Strategies for Improving Hybrid Layer Durability in Restorative Dentistry: A Narrative Review of Dentin Biomodifiers
Keywords:
Dentin biomodification, Collagen cross-linkers, Proanthocyanidin, Glutaraldehyde, Ethyldimethylaminopropyl carbodiimide, Anacardium, Riboflavin.
Abstract
Objectives: To perform a true analysis of scholarly sources on various dentin biomodifiers used in dental adhesive advancements.
Methodology: A comprehensive search was performed for additional relevant literature to identify peer-reviewed articles. This focused mainly on the hierarchical structure of dentin, various biomodifiers, and studies exploring their dentinal applications.
Result: Dentin biomodifier strategies are broadly classified into synthetic and natural . Further these are divided into physical and chemical methods. All of these approaches demonstrate unique mechanisms of interaction with dentin tissue. While originally believed to rely solely on non-enzymatic collagen cross-linking induced by intra- or intermolecular collagen bonding for dentin biomodification. It is now understood that various correlation with other components of dentin are crucial for ensuring biomodification which prolongs the mechanical integrity and biological stability for dentinal bonding. Oligomeric proanthocyanidins (PAs) demonstrate strong bioactivity however their complex chemical composition requires a thorough analysis of key constituents to develop standardized, sustainable intervention materials prior to progressing to advanced clinical evaluation.
Essence: Gaining insight into dentin’s hierarchical structure and the specific effects of therapeutic agents will support their application in enhancing the dentin-biomaterial interface and managing dental caries.
References
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25. Kamal SA, Garlapati R, Bolla N, Vemuri S, Banu MA, Suvarna YL. An in vitro assessment of the influence of dentinal pretreatment with chlorhexidine, nonthermal atmospheric plasma, chitosan, and proanthocyanidins on shear bond strength to composite. Journal of Conservative Dentistry and Endodontics. 2024 Aug 1;27(8):873-7.
26. Agarwal M, Nagpal R, Singh UP, Mishra CC, Parveen Y. Effect of Dentin Biomodification on Resin Dentin Bond Strength. J Dent. 2023;10:101.
27. Mira L, Fernandez MT, Santos M, Rocha R, Jennings KR, et al. (2002) Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity. Free Radic Res 36(11): 1199-1208.
28. Seseogullari-Dirihan R, Atay MT, Pashley DH, Tezvergil-Mutluay A. Inhibitory effect of curcuminoid pretreatments on endogenous dentin proteases. Dental materials journal. 2018 May 28;37(3):445-52.
29. Govil SA, Asthana G, Sail VA. Bonding strategies to deal with caries-affected dentin using cross-linking agents: Grape seed extract, green tea extract, and glutaraldehyde–An: in vitro: study. Journal of Conservative Dentistry and Endodontics. 2023 Jan 1;26(1):108-12.
30. Mehmood N, Nagpal R, Singh UP, Agarwal M. Effect of dentin biomodification techniques on the stability of the bonded interface. Journal of Conservative Dentistry and Endodontics. 2021 May 1;24(3):265-70.
31. Ingle AS, Devadiga D, Jain N, Bhardwaj S. Biomimetic remineralization of eroded dentin by synergistic effect of calcium phosphate and plant-based biomodifying agents: An in vitro study. Journal of Conservative Dentistry and Endodontics. 2024 Dec 1;27(12):1221-7.
32. Omanakuttan A, Nambiar J, Harris RM, Bose C, Varghese RK (2012) Anacardic acid inhibits the catalytic activity of matrix metalloproteinase -2 and matrix metalloproteinase-9. Mol Pharmacol 82(4): 614-622.
33. Machado AC, Dezan Junior E, Gomes-Filho JE, Cintra LTA, Ruviére DB, Zoccal R, et al. Evaluation of tissue reaction to Aroeira (Myracrodruon urundeuva) extracts: a histologic and edemogenic study. J Appl Oral Sci 2012;20(4):414–8.
34. Moreira MA, Souza NO, Sousa RS, Freitas DQ, Lemos MV, De Paula DM, Maia FJ, Lomonaco D, Mazzetto SE, Feitosa VP. Efficacy of new natural biomodification agents from Anacardiaceae extracts on dentin collagen cross-linking. Dental materials. 2017 Oct 1;33(10):1103-9.
35. Borges BCD, Souza JB, de Oliveira FS, Menezes M de S, Dias CTS, de Souza Costa CA, et al. Influence of pH and application time of proanthocyanidin on dentin properties and resin-dentin bonding. Dent Mater. 2021;37(6):891–9.
36. Brackett MG, Li N, Brackett WW, Sword RJ, Qi YP, Niu LN, et al. Efficacy of carbodiimide and ethanol wet-bonding in stabilizing resin-dentin bonds. J Adhes Dent. 2013;15(3):275–82.
37. Perin LE, Souza RO, Ferreira CL, Ramos LBO, Martins LRM. Stability of chitosan-based solutions for use in dental bonding. J Appl Oral Sci. 2020;28:e20200314.
38. Prakki A, Mondelli RF, Kalachandra S, Vieira S, Pereira JC. Light-sensitive behavior and storage stability of dentin biomodification agents. Acta Odontol Scand. 2022;80(4):245–50.
2. Al‐Ammar A, Drummond JL, Bedran‐Russo AK. The use of collagen cross‐linking agents to enhance dentin bond strength. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2009 Oct;91(1):419-24.
3. Orban B, Bhaskar SN. Orban's Oral Histology and Embryology. 15th ed. St. Louis: Mosby;2015
4. Nanci A. Ten Cate's Oral Histology: Development, Structure, and Function. 9th ed. St. Louis: Elsevier; 2018.
5. Breschi L, Maravic T, Cunha SR, Comba A, Cadenaro M, Tjäderhane L, Pashley DH, Tay FR, Mazzoni A. Dentin bonding systems: From dentin collagen structure to bond preservation and clinical applications. Dental Materials. 2018 Jan 1;34(1):78-96.
6. Niu LN, Zhang W, Pashley DH, Breschi L, Mao J, et al. Biomimetic remineralization of dentin. Dental Materials. 2014; 30: 77-96.
7. Singh P, Nagpal R, Singh UP, Manuja N. Effect of carbodiimide on the structural stability of resin/dentin interface. Journal of conservative dentistry. 2016 Nov 1;19(6):501-9.
8. Liu R, Fang M, Xiao Y, Li F, Yu L, Zhao S, et al. The effect of transient proanthocyanidins preconditioning on the cross-linking and mechanical properties of demineralized dentin. J Mater Sci Mater Med 2011;22:2403–11.
9. de Freitas BD, da Ponte AM, Farias FR, Feitosa VP, de Paula DM. Dentin biomodification agents in dentistry–A critical review. Oral Health and Dental Management. 2019;18(3).
10. Hass V, Luque-Martinez IV, Gutierrez MF, Moreira CG, Gotti VB, Feitosa VP, Koller G, Otuki MF, Loguercio AD, Reis A. Collagen cross-linkers on dentin bonding: Stability of the adhesive interfaces, degree of conversion of the adhesive, cytotoxicity and in situ MMP inhibition. Dental Materials. 2016 Jun 1;32(6):732-41.
11. Liu Y, Wang Y. Effect of proanthocyanidins and photo-initiators on photo-polymerization of a dental adhesive. J Dent 2013;41:71–9.
12. Chiang YS, Chen YL, Chuang SF, Wu CM, Wei PJ, et al. Riboflavin-ultraviolet-A-induced collagen cross-linking treatments in improving dentin bonding. Dental Material. 2013; 29: 682-692.
13. Adamiak K, Sionkowska A. Current methods of collagen cross-linking. International Journal of Biological Macromolecules. 2020 Oct 15;161:550-60.
14. Cai J, Palamara JE, Burrow MF. Effects of collagen crosslinkers on dentine: A literature review. Calcified Tissue International. 2018 Mar;102:265-79.
15. Sabatini C, Scheffel DL, Scheffel RH, Agee KA, Rouch K, Takahashi M, Breschi L, Mazzoni A, Tjaderhane L, Tay FR, Pashley DH (2014) Inhibition of endogenous human dentin MMPs by Gluma. Dent Mater 30:752–758
16. Tezvergil Mutluay A, Mutluay MM, Agee KA, Seseogullari Dirihan R, Hoshika T, et al. Carbodiimide cross-linking inactivates soluble and matrix-bound MMPs, in vitro. Journal of Dental Research. 2012; 91: 192-196.
17. Singh P, Nagpal R, Singh UP, Manuja N. Effect of carbodiimide on the structural stability of resin/dentin interface. Journal of conservative dentistry. 2016 Nov 1;19(6):501-9.
18. Scheffel DL, Hebling J, Scheffel RH, Agee KA, Cadenaro M, Turco G, Breschi L, Mazzoni A, Costa CA, Pashley DH (2014) Stabilization of dentin matrix after cross-linking treatments, in vitro. Dent Mater 30:227–233
19. Seseogullari-Dirihan R, Apollonio F, Mazzoni A, Tjaderhane L, Pashley D, Breschi L, Tezvergil-Mutluay A. Use of crosslinkers to inactivate dentin MMPs. Dental Materials. 2016 Mar 1;32(3):423-32.
20. Breschi L, Martin P, Mazzoni A, Nato F, Carrilho M, Tjäderhane L, Visintini E, Cadenaro M, Tay FR, Dorigo ED, Pashley DH. Use of a specific MMP-inhibitor (galardin) for preservation of hybrid layer. Dental Materials. 2010 Jun 1;26(6):571-8.
21. Singh R, Shitiz K, Singh A. Chitin and chitosan: biopolymers for wound management. International wound journal. 2017 Dec;14(6):1276-89.
22. Adamiak K, Sionkowska A. Current methods of collagen cross-linking. International Journal of Biological Macromolecules. 2020 Oct 15;161:550-60.
23. Nikhil V, Jaiswal S, Bansal P, Arora R, Raj S, et al. Effect of phytic acid, ethylenediaminetetraacetic acid, and chitosan solutions on microhardness of the human radicular dentin. Journal of Conservative Dentistry. 2016; 19: 179-183.
24. Meher R, Mallick RR, Sarangi P, Jena A, Suman S, Sharma G. Optimization of chitosan nanoparticle dentin pretreatment with different concentrations and application times to improve bonding at resin-dentin interface. Journal of Conservative Dentistry and Endodontics. 2025 Mar 1;28(3):248-52.
25. Kamal SA, Garlapati R, Bolla N, Vemuri S, Banu MA, Suvarna YL. An in vitro assessment of the influence of dentinal pretreatment with chlorhexidine, nonthermal atmospheric plasma, chitosan, and proanthocyanidins on shear bond strength to composite. Journal of Conservative Dentistry and Endodontics. 2024 Aug 1;27(8):873-7.
26. Agarwal M, Nagpal R, Singh UP, Mishra CC, Parveen Y. Effect of Dentin Biomodification on Resin Dentin Bond Strength. J Dent. 2023;10:101.
27. Mira L, Fernandez MT, Santos M, Rocha R, Jennings KR, et al. (2002) Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity. Free Radic Res 36(11): 1199-1208.
28. Seseogullari-Dirihan R, Atay MT, Pashley DH, Tezvergil-Mutluay A. Inhibitory effect of curcuminoid pretreatments on endogenous dentin proteases. Dental materials journal. 2018 May 28;37(3):445-52.
29. Govil SA, Asthana G, Sail VA. Bonding strategies to deal with caries-affected dentin using cross-linking agents: Grape seed extract, green tea extract, and glutaraldehyde–An: in vitro: study. Journal of Conservative Dentistry and Endodontics. 2023 Jan 1;26(1):108-12.
30. Mehmood N, Nagpal R, Singh UP, Agarwal M. Effect of dentin biomodification techniques on the stability of the bonded interface. Journal of Conservative Dentistry and Endodontics. 2021 May 1;24(3):265-70.
31. Ingle AS, Devadiga D, Jain N, Bhardwaj S. Biomimetic remineralization of eroded dentin by synergistic effect of calcium phosphate and plant-based biomodifying agents: An in vitro study. Journal of Conservative Dentistry and Endodontics. 2024 Dec 1;27(12):1221-7.
32. Omanakuttan A, Nambiar J, Harris RM, Bose C, Varghese RK (2012) Anacardic acid inhibits the catalytic activity of matrix metalloproteinase -2 and matrix metalloproteinase-9. Mol Pharmacol 82(4): 614-622.
33. Machado AC, Dezan Junior E, Gomes-Filho JE, Cintra LTA, Ruviére DB, Zoccal R, et al. Evaluation of tissue reaction to Aroeira (Myracrodruon urundeuva) extracts: a histologic and edemogenic study. J Appl Oral Sci 2012;20(4):414–8.
34. Moreira MA, Souza NO, Sousa RS, Freitas DQ, Lemos MV, De Paula DM, Maia FJ, Lomonaco D, Mazzetto SE, Feitosa VP. Efficacy of new natural biomodification agents from Anacardiaceae extracts on dentin collagen cross-linking. Dental materials. 2017 Oct 1;33(10):1103-9.
35. Borges BCD, Souza JB, de Oliveira FS, Menezes M de S, Dias CTS, de Souza Costa CA, et al. Influence of pH and application time of proanthocyanidin on dentin properties and resin-dentin bonding. Dent Mater. 2021;37(6):891–9.
36. Brackett MG, Li N, Brackett WW, Sword RJ, Qi YP, Niu LN, et al. Efficacy of carbodiimide and ethanol wet-bonding in stabilizing resin-dentin bonds. J Adhes Dent. 2013;15(3):275–82.
37. Perin LE, Souza RO, Ferreira CL, Ramos LBO, Martins LRM. Stability of chitosan-based solutions for use in dental bonding. J Appl Oral Sci. 2020;28:e20200314.
38. Prakki A, Mondelli RF, Kalachandra S, Vieira S, Pereira JC. Light-sensitive behavior and storage stability of dentin biomodification agents. Acta Odontol Scand. 2022;80(4):245–50.
Published
2025-10-06
How to Cite
Mohit Kumar Jyotiyana, B Prasad, A., Deepak Raisingani, & Harshit Srivastava. (2025). Strategies for Improving Hybrid Layer Durability in Restorative Dentistry: A Narrative Review of Dentin Biomodifiers. UNIVERSITY JOURNAL OF DENTAL SCIENCES, 11(3), 92-99. https://doi.org/10.21276/ujds.2025.v11.i3.18
Section
Review Article
