Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review

ÖZALP, Nurhan; Çimen, Ceren

doi:10.52037/eads.2021.0002

Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review

Ceren ÇİMEN, (Ankara Üniversitesi, Diş Hekimliği Fakültesi, Çocuk Diş Hekimliği Anabilim Dalı, Ankara, Türkiye)

Nurhan ÖZALP (Ankara Üniversitesi, Diş Hekimliği Fakültesi, Çocuk Diş Hekimliği Anabilim Dalı, Ankara, Türkiye)

European annals of dental sciences (Online)

1 1

Yıl: 2021 Cilt: 48 Sayı: 1 Sayfa Aralığı: 33 - 39 Metin Dili: İngilizce DOI: 10.52037/eads.2021.0002 İndeks Tarihi: 29-07-2022

Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review

Öz:

Biocompatibility is described as an appropriate biological response of a biomaterial in a living organism. It is known that biomaterials are not inert and the materials should be tested before they are allowed to be used in clinical practice. Various test methods have been developed and protocols have been determined for this purpose. Resin-based restorative materials are extensively used in dentistry due to the increased aesthetic demands of patients and the ease of use in clinical practice. As the restorative materials function in the mouth for long years, concerns regarding the biocompatibility of resin-based restorative materials become more important. Regarding the importance of this issue, the purpose of this review is to evaluate the local and systemic potential toxicity of resin-based restorative materials, toxicity test methods, and the mechanism of the cytotoxicity in living tissues.

Anahtar Kelime: cytotoxicity dental restorative material biocompatibility photopolymerization resin monomer

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. Perrotti V, Piattelli A, Quaranta A, Gómez-Moreno G, Iezzi G. 1. In: Shelton R, editor. Biocompatibility of dental biomaterials. Elsevier; 2017. p. 1–7.
2. Schmalz G, Arenholt-Bindslev D. Biocompatibility of dental materials. Vol. 1.. vol. 1. Berlin: Springer; 2009.
3. Wataha JC. Principles of biocompatibility for dental practitioners. J Prosthet Dent. 2001;86(2):203–209. doi:10.1067/mpr.2001.117056.
4. Freshney RI. Culture of animal cells: a manual of basic technique and specialized applications. John Wiley & Sons; 2015.
5. Sakaguchi RL PJ ferracane J. Craig’s restorative dental materials 14th ed. Philadelphia, PA: Elsevier/Mosby; 2018.
6. Urcan E, Haertel U, Styllou M, Hickel R, Scherthan H, Reichl FX. Real-time xCELLigence impedance analysis of the cytotoxicity of dental composite components on human gingival fibroblasts. Dent Mater. 2010;26(1):51–58. doi:10.1016/j.dental.2009.08.007.
7. Teng Z, Kuang X, Wang J, Zhang X. Real-time cell analysis–a new method for dynamic, quantitative measurement of infectious viruses and antiserum neutralizing activity. J Virol Methods. 2013;193(2):364–370. doi:10.1016/j.jviromet.2013.06.034.
8. Balkan A, Balkan M. Hayvan Çalismalarinda Etik, Laboratuar Standardizasyonu ve Hayvan Bakimi ile Ilgili Yasal Zorunluluklar. Turk Toraks Dergisi. 2013;14:6. doi:10.5152/ttd.2013.44.
9. Murray PE, García Godoy C, García Godoy F. How is the biocompatibilty of dental biomaterials evaluated? Med Oral Patol Oral Cir Bucal. 2007;12(3):E258–266.
10. Goldberg M. In vitro and in vivo studies on the toxicity of dental resin components: a review. Clin Oral Investig. 2008;12(1):1–8. doi:10.1007/s00784-007-0162-8.
11. Zorzin J, Maier E, Harre S, Fey T, Belli R, Lohbauer U, et al. Bulk-fill resin composites: polymerization properties and extended light curing. Dent Mater. 2015;31(3):293–301. doi:10.1016/j.dental.2014.12.010.
12. Pratap B, Gupta RK, Bhardwaj B, Nag M. Resin based restorative dental materials: characteristics and future perspectives. Jpn Dent Sci Rev. 2019;55(1):126–138. doi:10.1016/j.jdsr.2019.09.004.
13. Leprince JG, Palin WM, Hadis MA, Devaux J, Leloup G. Progress in dimethacrylate-based dental composite technology and curing efficiency. Dent Mater. 2013;29(2):139– 156. doi:10.1016/j.dental.2012.11.005.
14. Komurcuoglu E, Olmez S, Vural N. Evaluation of residual monomer elimination methods in three different fissure sealants in vitro. J Oral Rehabil. 2005;32(2):116–121. doi:10.1111/j.1365-2842.2004.01405.x.
15. Ferracane JL. Elution of leachable components from composites. J Oral Rehabil. 1994;21(4):441–452. doi:10.1111/j.1365-2842.1994.tb01158.x.
16. Putzeys E, De Nys S, Cokic SM, Duca RC, Vanoirbeek J, Godderis L, et al. Long-term elution of monomers from resin-based dental composites. Dental Materials. 2019;35(3):477–485. doi:10.1016/j.dental.2019.01.005.
17. Hensten-Pettersen A. Skin and mucosal reactions associated with dental materials. Eur J Oral Sci. 1998;106(2 Pt 2):707.
18. Lacerda-Santos R, de Meneses IHC, de Morais Sampaio GA, Pithon MM, Alves PM. Effect of degree of conversion on in vivo biocompatibility of flowable resin used for bioprotection of mini-implants. Angle Orthod. 2016;86(1):157–163. doi:10.2319/112914-856.1.
19. Lee MJ, Kim MJ, Kwon JS, Lee SB, Kim KM. Cytotoxicity of Light-Cured Dental Materials according to Different Sample Preparation Methods. Materials. 2017;10(3):288. doi:10.3390/ma10030288.
20. Zabrovsky A, Beyth N, Pietrokovski Y, Ben-Gal G, HouriHaddad Y. In: Shelton R, editor. 5 - Biocompatibility and functionality of dental restorative materials. Elsevier; 2017. p. 63–75. doi:10.1016/B978-0-08-100884-3.00005-9.
21. Moharamzadeh K, Van Noort R, Brook IM, Scutt AM. HPLC analysis of components released from dental composites with different resin compositions using different extraction media. J Mater Sci Mater Med. 2007;18(1):133–137. doi:10.1007/s10856-006-0671-z.
22. Spencer P, Ye Q, Misra A, Goncalves SdP, Laurence J. Proteins, pathogens, and failure at the compositetooth interface. J Dent Res. 2014;93(12):1243–1249. doi:10.1177/0022034514550039.
23. Mazzoni A, Tjäderhane L, Checchi V, Di Lenarda R, Salo T, Tay FR, et al. Role of Dentin MMPs in Caries Progression and Bond Stability. J Dent Res. 2015;94(2):241–251. doi:10.1177/0022034514562833.
24. Alshali RZ, Salim NA, Sung R, Satterthwaite JD, Silikas N. Analysis of long-term monomer elution from bulk-fill and conventional resin-composites using high performance liquid chromatography. Dent Mater. 2015;31(12):1587– 1598. doi:10.1016/j.dental.2015.10.006.
25. Polydorou O, König A, Hellwig E, Kümmerer K. Long-term release of monomers from modern dental-composite materials. Eur J Oral Sci. 2009;117(1):68–75. doi:10.1111/j.1600- 0722.2008.00594.x.
26. Emmler J, Seiss M, Kreppel H, Reichl FX, Hickel R, Kehe K. Cytotoxicity of the dental composite component TEGDMA and selected metabolic by-products in human pulmonary cells. Dent Mater. 2008;24(12):1670–1675. doi:10.1016/j.dental.2008.04.001.
27. Oysaed H, Ruyter IE, Sjøvik Kleven IJ. Release of formaldehyde from dental composites. J Dent Res. 1988;67(10):1289–1294. doi:10.1177/00220345880670100901.
28. Reichl FX, Durner J, Hickel R, Spahl W, Kehe K, Walther U, et al. Uptake, clearance and metabolism of TEGDMA in guinea pigs. Dent Mater. 2002;18(8):581–589. doi:10.1016/s0109-5641(01)00094-x.
29. Evans SF, Kobrosly RW, Barrett ES, Thurston SW, Calafat AM, Weiss B, et al. Prenatal bisphenol A exposure and maternally reported behavior in boys and girls. Neurotoxicology. 2014;45:91–99. doi:10.1016/j.neuro.2014.10.003.
30. Hong SB, Hong YC, Kim JW, Park EJ, Shin MS, Kim BN, et al. Bisphenol A in relation to behavior and learning of schoolage children. J Child Psychol Psychiatry. 2013;54(8):890– 899. doi:10.1111/jcpp.12050.
31. Miodovnik A, Engel SM, Zhu C, Ye X, Soorya LV, Silva MJ, et al. Endocrine disruptors and childhood social impairment. Neurotoxicology. 2011;32(2):261–267. doi:10.1016/j.neuro.2010.12.009.
32. Gundert-Remy U, Bodin J, Bosetti C, FitzGerald R, Hanberg A, Hass U, et al. Bisphenol A (BPA) hazard assessment protocol. EFSA Supporting Publications. 2017;14(12):1354E. doi:10.2903/sp.efsa.2017.EN-1354.
33. Assessing and Managing Chemicals under TSCA [Web Page];. Available from: http://www.epa.gov/oppt/ existingchemicals/pubs/actionplans/bpa.html.
34. Kang YG, Kim JY, Kim J, Won PJ, Nam JH. Release of bisphenol A from resin composite used to bond orthodontic lingual retainers. American Journal of Orthodontics and Dentofacial Orthopedics. 2011;140(6):779– 789. doi:10.1016/j.ajodo.2011.04.022.
35. Fleisch AF, Sheffield PE, Chinn C, Edelstein BL, Landrigan PJ. Bisphenol A and related compounds in dental materials. Pediatrics. 2010;126(4):760–768. doi:10.1542/peds.2009- 2693.
36. Tarumi H, Imazato S, Narimatsu M, Matsuo M, Ebisu S. Estrogenicity of fissure sealants and adhesive resins determined by reporter gene assay. J Dent Res. 2000;79(11):1838–1843. doi:10.1177/00220345000790110401.
37. Berge TLL, Lygre GB, Lie SA, Lindh CH, Björkman L. Bisphenol A in human saliva and urine before and after treatment with dental polymer-based restorative materials. Eur J Oral Sci. 2019;127(5):435–444. doi:10.1111/eos.12647.
38. Lee JH, Yi SK, Kim SY, Kim JS, Son SA, Jeong SH, et al. Salivary bisphenol A levels and their association with composite resin restoration. Chemosphere. 2017;172:46–51. doi:10.1016/j.chemosphere.2016.12.123.
39. Manoj MK, Ramakrishnan R, Babjee S, Nasim R. Highperformance liquid chromatography analysis of salivary bisphenol A levels from light-cured and chemically cured orthodontic adhesives. Am J Orthod Dentofacial Orthop. 2018;154(6):803–808. doi:10.1016/j.ajodo.2018.02.008.
40. Kingman A, Hyman J, Masten SA, Jayaram B, Smith C, Eichmiller F, et al. Bisphenol A and other compounds in human saliva and urine associated with the placement of composite restorations. J Am Dent Assoc. 2012;143(12):1292–1302. doi:10.14219/jada.archive.2012.0090.
41. Martin M, Bajet D, Woods J, Dills R, Poulten E. Detection of dental composite and sealant resin components in urine. Oral Surg Oral Med Oral Pathol Oral Radiol. 2005;4(99):429. doi:10.1016/j.tripleo.2005.02.014.
42. Marzouk T, Sathyanarayana S, Kim AS, Seminario AL, McKinney CM. A Systematic Review of Exposure to Bisphenol A from Dental Treatment. JDR Clin Trans Res. 2019;4(2):106– 115. doi:10.1177/2380084418816079.
43. Maserejian NN, Trachtenberg FL, Wheaton OB, Calafat AM, Ranganathan G, Kim HY, et al. Changes in urinary bisphenol A concentrations associated with placement of dental composite restorations in children and adolescents. J Am Dent Assoc. 2016;147(8):620–630. doi:10.1016/j.adaj.2016.02.020.
44. Moreira MR, Matos LG, de Souza ID, Brigante TA, Queiroz ME, Romano FL, et al. Bisphenol A release from orthodontic adhesives measured in vitro and in vivo with gas chromatography. Am J Orthod Dentofacial Orthop. 2017;151(3):477–483. doi:10.1016/j.ajodo.2016.07.019.
45. Maserejian NN, Shrader P, Trachtenberg FL, Hauser R, Bellinger DC, Tavares M. Dental sealants and flowable composite restorations and psychosocial, neuropsychological, and physical development in children. Pediatr Dent. 2014;36(1):68–75.
46. Paula AB, Toste D, Marinho A, Amaro I, Marto CM, Coelho A, et al. Once resin composites and dental sealants release Bisphenol-A, How might this affect our clinical management?—A systematic review. Int J Environ Res Public Health. 2019;16(9):1627. doi:10.3390/ijerph16091627
47. Sasaki N, Okuda K, Kato T, Kakishima H, Okuma H, Abe K, et al. Salivary bisphenol-A levels detected by ELISA after restoration with composite resin. J Mater Sci Mater Med. 2005;16(4):297–300. doi:10.1007/s10856-005-0627-8.
48. Eramo S, Urbani G, Sfasciotti GL, Brugnoletti O, Bossù M, Polimeni A. Estrogenicity of bisphenol A released from sealants and composites: a review of the literature. Ann Stomatol (Roma). 2010;1(3-4):14–21.
49. Wada H, Tarumi H, Imazato S, Narimatsu M, Ebisu S. In vitro Estrogenicity of Resin Composites. J Dent Res. 2004;83(3):222–226. doi:10.1177/154405910408300307.
50. Manabe A, Kaneko S, Numazawa S, Itoh K, Inoue M, Hisamitsu H, et al. Detection of bisphenol-A in dental materials by gas chromatography-mass spectrometry. Dent Mater J. 2000;19(1):75–86. doi:10.4012/dmj.19.75.
51. Schmalz G, Preiss A, Arenholt-Bindslev D. BisphenolA content of resin monomers and related degradation products. Clin Oral Investig. 1999;3(3):114–119. doi:10.1007/s007840050088.
52. Al-Hiyasat AS, Darmani H, Milhem MM. Cytotoxicity evaluation of dental resin composites and their flowable derivatives. Clin Oral Investig. 2005;9(1):21–25. doi:10.1007/s00784-004-0293-0.
53. Gupta SK, Saxena P, Pant VA, Pant AB. Release and toxicity of dental resin composite. Toxicol Int. 2012;19(3):225. doi:10.4103/0971-6580.103652.
54. Marquardt W, Seiss M, Hickel R, Reichl FX. Volatile methacrylates in dental practices. J Adhes Dent. 2009;11(2):101–107. doi:10.3290/j.jad.a15321.
55. Van Landuyt KL, Nawrot T, Geebelen B, De Munck J, Snauwaert J, Yoshihara K, et al. How much do resin-based dental materials release? A metaanalytical approach. Dent Mater. 2011;27(8):723–747. doi:10.1016/j.dental.2011.05.001.
56. Al-Hiyasat AS, Darmani H. In vivo effects of BISGMA—a component of dental composite—on male mouse reproduction and fertility. J Biomed Mater Res A. 2006;78A(1):66– 72. doi:https://doi.org/10.1002/jbm.a.30667.
57. Seiss M, Marquardt W, Hickel R, Reichl FX. Excretion of dental resin monomers and metabolic intermediates via urine in guinea pigs. Dent Mater. 2009;25(4):481–485. doi:10.1016/j.dental.2008.08.013.
58. Guidance on the Application of the CLP Criteria [Web Page];. Available from: https://echa. europa.eu/documents/10162/23047722/clp_criteria_hh_ revised_draft_guidance_rev_7_rac_forum_201305_en.pdf/ fddb2d48-4007-47b3-9816-50d2b8ea33d0.
59. Gonçalves F, Campos LMdP, Rodrigues-Júnior EC, Costa FV, Marques PA, Francci CE, et al. A comparative study of bulk-fill composites: degree of conversion, postgel shrinkage and cytotoxicity. Braz Oral Res. 2018;32. doi:10.1590/1807-3107bor-2018.vol32.0017.
60. Nascimento AS, Lima DB, Fook MVL, Albuquerque MSd, Sabino MA, Borges SMP, et al. Physicomechanical characterization and biological evaluation of bulk-fill composite resin. Braz Oral Res. 2018;32. doi:10.1590/1807-3107bor2018.vol32.0107.
61. Susila AV, Balasubramanian V. Correlation of elution and sensitivity of cell lines to dental composites. Dental Materials. 2016;32(3):e63–e72. doi:10.1016/j.dental.2015.11.011.
62. Geurtsen W, Lehmann F, Spahl W, Leyhausen G. Cytotoxicity of 35 dental resin composite monomers/additives in permanent 3T3 and three human primary fibroblast cultures. J Biomed Mater Res A. 1998;41(3):474–480. doi:10.1002/(sici)1097-4636(19980905)41:3<474::aidjbm18>3.0.co;2-i.
63. Brzović Rajić V, Želježić D, Malčić Ivanišević A, Verzak Z, Baraba A, Miletić I. Cytotoxicity and Genotoxicity of Resin Based Dental Materials in Human Lymphocytes In Vitro. Acta Clin Croat. 2018;57(2):278–285. doi:10.20471/acc.2018.57.02.07.
64. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012;5(1):9–19. doi:10.1097/WOX.0b013e3182439613.
65. Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J. 2016;15(1):71. doi:10.1186/s12937-016-0186-5.
66. Engelmann J, Janke V, Volk J, Leyhausen G, Von Neuhoff N, Schlegelberger B, et al. Effects of BisGMA on glutathione metabolism and apoptosis in human gingival fibroblasts in vitro. Biomaterials. 2004;25(19):4573–4580. doi:10.1016/j.biomaterials.2003.11.048.
67. Volk J, Engelmann J, Leyhausen G, Geurtsen W. Effects of three resin monomers on the cellular glutathione concentration of cultured human gingival fibroblasts. Dent Mater. 2006;22(6):499–505. doi:10.1016/j.dental.2005.06.002.
68. Chang HH, Guo MK, Kasten FH, Chang MC, Huang GF, Wang YL, et al. Stimulation of glutathione depletion, ROS production and cell cycle arrest of dental pulp cells and gingival epithelial cells by HEMA. Biomaterials. 2005;26(7):745–753. doi:10.1016/j.biomaterials.2004.03.021.
69. Chang MC, Chen LI, Chan CP, Lee JJ, Wang TM, Yang TT, et al. The role of reactive oxygen species and hemeoxygenase-1 expression in the cytotoxicity, cell cycle alteration and apoptosis of dental pulp cells induced by BisGMA. Biomaterials. 2010;31(32):8164–8171. doi:10.1016/j.biomaterials.2010.07.049.
70. Stanislawski L, Lefeuvre M, Bourd K, Soheili-Majd E, Goldberg M, Périanin A. TEGDMA-induced toxicity in human fibroblasts is associated with early and drastic glutathione depletion with subsequent production of oxygen reactive species. J Biomed Mater Res A. 2003;66(3):476– 482. doi:10.1002/jbm.a.10600.
71. Chang HH, Chang MC, Wang HH, Huang GF, Lee YL, Wang YL, et al. Urethane dimethacrylate induces cytotoxicity and regulates cyclooxygenase-2, hemeoxygenase and carboxylesterase expression in human dental pulp cells. Acta Biomater. 2014;10(2):722–731. doi:10.1016/j.actbio.2013.10.006.
72. Nocca G, De Palma F, Minucci A, De Sole P, Martorana GE, Callà C, et al. Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins. J Dent. 2007;35(3):187–194. Available from: http://www.sciencedirect.com/science/article/pii/ S0300571206001503. doi:10.1016/j.jdent.2006.07.008.
73. Schweikl H, Hartmann A, Hiller KA, Spagnuolo G, Bolay C, Brockhoff G, et al. Inhibition of TEGDMA and HEMA-induced genotoxicity and cell cycle arrest by N-acetylcysteine. Dent Mater. 2007;23(6):688–695. doi:10.1016/j.dental.2006.06.021.
74. Schweikl H, Spagnuolo G, Schmalz G. Genetic and cellular toxicology of dental resin monomers. J Dent Res. 2006;85(10):870–877. doi:10.1177/154405910608501001.
75. Reichl FX, Esters M, Simon S, Seiss M, Kehe K, Kleinsasser N, et al. Cell death effects of resin-based dental material compounds and mercurials in human gingival fibroblasts. Arch Toxicol. 2006;80(6):370–377. doi:10.1007/s00204- 005-0044-2.
76. Ahmed RH, Aref MI, Hassan RM, Mohammed NR. Cytotoxic effect of composite resin and amalgam filling materials on human labial and buccal epithelium. Nature and science. 2010;8(10):48–53.
77. Issa Y, Watts D, Brunton P, Waters C, Duxbury A. Resin composite monomers alter MTT and LDH activity of human gingival fibroblasts in vitro. Dent Mater. 2004;20(1):12–20. doi:10.1016/S0109-5641(03)00053-8.
78. Johnson MD, Schilz J, Djordjevic MV, Rice JR, Shields PG. Evaluation of in vitro assays for assessing the toxicity of cigarette smoke and smokeless tobacco. Cancer Epidemiol Biomarkers Prev. 2009;18(12):3263–3304. doi:10.1158/1055-9965.EPI-09-0965.
79. Huang FM, Kuan YH, Lee SS, Chang YC. Cytotoxicity and genotoxicity of triethyleneglycol-dimethacrylate in macrophages involved in DNA damage and caspases activation. Environ Toxicol. 2015;30(5):581–588. doi:10.1002/tox.21935.
80. Shehata M, Durner J, Eldenez A, Van Landuyt K, Styllou P, Rothmund L, et al. Cytotoxicity and induction of DNA double-strand breaks by components leached from dental composites in primary human gingival fibroblasts. Dent Mater. 2013;29(9):971–979. doi:10.1016/j.dental.2013.07.007.
81. Wisniewska-Jarosinska M, Poplawski T, Chojnacki CJ, Pawlowska E, Krupa R, Szczepanska J, et al. Independent and combined cytotoxicity and genotoxicity of triethylene glycol dimethacrylate and urethane dimethacrylate. Mol Biol Rep. 2011;38(7):4603–4611. doi:10.1007/s11033-010- 0593-1.
82. Li Y, Kuan Y, Huang F, Chang Y. The role of DNA damage and caspase activation in cytotoxicity and genotoxicity of macrophages induced by bisphenol-Aglycidyldimethacrylate. Int Endod J. 2012;45(6):499–507. doi:10.1111/j.1365-2591.2011.02001.x.
83. Di Pietro A, Visalli G, La Maestra S, Micale R, Baluce B, Matarese G, et al. Biomonitoring of DNA damage in peripheral blood lymphocytes of subjects with dental restorative fillings. Mutat Res/Genet Toxicol Environ Mutagen. 2008;650(2):115–122. doi:10.1016/j.mrgentox.2007.10.023.
84. Pettini F, Savino M, Corsalini M, Cantore S, Ballini A. Cytogenetic genotoxic investigation in peripheral blood lymphocytes of subjects with dental composite restorative filling materials. J Biol Regul Homeost. 2015;29(1):229–233.
85. Tadin A, Marovic D, Galic N, Milevoj A, Medvedec Mikic I, Zeljezic D. Genotoxic biomonitoring of flowable and non-flowable composite resins in peripheral blood leukocytes. Acta Odontol Scand. 2013;71(3-4):923–929. doi:10.3109/00016357.2012.734419.
86. Hansel C, Leyhausen G, Mai UE, Geurtsen W. Effects of various resin composite (co)monomers and extracts on two caries-associated micro-organisms in vitro. J Dent Res. 1998;77(1):60–67. doi:10.1177/00220345980770010601.
87. Khalichi P, Cvitkovitch DG, Santerre JP. Effect of composite resin biodegradation products on oral streptococcal growth. Biomaterials. 2004;25(24):5467–5472. doi:10.1016/j.biomaterials.2003.12.056.
88. Bergenholtz G. Evidence for bacterial causation of adverse pulpal responses in resin-based dental restorations. Crit Rev Oral Biol Med. 2000;11(4):467–480. doi:10.1177/10454411000110040501.
89. Di Giulio M, D’Ercole S, Zara S, Cellini L. Streptococcus mitis/human gingival fibroblasts co-culture: The best natural association in answer to the 2-hydroxyethyl methacrylate release. APMIS. 2012;120:139–146. doi:10.1111/j.1600- 0463.2011.02828.x.

APA	Çimen C, ÖZALP N (2021). Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. , 33 - 39. 10.52037/eads.2021.0002
Chicago	Çimen Ceren,ÖZALP Nurhan Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. (2021): 33 - 39. 10.52037/eads.2021.0002
MLA	Çimen Ceren,ÖZALP Nurhan Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. , 2021, ss.33 - 39. 10.52037/eads.2021.0002
AMA	Çimen C,ÖZALP N Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. . 2021; 33 - 39. 10.52037/eads.2021.0002
Vancouver	Çimen C,ÖZALP N Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. . 2021; 33 - 39. 10.52037/eads.2021.0002
IEEE	Çimen C,ÖZALP N "Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review." , ss.33 - 39, 2021. 10.52037/eads.2021.0002
ISNAD	Çimen, Ceren - ÖZALP, Nurhan. "Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review". (2021), 33-39. https://doi.org/10.52037/eads.2021.0002

APA	Çimen C, ÖZALP N (2021). Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. European annals of dental sciences (Online), 48(1), 33 - 39. 10.52037/eads.2021.0002
Chicago	Çimen Ceren,ÖZALP Nurhan Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. European annals of dental sciences (Online) 48, no.1 (2021): 33 - 39. 10.52037/eads.2021.0002
MLA	Çimen Ceren,ÖZALP Nurhan Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. European annals of dental sciences (Online), vol.48, no.1, 2021, ss.33 - 39. 10.52037/eads.2021.0002
AMA	Çimen C,ÖZALP N Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. European annals of dental sciences (Online). 2021; 48(1): 33 - 39. 10.52037/eads.2021.0002
Vancouver	Çimen C,ÖZALP N Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review. European annals of dental sciences (Online). 2021; 48(1): 33 - 39. 10.52037/eads.2021.0002
IEEE	Çimen C,ÖZALP N "Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review." European annals of dental sciences (Online), 48, ss.33 - 39, 2021. 10.52037/eads.2021.0002
ISNAD	Çimen, Ceren - ÖZALP, Nurhan. "Biocompatibility Evaluation of Resin-Based Restorative Materials: A Review". European annals of dental sciences (Online) 48/1 (2021), 33-39. https://doi.org/10.52037/eads.2021.0002