Evaluation of Casein Phosphopeptide–Amorphous Calcium Phosphate Effect on the Bond Strength of Self-etch Adhesives to Dentin: A Systematic Review

INTRODUCTION

Dental caries is slowed down by a novel bioactive substance called casein phosphopeptide–amorphous calcium phosphate (CPP–ACP), which is generated from the milk protein casein. The sequence of clusters is “-Ser (P)-Ser (P)-Ser (P).” The main phosphoprotein in cow’s milk, casein, makes for nearly 80% of its total protein content.¹ Furthermore, CPP–ACP’s antibacterial and anticalculus properties can prevent demineralization, encourage remineralization of enamel, and postpone the formation of biofilms.² Also, CPP–ACP maintains the condition of supersaturation at the tooth structure by gradually raising the calcium phosphate content in plaque. As a result, it may serve as a calcium phosphate reservoir, buffering the activities of free calcium and phosphate ions.³

Caries can be treated non-invasively by topical CPP–ACP therapy. By preserving ionic phosphate and calcium supersaturation, it has been demonstrated to be useful in halting dentin caries by manipulating bioavailable calcium phosphate levels.⁴ They can also block the dentinal tubules and reduce the sensitivity; in cases of erosion, it neutralizes acid challenges from internal and external acid sources, and the biomimetic mineralization of dentin is induced through apatite formation along and between the phosphorylated dentin collagen fibers.^5–7

Dental adhesives are resin monomer solutions containing solvents, curing initiators, inhibitors or stabilizers, and, occasionally, inorganic fillers. Buonocore founded adhesive dentistry in 1955 after discovering the advantages of acid etching. The idea of a generation has changed in dental adhesives due to the complexity of bonding agents, which ranges from “no etch” to “total etch” (fourth and fifth generations) to “self-etch” (sixth, seventh, and eighth generation) systems.⁸ Self-etch adhesive systems are thought to be simplified adhesive materials because they do not need a separate acid conditioning process or wet post-rinse management. They are also thought to be straightforward to use and attach chemically to the tooth structure.⁹

Since CPP–ACP is being used more often to treat caries, it is possible that CPP–ACP was applied to the dentin surface of cavities prior to the restoration being placed. It is crucial to look into whether this will have an impact on how well self-etch adhesives adhere to dentin. The purpose of this systematic study is to assess the impact of CPP–ACP on the dentin bond strength of self-etch adhesives.

MATERIALS AND METHODS

The present study corresponded to the recommendations of the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) criteria, as available at http://www.prisma-statement.org. The registration number for this systematic review on PROSPERO is CRD42021240001. Four examiners conducted an independent search, using the electronic databases Medline (via PubMed) and Google Scholar to find publications published up until November 2021 without any year restrictions. Only articles written in the English language were taken into consideration for the review. The search keywords were “CPP–ACP (Title/Abstract)” OR “tooth mousse (Title/Abstract)” OR “MI-paste (Title/Abstract)” AND “bond strength (Title/Abstract)” OR “tensile bond strength (Title/Abstract)” OR “microtensile bond strength (Title/Abstract)” OR “shear bond strength (Title/Abstract).” Two authors of this study independently selected the retrieved studies by examining the titles and abstracts. When it was unable to evaluate the research-based just on their titles and abstracts, the complete text was accessible. Reading whole texts and selecting studies for inclusion based on eligibility requirements using the PICOS approach constitute the second stage. Duplicate studies in the database search were taken into consideration only once, and disagreements on the inclusion of a study were resolved by consensus with a third author. The reason for the exclusion of these studies is articles related to the bond strength of enamel, orthodontic brackets and dentin of primary teeth; studies in which CPP–ACP was not used as an intervention agent; studies are excluded if there was no control group (CG) as before and after studies and studies showed the strength of etch-and-rinse adhesives, glass ionomer cement as measured following application of CPP–ACP. The inclusion and exclusion criteria are given in Table 1.

RESULTS

A total of 479 published papers were found in the databases at first as a consequence of the search; however, 58 studies were eliminated since they were duplicates. A total of 26 studies were then included after titles and abstracts from 421 suitable papers were analyzed. The studies’ failure to meet the inclusion criteria was the primary cause of the papers’ rejection. Following a thorough review, thirteen studies were eliminated. A total of 13 studies in all were chosen for the systematic review as a result. Figure 1 shows the search strategy and results for the selection of studies.

DISCUSSION

Demineralization of tooth surface due to caries which requires prolonged application of therapeutic agents to repair enamel. Oral therapeutic agents which applied periodically must have desirable properties such as “high substantivity” or long-term activity. Furthermore, CPP–ACP shows the highest oral substantivity and higher anticariogenic properties.¹¹ Moreover, CPP–ACP can expose collagen fibers and increase mineral content as it has a remineralizing ability which would also enhance dentin bond strength and durability when applied to caries-affected dentin (CAD).¹²

An assessment was conducted on the caliber of every included study. One need for this evaluation was random allocation, which aims toward ensuring that every lesion has an equal chance of getting any of the experimental studies. Every study that was included provided sufficient procedures for assigning participants at random. Performance bias is another factor in evaluating quality, and it should be prevented by appropriately blinding participants and personnel. Only one study had mentioned about the blinding of the operator of the testing machine.¹³ Due to the nature of the interventions, it was not possible to blind participants or the primary investigator to the interventions, as no other study had addressed the topic of participant or investigator blinding. Since both the participants and the operators were aware of the experimental technique, the risk of performance bias was deemed to be medium. The evaluation was predicated on the explanation of the following parameters for the quality assessment of the study: The use of teeth free of caries or restorations, the quantity of materials used, the number of materials used, the presence of a comparison group, random group assignment, the description of sample size calculation, study conducted by a single operator, and the blinding of the observer operating the machine.

Out of the 13 studies included, two studies (15.4%) presented with a low risk of bias; nine studies (69.2%) presented a medium risk of bias, whereas the remaining two studies (15.4%) presented with a high risk of bias (Table 3).^12–24 None of the studies mentioned sample size estimation. Only two studies had mentioned about single operator carrying out all the experiments.^16,20 Only three studies had not mentioned whether included teeth samples were restored or caries-free in the experimental study.^12,13,24 Four studies mentioned the quantity of material that had been used in the experimental protocol.^16–18,20 All the authors followed the manufacturing instructions as given in the product details that were used in their study. In most of the study groups, CPP–ACP was applied over a sound dentin structure. In two studies, CAD groups, and in another two studies, demineralized dentin was used.^12,16,20,22

Adebayo et al. reported that the Tooth Mousse™ application was not significantly affected. Regardless of the adhesive technique employed, Bahari et al.¹³ reported that surface-treating CAD with CPP–ACP had no appreciable impact on bond strength. Four studies measured shear bond strength (SBS), eight studies measured tensile bond strength, and only one research discussed the interfaces between resin and dentin have been studied using field-emission scanning electron microscopes (FE-SEMs).^13–24 According to the results of the study by Barbosa–Martins et al.,¹⁶ pretreating demineralized dentin with remineralizing materials has been shown to be an effective, workable way to improve bonding while according to Doozandeh and Mirmohammadi¹² etching dentin affected by caries for up to 45 seconds could improve its SBS and bring it almost to that of normal dentin (ND). Pretreatment with MI Paste™ did not significantly affect the SBS of the etch-and-rinse adhesive in CAD. Kamozaki et al.¹⁷ The microtensile bond strength of softened dentin was unaffected by the CPP–ACP-based pastes while Krithi et al.¹⁸ stated that reduction in bond strength when CPP–ACP was used as a remineralizing agent. Pei et al.¹⁹ and Zorba et al.²⁴ mentioned that the shear bond strength of different adhesive systems used to bond resin composite to dentin is unaffected by the application of different desensitizing agents. Shafiei et al.²⁰ stated that CPP–ACP increases bond strength when applied before adhesive. Sattabanasuk et al.²¹ concluded that CPP–ACP on the dentin surface may improve the bonding performance of self-etch adhesive systems but reduce the effectiveness of etch-and-rinse adhesive systems. According to the findings of the study by Tayal et al.,²² the binding strength of the CPP–ACP specimens was considerably decreased following previous etching. According to Torkani et al.,²³ the microtensile bond strength when using G-Bond™ (GB) is noticeably stronger after dentin treatment with CPP–ACP as opposed to when CPP–ACP is not used.

As this is the first comprehensive analysis of how CPP–ACP affects the strength of self-etch adhesives’ bond with dentin. The fact that the authors conducted the review in accordance with the PRISMA guidelines is another strength of the study.

One limitation is that the variability among the included studies regarding their methodology, such as CPP–ACP and adhesive application protocol (e.g., different comparative groups, etchant concentration, and time application). In none of the research studies, a sample size calculation is done. Furthermore, the study’s teeth’s caries-free and repaired categories lacked uniformity in the selection process. Only two studies methodology performed by a single operator and one study in which blinding of the operator was done to reduce inter-operator bias.^13,16,20 Because of the inconsistent approaches and impossibility of comparing the different therapies used and the different study designs of the included studies, a meta-analysis was not advised. Restricted access for searching numerous databases is another study drawback.

CONCLUSION

The study’s results and risk of bias evaluation indicated that the current review study’s risk of bias was medium. The degree of variance among the included research makes it impossible to draw conclusions about how CPP–ACP application affects dentin’s ability to bind to self-etch adhesives.

ORCID

Suyash Joshi https://orcid.org/0000-0002-1976-2676

Nupur Ninawe https://orcid.org/0000-0003-1403-4634

Hemraj Badhe https://orcid.org/0000-0001-6030-6317

Shivani Bhadule https://orcid.org/0000-0002-8567-5896

Karthika Krishnakumar https://orcid.org/0000-0002-6011-7337

Nilam V Honaje https://orcid.org/0000-0001-6738-5046

REFERENCES

1. Azarpazhooh A, Limeback H. Clinical efficacy of casein derivatives: A systematic review of the literature. J Am Dent Assoc 2008;139(7):915–924. DOI: 10.14219/jada.archive.2008.0278.

2. Divyapriya GK, Yavagal PC, Veeresh DJ. Casein phosphopeptide–amorphous calcium phosphate in dentistry: An update. Int J Oral Health Sci 2016;6(1):18. DOI: 10.4103/2231-6027.186660.

3. Gagnaire V, Pierre A, Molle D, et al. Phosphopeptides interacting with colloidal calcium phosphate isolated by tryptic hydrolysis of bovine casein micelles. J Dairy Res 1996;63(3):405–422. DOI: 10.1017/s0022029900031927.

4. Llena C, Forner L, Baca P. Anticariogenicity of casein phosphopeptide–amorphous calcium phosphate: A review of the literature. J Contemp Dent Pract 2009;10(3):1–9. PMID: 19430620.

5. Reynolds EC. Remineralization of enamel subsurface lesions by casein phosphopeptide-stabilized calcium phosphate solutions. J Dent Res 1997;76(9):1587–1595. DOI: 10.1177/00220345970760091101.

6. Al Batayneh O. Clinical applications of Tooth Mousse^TM and other CPP–ACP products in caries prevention: Evidence-based recommendations. Smile Dent J 2009:4(1):8–12. Available from: https://www.researchgate.net/publication/220042410_The_clinical_applications_of_Tooth_Mousse_TM_and_CPP-ACP_products_in_caries_prevention_evidence-_based_recommendations.

7. Cao Y, Mei ML, Xu J, et al. Biomimetic mineralisation of phosphorylated dentine by CPP–ACP. J Dent 2013;41(9):818–825. DOI: 10.1016/j.jdent.2013.06.008.

8. Giannini M, Makishi P, Ayres AP, et al. Self-etch adhesive systems: A literature review. Braz Dent J 2015;26(1):3–10. DOI: 10.1590/0103-6440201302442.

9. Farooq I, Moheet IA, Imran Z, et al. A review of novel dental caries preventive material: Casein phosphopeptide–amorphous calcium phosphate (CPP–ACP) complex. King saud university J Dent Sci 2013;1;4(2):47–51. DOI: DOI: 10.1016/j.ksujds.2013.03.004.

10. AlShwaimi E, Bogari D, Ajaj R, et al. In vitro antimicrobial effectiveness of root canal sealers against Enterococcus faecalis: A systematic review. J Endod 2016;42(11):1588–1597. DOI: 10.1016/j.joen.2016.08.001.

11. Cross KJ, Huq NL, Reynolds EC. Casein phosphopeptides in oral health-chemistry and clinical applications. Curr Pharm Des 2007;13(8):793–800. DOI: 10.2174/138161207780363086.

12. Doozandeh M, Mirmohammadi M. The simultaneous effect of extended etching time and casein phosphopeptide–amorphous calcium phosphate containing paste application on shear bond strength of etch-and-rinse adhesive to caries-affected dentin. J Contemp Dent Pract 2015;16(10):794–799. DOI: 10.5005/djas-10024-1759.

13. Bahari M, Oskoee SS, Kimyai S, et al. Effect of casein phosphopeptide–amorphous calcium phosphate treatment on microtensile bond strength to carious affected dentin using two adhesive J Dent Res Dent Clin Dent Prospects 2014;8(3):141. DOI: 10.5681/joddd.2014.026.

14. Adebayo OA, Burrow MF, Tyas MJ. Dentine bonding after CPP–ACP paste treatment with and without conditioning. J Dent 2008;36(12):1013–1024. DOI: 10.1016/j.jdent.2008.08.011.

15. Adebayo OA, Burrow MF, Tyas MJ. Resin–dentine interfacial morphology following CPP–ACP treatment. J Dent 2010;38(2):96–105. DOI: 10.1016/j.jdent.2009.09.007.

16. Barbosa–Martins LF, de Sousa JP, de Castilho AR, et al. Enhancing bond strength on demineralized dentin by pre-treatment with selective remineralising agents. J Mech Behav Biomed Mater 2018;81:214–221. DOI: 10.1016/j.jmbbm.2018.03.007.

17. Kamozaki MB, Prakki A, Perote LCCC, et al. The effect of CPP–ACP and Nd:YAG laser on the bond strength of softened dentin. Braz Oral Res 2015;29:S1806-83242015000100268. DOI: 10.1590/1807-3107BOR-2015.vol29.0068.

18. Krithi B, Vidhya S, Mahalaxmi S. Microshear bond strength of composite resin to demineralized dentin after remineralization with sodium fluoride, CPP–ACP and NovaMin containing dentifrices. J Oral Biol Craniofac Res 2020;10(2):122–127. DOI: 10.1016/j.jobcr.2020.03.007.

19. Pei D, Liu S, Huang C, et al. Effect of pretreatment with calcium‐containing desensitizer on the dentine bonding of mild self‐etch adhesives. Eur J Oral Sci 2013;121 (3 Pt 1):204–210. DOI: 10.1111/eos.12047.

20. Shafiei F, Derafshi R, Memarpour M. Bond strength of self-adhering materials: Effect of dentin-desensitizing treatment with a CPP–ACP paste. Int J Periodontics Restorative Dent 2017;1;37(6):337–343. DOI: 10.11607/prd.2850.

21. Sattabanasuk V, Burrow MF, Shimada Y, et al. Resin bonding to dentine after casein phosphopeptide–amorphous calcium phosphate (CPP–ACP) treatments. J Adhes Sci Technol 2009;1;23(7–8):1149–1161. DOI: 10.1163/156856109X432686.

22. Tayal SC, Dhillon J, Tayal A. Effect of prior etching on bond strength of self-etch adhesive in case of sensitive teeth treated with CPP–ACP. Dent J Adv Stud 2013;1(01):009–014. DOI: 10.1055/s-0038-1670585.

23. Torkani MA, Mesbahi S, Abdollahi AA. Effect of casein phosphopeptide amorphous calcium phosphate conditioning on microtensile bond strength of three adhesive systems to deep dentin. Front Dent 2020;17:34. DOI: 10.18502/fid.v17i34.5198.

24. Zorba YO, Erdemir A, Ercan E, et al. The effects of three different desensitizing agents on the shear bond strength of composite resin bonding agents. J Mech Behav Biomed Mater 2010;3(5):399–404. DOI: 10.1016/j.jmbbm.2010.03.003.