Polymer-induced liquid precursors: How are they being used and what is the effect on dentin remineralization? A scoping review

Abstract

To identify the effectiveness of polymer-induced liquid precursors (PILP) on dentin remineralization and the assessment approaches used to evaluate remineralization. The analyses were done into six stages: (1) Identifying the research question; (2) Identifying the studies; (3) Selecting relevant studies; (4) Plotting the data; (5) Reporting results; and (6) Risk of bias. The searches were carried out in the following databases: PubMed, Web of Science, and Scopus. A total of 247 articles were identified in the electronic database search. After applying the eligibility criteria, only 12 articles were included for data extraction. The outcomes of dentin remineralization patterns were plotted in association to PILP agent type and application mode. The intrafibrillar mineralization occurred in 78% of studies where polyaspartic acid (pAsp) was used, and 50% when the polyacrylic acid (PAA) was used. All the studies where PILP was used in a restorative material (resin composite, glass ionomer, and adhesive system)—extra and intrafibrillar mineralization pattern was found. The association of PILP agents with other materials with potential for mineralization showed beneficial results in remineralization, since they provide a medium to high concentration of calcium and phosphate. The pAsp showed better results for interfibrillar remineralization when compared to PAA. The association with Ca/P release materials or solution Ca P are essentials for mineralization via PILP agent. Further studies are needed to assess the effectiveness of remineralization through PILP agents because the level of evidence of the studies was low.

Keywords

Tooth remineralization dentin dental materials

Introduction

The caries-affected dentin (CAD) presents altered physical and chemical properties, because of successive cycles of des- and remineralization. CAD has reduced inter-tubular mineral content¹ revealing the loss of calcium, phosphate, and magnesium, which make the substrate porous and with low mechanical properties.² Transmission electron microscopy (TEM) observations have revealed that when the adhesive systems are applied on this substrate, a porous zone appears beneath the hybrid layer, leaving the collagen fibrils unprotected.³

Dentinal collagen exposed by etch-and-rinse systems has been reported to be highly vulnerable to hydrolytic and enzymatic degradation processes.⁴ In addition, self-etch adhesives use calcium to chemically bond to molecules like methacryloyloxydecyl dihydrogen phosphate (MDP) of the adhesive systems and form stable salts. As the mineral content on CAD is reduced, it has been pointed out as one of the possible reasons for the low bond strength reported on long-term basis.⁵ Breschi et al.⁶ have also reported less bond strength, long-term degradation, and a compromised longevity of the restorations on CAD. For that reason, the remineralization of demineralized dentin should represent a favorable impact on the adhesion to resin monomers.

The strategies to remineralize dentin consist of two main mechanisms. The first is the classical remineralization, where calcium and phosphate ions are deposited on the existing apatite crystals.⁷ However, with the traditional ion-based pathway, remineralization does not occur in places where crystals are absent.⁸ It was observed that the deposit of mineral occurs superficially or only on the extrafibrillar portion of the dentin, without achieving intrafibrillar mineralization.^9
–11 The second mechanism, the non-classical pathway, is based on biomimetic agents analogous to non-collagenous proteins that mineralize the intrafibrillar collagen. This mineralization increases the mechanical properties of dentin,^11,12 and also protects collagen molecules from external challenges—such as temperature, endogenous enzymes, bacterial acids, and other chemical factors.¹³ The Gower group suggested a model of remineralization using a PILP (polymers-induced liquid precursors) process based on the formation of a liquid precursor system induced by polymer¹⁴ and were successful in remineralizing a variety of organic matrices.¹⁵

The PILP process consists of adding anionic polymers to a supersaturated mineralization solution, in order to induce the formation of an amorphous calcium phosphate (ACP) precursor that mineralizes the intrafibrillar collagen.^9,14,16 PILP agents aim to stabilize the calcium phosphate ions, preventing spontaneous nucleation, and mineral precipitation before reaching the desired location.^14,17,18 In the lumen of collagen fibrils, PILP agents have the ability to deposit their content, forming an amorphous calcium phosphate. Then, the ACP will transform into apatite crystallites oriented in a similar way to the nanocrystals observed in mineralized tissues.^14,19

Some molecules such as osteopontin,²⁰ poly acrylic acid (PAA),²¹ and polyaspartic acid (pAsp)¹⁶ are considered PILP agents. Aspartic acid was the first PILP agent used for biomimetic remineralization in dentin,¹⁶ and most of the studies available to date evaluate it. However, there is still some controversy as to whether PILP agents can actually remineralize apatite in collagen tissues, mainly whether it is able to promote intrafibrillar remineralization.

There are several ways to evaluate the effects of biomimetic agents on demineralized dentin: chemically, by crystallographic parameters and by the mechanical properties of dentin—but there is still no consensus on which is more suitable.¹⁸ Thus, this review aimed to evaluate the available scientific evidence on the effectiveness of PILP agents on dentin remineralization, and the results related to the chemical, crystallographic, and mechanical properties in the treated dentin.

Materials and methods

Study design

The “scoping review” was the research methodology selected. This methodology maps the existing literature on a complex topic being reviewed for the first time in terms of volume, nature, and characteristics of primary research. We assess the literature on polymer-induced liquid precursors (PILP) for dentin remineralization. The methodology was divided into six stages according to Arskey and O’Malley’s²²: (1) Identification of the research question; (2) Identification of studies; (3) Selection of relevant studies; (4) Charting the Data; (5) Report of results; and (6) Risk of bias.

Stage I: “Research question.”

Is there scientific evidence that PILP agents induce intrafibrillar and extrafibrillar mineralization in dentin?

Stage II: Identification of studies

PubMed, Web of Science, and Scopus databases were searched. The search strategy developed for PubMed (Table 1) was used as a blueprint and adapted to the other databases. Two hundred and forty-seven articles were found and grouped with the EndNote program (Clarivate Analytics—Online Version), then duplicates were excluded leaving 209 articles. The flowchart for the search and screening strategy can be seen in Figure 1.

Table 1.

PubMed search strategy.

#1	(((Dentin) OR (Dentine)) OR (Dentines)) OR (Dentins)
#2	((((((((PILP) OR (Osteopontin)) OR (polymer-induced liquid-precursor)) OR (Polyaspartic acid)) OR (Polyaspartate)) OR (Poly(acrylic acid))) OR (pAsp)) OR (OPN)) OR (Poly-L-aspartic acid)
#3	((((((Biomineralization) OR (Biocrystallization)) OR (Biocrystallizations)) OR (Biomineralizations)) OR (Bioprecipitation)) OR (Bioprecipitations)) OR (Remineralization)
#4	#1 and #2 and #3

Figure 1.

PRISMA flowchart of literature search.

Stage III: Selection of relevant studies

Abstracts of the 209 studies found were revised, and 175 abstracts that not corresponding to the research question of this review were excluded. The selection of the studies was performed by two evaluators separately. In case of doubt, a third evaluator was included.

After the selection phase, the articles were assessed according to the following criteria:

Inclusion criteria: Studies that evaluate dentin remineralization using PILP; in-vitro and in-vivo studies; articles in English; publication date from 2008 to 2020.

Exclusion criteria: Studies that evaluate remineralization in bone; animal collagen and enamel; articles in languages other than English; literature reviews.

Stage IV: Charting the data

The data obtained from all studies were allocated in a spreadsheet (Microsoft Excel) to perform the data extraction regarding the type of PILP agent, association with restorative material, assessment methodology, type of mineralization, objective, main results, and conclusion. This stage was performed by two calibrated authors.

Stage V: Report of results

The extracted data were organized according to: (1) Type of PILP; (2) PILP Application method; (3) Biomimetic remineralizing effect on dentin. In addition, a table was prepared with the main information for each article (Table 2).

Table 2.

Description of objectives, type of PILP, method of application, method of assessment, and principal results of the studies.

Author	Aim	PILP type	In association with other mineralization agent	Inserted in a restorative material	Remineralization assessment	Results	Risk of bias
Bacino et al.²³	Functionally remineralize artificial lesions in dentin with a PILP part of a restorative material	pAsp	RMGI	Yes, RMGI	Dehydration shrinkage, EDS, SEM, reflective light microscopy, and transducer-based nanoindenter	The association between RMGI and pAsp recovered substantially the elastic modulus on dentin, suggesting that functional remineralization (intra and extrafibrillar mineralization). Pores developed in RMGI when pAsp was added.	Medium
Burwell et al.²⁴	To restore the mechanical properties of demineralized dentin matrix using PILP agents	pAsp	CaP	No	MicroXCT, depth of dentin shrinkage, EDS, nanoindentation, and SEM	Functional remineralization of partially demineralized human dentin occurred with recovery of mechanical properties, with progressive intra- and extra-fibrillar mineralization initiated in the depth of the lesion.	High
Kim et al.⁸	To remineralize collagen matrizes via dual biomimetic analogs	PAA	MTA/PVP acid	No	TEM	In the presence of dual biomimetic analogs in a remineralization medium, intrafibrillar remineralization of completely demineralized collagen matrices via a bot- tom–up crystallization mechanism can be achieved.	Medium
Lausch et al.²⁵	To present a model of collagen biomineralization based on demineralized tissue sections of mouse molars.	pAsp	CaP	No	EDS, TEM, and light microscopy	Only solutions with relatively high phosphate concentration, stabilized with pAsp, produced a structure mimicking the mineral-matrix relationship of mineralized connective tissues	Medium
Nurrohman et al.²⁶	To investigate the nanomechanical properties during the demineralization and remineralization process in the absence or presence of PI following PILP treatments.	pAsp	CaP	No	AFM, FTIR MicroXCT, SEM, TEM, and optical microscopy	The supplementation of pAsp comprised PILP mineralization treatments with protease inhibitors did not improve the overall results on mechanical recovery of the lesion.	High
Osorio et al.²⁷	To ascertain whether biomimetic phosphoprotein analogs improve bonding efficacy and dentine remineralization ability of a novel zinc-doped Portland-based resinous sealing cement.	pAsp	TMP/MTA	No	MTBS and Raman spectrometer	pAsp application onto demineralized dentine produced an inhibition or delay of mineral phase crystallization, enhancing the remineralization potential of the Portland microfillers at the resin–dentine bonded interface.	Medium
Sadoon et al.²⁸	To evaluate the remineralizing ability of these pulp protecting materials in presence and in absence of non-collagenous proteins analogs.	PAA	TMP/Biodentine/Lime-lite	No	Vickers microhardness, EDS, and optical microscopy	The application of biomimetic analogs together with both cement materials has significantly enriched the surface with ions essential for remineralization process.	High
Saeki et al.¹⁹	To evaluate if the artificial lesions created by lactate respond similarly to PILP remineralization treatment as acetate lesions of the same depth.	pAsp	CaP	No	AFM (elastic modulus), AFM, TEM, and optical microscopy	The PILP process provided significant recovery of both structure and mechanical properties for artificial lesions produced with acetate or lactate.	Low
Sauro et al.²⁹	To evaluate the remineralization of acid-etched dentin pre-treated with primers containing biomimetic analogs and bonded using an ion-releasing light-curable resin-based material.	pAsp	Beta-TCP/TMP/MTA	No	FTIR, AFM, MEV, confocal, and SEM	Both biomimetic primers induced phosphate uptake by acid-etched dentin.	Medium
Saxena et al.²¹	To evaluate dual analog system using a tripolyphosphate (TPP) “templating analog” and a PAA or pAsp “sequestration analog.”	pAsp/PAA	TPP/CaP	No	EDS, TEM, MEV, XDR, and TGA	TPP enhanced overall mineralization of specimens that were PILP-remineralized using pAsp. PAA was unable to remineralize demineralized dentin slices under the conditions employed.	Medium
Thula-Mata et al.¹⁶	To determine if PILP agent is capable of calcium phosphate mineral formation throughout multiple levels of the dentin hierarcical structure.	pAsp	CaP	No	MEV, TEM, and XDR	Dentin samples remineralized by PAA presented a surface morphology more similar to the intact mineralized dentin’s architecture than the conventional nucleation and growth method.	High
Wang et al.³⁰	To evaluate a novel adhesive with PAA stabilized amorphous calcium phosphate (PAA-ACP) nanoparticles	PAA	ACP	Yes, adhesive	TEM, SAED, HRTEM, and XDR	The adhesive induced extra- and intra-fibrillar remineralization, in dentin substrate.	Low

Pasp: polyaspartic acid; PAA: polyacrylic acid; RMGI: resin modified glass ionomer; EDS: energy dispersive spectroscopy; AFM: atomic force microscopy; FTIR: Fourier transform infrared; SEM: scanning electron microscopy; Microxct: microspectroscopy, micro X-ray computed tomography; Cap: calcium phosphate; MTA: mineral trioxide aggregate; PVP: polyvinylpyrrolidone; TEM: transmission electron microscopy; TMP: sodium trimetaphosphate; TGA: thermogravimetric analysis; SAED: selected area electron diffraction; MTBS: microtensile bond strength testing; TCP: tricalcium phosphate; ACP: amorphous calcium phosphate; XDR: extended detection and response; HRTEM: high resolution transmission electron microscopy.

Stage VI: Risk of bias

All included studies were assessed for risk of bias. The following topics were evaluated: Sampling bias-sample size, Sampling Bias-Blindness, Conflict Bias, Sampling statistic, Assessment Bias and Funding Bias (Table 3). The risk of bias was assessed by two evaluators (MAAF and PANS) considering the patterns described in Table 3, in case of disagreement a third evaluator (CSG) was recruited to define the analysis.

Table 3.

Quality assessment list.

Sampling bias—randomization
- Low risk: if the study authors describe a random process to assign samples
- High risk: if the process of assigning the samples was not random or no clear information was given to decide
- Unclear: if the study cite random process but the process is not clear

Sampling bias—sample size
- Low risk: if the study authors describe the sample size calculation or justification
- High risk: if the sample size justification was not reported
- Unclear: if the study cite sample size calculation but the process is not clear

Assessment bias
- Low risk: if the study authors present all results and discuss is appropriated.
- High risk: if the study authors not present all results
- Unclear: if the study authors present all results and discuss is not appropriated.

Sampling statistic
- Low risk: if the study described the statistic and the test was appropriated
- High risk: if the study no did statistic test, or do inappropriate statistic, or not describe the significance level
- Unclear: if the study described the statistic but the process is not clear

Conflict bias
- Low risk: if “no conflict of interest” was reported
- High risk: if there was a conflict of interest, or information not reported.

Funding bias
- Low risk: if no funding bias was apparent.
- High: if there was a funding bias.
- Unclear: if no clear information was given to decide

All evaluators judged each item as “low,” “unclear,” or “high.” The risk of bias for each study was established according to the number of items marked with “low bias.” Studies that presented between 6 and 5 items at risk of “low bias” were classified as “low risk”; 4–3 items at risk of “low bias” were classified as “unclear”; and 2 or less items at risk of “low bias” were classified as “high risk.”

Results

A total of 247 articles were identified in the electronic database search. After removing the duplicated studies, 209 remained. Among them, 175 were excluded based on the title and abstract. The 34 full-text studies assessed for eligibility, 12 remained and were included in this scoping review (Figure 1). These studies ranged in publication date from 2010 to 2020.

The risk of bias for included studies can be observed in Table 4. Only two articles showed low risk of bias. Six articles showed a medium risk of bias, and four had a high risk of bias. For all studies, the sample size was neglected (high risk)—being an important factor for the quality of the studies.

Table 4.

Risk of bias.

	Bacino et al.²³	Burwell et al.²⁴	Kim et al.⁸	Lausch et al.²⁵	Nurrohman et al.²⁶	Osorio et al.²⁷	Sadoon et al.²⁸	Saeki et al.¹⁹	Sauro et al.²⁹	Saxena et al.²¹	Thula-Mata et al.¹⁶	Wang et al.³⁰
High	3	4	2	3	3	2	4	1	3	2	4	1
Assessment bias							X
Conflict bias	X	X	X	X			X		X		X
Funding bias					X
Sampling bias-blindness	X	X		X	X	X	X		X	X	X
Sampling bias-sample size	X	X	X	X	X	X	X	X	X	X	X	X
Sampling statistic		X									X
Low	3	1	4	3	2	3		5	3	4	2	5
Assessment bias	X	X	X	X	X	X		X	X	X	X	X
Conflict bias					X	X		X		X		X
Funding bias	X		X	X		X		X	X	X	X	X
Sampling bias-blindness			X					X				X
Sampling statistic	X		X	X				X	X	X		X
Unclear		1			1	1	2
Funding bias		X					X
Sampling statistic					X	X	X
Risk of bias	Medium	High	Medium	Medium	High	Medium	High	Low	Medium	Medium	High	Low

The principal findings of this study are shown in Table 2. The outcomes of dentin mineralization pattern were plotted in association with PILP type and application mode (Figures 2 and 3). The intrafibrillar mineralization occurred in 78% of studies (seven articles^{16,21,23,24,26,27,29}) where polyaspartic acid was used. When polyacrylic acid was used the intrafibrillar mineralization was 50% (two articles^8,30; Figure 2).

Figure 2.

Dentin mineralization pattern according to the type of PILP.

Figure 3.

Dentin mineralization pattern according to the PILP application mode.

All two studies^23,30 where PILP was applied together with the restorative material showed extra and intrafibrillar mineralization (Figure 3). When the material was applied on dentin, 64% of the studies (seven articles^{8,16,21,24,26,27,29}) demonstrated extra and intra-fibrillar mineralization. Of these, one article⁸ used polyacrylic acid and 6^{16,21,24,26,27,29} articles polyaspartic acid. The 36% of the works where there was extrafibrillar mineralization when the material was applied on the dentin were composed of two articles that used polyacrylic acid^21,28 and two article that used polyaspartic acid^19,25 (Figure 3).

Discussion

Our findings revealed that in most of the studies PILP agents promoted intra and extrafibrillar mineralization in dentin where pAsp was used in 69% of the studies, and 78% of them demonstrated to promote intrafibrillar remineralization.^{8,16,21,23,24,26,27,29,30}

A PILP is an anionic polymer that acts as an analog of non-collagenous extracellular matrix proteins, regulating mineral deposition, and resulting in biomimetic mineralization.³¹ This means that remineralization occurs from the bottom to the top of the cavity (in nanoscale) following the non-classical theory of mineralization.⁸ Due to the polymers size, it is able to penetrate in the intrafibrillar spaces of dentin. Then, the PILP sequesters calcium ions that build up a positive charge to sequester phosphate (the opposite charge) to induce the formation of a nanoprecursor of ACP and promote mineralization.³²

Two types of PILP have been used for this purpose, PAA and pAsp—the latter being used in most studies and obtaining the best results. This can be explained because pAsp will avoid crystal precipitation, while allowing calcium and phosphate to remain available to diffuse in the dentin collagen.²⁷ Thus, the remineralization initiation process occurs more slowly (7 days) with pAsp than with other agents, and at the same time it is possible to obtain a greater mineral recovery of the tissue.²⁴

For the PAA, the intrafibrillar remineralization happened in 50% of the studies (Figure 2).^8,21,28,30 A study that compared PAA with pAsp, showed less mineralization for PAA.²¹ The results were probably related to the lower molecular weight of PAA (1.8 kDa) compared to pAsp (27 kDa).²¹ According to the “concept of molecules selective permeability in collagen,” molecules larger than 40 kDa are excluded from the intrafibrillar water compartments of the fibrillar collagen, whereas molecules smaller than 6 kDa cannot remain in the intrafibrillar spaces.¹⁸ Thus, nucleation was overly inhibited in the PAA groups.²¹ Demonstrating that mineralization is facilitated by a range of molecular weights both above and below the critical 6 kDa level. Another possible explanation is that, in contrast to polyacrylic acid (PAA), polyaspartic acid (pAsp) possesses terminal amine groups, allowing it to closely mimic the structure of non-collagenous proteins essential to the remineralization process. This unique feature of pAsp potentially facilitates stronger interactions with the mineral phase.⁸ Additionally, a comprehensive exploration of other characteristics, including the stereochemistry and molecular weight of the polymer, could shed light on how specific properties of polyaspartic acid contribute to its enhanced mineralization performance. On the other hand, the intrafibrillar mineralization was efficient when PAA was incorporated with ACP nanoparticles, being a promising strategy for future research.³⁰

Another approach is the association of tripolyphosphate (TPP) with a PILP where an improved mineralization process was showed.²¹ TPP acts as a dual-analog system, where the TPP serves as a “templating analog,” mimicking the highly phosphorylated domains within many non-collagenous proteins. In contrast, the PAA is referred to as the “sequestration analog” because it contains repeated carboxylic acid side chains that mimic the acidic domains on many non-collagenous proteins—which are thought to play a role in stabilizing amorphous calcium phosphate precursors.²¹ Saxena et al.²¹ used PAA and pAsp after pretreatment of collagen with TPP and obtained promising results—increasing general mineralization. TPP seemed to have the function of inhibiting mineralization on the substrate surfaces, leaving the tubules open, allowing the PILP to penetrate. Besides, it may be inhibiting mineral formation by chelating Ca²⁺ ions and preventing them from associating with free phosphates. However, neither PILP alone nor PILP with TPP pretreatment could fully remineralize these substrates at all depths.

Additionally, some studies also associated PILP agents with other materials with mineralization potential, like supersaturated Ca P solutions, sodium trimetaphosphate (TMP), Portland cement (MTA), and beta tricalcium phosphate (β-TCP; Table 2). The studies showed that these associations are essential in producing biomimetic mineralized tissue since a medium with relatively high calcium-phosphate (CaP) concentration is necessary for mineralization,²⁵ which may be the reason most studies assessed hypersaturated CaP solutions.²⁷ Other studies^8,27,29 reported that the use of doped resin composites with Portland cement and β-TCP over the PILP layer were important for calcium and phosphate release. In addition, it was shown that when PILP was not associated with these ion-releasing materials, mineralization did not occur.²⁹

TMP is a substantial source of P ions and it was used in three studies.^27
–29 Although in the study by Osorio et al.²⁷ the association between TMP and pAsp was not favorable, other studies have shown that TMP can contribute to intrafibrillar mineralization.^28,29

PILP agents have only been associated with restorative materials in two studies (Resin-Modified Glass-Ionomer (RGMI) and adhesives), which showed no influence on the mechanism of PILP extra and intrafibrillar remineralization.^23,30 Bacino et al.²³ promoted remineralization adding up to 40% wt of pAsp powder in glass ionomer. However, pAsp does not integrate well within the resin matrix of the cement—instead it separates from the matrix phase forming pores, which negatively impacted on the mechanical properties of the cement. Wang et al.³⁰ found that PAA added to an adhesive was able to remineralize intra and extrafibrillar zones. This is of great advantage since during a restorative procedure the regular adhesives cannot penetrate the intrafibrillar areas, and then they are filled with water. PILP agents are able to penetrate into those regions and promote remineralization.⁸ However, more studies are needed—especially in vivo.

Nanomechanical properties, mineral composition (Ca and P), and images showing direct evidence of mineral deposition and crystal growth were the most common properties assessed, and should be employed to have reliable remineralization outcomes and conclusions. The methods used to assess mineral density, such as energy-dispersive X-ray spectroscopy (EDS) and 3D X-ray computed tomography (XCT), not always corresponded to the results for mechanical properties,²⁴ but are probably more accurate than solely image analyses like Scanning Electron Microscopy (SEM). Saxena et al.²¹ observed remineralization in their specimens using SEM; however, when evaluated through EDS, the intrafibrillar mineral deposition was much lower than expected.²¹ Transmission Electron Microscopy (TEM) was the most used methodology because its high magnification allows examining the presence, orientation, or dislocations of crystals.⁸ However, the quality of the equipment is crucial, as Kim et al.⁸ showed problems to interpret their results for such reasons. X-ray diffraction (XDR) was also very useful to identify the nature and crystallinity of the mineral formed by PILP treatments.²⁴

Two methodologies that were less used were dehydration shrinkage and nanomechanical tests of the remineralized dentin lesion; however, they are suitable indicators of functional remineralization of dentin matrices. Burwell et al.²⁴ found that the PILP used recovered the full mineral density, but the modulus (nano-indentation) was not fully reestablished since it is believed that intrafibrillar mineralization is the one that increases the mechanical properties.^11,16 In this test, it is worthy to highlight that the nanoindentations should be performed on hydrated tissue, since dehydration alters the mechanical response of the collagenous matrix and provides little information about the functionality of dentin. So, when carious or partially demineralized dentin is measured dry, the demineralized portion collapses and its measurement gives erroneously high values as showed by Bertassoni et al.¹¹

The studies evaluated in this review showed several limitations. Most studies were in-vitro, and the caries lesions were produced by chemical methods. In vivo and in vitro studies inducing caries by the biological method are necessary. Only two studies presented low risk of bias, and none reported the sample calculation. Future studies should describe with more detail the methodologic aspects.

Thus, the available information on biomimetic mineralization by PILP in dentin remains limited. Further studies, particularly in vivo, employing rigorous methodologies, are needed to assess the effectiveness of remineralization through PILP agents, considering the low level of evidence found in the existing studies

Conclusion

The pAsp showed better results for interfibrillar remineralization when compared to PAA. The association with materials with Ca P release or Ca P solutions are essentials for mineralization via PILP agent. Further studies are needed to assess the effectiveness of remineralization through PILP agents since the level of evidence of the studies was low.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors thank the Coordination for the Improvement of Higher Education Personnel (CAPES) by the financial support (Code 001).

ORCID iD

May Anny Alves Fraga

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