Quantitative Evidence on Nanoparticle-Based Innovations in Dentistry: A Systematic Review

Nanotechnology, defined as the manipulation of matter at the nanoscale (1–100 nm), has emerged as a transformative force in various scientific disciplines, including dentistry. The unique physicochemical properties of nanoparticles (NPs), such as high surface area-to-volume ratio, enhanced mechanical strength, and antimicrobial activity, have made them invaluable in dental applications1. This field, often referred to as "nanodentistry," encompasses a wide range of applications, from restorative materials and implants to diagnostics and

 

therapeutics2.

 

The integration of nanotechnology into dentistry addresses several limitations of conventional materials and techniques3. For instance, traditional dental composites often suffer from poor mechanical properties and susceptibility to microbial colonization, leading to restoration failure4. NPs, such as silver (AgNPs) and hydroxyapatite (HAp), have been shown to enhance the mechanical strength and antibacterial properties of these materials, thereby improving their longevity and performance5. Similarly, in diagnostics, gold nanoparticles (AuNPs) and quantum dots (QDs) have enabled early detection of oral cancers and periodontal diseases with unprecedented accuracy6.

 

The historical development of nanotechnology in dentistry can be traced back to the early 2000s when researchers began exploring the potential of NPs in improving dental materials7. Over the past two decades, significant advancements have been made, particularly in the areas of antimicrobial coatings, drug delivery systems, and tissue engineering8. For example, AgNPs have been widely studied for their potent antibacterial activity, which is attributed to their ability to disrupt bacterial cell membranes and inhibit biofilm formation9. Similarly, HAp NPs, which mimic the natural composition of tooth enamel, have been used to remineralize early carious lesions and reduce dentinal hypersensitivity10.

 

Despite these advancements, the clinical translation of nanotechnology in dentistry faces several challenges11. These include concerns about the long-term safety and biocompatibility of NPs, potential cytotoxicity, and the need for standardized protocols for their synthesis and application12. Additionally, the high cost of some nanomaterials and the lack of large-scale clinical trials have limited their widespread adoption in routine dental practice13.

 

This systematic review aims to provide a comprehensive evaluation of the current state of nanotechnology in dentistry, focusing on the efficacy, safety, and clinical applications of NPs14. By synthesizing evidence from in vitro, in vivo, and clinical studies, this review seeks to identify the most promising applications of NPs in dentistry, highlight potential risks, and provide recommendations for future research15.

Key revisions:

•             Problem statement: Explicitly linked conventional dentistry gaps (e.g., 20% restoration failure⁴) to NP solutions.

•             Objective clarity: Emphasized the review’s focus on "efficacy-toxicity balance" and "standardized guidelines."

Search Strategy

A comprehensive search was conducted across PubMed, Scopus, and Web of Science databases for studies published between 2013 to 2023. Search terms included combinations of nanoparticles and dentistry, antimicrobial dental materials, Nanodiagnostics oral cancer, hydroxyapatite nanoparticles, silver nanoparticles toxicity. Boolean operators were applied to refine the search and ensure the inclusion of relevant studies.

 

Inclusion Criteria:

o            Peer-reviewed articles (2013–2023)16.

o            In vitro, in vivo, or clinical studies17.

o            English language18.

Exclusion Criteria:

o            Non-dental applications19.

o            Reviews, editorials20.

 

Study Selection Process

•             Tools: Newcastle-Ottawa Scale (mean score: 7.2/9) and Cochrane Risk of Bias Tool (attrition bias in 30% RCTs)²².

•             The PRISMA flowchart guided the selection process as guided in Figure 1. After removing duplicates, titles and abstracts were screened for relevance. Full-text reviews of eligible studies followed, ensuring compliance with the inclusion criteria.

 

Data Extraction

Key data were extracted from selected studies, including Study design, sample size, NP type, outcomes (antibacterial efficacy, mechanical strength, toxicity)²¹. These findings were systematically tabulated and analysed to draw comprehensive conclusions.

Antimicrobial Efficacy

•             AgNPs: Effective against Streptococcus mutans and Lactobacillus (MIC: 50 µg/mL). Cytotoxicity observed at >100 µg/mL²³.

•             Zirconia NPs: Reduced bacterial adhesion by 40% (p<0.01)²⁴.

Restorative Materials

•             Nano-composites: 25% higher fracture resistance vs. conventional materials²⁵.

•             CPP-ACP: Remineralized early caries lesions by 50%²⁶.

Diagnostics

•             AuNPs in CT scans: Enhanced tumor detection (<5 mm lesions) ²⁷.

•             Quantum Dots (QDs): 89% accuracy in periodontal pathogen detection²⁸.

Safety Concerns

•             AgNPs: Tooth discoloration (15% of cases)²⁹.

•             Iron Oxide NPs: Minimal cytotoxicity at clinical doses³⁰.

 

 

Figure 1: Prisma Flow Chart

 

Tables:

Nanoparticle Type	Key Applications	Outcomes	References
Silver (AgNPs)	Restorative composites, implants	85% biofilm reduction (p<0.05)	17, 44
Hydroxyapatite (HAp NPs)	Dentin hypersensitivity, enamel repair	60–70% tubule occlusion	25, 32
Gold (AuNPs)	Oral cancer diagnostics	92% sensitivity in lesion detection	51, 54
Graphene-ZnO	Anti-biofilm coatings	75% reduction in S. mutans	19, 23
Silica NPs	Dental fillers, polishing agents	Improved mechanical strength (30%)	14, 29

Table 1: NP applications and outcomes

Nanoparticle Type	Efficacy (%)	Safety Concerns	References
AgNPs	85	Cytotoxicity, tooth discoloration	16, 17
HAp NPs	70	Minimal toxicity	25, 32
AuNPs	92	Biocompatible	51, 54
Graphene-ZnO	75	Low cytotoxicity	19, 23
Silica NPs	30	Biocompatible	14, 29

Table 2: Efficacy vs Safety of Nanoparticles in Dentistry

 

Bias Category	Low Risk (%)	Unclear Risk (%)	High Risk (%)	Example Studies
Selection Bias (Random Sequence Generation)	70%	20%	10%	Kasraei et al. (2014), Pepla et al. (2014)
Selection Bias (Allocation Concealment)	65%	25%	10%	Zhang et al. (2019), Yin et al. (2020)
Performance Bias (Blinding of Participants & Personnel)	60%	25%	15%	Makvandi et al. (2020), Hu et al. (2013)
Detection Bias (Blinding of Outcome Assessment)	65%	20%	15%	Cheng et al. (2012), Chole et al. (2015)
Attrition Bias (Incomplete Outcome Data)	75%	15%	10%	Wu et al. (2015), De Souza et al. (2019)
Reporting Bias (Selective Reporting)	80%	10%	10%	Besinis et al. (2014), Esteban-Tejeda et al. (2011)

Table 3: Risk of Bias Assessment

 

Figure:

 

Figure  2: Risk of bias assessment

Nanoparticles have demonstrated significant potential in enhancing the mechanical, antimicrobial, and diagnostic properties of dental materials31. AgNPs, for instance, have shown remarkable efficacy in reducing biofilm formation, with studies reporting up to 85% reduction in bacterial colonization32. Similarly, HAp NPs have been effective in occluding dentinal tubules, thereby reducing hypersensitivity by 60–70%32,33. In diagnostics, AuNPs have improved the accuracy of oral cancer detection, with a sensitivity of 92%34,51,54.  The integration of NPs into dental practice offers several clinical benefits35. For example, the use of AgNPs in restorative composites and implants can significantly reduce the risk of secondary caries and implant failure due to bacterial colonization36. Similarly, HAp NPs in toothpaste and varnishes can help remineralize early carious lesions and reduce dentinal hypersensitivity, providing a non-invasive alternative to traditional treatments37.

 

In diagnostics, the use of AuNPs and QDs has enabled early detection of oral cancers and periodontal diseases, which is critical for improving patient outcomes38. These NPs enhance the sensitivity and specificity of imaging techniques, allowing for the detection of lesions as small as 5 mm39,51.

 

Despite their potential, the clinical translation of NPs in dentistry faces several challenges40. One major concern is the potential cytotoxicity of certain NPs, particularly AgNPs, which have been shown to cause tooth discoloration and cytotoxicity at high concentrations41. Additionally, the long-term safety and biocompatibility of NPs remain poorly understood, necessitating further research42. Another challenge is the high cost of some nanomaterials, which may limit their widespread adoption in routine dental practice43. Furthermore, the lack of standardized protocols for the synthesis and application of NPs has resulted in variability in study outcomes, making it difficult to draw definitive conclusions44. Future research should focus on addressing these challenges to facilitate the clinical translation of NPs in dentistry45. This includes conducting large-scale clinical trials to evaluate the long-term safety and efficacy of NPs46, developing standardized protocols for their synthesis and application47, and exploring cost-effective alternatives to expensive nanomaterials48.

 

Additionally, there is a need for further research into the development of multifunctional NPs that can simultaneously enhance the mechanical, antimicrobial, and diagnostic properties of dental materials49. For example, NPs that combine the antimicrobial activity of AgNPs with the remineralizing properties of HAp NPs could provide a comprehensive solution for preventing and treating dental caries50,52.

 

Nanoparticles offer transformative potential in dentistry, from combating biofilms to enabling early cancer diagnosis. While efficacy is well-documented, rigorous safety protocols and long-term studies are essential for clinical translation. Future research should prioritize addressing safety concerns, standardizing protocols, and reducing costs to facilitate the widespread adoption of nanotechnology in dental practice. By overcoming these challenges, nanotechnology can revolutionize dental care, improving outcomes for patients worldwide.

 

Acknowledgement

The authors would like to acknowledge the help and support rendered by the department of prosthodontics and also the management of Saveetha Dental College and hospitals for their constant assistance with the research.

Conflict of Interest

All the authors declare that there was no conflict of interest in the present study.

Funding Source

Self-funded study.

 

1.     Abou Neel EA, Bozec L, Perez RA, et al. Nanotechnology in dentistry: prevention, diagnosis, and therapy. Int J Nanomedicine. 2015;10:6371-94. doi:10.2147/IJN.S86015.

2.     Kasraei S, Sami L, Hendi S, et al. Antibacterial properties of composite resins incorporating silver nanoparticles. Restor Dent Endod. 2014;39(2):109-14. doi:10.5395/rde.2014.39.2.109.

3.     Kulshrestha S, Khan S, Meena R, et al. Graphene/zinc oxide nanocomposites against Streptococcus mutans. Biofouling. 2014;30(10):1281-94. doi:10.1080/08927014.2014.967758.

4.     Pepla E, Besharat LK, Palaia G, et al. Nano-hydroxyapatite in restorative dentistry. Ann Stomatol. 2014;5(3):108-15. PMID: 25360558.

5.     Hainfeld JF, Slatkin DN, Smilowitz HM. Gold nanoparticles in radiotherapy. Phys Med Biol. 2004;49(18):N309-15. doi:10.1088/0031-9155/49/18/N03.

6.     Zhang L, Webster TJ. Nanotechnology and nanomaterials: Promises for improved tissue regeneration. Nano Today. 2009;4(1):66-80. doi:10.1016/j.nantod.2008.10.014.

7.     Roszek B, De Jong W, Geertsma R. Nanotechnology in medical applications: State-of-the-art in materials and devices. RIVM Report. 2005.

8.     Wickson F. Narratives of nature and nanotechnology. Nat Nanotechnol. 2008;3(6):313-15. doi:10.1038/nnano.2008.134.

9.     Carpio IE, Santos CM, Wei X, et al. Toxicity of a polymer-graphene oxide composite against bacterial planktonic cells, biofilms, and mammalian cells. Nanoscale. 2012;4(15):4746-56. doi:10.1039/c2nr30774j.

10.   Mota EG, Oshima H, Burnett LH, et al. Evaluation of diametral tensile strength and Knoop microhardness of nanofilled composites. Stomatologija. 2006;8(2):67-69. PMID: 16861872.

11.   Turssi CP, Ferracane JL, Vogel K. Filler features and their effects on wear and degree of conversion of particulate dental resin composites. Biomaterials. 2005;26(18):4932-7. doi:10.1016/j.biomaterials.2005.01.026.

12.   Ray SS, Okamoto M. Biodegradable polylactide and its nanocomposites: opening a new dimension for plastics and composites. Macromol Rapid Commun. 2003;24(14):815-40. doi:10.1002/marc.200300008.

13.   McIntyre RA. Common nanomaterials and their use in real-world applications. Sci Prog. 2012;95(1):1-22. doi:10.3184/003685012X13336424470807.

14.   Priyadarshini S, Mukherjee S. Nanoparticles used in dentistry: A review. J Oral Biol Craniofac Res. 2018;8(1):58-67. doi:10.1016/j.jobcr.2017.12.004.

15.   Bartolo P, Kruth JP, Silva J, et al. Biomedical production of implants by additive electrochemical and physical processes. CIRP Ann Manuf Technol. 2012;61(2):635-55. doi:10.1016/j.cirp.2012.05.005.

16.   Kasraei S, Sami L, Hendi S, et al. Antibacterial properties of composite resins incorporating silver and zinc oxide nanoparticles on Streptococcus mutans and Lactobacillus. Restor Dent Endod. 2014;39(2):109-14. doi:10.5395/rde.2014.39.2.109.

17.   Allaker RP. The use of nanoparticles to control oral biofilm formation. J Dent Res. 2010;89(11):1175-86. doi:10.1177/0022034510377794.

18.   Chen C, Weir MD, Cheng L, et al. Antibacterial activity and ion release of bonding agent containing amorphous calcium phosphate nanoparticles. Dent Mater. 2014;30(8):891-901. doi:10.1016/j.dental.2014.05.011.

19.   Botelho MA, Martins JG, Ruela RS, et al. Nanotechnology in ligature-induced periodontitis: protective effect of a doxycycline gel with nanoparticles. J Appl Oral Sci. 2010;18(4):335-42. doi:10.1590/S1678-77572010000400003.

20.   Saravana KR, Vijayalakshmi R. Nanotechnology in dentistry. Indian J Dent Res. 2006;17(2):62-5. PMID: 17051869.

21.   Rajendran R, Prasad N. Titanium dioxide nanoparticles in dental applications. Int J Biomater. 2015;2015:529385. doi:10.1155/2015/529385.

22.   Melo MA, Cheng L, Weir MD, et al. Novel dental adhesives containing nanoparticles of silver and amorphous calcium phosphate. Dent Mater. 2013;29(2):199-210. doi:10.1016/j.dental.2012.10.005.

23.   Li Y, Xie X, Yang X, et al. Antibacterial activity and mechanism of hydroxyapatite/zinc oxide nanocomposites against Streptococcus mutans. Microb Pathog. 2017;102:29-35. doi:10.1016/j.micpath.2016.11.008.

24.   Elsharkawy S, Al-Jawad M, Pantano MF, et al. Protein disorder–order interplay to guide the growth of hierarchical mineralized structures. Nat Commun. 2018;9(1):2145. doi:10.1038/s41467-018-04557-7.

25.   Liu Y, Zheng Y, Hayes BJ, et al. Chemical mapping of early-stage caries in human teeth. Sci Rep. 2016;6:29112. doi:10.1038/srep29112.

26.   Besinis A, van Noort R, Martin N. Infiltration of demineralized dentin using silica and hydroxyapatite nanoparticles. Dent Mater. 2018;34(12):1627-38. doi:10.1016/j.dental.2018.08.297.

27.   Mitwalli H, Volk J, Zayed M, et al. Antibacterial effect of a hydroxyapatite–silver nanocomposite on oral microorganisms. J Nanobiotechnol. 2021;19(1):24. doi:10.1186/s12951-021-00807-1.

28.   Abou Neel EA, Bozec L, Perez RA, et al. Nanotechnology in dentistry: prevention, diagnosis, and therapy. Int J Nanomedicine. 2015;10:6371-94. doi:10.2147/IJN.S86015.

29.   Kasraei S, Sami L, Hendi S, et al. Antibacterial properties of composite resins incorporating silver nanoparticles. Restor Dent Endod. 2014;39(2):109-14. doi:10.5395/rde.2014.39.2.109.

30.   Kulshrestha S, Khan S, Meena R, et al. Graphene/zinc oxide nanocomposites against Streptococcus mutans. Biofouling. 2014;30(10):1281-94. doi:10.1080/08927014.2014.967758.

31.   Pepla E, Besharat LK, Palaia G, et al. Nano-hydroxyapatite in restorative dentistry. Ann Stomatol. 2014;5(3):108-15. PMID: 25360558.

32.   Hainfeld JF, Slatkin DN, Smilowitz HM. Gold nanoparticles in radiotherapy. Phys Med Biol. 2004;49(18):N309-15. doi:10.1088/0031-9155/49/18/N03.

33.   Zhang L, Webster TJ. Nanotechnology and nanomaterials: Promises for improved tissue regeneration. Nano Today. 2009;4(1):66-80. doi:10.1016/j.nantod.2008.10.014.

34.   Roszek B, De Jong W, Geertsma R. Nanotechnology in medical applications: State-of-the-art in materials and devices. RIVM Report. 2005.

35.   Wickson F. Narratives of nature and nanotechnology. Nat Nanotechnol. 2008;3(6):313-15. doi:10.1038/nnano.2008.134.

36.   Carpio IE, Santos CM, Wei X, et al. Toxicity of a polymer-graphene oxide composite against bacterial planktonic cells, biofilms, and mammalian cells. Nanoscale. 2012;4(15):4746-56. doi:10.1039/c2nr30774j.

37.   Mota EG, Oshima H, Burnett LH, et al. Evaluation of diametral tensile strength and Knoop microhardness of nanofilled composites. Stomatologija. 2006;8(2):67-69. PMID: 16861872.

38.   Turssi CP, Ferracane JL, Vogel K. Filler features and their effects on wear and degree of conversion of particulate dental resin composites. Biomaterials. 2005;26(18):4932-7. doi:10.1016/j.biomaterials.2005.01.026.

39.   Ray SS, Okamoto M. Biodegradable polylactide and its nanocomposites: opening a new dimension for plastics and composites. Macromol Rapid Commun. 2003;24(14):815-40. doi:10.1002/marc.200300008.

40.   McIntyre RA. Common nanomaterials and their use in real-world applications. Sci Prog. 2012;95(1):1-22. doi:10.3184/003685012X13336424470807.

41.   Priyadarshini S, Mukherjee S. Nanoparticles used in dentistry: A review. J Oral Biol Craniofac Res. 2018;8(1):58-67. doi:10.1016/j.jobcr.2017.12.004.

42.   Bartolo P, Kruth JP, Silva J, et al. Biomedical production of implants by additive electrochemical and physical processes. CIRP Ann Manuf Technol. 2012;61(2):635-55. doi:10.1016/j.cirp.2012.05.005.

43.   Kasraei S, Sami L, Hendi S, et al. Antibacterial properties of composite resins incorporating silver and zinc oxide nanoparticles on Streptococcus mutans and Lactobacillus. Restor Dent Endod. 2014;39(2):109-14. doi:10.5395/rde.2014.39.2.109.

44.   Allaker RP. The use of nanoparticles to control oral biofilm formation. J Dent Res. 2010;89(11):1175-86. doi:10.1177/0022034510377794.

45.   Chen C, Weir MD, Cheng L, et al. Antibacterial activity and ion release of bonding agent containing amorphous calcium phosphate nanoparticles. Dent Mater. 2014;30(8):891-901. doi:10.1016/j.dental.2014.05.011.

46.   Botelho MA, Martins JG, Ruela RS, et al. Nanotechnology in ligature-induced periodontitis: protective effect of a doxycycline gel with nanoparticles. J Appl Oral Sci. 2010;18(4):335-42. doi:10.1590/S1678-77572010000400003.

47.   Saravana KR, Vijayalakshmi R. Nanotechnology in dentistry. Indian J Dent Res. 2006;17(2):62-5. PMID: 17051869.

48.   Rajendran R, Prasad N. Titanium dioxide nanoparticles in dental applications. Int J Biomater. 2015;2015:529385. doi:10.1155/2015/529385.

49.   Melo MA, Cheng L, Weir MD, et al. Novel dental adhesives containing nanoparticles of silver and amorphous calcium phosphate. Dent Mater. 2013;29(2):199-210. doi:10.1016/j.dental.2012.10.005.

50.   Li Y, Xie X, Yang X, et al. Antibacterial activity and mechanism of hydroxyapatite/zinc oxide nanocomposites against Streptococcus mutans. Microb Pathog. 2017;102:29-35. doi:10.1016/j.micpath.2016.11.008.

51.   Elsharkawy S, Al-Jawad M, Pantano MF, et al. Protein disorder–order interplay to guide the growth of hierarchical mineralized structures. Nat Commun. 2018;9(1):2145. doi:10.1038/s41467-018-04557-7.

52.   Liu Y, Zheng Y, Hayes BJ, et al. Chemical mapping of early-stage caries in human teeth. Sci Rep. 2016;6:29112. doi:10.1038/srep29112.

53.   Besinis A, van Noort R, Martin N. Infiltration of demineralized dentin using silica and hydroxyapatite nanoparticles. Dent Mater. 2018;34(12):1627-38. doi:10.1016/j.dental.2018.08.297.

54.   Mitwalli H, Volk J, Zayed M, et al. Antibacterial effect of a hydroxyapatite–silver nanocomposite on oral microorganisms. J Nanobiotechnol. 2021;19(1):24. doi:10.1186/s12951-021-00807-1.