Managing dental caries among the paediatric population is a never-ending story. Although dental caries is preventable, it has affected more than 600 million children worldwide ^[1], and without prompt intervention, the disease can progress and increase the morbidity of the child ^[2]. With a better understanding of the etiological factors and behaviour of dental caries, the concept of caries management in the modern era has now changed ^[3]. The minimal intervention dentistry (MID) concept has been introduced, emphasising early detection of dental caries and the promotion of preventive therapy. Advancement of the lesion should be managed by adopting the minimally invasive operative approach ^[4]. Thanking Buonocore ^[5] and Bowen ^[6] for their discovery of the acid etching technique and the bisphenol A-glycidyl methacrylate (Bis-GMA) resin monomer, respectively, various resin-based dental materials that support the MID concept have been developed.

Resin infiltrant (RI), marketed as Icon^® (DMG, Hamburg, Germany), is among the products that benefited from Buonocore’s and Bowen’s breakthrough discovery. The RI technique has emerged as one of the important tools that support the MID concept in managing non-cavitated carious lesions, using the tagline ‘Drilling? No thanks!’. This novel material uses the concept of infiltrating the caries lesion using a low-viscosity resin in an attempt to arrest the progression of the non-cavitated caries lesion without the need of removing the tooth structure. This concept is highly desirable and well appreciated, especially in the field of Paediatric Dentistry, since the drilling procedure may not be well-tolerated by young and highly anxious children ^[7].

2. Development of RI

2.1. The Resin Monomer

Surprisingly, the idea of infiltrating early caries lesions has existed for more than five decades. Researchers since the 1970s have conducted many in vitro and in vivo studies to find the right material that is able to infiltrate the early enamel lesion effectively [8,9,10,11,12,13]^{[8][9][10][11][12][13]}. Going back to 1975, Davila and colleagues ^[8] investigated the potential ability of adhesives to seal early enamel lesions. They proposed an idea that the demineralised surface of the lesion would act as a suitable locus for the adhesives to infiltrate, sealing the lesion entrance and spaces, thus arresting the ongoing demineralisation and preventing cavity formation. They managed to infiltrate the artificial caries lesion with adhesives in vitro with deeper penetration depth seen in the lesions pre-treated with acid conditioning ^[8]. A year later, Robinson et al. ^[9] used an experimental resorcinol-formaldehyde resin to occlude the pores of early enamel lesions. The resin occluded up to 90% of the pores after the second and third time of applications and simultaneously reduced the progression of the demineralisation. However, due to the potential cytotoxic hazard of the resin, mainly towards the vital dentine and pulp tissue, the use of the resin was discontinued [9,10]^[9][10]. The authors later suggested that the infiltrating resin should meet a certain standard: low viscosity, hydrophilic, anti-bacterial, non-toxic, aesthetically acceptable and able to polymerise into a solid state. The latter recommendation may give extra strength to the weakened enamel structure following demineralisation ^[10]. These two early experiments have opened the ‘floodgates’ to various in vitro and in vivo studies focusing on developing resins that can infiltrate and halt the progression of early enamel lesions. Earlier studies have used unfilled resin in the form of dental adhesives and sealants as the infiltrating agent. In vitro studies on an artificial caries model shows some potential, where all of the studies reported a reduction in caries progression as compared to the control [11,12,13]^[11][12][13]. In one study by Robinson et al. ^[11], they observed that 60% of the pores were occluded following the infiltration process. Clinical evaluations on the success of sealing the enamel lesion using sealants and adhesives among children were carried out by Gomez et al. ^[14] and later Martignon et al. ^[15]. While the latter reported a significantly reduced but still relatively high lesion progression (43.5%) over 18 months of observation, the former found no significant difference between the infiltrated and control lesion in their 24-month clinical study. It was suggested that the findings might be due to the disintegration of the material over time or inadequate sealing of the lesion ^[14]. This reflects the inability of the sealants and adhesives to penetrate deep into the lesion and, therefore, only showed superficial penetration into natural enamel lesions ^[16]. This led to a series of in vitro and in vivo studies led by Meyer-Lueckel and Paris [17,18]^[17][18] to develop a new material that does not disintegrate easily, has a good sealing ability and is able to penetrate deep into the base of the porous enamel lesion. The penetration ability of the material into a porous structure is best explained by the Washburn equation ^[19]. Based on the equation, the porous solid (in this context, the enamel structure) was regarded as a structure consisting of a collection of open capillaries, which can be penetrated by liquids driven by the capillary forces. Further, a material with high penetration coefficient (PC) can penetrate deeper and faster into the porous structure ^[20] and, upon hardening, can directly occlude and seals the porosity ^[17]. An earlier experiment conducted by Meyer-Lueckel and Paris ^[17] showed that materials with PC of more than 100 cm/s might be more suitable for application as ‘infiltrants’ for the treatment of early enamel lesions as compared to fissure sealants and adhesives. Furthermore, the same authors also found that resin materials with high triethylene glycol dimethacrylate (TEGDMA) concentrations tended to show better inhibition of lesion progression. This effect can probably be attributed to the better penetration capabilities of TEGDMA-based resins ^[17]. Their experimental resins using a mixture of TEDGMA, 2-hydroxyethyl methacrylate (HEMA), and ethanol showed the highest PC value, attributed to their low contact angle and low viscosity of these components. However, the mixture consisting of HEMA and ethanol showed inadequate hardening and was thus deemed unsuitable for infiltration of porous enamel. The mixture of resin monomer TEDGMA and ethanol, on the other hand, showed high PC value and sufficient hardening ^[18], suggesting that these two components would be the benchmark for the future development of RI. Further studies on the development of RI were based on the different formulations of TEDGMA and ethanol. Paris et al. ^[18] found that 99% of TEDGMA-containing resin gave a PC value of 204 cm/s, while the addition of TEDGMA and ethanol as solvents gave a PC value of 391 cm/s. The addition of solvent has been shown to increase the penetration coefficient and, consequently, the penetration depths, but inhomogeneities and uncured areas within the resin layer may occur, which can lead to incomplete polymerisation. Therefore, the authors suggest that the addition of ethanol to increase penetration abilities should be carefully balanced with the potentially impaired properties of the cured material. They later concluded that low-viscosity RIs, based mainly on TEGDMA, had relatively high PC and were capable of inhibiting the progression of both artificial ^[21] and natural enamel caries lesions ^[22]. The high PC values also allow the material penetrates deep into the lesion body in a low-demineralising environment [23^[23][24],24], and a 3 min application is sufficient to completely occlude the pores of the early enamel lesion ^[25].

2.2. Etching

As described by the Washburn equation, the infiltration of resin into the porous enamel lesion is driven by capillary forces. The infiltration of the resin is strongly influenced by both the pore volume and the capillary radius of the solid to be penetrated. In the case of infiltrating early caries lesions, the presence of the highly mineralised surface layer with low pore volume might prevent the penetration of the infiltrating resin into the subsurface porosities underneath it ^[26]. Elimination of the surface layer to expose the porous subsurface lesion is desirable to aid the penetration of the resin. To achieve this, pre-treatment conditioning of the surface layer is needed prior to the infiltration process ^[16]. In restorative dentistry, acid etching has been identified as the core step in pre-treatment conditioning of the enamel surface prior to the placement of resin composite. Etching the enamel with 30–40% phosphoric acid resulted in selective demineralisation of the enamel prisms of varying irregularities and microporosities ^[27]. This allows the low-viscosity resins to ‘penetrate’ the microporosities, forming resin tags and micromechanical interlocking between the resins and the enamel ^[28]. Inspired by the success of the acid etching technique, a similar application might work for RI. Grey and Shellis ^[29] successfully etched the artificial enamel caries with 36% phosphoric acid, which improved the penetration of the resin into the subsurface enamel lesion. Their in vitro results, however, cannot be replicated in the actual clinical scenario. Meyer-Lueckel et al. ^[30] found out that the penetration depth of the resin into the enamel porosities between the artificial and natural caries lesion was different. They postulated that the mineral content of the surface layer in natural caries lesions might be higher and more inhomogeneous due to the continuous cycles of de- and remineralisation in the oral cavity. They later concluded that complete erosion of the surface layer is necessary to expose the subsurface lesion prior to infiltration with low-viscosity resins. Two in vitro studies carried out by Meyer-Lueckel, Paris and their team [30,31]^[30][31] have demonstrated that in comparison to 37% phosphoric acid and 5% hydrochloric acid, the use of 15% hydrochloric acid gel for 90–120 s was effective in not only eroding the surface layer but led to nearly complete removal of the structure. This leads to exposure of the subsurface enamel lesion, which is ready to be infiltrated by the resin. However, without pre-treatment of the surface layer, penetration of resin was limited ^[29] and almost impossible for it to reach the subsurface enamel lesion. Elimination of the surface layer also can be performed mechanically, for instance, by using a diamond bur or polishing strip ^[32]. However, this procedure would cause occlusion of the lesion pores by smear layer, which later will affect the infiltration process of the resins. Furthermore, the reduction of the surface layer mechanically is difficult to control ^[30]. Thus, optimum surface erosion seems the best option in allowing the penetration of the low-viscosity resin into the subsurface enamel lesion effectively.

2.3. Ethanol

The use of ethanol as a solvent is believed to reduce the viscosity of the penetrating resin, as well as remove the remaining residual water that might be present at the bottom of the body lesion. Meyer-Lueckel et al. ^[16] found that the addition of ethanol enhanced the penetration ability of dental adhesives. Similar results were found with the experimental resin that they developed. The addition of 10% and 20% of ethanol had shown to increase the PC as well as the penetration depth [17,18]^[17][18]. Therefore, it can be assumed that a solvent like ethanol might affect the penetration behaviour positively. Alas, there is concern regarding the addition of the evaporating solvent that might possibly cause inhomogeneities and incomplete polymerised areas within the resin itself ^[18]. Paris et al. ^[33] conducted an in vitro study on extracted primary molars using experimental resins with and without the addition of ethanol. Although the PC value of ethanol-containing resin is higher, both the solvent-free and ethanol-containing resins managed to infiltrate the lesion completely. Hence, the authors suggest that concerning the potential effect of ethanol on the polymerisation of the RI, a solvent-free infiltrant is preferable ^[33]. In order to facilitate the removal of residual water and protein within the body lesion, the commercially available RI add-ons another step: pre-treatment of the enamel surface with ethanol following the acid etching procedure. A summary of the main studies related to the development of the current RI is shown in Table 1.