The effect of hydroxyapatite and growth factors on reparative dentine formation in the therapy of injured pulp

  • Zorana Veličković University of Priština/Kosovska Mitrovica, Faculty of Medicine, Clinic for Dental Medicine, Kosovska Mitrovica, Serbia
  • Dušan Živković University of Priština/Kosovska Mitrovica, Faculty of Medicine, Clinic for Dental Medicine, Kosovska Mitrovica, Serbia
  • Marija Bubalo Military Medical Academy Belgrade, Dental Clinic
  • Milan Živković University of Priština/Kosovska Mitrovica, Faculty of Medicine, Clinic for Dental Medicine, Kosovska Mitrovica, Serbia
  • Aleksandar Mitić University of Niš, Faculty of Medicine, Clinic for Dental Medicine, Niš, Serbia
  • Milan Miladinović University of Priština/Kosovska Mitrovica, Faculty of Medicine, Clinic for Dental Medicine, Kosovska Mitrovica, Serbia
  • Miloš Duka Military Medical Academy Belgrade, Clinic for Dental Medicine, Belgrade, Serbia
  • Dragoslav Lazić University of Priština/Kosovska Mitrovica, Faculty of Medicine, Clinic for Dental Medicine, Kosovska Mitrovica, Serbia
Keywords: dental pulp;, dental pulp capping;, dentine;, rabbits;, minerals

Abstract


Background/Aim. The studies of hydroxyapatite (HAp) and growth factors as the materials used for direct pulp capping have produced conflicting results for both the issue of the inflammatory response and the issue of calcified bridge formation. Hap/poly (lactide-co-glycolide) (HAp/PLGA) is a bioresorbable polymer with demonstrated good characteristics as the carrier for the bone morphogenetic protein necessary in bone tissue regeneration. The role of growth factors in dental tissue reparation (in both reactionary and reparative dentinogenesis) represents the new foundation and provides a different approach to dental pulp treatment. Growth factors – transforming growth factor beta-1 (TGF-β-1) – directly induce morphological and functional differentiation of neo-odontoblasts. The aim of this study was to investigate the effect of calcium HAp/PLGA and growth factors (TGF β-1) in the formation of a calcified tissue – dentine bridge – on the teeth of our experimental model. Methods. In this experimental study, rodent (rabbit) teeth were used as the animal model. After the trepanation of pulp space with sterile steel drills, the pulp was capped with calcium HAp/PLGA (experimental group I; n = 60); calcium HAp/PLGA combined with TGF β-1 growth factor (experimental group II; n = 60), and there was a control group of intact teeth (n = 20). The experiment was performed in general anesthesia. The animals were kept alive for 1, 3, and 6 months. The extracted teeth were adequately prepared for scanning electron microscopy. Results. Scanning electron microscopy demonstrated that the number of teeth with calcified tissue in the form of dental bridges in the HAp/PLGA+TGF β-1 group, 6 months after the treatment, was statistically significantly greater (66.67%) than after 3 months (26.67%), at the statistical significance level of p < 0.05. Conclusion. Direct pulp capping covers the artificially exposed dental pulp and makes possible the formation of a dentine bridge (a tubular structure composed of reparative dentine) in the period of 3 months.

Author Biography

Zorana Veličković, University of Priština/Kosovska Mitrovica, Faculty of Medicine, Clinic for Dental Medicine, Kosovska Mitrovica, Serbia

Telestomatologija, Telemedicina, Oralna hirurgija, Kompjuterizovana stomatologija, Internet, Digitalizacija u stomatologiji

References

Zhang S, Yang X, Fan M. BioAggregate and iRoot BP Plus op-timize the proliferation and mineralization ability of human dental pulp cells. Int Endod J 2013; 46(10): 923‒9.

Živojinović V. Biological aspects of use of calcium hydroxyap-atite and mineral trioxide aggregate in the treatment of dis-eased pulp. [dissertation]. Belgrade: University of Belgrade, Faculty of Dentistry; 2008. (Serbian)

Teodorović N. Primena keramičkih biomaterijala u lečenju kana-la korena zuba. [dissertation]. Belgrade: University of Bel-grade, Faculty of Dentistry; 1998. (Serbian)

Witherspoon DE, Small JC, Harris GZ. Mineral trioxide aggre-gate pulpotomies: a case series outcomes assessment. J Am Dent Assoc 2006; 137(5): 610‒8.

Petrović M. Biological activity of composite cellular carriers based on highly porous hydroxyapatites and their impact in bone tissue engineering. [dissertation]. Belgrade: University of Belgrade, Faculty of Dentistry; 2012. (Serbian)

Petrović V. Modalities of use of hydroxyapatite in apexogene-sis. [dissertation]. Belgrade: University of Belgrade, Faculty of Dentistry; 2008. (Serbian)

Suwanprateeb J, Thammarakcharoen F, Wasoontararat K, Chokevivat W, Phanphiriya P. Preparation and characterization of na-nosized silver phosphate loaded hydroxyapatite by single step co-conversion process. Mat Sci Eng 2012; 32(1): 2122‒8.

Liu WN, Chang J, Zhu YQ, Zhang M. Effect of tricalcium alu-minate on the properties of tricalcium silicate-tricalcium alu-minate mixtures: setting time, mechanical strength and bio-compatibility. Int Endod J 2011; 44(1): 41‒50.

Song Y, Lin K, He S, Wang C, Zhang S, Li D, et al. Nano-biphasic calcium phosphate/polyvinyl alcohol composites with enhanced bioactivity for bone repair via low-temperature three-dimensional printing and loading with platelet-rich fi-brin. Int J Nanomedicine 2018; 13: 505‒23.

Khalil WA, Eid NF. Biocompatibility of BioAggregate and mineral trioxide aggregate on the liver and kidney. Int Endod J 2013; 46(8): 730‒7.

Kong D, Chen Z. Evaluation of the interaction between hy-droxyapatite and bisphosphonate by nonlinear capillary elec-trochromatography. J Sep Sci 2017; 40(9): 2030‒6.

Gangolli RA, Devlin SM, Gerstenhaber JA, Lelkes PI, Yang M. A Bilayered Poly (Lactic-Co-Glycolic Acid) Scaffold Provides Differential Cues for the Differentiation of Dental Pulp Stem Cells. Tissue Eng Part A 2019; 25(3-4): 224‒33.

Popović Bajić M, Danilović V, Prokić BB, Prokić B, Jokanov-ić V, Živković S. Biodentin used for direct pulp capping. Stom Glas S 2014; 61(2): 67‒74.

Katge FA, Patil DP. Comparative Analysis of 2 Calcium Sili-cate-based Cements (Biodentine and Mineral Trioxide Aggre-gate) as Direct Pulp-capping Agent in Young Permanent Mo-lars: A Split Mouth Study. J Endod 2017; 43(4): 507‒13.

Fuzinatto RN, Farina AP, Souza MA, Miyagaki DC, Randi Fer-raz CC, Cecchin D. Effects of an endodontic auxiliary chemical substance on the bond strength of two methacrylate-based en-dodontic sealers to dentin. Microsc Res Tech 2017; 80(6): 627‒33.

Lickorish D, Ramshaw JA, Werkmeister JA, Glattauer V, Howlett CR. Collagen-hydroxyapatite composite prepared by biomi-metic process. J Biomed Mater Res 2004; 68(1): 19‒27.

Unda FJ, Martín A, Hernandez C, Pérez-Nanclares G, Hilario E, Aréchaga J. FGFs-1 and -2, and TGF beta 1 as inductive sig-nals modulating in vitro odontoblast differentiation. Adv Dent Res 2001; 15: 34‒7.

Leong DJ, Setzer FC, Trope M, Karabucak B. Biocompatibility of two experimental scaffolds for regenerative endodontics. Res-tor Dent Endod 2016; 41(2): 98‒105.

Gala-Garcia A, Texiera KI, Wykrota FH, Sinisterra RD, Cortes ME. Bioceramic- Poly (glycolic)-poly (lactic acid) composite induces mineralized barrier after direct capping of rat tooth pulp tissue. Brazil Oral Res 2010; 24(1): 8‒14.

Li F, Liu X, Zhao S, Wu H, Xu HH. Porous chitosan bilayer membrane containing TGF-β1 loaded microspheres for pulp capping and reparative dentin formation in a dog model. Dent Mater 2014; 30(2): 172‒81.

Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK et al. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A 2000; 97(6): 2626‒31.

Popović- Bajić M. Impact of amelogenin, growth factors and new nanostructural materials based on calcium silicate ce-ments on pulp regeneration. [dissertation]. Belgrade: Universi-ty of Belgrade, Faculty of Dentistry; 2016. (Serbian)

Besinis A, van Noort R, Martin N. Remineralization potential of fully demineralized dentin infiltrated with silica and hydroxy-apatite nanoparticles. Dent Mater 2014; 30(3): 249‒62.

Luiz de Oliveira da Rosa W, Machado da Silva T, Fernando De-marco F, Piva E, Fernandes da Silva A. Could the application of bioactive molecules improve vital pulp therapy success? A sys-tematic review. J Biomed Mater Res A 2017; 105(3): 941‒56.

Tziafas D, Smith AJ, Lesot H. Designing new treatment strate-gies in vital pulp therapy. J Dent 2000; 28(2): 77‒92.

Asgary S, Shahabi S, Jafarzadeh T, Amini S, Kheirieh S. The properties of a new endodontic material. J Endod 2008; 34(8): 990‒3.

Melin M, Joffre-Romeas A, Farges JC, Couble ML, Magloire H, Bleicher F. Effects of TGF-beta 1 on dental pulp cells in cul-tured human tooth slices. J Dent Res 2000; 79(9): 1689‒96.

Zarrabi MH, Javidi M, Jafarian AH, Joushan B. Histologic as-sessment of human pulp response to capping with mineral tri-oxide aggregate and a novel endodontic cement. J Endod 2010; 36(11): 1778‒81.

Moon HJ, Kim KN, Kim KM, Choi SH, Kim CK, Kim KD, et al. Bone formation in calvarial defects of Sprague-Dawley rats bytransplantation of calcium phosphate glass. J Biomed Mater Res A 2005; 74(3): 497‒502.

Pissiotis E, Spangberg LS. Biological evaluation of collagen gels containing calcium hydroxide and hydroxyapatite. J Endod 1990; 16(10): 468‒73.

van Noort R, Brown D, Clarke R, Combe EC, Curtis R, Lloyd CH, et al. Dental materials: 1992 literature review. J Dent 1994; 22(1): 5‒28.

Tziafas D, Pantelidou O, Alvanou A, Belibasakis G, Papadimitriou S. The dentinogenic effect of mineral trioxide aggregate (MTA) in short term capping experiments. Int Endod J 2002; 35(3): 245‒54.

Chang KC, Chang CC, Chen WT, Hsu CK, Lin FH, Lin CP. Development of calcium phosphate/sulfate biphasic cement for vital pulp therapy. Dent Mater 2014; 30(12): e362‒70.

Swarup SJ, Rao A, Boaz K, Srikant N, Shenoy R. Pulpal response to nano hydroxyapatite, mineral trioxide aggregate and calci-um hydroxide when used as a direct pulp capping agent: an in vivo study. J Clin Pediatr Dent 2014; 38(3): 201‒6.

Popović Bajić M, Danilović V, Prokić B, Milošević V, Živković S. Histologocal effects of Emdogain Gel on exposed dental 10 pulp. 20th Congress of the Balkan Stomatological Society (BaSS); Bucharest; 2015. (oral presentation)

Hebling J, Giro EM, Costa CA. Biocompatibility of an adhesive system applied to exposed human dental pulp. J Endod 1999; 25(10): 676‒82.

Mjör IA. Pulp-dentin biology in restorative dentistry. Part 7: The exposed pulp. Quintessence Int 2002; 33(2): 113‒35.

Shahravan A, Jalali SP, Torabi M, Haghdoost AA, Gorjestani H. Ahistological study of pulp reaction to various water/powder ratios of white mineral trioxide aggregate as pulp-capping ma-terial in human teeth: a double-blinded, randomized con-trolled trial. Int Endod J 2011; 44(11): 1029‒33.

Accorinte Mde L, Holland R, Reis A, Bortoluzzi MC, Murata SS, Dezan E Jr, et al. Evaluation of mineral trioxide aggregate and calcium hydroxide cement as pulp-capping agents in human teeth. J Endod 2008; 34(1): 1‒6.

Chen CL, Huang TH, Ding SJ, Shie MY, Kao CT. Comparison of calcium and silicate cement and mineral trioxide aggregate biologic effects and bone markers expression in MG63 cells. J Endod 2009; 35(5): 682‒5.

Bègue-Kirn C, Smith AJ, Ruch JV, Wozney JM, Purchio A, Hart-mann D, et al. Effects of dentin proteins, transforming growth factor beta 1 (TGF beta 1) and bone morphogenetic protein 2 (BMP2) on the differentiation of odontoblast in vitro. Int J Dev Biol 1992; 36(4): 491‒503.

Piattelli A, Rubini C, Fioroni M, Tripodi D, Strocchi R. Trans-forming growth factor-beta 1 (TGF-beta 1) expression in normal healthy pulps and in those with irreversible pulpitis. Int Endod J 2004; 37(2): 114‒9.

Jabbarifar E, Razavi SM, Ahmadi N. Histopathologic responses of dog's dental pulp to mineral trioxide aggregate, bio active glass, formocresol, hydroxyapatite. Dent Res J (Isfahan) 2007; 4: 83–7.

Popović Bajić M, Jokanović V, Danolović V, Živković S. Histological Evaluation of Direct Pulp Capping with Novel Nanostructur-al Materials based on Active Silicate Cements on Pulp Tissue. 47th Meeting of the Continental European Division of the In-ternational Association for Dental Research (CED-IADR). Belek, Antalya; 2015. (poster presentations)

Nowicka A, Wilk G, Lipski M, Kołecki J, Buczkowska-Radlińska J. Tomographic Evaluation of Reparative Dentin Formation after Direct Pulp Capping with Ca(OH)2, MTA, Biodentine, and Dentin Bonding System in Human Teeth. J Endod 2015; 41(8): 1234‒40.

Published
2021/03/18
Section
Original Paper