, have already been identified as demonstrating histological differentiations within the dentinal structure .
The dentinal tubules, filled with glycoprotein, give dentine a high permeability [3, 4]. The mixture of collagen fibres, noncollagenous proteins, and glycosaminoglycans (GAGs) provides a matrix capable of absorbing a large amount of water, which explains the natural humidity of this substrate . Most collagen fibres in the organic matrix are classified as Type I collagens, having a diameter of 50–100 nm, and are distributed obliquely or perpendicularly around the dentinal tubules. The number of collagen fibres decreases from superficial to deep dentine due to the fact that the latter has larger dentinal tubules .
Root dentine is characterized by the presence of dentinal tubules starting from the pulp and moving to the interface with the cementum (Figure 9.1) . The tubules contain cytoplasmic extensions of the odontoblasts and are filled with glycoprotein solution containing approximately 12% water. Compared to the coronal dentine, root dentine has a smaller amount of intertubular dentine and a smaller number, density, and diameter of dentinal tubules . In root dentine, the number of dentinal tubules decreases towards the apical region, where the dentin is quite irregular, translucent, and may be devoid of tubules entirely (Figure 9.2) . When dentinal tubules are present in this region, they are usually sclerotic and obliterated with minerals that resemble those of the peritubular dentine . In addition, unlike in human enamel, which is made up of approximately 97% minerals, 2% water, and 1% organic matrix , a very humid environment is found throughout root dentine . The complexity of the anatomical structure of root dentine complicates durable adhesion of resin‐based materials in this region.
9.2 Adhesion to Human Dentine
The adhesion of restorative or capping materials to human dentine has been a matter of controversy in the dental literature [10, 11]. The wide variation in dentinal structure in the same tooth makes dentine a very complex substrate in this regard . However, the differences between coronal and root dentine are not a barrier to dentin adhesion . Bonding techniques are typically very sensitive to humidity, being influenced by substrate type, adhesive system, and application technique. Thus, standardization of procedures and care during clinical steps are fundamental to the success of the adhesive protocol.
The longevity of the adhesive interface is directly related to the quality of the hybrid layer , comprising the bond between the polymer present in the adhesive resin and the collagen present in dentine. When acid etching is performed in dentine, demineralization, collagen fibre exposure, and light opening of dentinal tubules have been observed [14, 15]. The primer applied to the demineralized dentine then maintains the collagen structure and may increase the free surface energy. In addition, after promoting evaporation of water and solvent, the primer binds to the adhesive resin, causing it to penetrate capillary into the dentinal tubules . A decreasing number, density, and diameter of the dentinal tubules in different root areas can lead to a significant reduction in the thickness of the hybrid layer from cervical to apical .
Conventional bonding can be employed to restore vital and nonvital teeth . In conventional bonding systems, also known as total‐etch adhesive systems, dental tissues are conditioned with phosphoric acid, followed by the application of adhesive resin in two (primer and adhesive present in the same solution) or three (primer and adhesive applied separately) clinical steps. When the acid is applied to the enamel, demineralization of this substrate creates microporosities, which will then be filled by the hydrophobic resin monomers present in the adhesive, helping in the micromechanical retention of the restoration. On dentine, phosphoric acid removes the smear layer, exposing collagen fibres, which will be infiltrated by resinous monomers to form the hybrid layer .
Commercially available self‐etching systems can be classified according to the number of operative steps into ‘two‐step’ and ‘all‐in‐one’ systems; this classification affects the adhesion quality to dentine (Figure 9.3). In self‐etching adhesives, primers can partially demineralize the underlying dentine whilst simultaneously providing monomers to fill the created microporosities. In ‘two‐step’ systems, washing the surface after acid etching is unnecessary and thus maintenance of the interfibrillary spaces by humidity is not required as demineralization products and acid etching residues are incorporated and polymerized with the adhesive resin to the dentine [4, 19]. These agents may have acid‐functionalized monomers in their composition, such as 10‐methacryloyloxydecyl dihydrogen phosphate (10‐MDP), which favour dentine surface demineralization due to the maintenance of a local pH between 1.5 and 3.0, at which range acid groups bind to the hydroxyapatite, forming suitable adhesion between the methacrylate network and the dentine . In single‐step adhesives, the three basic components (acid, primer, and adhesive resin) are combined where dentine substrate hybridization is achieved in a single clinical step [20, 21].
Regardless of the adhesive system employed, studies agree on the need for micromechanical enticement resulting from the bond between the adhesive resin and the collagen present in the dentinal tubules, which is primarily responsible for the quality of the adhesive interface [4, 22]. The stronger the bond, the better the marginal sealing, the less the microleakage, and the longer the survival of the restorations. However, according to some studies, there is no direct and significant correlation between bond strength and marginal sealing . Microleakage has been suggested as the major factor responsible for the degradation of the adhesive interface over time, despite the previously achieved bond‐strength results [24–26]. When water can penetrate existing spaces, usually as a result of incomplete penetration of the resin into demineralized dentine, the bond strength may decrease, marginal discolouration and secondary caries may occur, and postoperative sensitivity may increase [25, 27]. Likewise, with regard to the longevity of the filling in the intraradicular system, the quality of adhesion on the coronal dentine is essential.
9.3 Adhesion to Root Dentine in Vital Teeth
Vital teeth with cervical lesions and deep cavities exhibit root dentine exposure, most often associated with dentine sensitivity [4, 15]. According to the hydrodynamic theory, when enamel is lost and dentine is exposed, a change in dentine fluid velocity can stimulate pain receptors found in the most inner portions of the tubules or predentine, causing sensitivity [3, 4].
In shallow cavities, dentine has a smaller amount of dentinal tubules (20.000 mm2), with an average diameter of 0.6 μm, and a predominance of intertubular dentine (96% of the area), which is rich in collagen. Already in deep cavities, the amount of tubules is about 45.000 mm2, with an average diameter of 2.4 μm, and there is a small amount of intertubular dentine (12% of the area) . This is fundamental to undertaking restoration with proper sealing on these substrates. In addition, it is important to highlight the fact that different dentine substrate patterns can be found in a single tooth, making it impossible to obtain a homogeneous hybrid layer over the entire length of cavity preparations. Variations in the presence of caries (infected, contaminated, sclerosed, reactive, or repair tertiary dentine), tubular orientation (transverse, longitudinal, or oblique section), and depth (superficial, middle, or deep) also present a compromised dentine on which to bond [19, 29].
During cavity preparation for direct or indirect restorations, dentine is covered by a layer containing remnants of dental structure, saliva, and bacteria. This layer, known as the smear layer, blocks the entry of adhesive resin to dentinal tubules and decreases dentinal permeability by up to 86% . However, it can be easily removed by conditioning with 30–40% phosphoric acid for 15–20 seconds . Acid etching of the dentine surface removes the smear layer and enables the bonding of resin‐based materials to demineralized dentine, allowing sealing by adhesive resin and helping prevent postoperative hypersensitivity and recurrent caries .
In the bonding procedure, the humidity of the dentine should be maintained, since the mesh of collagen fibres separated by 15–20 nm‐wide spaces is supported by the presence of water . If the dentine surface is excessively dry, collagen fibres without mineral support can collapse, closing the microscopic spaces created during conditioning, which are critical for the longevity of the adhesion. On the other hand, excess moisture on the dentinal surface impairs the bond strength and sealing of dentinal tubules .
One other important aspect in this regard is the polymerization contraction that occurs during the making of direct restorations using resin composite. When resin‐based materials polymerize, the monomer molecules join together to form intertwining chains and the mass is reduced by about 2–7%. The strength of polymerization shrinkage often exceeds the bond strength of dentine adhesives to dentine, which may result in failures due to dental surfaces yielding to weaker adhesion [21, 32].
9.4 Pulp Protection Materials and Their Effect on Adhesion to Dentine
The preservation of pulp vitality depends on a number of clinical factors. The use of pulp‐capping biomaterials on deep dentine can also preserve vitality, as the success of vital pulp treatment is dependent on the choice of materials when remaining dentine thickness is less than 0.5 mm . Adequate management of the pulp tissues is necessary , followed by placement of an adequate pulp‐protection material. Compounds such as calcium hydroxide (CH) have been used for over a century, but the most recent guidelines  suggest the use of glass ionomer cement (GIC) or of hydraulic calcium silicate cements (HCSCs), such as mineral trioxide aggregate (MTA) or Biodentine (Septodont, Saint Maur des Fosses, France), placed over disinfected dentine.
CH is a biocompatible material  with antimicrobial properties  that stimulates the formation of sclerotic dentine . When it is first applied to the exposed pulp, superficial necrosis occurs , which induces a slight irritation that stimulates the pulp to repair, forming a bridge of sclerotic dentine through cell differentiation , extracellular matrix (ECM) secretion, and subsequent mineralization . However, CH cement does not have good adhesive properties  and is subject to dissolution over time , leading to the formation of dead spaces  and microleakage .
GICs are materials that involve a significant acid–base reaction as part of their setting, where the acid is a water‐soluble polymer and the base is a special glass . They are considered self‐etching cements, since they bond chemically to dentine through ion exchange at the tooth–material interface . They also have an insulating effect in relation to thermal changes in the oral environment , acting as antibacterial agents  and presenting low levels of marginal infiltration . However, their bond strength is considered low, with values ranging from 2.6 to 9.6 MPa for enamel and from 1.1 to 4.1 MPa for dentine .
MTA was the first HCSC available for clinical use and is composed of tricalcium and dicalcium silicate. It is recommended for pulp capping, pulpotomy, and treatment of immature teeth with nonvital pulps or open apices, due to its biocompatibility  and potential bioactivity [49, 50]. However, it has some critical shortcomings, namely its prolonged setting time , high solubility during setting , potential for discolouration [52, 53], and difficulty in handling [54, 55]. Its bond strength is influenced by its long setting time and its surface following acid conditioning .
The reaction of HCSCs with water leads to the formation of calcium silicate hydrate and CH ; the CH interacts with tissue fluids, resulting in bioactivity [49, 50]. Although several formulations are available on the market, Biodentine is the most optimized and specifically developed for pulp‐related procedures. Biodentine powder contains tricalcium silicate, zirconium oxide, and calcium carbonate, and its liquid is composed of water plus calcium chloride and a hydrosoluble polymer [54, 58, 59]. It has good sealing ability , relatively short setting time , high alkalinity , and good biocompatibility and bioactive potential [62, 63].
More recently, additives such as calcium phosphate , silicon oxide , and resin components  have been added to HCSCs, with the aim of improving biological activity , strengthening the material , and providing the ability to command cure the material in a way that avoids problems with bonding composite resin to the underlying substrate . Commercial examples of these cements are TotalFill (FKG Dentaire, La Chaux‐de‐Fonds, Switzerland), BioAggregate (Verio Dental, Vancouver, BC, Canada), and TheraCal LC (Bisco, Schaumburg, IL, USA), respectively. The solubility of TheraCal LC is reported to be less than that of MTA and CH , but the addition of resin induces important changes in its hydration properties .
The quality of the adhesion between pulp‐capping materials and resin composites is critical for optimal stress distribution at the interface, reduction of microleakage, and the general success and longevity of direct restorations. Resin composite is frequently the material of choice for placement over pulp‐capping materials because of the low loads applied on them, reducing the possibility of dislocation. Thus, acid etching has been employed on these materials, followed by the application of adhesive resin systems. However, studies demonstrate that acid etching results in the formation of porosities in the glass ionomer and in the destruction of part of the microstructure of Biodentine, reducing the adhesive strength [70, 71]. Primers that contain acetone or alcohol may affect the properties of CH, resulting in high erosion and lower compressive strength values . Water‐based adhesive resin systems may result in lower bond strength due to incomplete polymerization of monomers and the high water content of HCSCs, which can interfere with the polymerization of self‐etching adhesive resins . Although some authors recommend that materials such as MTA and Biodentine be covered with other materials, such as GIC