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Review Article Open Access

Chlorhexidine in Restorative Dentistry: Evidence, Controversies, and Clinical Implications

Annals of Medicine and Medical Sciences Volume 05 (2026), Version 02 February 27, 2026 pp. 245 - 250
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Abstract

Chlorhexidine is widely used in restorative dentistry because of its broad-spectrum antimicrobial activity, substantivity, and low cost. Beyond its antiseptic properties, chlorhexidine has attracted considerable interest due to its ability to inhibit dentin-derived matrix metalloproteinases and its potential to stabilize the resin–dentin hybrid layer. Despite strong mechanistic and in vitro evidence supporting these biological effects, their translation into consistent long-term clinical benefits remains uncertain. This narrative review critically evaluates the role of chlorhexidine in restorative dentistry from the perspectives of rational drug use and health technology assessment. Evidence from laboratory studies, randomized controlled clinical trials, and systematic reviews was synthesized to examine the pharmacological properties of chlorhexidine, its effects on dentin bonding, cytotoxic potential, and overall safety profile. Particular emphasis is placed on the discrepancy between promising in vitro findings and inconsistent clinical outcomes, as well as on concerns related to cytotoxicity, antimicrobial resistance, and adverse effects. The available evidence does not support the routine use of chlorhexidine in restorative procedures, underscoring the need for selective, indication-based application guided by robust clinical data and principles of rational drug use.

References
  1. Breschi L, Maravic T, Mazzitelli C, Josic U, Mancuso E, Cadenaro M, et al. The evolution of adhesive dentistry: From etch-and-rinse to universal bonding systems. Dent Mater. 2025; 41:141-158. DOI: 10.1016/j.dental.2024.11.011
  2. Awad Z. Impact of Disinfection Protocols on Dentin Bond Strength: Chlorhexidine vs. Sodium Hypochlorite. J Oral Med Dent Res. 2024;5(4):1-10. DOI:10.52793/JOMDR.2024.5(4)-69
  3. Bin-Shuwaish MS. Effects and Effectiveness of Cavity Disinfectants in Operative Dentistry: A Literature Review. J Contemp Dent Pract. 2016;17(10):867-879. DOI: 10.5005/jp-journals-10024-1946
  4. Yaghmoor RB, Jamal H, Abed H, Allan E, Ashley P, Young A. Incorporation of MMP inhibitors into dental adhesive systems and bond strength of coronal composite restorations: A systematic review and meta-analysis of in vitro studies. Jpn Dent Sci Rev. 2022; 58:298-315. DOI: 10.1016/j.jdsr.2022.09.004
  5. Bayraktar G, Yılmaz Göler AM, Öztürk Özener H. Klorheksidinin İnsan Diş Eti Fibroblast Hücre Canlılığı ve Sitotoksisitesi Üzerindeki Etkilerinin In Vitro Değerlendirilmesi. Eur J Res Dent. 2023;7(1):27-32. DOI: 10.29228/erd.40
  6. World Health Organization. Promoting rational use of medicines: core components. WHO Policy Perspectives on Medicines. 2002.
  7. Bakır Ş, Bakır EP, Polat G, Temizyürek S. Attitudes and behaviors of dentists regarding rational drug use. J Dent Sci Educ. 2024;2(3):70-80. DOI: 10.51271/JDSE-0038
  8. Kiuru O, Sinervo J, Vähänikkilä H, Anttonen V, Tjäderhane L. MMP inhibitors and dentin bonding: systematic review and meta-analysis. Int J Dent. 2021; 2021:9949699. DOI: 10.1155/2021/9949699
  9. Scaffa PMC, Vidal CMP, Barros N, Gesteira TF, Carmona AK, Breschi L, et al. Chlorhexidine inhibits the activity of dental cysteine cathepsins. J Dent Res. 2012;91(4):420-425. DOI: 10.1177/0022034511435329
  10. Lessa FCR, Aranha AMF, Nogueira I, Giro EMA, Hebling J, Costa CAS. Toxicity of chlorhexidine on odontoblast-like cells. J Appl Oral Sci. 2010;18(1):50-58. DOI: 10.1590/s1678-77572010000100010
  11. Brookes ZLS, Bescos R, Belfield LA, Ali K, Roberts A. Current uses of chlorhexidine for management of oral disease: a narrative review. J Dent. 2020; 103:103497. DOI: 10.1016/j.jdent.2020.103497
  12. Dinu S, Matichescu A, Buzatu R, Marcovici I, Geamantan-Sirbu A, Semenescu AD, et al. Insights into the Cytotoxicity and Irritant Potential of Chlorhexidine Digluconate: An In Vitro and In Ovo Safety Screening. Dent J. 2024; 12:221. DOI: 10.3390/dj12070221
  13. Turkistani A, Sonbul HM, Almarzouki M. Influence of chlorhexidine dentin disinfection on universal adhesive performance: Interfacial adaptation and bond strength assessments. PLoS ONE. 2024;19(12): e0315036. DOI: 10.1371/journal.pone.0315036
  14. Walsh T, Oliveira-Neto JM, Moore D. Chlorhexidine treatment for the prevention of dental caries in children and adolescents. Cochrane Database Syst Rev. 2015;4:CD008457. DOI: 10.1002/14651858.CD008457.pub2
  15. Dionysopoulos D. Effect of digluconate chlorhexidine on bond strength between dental adhesive systems and dentin: A systematic review. J Conserv Dent. 2016;19(1):11-16. DOI: 10.4103/0972-0707.173185
  16. Sartori N, Stolf SC, Silva SB, Lopes GC, Carrilho M. Influence of chlorhexidine digluconate on the clinical performance of adhesive restorations: a 3-year follow-up. J Dent. 2013;41(12):1188-1195. DOI: 10.1016/j.jdent.2013.09.004
  17. Montagner AF, Sarkis-Onofre R, Pereira-Cenci T, Cenci MS. MMP Inhibitors on Dentin Stability: A Systematic Review and Meta-analysis. J Dent Res. 2014;93(8):733-743. DOI: 10.1177/0022034514538046
  18. Carrilho MR, Carvalho RM, Sousa EN, Nicolau J, Breschi L, Mazzoni A, et al. Substantivity of chlorhexidine to human dentin. Dent Mater. 2010;26(8):779-785. DOI: 10.1016/j.dental.2010.04.002
  19. Lim KS, Kam PC. Chlorhexidine--pharmacology and clinical applications. Anaesth Intensive Care. 2008; 36:502-512. DOI: 10.1177/0310057X0803600404
  20. Poppolo Deus F, Ouanounou A. Chlorhexidine in Dentistry: Pharmacology, Uses, and Adverse Effects. Int Dent J. 2022; 72:269-277. DOI: 10.1016/j.identj.2022.01.005
  21. Breschi L, Maravic T, Comba A, Cunha SR, Loguercio AD, Reis A, et al. Chlorhexidine preserves the hybrid layer in vitro after 10-years aging. Dent Mater. 2020;36(5):672-680. DOI: 10.1016/j.dental.2020.03.009
  22. Moon, P. C., Weaver, J., & Brooks, C. N. (2010). Review of matrix metalloproteinases’ effect on the hybrid dentin bond layer stability and chlorhexidine clinical use to prevent bond failure. The open dentistry journal,4, 147. DOI: 10.2174/1874210601004010147
  23. Kim J, Mai S, Carrilho MR, Yiu CK, Pashley DH, Tay FR. An all-in-one adhesive does not etch beyond hybrid layers. J Dent Res. 2010; 89:482-487. DOI: 10.1177/0022034510363665
  24. Miranda C, Silva GV, Vieira MD, Costa SXS. Influence of the chlorhexidine application on adhesive interface stability: literature review. RSBO. 2014;11(3):276-285. DOI:10.21726/rsbo. v11i3.866
  25. Boaru MO, Tărăboanță I, Stoleriu S, Andrian S, Pancu G, Nica I, et al. The Influence of Chlorhexidine Gluconate Dentine Pre-Treatment on Adhesive Interface and Marginal Sealing. Medicina. 2023;59(2):278. DOI: 10.3390/medicina59020278
  26. De Munck J, Van Landuyt K, Peumans M, Poitevin A, Lambrechts P, Braem M, et al. A critical review of the durability of adhesion to tooth tissue: methods and results. J Dent Res. 2005;84(2):118-132. DOI: 10.1177/154405910508400204
  27. Pashley DH, Tay FR, Yiu C, Hashimoto M, Breschi L, Carvalho RM, et al. Collagen degradation by host-derived enzymes during aging. J Dent Res. 2004;83(3):216-221. DOI: 10.1177/154405910408300306
  28. Tjäderhane L, Nascimento FD, Breschi L, Mazzoni A, Tersariol ILS, Geraldeli S, et al. Optimizing dentin bond durability: strategies to prevent hydrolytic degradation of the hybrid layer. Dent Mater. 2013; 29:999-1011. DOI: 10.1016/j.dental.2013.07.016
  29. Mazzoni A, Pashley DH, Nishitani Y, Breschi L, Tjäderhane L, Toledano M, et al. Reactivation of inactivated endogenous proteolytic activities in phosphoric acid-etched dentine by etch-and-rinse adhesives. Biomaterials. 2006; 27:4470-4476. DOI: 10.1016/j.biomaterials.2006.01.040
  30. Mazzoni A, Scaffa P, Carrilho M, Tjäderhane L, Di Lenarda R, Polimeni A, et al. Effects of etch-and-rinse and self-etch adhesives on dentin MMP-2 and MMP-9. J Dent Res. 2013;92(1):82-86. DOI: 10.1177/0022034512467034
  31. DeVito-Moraes AG, Francci C, Vidal CM, Scaffa PM, Nesadal D, Yamasaki LC, et al. Phosphoric acid concentration affects dentinal MMPs activity. J Dent. 2016; 53:30-37. DOI: 10.1016/j.jdent.2016.06.002
  32. Malaquias P, Gutierrez MF, Hass V, Stanislawczuk R, Bandeca MC, Arrais CAG, et al. Two-year effects of chlorhexidine-containing adhesives on the in vitro durability of resin-dentin interfaces and modeling of drug release. Oper Dent. 2018;43(2):201-212. DOI: 10.2341/16-333-L
  33. Carrilho, M. R. O., Carvalho, R. M. D., De Goes, M. F., Di Hipolito, V., Geraldeli, S., Tay, F. R., ... & Tjäderhane, L. (2007). Chlorhexidine preserves dentin bond in vitro. Journal of dental research, 86(1), 90-94. DOI: 10.1177/154405910708600115
  34. Breschi L, Mazzoni A, Nato F, Carrilho M, Visintini E, Tjäderhane L, et al. Chlorhexidine stabilizes the adhesive interface: a 2-year in vitro study. Dent Mater. 2010;26(4):320-325. DOI: 10.1016/j.dental.2009.11.153
  35. Altıntop H, Kuru HE, Ertuğrul F, Türkün M, Küçükyılmaz E. A prospective randomized clinical trial and an in vitro evaluation of the microtensile bond strength of a chlorhexidine-containing dentin bonding agent and a bulk fill composite material in primary teeth. BMC Oral Health. 2025; 25:566. DOI: 10.1186/s12903-025-05960-0
  36. Coelho A, Vilhena L, Antunes M, Amaro I, Paula A, et al. (2022) Effect of Different Cavity Disinfectants on Adhesion to Dentin of Permanent Teeth. J Funct Biomater. 13(4):209. DOI: 10.3390/jfb13040209
  37. Liu JX, Werner J, Kirsch T, Zuckerman JD, Virk MS. Cytotoxicity evaluation of chlorhexidine gluconate on human fibroblasts, myoblasts, and osteoblasts. J Bone Jt Infect. 2018; 3:165-172. DOI: 10.7150/jbji.26355
  38. Pałka Ł, Nowakowska-Toporowska A, Dalewski B. Is Chlorhexidine in Dentistry an Ally or a Foe? A Narrative Review. Healthcare. 2022; 10:764. DOI: 10.3390/healthcare10050764
  39. Reis A, Carrilho M, Breschi L, Loguercio A. Overview of clinical alternatives to minimize the degradation of the resin-dentin bonds. Oper Dent. 2013;38: E103-27. DOI: 10.2341/12-258-LIT
  40. Fiorillo L, D’Amico C, Mehta V, Cicciù M, Cervino G. Chlorhexidine cytotoxicity on oral Behaviors: Last 20 Years systematic review. Oral Oncol Rep. 2024; 9:100245. DOI: 10.1016/j.oor.2024.100245
  41. Batra C, Alalshaikh M, Gregory RL, Windsor LJ, Blanchard SB, Hamada Y. An in vitro comparison of four antibacterial agents with and without nicotine and their effects on human gingival fibroblasts. J Periodontol. 2022;93(2): e24-e33. DOI: 10.1002/JPER.21-0262
  42. Bescos R, Ashworth A, Cutler C, Brookes ZL, Belfield L, Rodiles A, et al. Effects of Chlorhexidine mouthwash on the oral microbiome. Sci Rep. 2020; 10:5254. DOI: 10.1038/s41598-020-61912-4
  43. Deschepper M, Waegeman W, Eeckloo K, Vogelaers D, Blot S. Effects of chlorhexidine gluconate oral care on hospital mortality: A hospital-wide, observational cohort study. Intensive Care Med. 2018; 44:1017-1026. DOI: 10.1007/s00134-018-5171-3
  44. Matar MS, Elatta LSHA, Basheir WAS, Khalid KM, Babiker DH, Yousef BA (2025) Pharmacovigilance in dental practice: Opportunities for pharmacy–dentistry collaboration. Annals of Medicine and Medical Sciences, 1283-1290. https://ammspub.com/index.php/amms/article/view/362
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