Nanohydroxyapatite: Trends and Current Status

Nanohydroxyapatite: Trends and Current Status

Nanohydroxyapatite (NHAP) consists of nano-sized particles of hydroxyapatite (1 to 100 nanometers in size), and is considered a biomimetic material.1Bordea IR, Candrea S, Alexescu GT et al. Nano-hydroxyapatite use in dentistry: a systematic review. Drug Metab Rev 2020;52(2):319-32. doi: 10.1080/03602532.2020.1758713. Research has been and is currently being conducted on its potential uses in bone grafting materials, membranes for the treatment of periodontitis, scaffolds for bone regeneration in bony defects, for sinus augmentation, as an implant coating to promote osseointegration, for biofilm inhibition, and for remineralization.2Mitić D, Čarkić J, Jaćimović J, Lazarević M et al. The Impact of Nano-Hydroxyapatite Scaffold Enrichment on Bone Regeneration In Vivo-A Systematic Review. Biomimetics (Basel) 2024;9(7):386. doi: 10.3390/biomimetics9070386.^,3Nour M, Shawky M, Abaas RA et al. Two Stage Sinus Lifting Using Nanohydroxyapatite Particles Versus Deproteinized Bovine Bone: Randomized Clinical Trial. Clin Implant Dent Relat Res 2024 Oct 31. doi: 10.1111/cid.13410. ^,4Nevins M, Chen CY, Khang W, Kim DM. Clinical and histological efficacy of a new implant surface in achieving early and stable osseointegration: An in vivo study. Int J Oral Implantol (Berl) 2024;17(3):297-306.^,5Lucaciu PO, Repciuc CC, Matei IA et al. In Vivo Validation of a Nanostructured Electrospun Polycaprolactone Membrane Loaded with Gentamicin and Nano-Hydroxyapatite for the Treatment of Periodontitis. Membranes (Basel) 2024;14(3):60. doi: 10.3390/membranes14030060.^,6Senthil R. Formation of bone tissue apatite on starch-based nanofiber-capped nanohydroxyapatite and reduced graphene oxide: a preliminary study. Oral Maxillofac Surg 2024;29(1):6. doi: 10.1007/s10006-024-01303-5.^,7Huang Y, Han Q, Peng X et al. Disaggregated Nano-Hydroxyapatite (DnHAP) with Inhibitory Effects on Biofilms and Demineralization. J Dent Res 2023;102(7):777-84. doi: 10.1177/00220345231162349.^,8Souza AF, Souza MT, Damasceno JE et al. Effects of the Incorporation of Bioactive Particles on Physical Properties, Bioactivity and Penetration of Resin Enamel Infiltrant. Clin Cosmet Investig Dent 2023;15:31-43. doi: 10.2147/CCIDE.S398514.^,9Aref NS, Alsdrani RM. Surface topography and spectrophotometric assessment of white spot lesions restored with nano-hydroxyapatite-containing universal adhesive resin: an in-vitro study. BMC Oral Health 2023;23(1):911. doi: 10.1186/s12903-023-03642-3.^,10Ionescu AC, Cazzaniga G, Ottobelli M et al. Substituted Nano-Hydroxyapatite Toothpastes Reduce Biofilm Formation on Enamel and Resin-Based Composite Surfaces. J Funct Biomater 2020;11(2):36. doi: 10.3390/jfb11020036. In addition, NHAP has been researched as a desensitizing agent. In this article, we will briefly address dentinal hypersensitivity and then focus on NHAP in the prevention of demineralization and in remineralization.

Dentinal hypersensitivity

In a systematic review and meta-analysis of 6 randomized controlled trials with a 4-week follow-up, NHAP was found to effective as a desensitizer.11de Melo Alencar C, Freitas de Paula BL, Ortiz MIG et al. Clinical efficacy of nano-hydroxyapatite in dentin hypersensitivity: A systematic review and meta-analysis. J Dent 2019;82:11-21. In addition, in in vitro studies, occlusion of dentinal tubules was observed with applications of NHAP paste formulations.12Uslu YS, Donmez N, Gungor AS et al. Occluding Efficiency of Different Desensitizing Agents and Er,Cr:YSGG Laser on Dentin Tubules. Oper Dent 2024;49(2):166-77. doi: 10.2341/23-032-L. ^,13Sahin D, Deger C, Oglakci B et al. The Effects of a Novel Nanohydroxyapatite Gel and Er:YAG Laser Treatment on Dentin Hypersensitivity. Materials (Basel) 2023;16(19):6522. doi: 10.3390/ma16196522.^,14Bologa E, Stoleriu S, Nica I et al. The Effect of Three Desensitizing Toothpastes on Dentinal Tubules Occlusion and on Dentin Hardness. Biomedicines 2023;11(9):2464. doi: 10.3390/biomedicines11092464.^,15Gupta I, Chauhan S, Amaranath BJJ et al. Effect of Commercially Available Nano-Hydroxyapatite Containing Desensitizing Toothpaste and Mouthwash on Dentinal Tubular Occlusion: A SEM Analysis. J Pharm Bioallied Sci 2023;15(Suppl 2):S1027-29. doi:10.4103/jpbs.jpbs_243_23. ^,16Jena A, Kala S, Shashirekha G. Comparing the effectiveness of four desensitizing toothpastes on dentinal tubule occlusion: A scanning electron microscope analysis. J Conserv Dent 2017;20(4):269-72. doi: 10.4103/JCD.JCD_34_17.^,17Kulal R, Jayanti I, Sambashivaiah S, Bilchodmath S. An In-vitro Comparison of Nano Hydroxyapatite, Novamin and Proargin Desensitizing Toothpastes - A SEM Study. J Clin Diagn Res 2016;10(10):ZC51-54. doi: 10.7860/JCDR/2016/18991.8649.^,18Iwasaki M, Satou R, Sugihara N. Development of Root Caries Prevention by Nano-Hydroxyapatite Coating and Improvement of Dentin Acid Resistance. Materials (Basel) 2022;15(22):8263. doi: 10.3390/ma15228263. The application of NHAP crystals on teeth prior to bleaching with 35% hydrogen peroxide has also been found to result in the formation of deposits at the tooth surface, and to impede the diffusion of hydrogen peroxide into the pulp chamber, while not adversely affecting the efficacy of bleaching.19Murr CG, Favoreto MW, da Silva KL et al. Synthesis and characterization of different nano-hydroxyapatites and their impact on dental enamel following topical application for dental bleaching. J Dent 2024;149:105291. doi: 10.1016/j.jdent.2024.105291. In another in vitro study, NHAP again had no adverse effect on bleaching efficacy when teeth were bleached using 10% hydrogen peroxide.20da Freiria ACB, Ortiz MIG, de Sobral DFS et al. Nano-hydroxyapatite-induced remineralization of artificial white spot lesions after bleaching treatment with 10% carbamide peroxide. J Esthet Restor Dent 2022;34(8):1290-99. doi: 10.1111/jerd.12969.

Demineralization and remineralization studies

It has been proposed that NHAP could perform as an anti-caries agent, by supplying minerals that would result in a local environment supersaturated in calcium and phosphate adjacent to teeth21Huang SB, Gao SS, Cheng L, Yu HY. Remineralization potential of nano-hydroxyapatite on initial enamel lesions: an in vitro study. Caries Res 2011;45:460-8. doi: 10.1159/000331207. – and could therefore inhibit demineralization during acid attacks and promote remineralization. Here, we’ll examine the current status of the available research.

Systematic reviews
In the most recent systematic review of studies on NHAP formulations in the treatment of white spot lesions (WSL), 14 studies published up until August 2024 met the inclusion criteria.22Alajlan S, Baysan A. The effect of nano-hydroxyapatite on white spot lesions: A systematic review and meta-analysis. J Dent 2024:151:105402. doi: 10.1016/j.jdent.2024.105402. Based on testing enamel surface microhardness and laser fluorescence, the remineralization results were found to be promising for pure NHAP compared to fluoride alone. However, the studies were heterogeneous, 10 of 14 were laboratory studies (with 1 in situ and 3 in vivo), and the researchers noted a high risk of bias and the short-term follow-up. The evidence was found to be inconclusive. Similar conclusions were drawn in a second systematic review of five clinical studies (1 was in situ) on WSL and the use of NHAP together with fluoride.23Ortiz MIG, Gomes de Oliveira S, de Melo Alencar C et al. Remineralizing effect of the association of nano-hydroxyapatite and fluoride in the treatment of initial lesions of the enamel: A systematic review. J Dent 2024;145:104973. doi: 10.1016/j.jdent.2024.104973. The researchers noted the heterogeneity of the study designs with respect to treatment duration, method of application, and control groups. In an earlier systematic review, ten prospective controlled clinical studies were included (5 in vivo and 5 in situ), with in total 95 patients.24Wierichs RJ, Wolf TG, Campus G, Carvalho TS. Efficacy of nano-hydroxyapatite on caries prevention-a systematic review and meta-analysis. Clin Oral Investig 2022;26(4):3373-81. doi: 10.1007/s00784-022-04390-4. All studies included positive or negative control groups, or both. Sodium fluoride (NaF) was found to inhibit demineralization in the in situ studies and NHAP did not, while NHAP and NaF were found to be equally effective for remineralization. The researchers concluded that the evidence for NHAP was inconclusive and that 6 of 10 studies were at high risk of bias. The sections below highlight some of the methods and results of individual in vivo, in situ and in vitro studies.

Clinical studies – in vivo
In a single-blinded clinical study (2024) with interim visits and a 24-week follow-up, 45 four- to eight-year-olds with WSL were randomized into three equal groups that received: 1) a commercially-available NHAP serum (applied daily for 10 days); 2) 5% sodium fluoride varnish (NaFV) containing calcium phosphopeptide-amorphous calcium phosphate (CPP-ACP); or, 3) a nano-silver solution.25Annadurai T, Vundela RR, Chowdhary N et al. Evaluation of Remineralization Efficacy of Nanoparticle-based Materials on White Spot Lesions in Children: A Comparative Clinical Study. Int J Clin Pediatr Dent 2024;17(4):425-32. doi:10.5005/jp-journals-10005-2817. Remineralization was evaluated using standard photographic images of WSL and digitally determining the number of pixels for the WSL and the whole of the labial surface. The NHAP serum was found to remineralize WSL more than NaFV and the nano-silver solution. In a randomized clinical study, 50 patients wearing fixed orthodontic appliances were enrolled. Photographs were taken when the brackets were removed, and the patients received oral hygiene instructions and either a NHAP or fluoride dentifrice.26Badiee M, Jafari N, Fatemi S et al. Comparison of the effects of toothpastes containing nanohydroxyapatite and fluoride on white spot lesions in orthodontic patients: A randomized clinical trial. Dent Res J (Isfahan) 2020;17(5):354-9. Measurements were made using laser fluorescence, and a software program for pixel calculations of the images, and at the 6-month follow-up it was concluded that remineralization was superior with the NHAP dentifrice. In another randomized clinical study with almost 100 patients (in total 546 approximal enamel caries lesions), individuals received six months’ treatment with either a commercially-available 10% NHAP gel applied daily or gaseous ozone therapy at baseline and 2, 4 and 6 months; or both.27Grocholewicz K, Matkowska-Cichocka G, Makowiecki P et al.Effect of nano-hydroxyapatite and ozone on approximal initial caries: a randomized clinical trial. Sci Rep 2020;10(1):11192. doi: 10.1038/s41598-020-67885-8. Follow-up visits occurred at years one and two, and it was determined based on bitewing radiographs and optical density measurements that the combination treatment was more effective for remineralization than NHAP or ozone therapy alone. (Table 1)

Clinical studies - in situ
In a randomized double-blind two-arm crossover in situ study, 60 patients wore enamel blocks (total 128) with artificial caries lesions, brushed with a commercially-available 5% NHAP dentifrice and received 5% NHAP dental lotion or placebo that was applied daily for 14 days.28Amaechi BT, Alshareif DO, Azees PAA et al. Anti-caries evaluation of a nano-hydroxyapatite dental lotion for use after toothbrushing: An in situ study. J Dent 2021;115:103863. doi:10.1016/j.jdent.2021.103863. Based on mineral content comparisons using transverse microradiography (TMR), it was concluded that the NHAP dentifrice inhibited demineralization, and that adjunctive use of the serum enhanced remineralization compared to NHAP toothpaste alone. In a second in situ study with 8 subjects, bovine blocks with bonded brackets were exposed to sucrose challenges eight times daily and were treated either with an NHAP product twice-daily for 2 weeks followed by no treatment for a further 2 weeks or received no treatment.29Demito CF, Costa JVD, Fracasso MLC, Ramos AL. Efficacy of fluoride associated with nano-hydroxyapatite in reducing enamel demineralization adjacent to orthodontic brackets: in situ study. Dental Press J Orthod 2019;24(6):48-55. doi: 10.1590/2177-6709.24.6.048-055.oar. Using polarized light microscopy (PLM) it was found that applications of NHAP resulted in less demineralization. (Table 1)

Table 1. Clinical studies on remineralization of early caries lesions using NHAP

In vitro studies
Researched formulations of NHAP, positive and negative controls, the mix of products and delivery vehicles vary considerably, and in vitro studies have compared NHAP formulations with formulations containing fluoride and other products containing calcium and phosphate.

Dentifrices
In an investigation of 90 enamel samples with artificial caries lesions that were subjected to 3 weeks of pH-cycling, treatment with 1,450 ppm F or NHAP dentifrice increased samples’ surface microhardness, which did not occur with distilled water (negative control).30Mielczarek A, Michalik J. The effect of nano-hydroxyapatite toothpaste on enamel surface remineralization. An in vitro study. Am J Dent 2014;27(6):287-90. In another study with samples subjected to pH-cycling, twice-daily 2-minute applications of dentifrice slurries containing NHAP, tricalcium phosphate (TCP) or fluoride all resulted in gains in surface microhardness. Using PLM, the NHAP slurry was found to result in the largest decrease in caries depth.31Juntavee A, Juntavee N, Hirunmoon P. Remineralization Potential of Nanohydroxyapatite Toothpaste Compared with Tricalcium Phosphate and Fluoride Toothpaste on Artificial Carious Lesions. Int J Dent 2021;2021:5588832. doi: 10.1155/2021/5588832. The greatest increase in surface microhardness in another study was observed with immersion in a remineralizing solution containing NHAP dentifrice slurry, followed by samples immersed in solutions containing bioactive glass, CPP-ACP, or fluoride dentifrice slurries (decreasing order).32Geeta RD, Vallabhaneni S, Fatima K. Comparative evaluation of remineralization potential of nanohydroxyapatite crystals, bioactive glass, casein phosphopeptide-amorphous calcium phosphate, and fluoride on initial enamel lesion (scanning electron microscope analysis) - An in vitro study. J Conserv Dent 2020;23(3):275-9. doi: 10.4103/JCD.JCD_62_20.

In another study with artificial caries lesions, increased enamel surface microhardness resulted from the use of simulated toothbrushing with an experimental dentifrice containing NHAP and nanosilver particles.33Sevagaperumal A, Joel JR, Periyasamy S. Formulation and Evaluation of Characteristics, Remineralization Potential, and Antimicrobial Properties of Toothpaste Containing Nanohydroxyapatite and Nanosilver Particles: An In Vitro Study. Int J Clin Pediatr Dent 2024;17(6):630-36. In addition, based on SEMs and energy-dispersive X-ray spectroscopy (EDS) analyses, it was determined that remineralization had occurred. In a study using samples with artificial caries lesions and bonded orthodontic brackets, 20 samples each received treatment with a NHAP dentifrice or NHAP varnish, and the remaining 20 formed the control group. Based on SEM and EDX, it was concluded that the NHAP formulations could form a coating on the surface and remineralize the artificial caries lesions.34Samineni S, Rathore BS, Rohilla N et al. Evaluation of the Remineralisation of the Demineralized Enamel Surrounding Orthodontic Brackets using the Nano Hydroxyapatite: An Original Study. J Pharm Bioallied Sci 2023;15(Suppl 1):S175-9. doi:10.4103/jpbs.jpbs_447_22. In additional studies on NHAP dentifrices, superior increases in microhardness were found in comparison to amine fluoride, calcium sucrose phosphate, and CPP-ACP-F dentifrices (in descending order)35Gore AB, Patel SP, Gulve MN, Aher GB. Comparative evaluation of the remineralizing potential of different calcium and fluoride-based delivery systems on artificially demineralized enamel surface; an in vitro study. J Conserv Dent 2022;25(3):292-6. doi: 10.4103/jcd.jcd_5_22. ; and, based on polarized light microscopy, greater reductions in lesion depth compared to calcium phosphosilicate and fluoride dentifrice.36Manchery N, John J, Nagappan N et al. Remineralization potential of dentifrice containing nanohydroxyapatite on artificial carious lesions of enamel: A comparative in vitro study. Dent Res J (Isfahan) 2019;16(5):310-7.

In contrast, in other in vitro studies NHAP dentifrices were found to be less effective for remineralization than other dentifrice options. One study compared NHAP to NaF, NaF/stannous fluoride (NaF/SnF2), and calcium phosphosilicate.37Gümüştaş B, Birant S, Şişmanoğlu S. Ultrastructural investigation of the effect of toothpastes containing different remineralizing agents on demineralized enamel. J Esthet Restor Dent 2024;36(4):663-72. doi: 10.1111/jerd.13150. The NaF and NaF/SnF2 dentifrices were found to offer greater increases in surface microhardness and, based on SEM/EDX analyses, more surface deposition than NHAP dentifrice and greater fluoride binding to the demineralized enamel for the NaF/SnF2 dentifrice compared to NaF dentifrice. Pastes containing CPP-ACP-F or TCP-F demonstrated greater remineralization potential than NHAP paste in another study, based on SEM/EDX analyses.38Thimmaiah C, Shetty P, Shetty SB et al. Comparative analysis of the remineralization potential of CPP-ACP with Fluoride, Tri-Calcium Phosphate and Nano Hydroxyapatite using SEM/EDX - An in vitro study. J Clin Exp Dent 2019;11(12):e1120-26. doi:10.4317/jced.55941. In other studies, improvements in surface microhardness were similar for 1) NHAP-F paste (9,000 ppm F) and CPP-ACP-F paste (900 ppm F)39Talaat DA, Abdelrahman AA, Abdelaziz RH, Nagy D. Effect of Two Remineralizing Agents on Initial Caries-like Lesions in Young Permanent Teeth: An in Vitro Study. J Contemp Dent Pract 2018;19(10):1181-8.; 2) with twice-daily treatment for 5 days with 10% NHA or calcium phosphosilicate toothpaste40Haghgoo R, Ahmadvand M, Moshaverinia S. Remineralizing Effect of Topical NovaMin and Nano-hydroxyapatite on caries-like Lesions in Primary teeth. J Contemp Dent Pract 2016;17(8):645-9. doi: 10.5005/jp-journals-10024-1905.; and, 3) with 2 minutes daily treatment (30 days) using NHAP, CPP-ACP, or calcium phosphosilicate pastes41Biria M, Iranparvar P, Fatemi SM et al. In Vitro Effects of Three Fluoride-Free Pastes on Remineralization of Initial Enamel Carious Lesions. Pediatr Dent 2021;43(5):389-95..

Dentifrices and NaFV
Conflicting results have also been found for in vitro studies comparing NHAP with NaFV and other formulations. In comparing the surface microhardness of artificial caries lesions in enamel subjected to pH-cycling for 7 days, NHAP and CPP-ACP paste were found to improve microhardness more than NaFV.42Vitiello F, Tosco V, Monterubbianesi R et al. Remineralization Efficacy of Four Remineralizing Agents on Artificial Enamel Lesions: SEM-EDS Investigation. Materials (Basel) 2022;15(13):4398. doi: 10.3390/ma15134398. In addition, based on SEM and EDS, similar improvements in the surface morphology and mineral content at the surface were found for NHAP and CPP-ACP, and were comparable to the sound enamel samples (untreated). In another comparison in 48 samples with artificial caries lesions, 12 served as the control group. The remaining samples received either NaFV applied once prior to immersion in a demineralizing solution over a 7-day period, or applications of a commercially-available NHAP or CCP-ACP-F paste prior to each immersion.43de Carvalho FG, Vieira BR, Santos RL et al. In vitro effects of nano-hydroxyapatite paste on initial enamel carious lesions. Pediatr Dent 2014;36(3):85-9. At the end of 7 days, use of the NHAP paste was found to increase the surface microhardness more than NaFV, while no increase was found with use of CCP-ACP-F paste.

In contrast, in a second study with artificial caries lesions and pH-cycling, improvements in the enamel surface microhardness and mineral content (based on EDS results) were found to be greater for NaFV containing CPP-ACP than for NaF or NHAP dentifrices.44Salinovic I, Schauperl Z, Marcius M, Miletic I. The Effects of Three Remineralizing Agents on the Microhardness and Chemical Composition of Demineralized Enamel. Materials (Basel) 2021;14(20):6051. doi: 10.3390/ma14206051. In evaluating the impact on artificial caries lesions in both primary and permanent teeth in another study, images were taken at baseline and 40 days following one application of FV, or twice-daily two-minute use of CPP-ACP-F paste, bio-active glass ceramic or NHAP crystals.45Goel T, Singhal A, Singh I et al. Evaluation and Comparison of Self-applied Remineralizing Agents Using Confocal Microscopy: An In Vitro Study. Int J Clin Pediatr Dent 2020;13(Suppl 1):S34-9. doi:10.5005/jp-journals-10005-1863. Using confocal laser scanning microscopy (CLSM) and digital quantification it was determined that NaFV was most effective, and NHAP the least effective, for remineralization. In a third study with 45 artificial caries lesions, 15 samples received one application of NaFV prior to pH-cycling for 7 days while another 15 samples received two applications of a commercially-available NHAP paste, applied twice between two of the pH cycles.46Daas I, Badr S, Osman E. Comparison between Fluoride and Nano-hydroxyapatite in Remineralizing Initial Enamel Lesion: An in vitro Study. J Contemp Dent Pract 2018;19(3):306-12. The remaining 15 samples served as the control group. Based on laser fluorescence results, it was concluded that NaFV and NHAP paste were found to perform similarly, with less demineralization than the control group.

NHAP and other technologies
In some in vitro studies, NHAP test formulations were compared to other technologies. For example, in one recent in vitro study, an experimental hydrogel containing agarose loaded with enamel matrix derivative, with/without the addition of NHAP, was evaluated for remineralization of demineralized enamel with gel applications on days 2,4 and 6 using a phosphate solution at 37°C.47El Moshy S, Radwan IA, Matoug-Elwerfelli M et al. A Novel Nano-Hydroxyapatite Agarose-Based Hydrogel for Biomimetic Remineralization of Demineralized Human Enamel: An in-vitro Study. Clin Cosmet Investig Dent 2024;16:453-65. doi: 10.2147/CCIDE.S478045. It was found that the mean surface microhardness, as well as the levels of calcium, phosphorus and fluoride, were greater for the NHAP-containing hydrogel. In another study, laser irradiation (Er:YAG laser), an NHAP formulation and CCP-ACP paste were compared. The evaluation of demineralized teeth was performed with surface enamel microhardness tests, and SEMs for determination of the surface morphology.48Patil AT, Kulkarni TR, Sandhyarani B et al. The effect of nano-hydroxyapatite and casein phosphopeptide-amorphous calcium phosphate with and without laser irradiation on the microhardness and surface morphology of demineralized primary enamel: An in vitro experimental study. Dent Res J (Isfahan) 2024;21:47. Greater surface microhardness increases were observed for the NHAP formulation compared to CPP-ACP paste, both with and without the addition of laser irradiation, and for both the HNAP and CPP-ACP formulations the surface microhardness was enhanced by laser irradiation. It was concluded that the results were promising. In an investigation that included ozone therapy, remineralization of artificial caries lesions was found to be greater for TCP than for NHAP, and least for ozone remineralizing agents.49Shah SA, Sharma M, Ismail PMS et al. Evaluation of Remineralizing Capacity of Tricalcium Phosphate, Nano-Hydroxyapatite and Ozone Remineralizing Agents on the Artificial Carious Lesion. Indian J Dent Res 2024;35(1):84-7. doi: 10.4103/ijdr.ijdr_704_22. Lastly, superior improvements in dentin surface microhardness were found for samples subjected to infrared-activated 10% NHAP gel in comparison to CPP-ACP-fluoride paste (CPP-ACP-F) in another study.50Al-Qahtani AS, Almutairi B, Al-Hamdan RS, Alzahrani KM. Remineralizing pretreatment using casein phosphopeptide-amorphous calcium phosphate fluoride, self-assembling peptide, and nanohydroxyapatite gel activation via invisible infrared light on the dentin microhardness and micro shear bond strength to the composite restoration. Photodiagnosis Photodyn Ther 2024;47:104210. doi: 10.1016/j.pdpdt.2024.104210.

Other Considerations

As noted, study methodologies vary considerably, including the numerous testing methodologies were used across in vitro studies, such as the Knoop and Vickers microhardness tests, TMR, CLSM, polar light microscopy, SEM, EDX, EDS, laser fluorescence and pixel evaluation and comparison on digital images. Regarding their suitability for in vitro studies, both Knoop and Vickers microhardness tests are considered suitable for researching artificial early caries lesions.51Lippert F, Lynch RJM. Comparison of Knoop and Vickers surface microhardness and transverse microradiography for the study of early caries lesion formation in human and bovine enamel. Arch Oral Biol 2014;59(7):704-10. https://doi.org/10.1016/j.archoralbio.2014.04.005. Given that surface microhardness tests measure physical and mechanical characteristics, it has been recommended that additional techniques should be used that can evaluate mineral content and distribution.

Conclusions

NHAP is being researched in many disciplines within dentistry. Studies on the remineralization potential of NHAP are mainly in vitro, and are heterogeneous with respect to the type, concentration and vehicle for NHAP, comparisons with existing interventions, follow-up period and testing methods. The results of some studies are promising for NHAP as a potential alternative to fluoride. However, conflicting results can be found across studies, and based on the conclusions of existing systematic reviews the evidence is inconclusive with a limited number of studies and some at high risk of bias.22Alajlan S, Baysan A. The effect of nano-hydroxyapatite on white spot lesions: A systematic review and meta-analysis. J Dent 2024:151:105402. doi: 10.1016/j.jdent.2024.105402. ^,23Ortiz MIG, Gomes de Oliveira S, de Melo Alencar C et al. Remineralizing effect of the association of nano-hydroxyapatite and fluoride in the treatment of initial lesions of the enamel: A systematic review. J Dent 2024;145:104973. doi: 10.1016/j.jdent.2024.104973.^,24Wierichs RJ, Wolf TG, Campus G, Carvalho TS. Efficacy of nano-hydroxyapatite on caries prevention-a systematic review and meta-analysis. Clin Oral Investig 2022;26(4):3373-81. doi: 10.1007/s00784-022-04390-4. It has been recommended that longer-term and robust randomized controlled clinical trials be conducted to obtain further evidence on the remineralization potential of NHAP.52Philip N. State of the Art Enamel Remineralization Systems: The Next Frontier in Caries Management. Caries Res 2019;53(3):284-95. doi: 10.1159/000493031.

References

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