Advertisement

Clinical Oral Investigations

, Volume 19, Issue 8, pp 2075–2089 | Cite as

Calcium silicate/calcium phosphate biphasic cements for vital pulp therapy: chemical-physical properties and human pulp cells response

  • M. G. GandolfiEmail author
  • G. Spagnuolo
  • F. Siboni
  • A. Procino
  • V. Rivieccio
  • G. A. Pelliccioni
  • C. Prati
  • S. Rengo
Original Article

Abstract

Objectives

The aim was to test the properties of experimental calcium silicate/calcium phosphate biphasic cements with hydraulic properties designed for vital pulp therapy as direct pulp cap and pulpotomy.

Methods

CaSi-αTCP and CaSi-DCDP were tested for ion-releasing ability, solubility, water sorption, porosity, ability to nucleate calcium phosphates, and odontoblastic differentiation—alkaline phosphatase (ALP) and osteocalcin (OCN) upregulation—of primary human dental pulp cells (HDPCs).

Results

The materials showed high Ca and OH release, high open pore volume and apparent porosity, and a pronounced ability to nucleate calcium phosphates on their surface. HDPCs treated with CaSi-αTCP showed a strong upregulation of ALP and OCN genes, namely a tenfold increase for OCN and a threefold increase for ALP compared to the control cells. Conversely, CaSi-DCDP induced a pronounced OCN gene upregulation but had no effect on ALP gene regulation.

Conclusions

Both cements showed high biointeractivity (release of Ca and OH ions) correlated with their marked ability to nucleate calcium phosphates. CaSi-αTCP cement proved to be a potent inducer of ALP and OCN genes as characteristic markers of mineralization processes normally poorly expressed by HDPCs.

Clinical relevance

Calcium silicate/calcium phosphate cements appear to be attractive new materials for vital pulp therapy as they may provide odontogenic/dentinogenic chemical signals for pulp regeneration and healing, and dentin formation in regenerative endodontics.

Keywords

Calcium silicate cements Calcium phosphate cements MTA Pulp cells Pulp therapy Biointeractivity Calcium release Dentine regeneration pH Porosity Solubility Genes activation Alkaline phosphatase Osteocalcin Regenerative dentistry 

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Gandolfi MG, Siboni F, Botero T, Bossù M, Riccitiello F, Prati C (2014) Calcium silicate and calcium hydroxide materials for pulp capping: biointeractivity, porosity, solubility and bioactivity of current formulations. J Appl Biomater Funct Mater, in press; doi:  10.5301/jabfm.5000201.
  2. 2.
    Parirokh M, Torabinejad M (2010) Mineral trioxide aggregate: a comprehensive literature review—part III: clinical applications, drawbacks, and mechanism of action. J Endod 36:400–413CrossRefPubMedGoogle Scholar
  3. 3.
    Okiji T, Yoshiba K (2009) Reparative dentinogenesis induced by mineral trioxide aggregate: a review from the biological and physicochemical points of view. Int J Dent 2009:1–12CrossRefGoogle Scholar
  4. 4.
    Gandolfi MG, Van Landuyt K, Taddei P, Modena E, Van Meerbeek B, Prati C (2010) ESEM-EDX and Raman techniques to study MTA calcium-silicate cements in wet conditions and in real-time. J Endod 36:851–857CrossRefPubMedGoogle Scholar
  5. 5.
    Gandolfi MG, Taddei P, Modena E, Siboni F, Prati C (2013) Biointeractivity-related vs chemi/physisorption-related apatite precursor-forming ability of current root end filling materials. J Biomed Mater Res B Appl Biomater 101:1107–1123CrossRefPubMedGoogle Scholar
  6. 6.
    Gandolfi MG, Prati C (2010) MTA and F-doped MTA cements used as sealers with warm gutta-percha. Long-term sealing ability study. Int Endod J 43:889–901CrossRefPubMedGoogle Scholar
  7. 7.
    Gandolfi MG, Iacono F, Agee K, Siboni F, Tay F, Pashley DH, Prati C (2009) Setting time and expansion in different soaking media of experimental accelerated calcium-silicate cements and ProRoot MTA. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108:e39–e45CrossRefPubMedGoogle Scholar
  8. 8.
    Gandolfi MG (2012) A new method for evaluating the pulpward diffusion of Ca and OH ions through coronal dentin into the pulp. Iranian Endod J 7:189–197Google Scholar
  9. 9.
    D’Antò V, Di Caprio MP, Ametrano G, Simeone M, Rengo S, Spagnuolo G (2010) Effect of mineral trioxide aggregate on mesenchymal stem cells. J Endod 36:1839–1843CrossRefPubMedGoogle Scholar
  10. 10.
    Gandolfi MG, Shah SN, Feng R, Prati C, Akintoye SO (2011) Biomimetic calcium-silicate cements support differentiation of human orofacial mesenchymal stem cells. J Endod 37:1102–1108PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Moghadame-Jafari S, Mantellini MG, Botero TM, McDonald NJ, Nor JE (2005) Effect of ProRoot MTA on pulp cell apoptosis and proliferation in vitro. J Endod 31:387–391CrossRefGoogle Scholar
  12. 12.
    Takita T, Hayashi M, Takeichi O, Ogiso B, Suzuki N, Otsuka K, Ito K (2006) Effect of mineral trioxide aggregate on proliferation of cultured human dental pulp cells. Int Endod J 39:415–422CrossRefPubMedGoogle Scholar
  13. 13.
    Paranjpe A, Smoot T, Zhang H, Johnson JD (2011) Direct contact with Mineral Trioxide Aggregate activates and differentiates human dental pulp cells. J Endod 37:1691–1695PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Chen CC, Shie MY, Ding SJ (2011) Human dental pulp cell responses to new calcium silicate-based endodontic materials. Int Endod J 44:836–842CrossRefPubMedGoogle Scholar
  15. 15.
    Liu CH, Hung C Jr, Huang TH, Lin CC, Kao CT, Shie MY (2014) Odontogenic differentiation of human dental pulp cells by calcium silicate materials stimulating via FGFR/ERK signaling pathway. Mater Sci Eng C 43:359–366CrossRefGoogle Scholar
  16. 16.
    Gandolfi MG, Taddei P, Tinti A, Dorigo De Stefano E, Prati C (2011) Alpha-TCP improves the apatite-formation ability of calcium-silicate hydraulic cement soaked in phosphate solutions. Mater Sci Eng C 31:1412–1422CrossRefGoogle Scholar
  17. 17.
    Taddei P, Tinti A, Gandolfi MG, Rossi PL, Prati C (2009) Ageing of calcium silicate cements for endodontic use in simulated body fluids: a micro-Raman study. J Raman Spectrosc 40:1858–1866CrossRefGoogle Scholar
  18. 18.
    Yubao L, Xingdong Z, de Groat K (1997) Hydrolysis and phase transition of alpha-tricalcium phosphate. Biomaterials 18:737–741CrossRefGoogle Scholar
  19. 19.
    TenHuisen KS, Brown PW (1998) Formation of calcium-deficient hydroxyapatite from a-tricalcium phosphate. Biomaterials 19:2209–2217CrossRefPubMedGoogle Scholar
  20. 20.
    Fernandez E, Ginebra MP, Boltong MG, Driessens FCM, Ginebra J, De Maeyer EAP, Verbeeck RMH, Planell JA (1996) Kinetic study of the setting reaction of a calcium phosphate bone cement. J Biomed Mater Res 32:367–374CrossRefPubMedGoogle Scholar
  21. 21.
    Driessens FCM, Wolke JGC, Jansen JA (2012) A new theoretical approach to calcium phosphates, aqueous solutions and bone remodeling. J Austr Ceram Soc 48:144–149Google Scholar
  22. 22.
    Ginebra MP, Fernandez E, Driessens FCM, Planell JA (1999) Modeling of the hydrolysis of α-tricalcium phosphate. J Amer Ceram Soc 82:2808–2812CrossRefGoogle Scholar
  23. 23.
    Ishikawa K (2008) Calcium phosphate cement. In Bioceramics and Their Clinical Application; Kokubo T. Ed.; CRC Press: New York, NY, USA; pp. 438-463.Google Scholar
  24. 24.
    Driessens FC, Planell JA, Boltong MG, Khairoun I, Ginebra MP (1998) Osteotransductive bone cements. Proc Inst Mech Eng H: J Eng Med 212:427–435CrossRefGoogle Scholar
  25. 25.
    Gandolfi MG, Taddei P, Siboni F, Modena E, Ciapetti G, Prati C (2011) Development of the foremost light-curable calcium-silicate MTA cement as root-end in oral surgery. Chemical-physical properties, bioactivity and biological behaviour. Dent Mater 27:e134–e157CrossRefPubMedGoogle Scholar
  26. 26.
    Spagnuolo G, D’Antò V, Valletta R, Strisciuglio C, Schmalz G, Schweikl H, Rengo S (2008) Effect of 2-hydroxyethyl methacrylate on human pulp cell survival pathways ERK and AKT. J Endod 34:684–688CrossRefPubMedGoogle Scholar
  27. 27.
    Lee DH, Kim NR, Ahn SJ, Yang HC (2006) Effect of passage number on human dental pulp cell proliferation and differentiation. Biomater Res 10:74–77Google Scholar
  28. 28.
    Borra RC, Lotufo MA, Gagioti SM, Barros Fde M, Andrade PM (2009) A simple method to measure cell viability in proliferation and cytotoxicity assays. Braz Oral Res 23:255–262CrossRefPubMedGoogle Scholar
  29. 29.
    Holland PM, Abramson RD, Watson R, Gelfand DH (1991) Detection of specific polymerase chain reaction product by utilizing the 5’-3’ exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci U S A 88:727–780CrossRefGoogle Scholar
  30. 30.
    Chow LC (2010) Next generation calcium phosphate-based biomaterials. Dent Mater J 28:1–10CrossRefGoogle Scholar
  31. 31.
    Fernández E, Gil FJ, Ginebra MP, Driessens FCM, Planell JA, Best SM (1999) Calcium phosphate bone cements for clinical applications. Part I: solution chemistry. J Mater Sci: Mater Med 10:169–176Google Scholar
  32. 32.
    Lee SK, Lee SK, Lee SI, Park JH, Jang JH, Kim HW, Kim EC (2010) Effect of calcium phosphate cements on growth and odontoblastic differentiation in human dental pulp cells. J Endod 36:1537–1542CrossRefPubMedGoogle Scholar
  33. 33.
    Eyckmans J, Roberts SJ, Bolander J, Schrooten J (2013) Mapping calcium phosphate activated gene networks as a strategy for targeted osteoinduction of human progenitors. Biomaterials 34:4612–4621PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Hakki SS, Bozkurt BS, Gandolfi MG, Prati C, Belli S (2013) The response of cementoblasts to calcium phosphate resin-based and calcium silicate-based commercial sealers. Int Endod J 46:242–252CrossRefPubMedGoogle Scholar
  35. 35.
    Schröder U (1985) Effects of calcium hydroxide-containing pulp-capping agents on pulp cell migration, proliferation, and differentiation. J Dent Res 64:541–548PubMedGoogle Scholar
  36. 36.
    Scarano A, Manzon L, Di Giorgio R, Orsini G, Tripoli D, Piatelli A (2003) Direct capping with four different materials in humans: histological analysis of odontoblast activity. J Endod 29:729–734CrossRefPubMedGoogle Scholar
  37. 37.
    Lopez-Cazaux S, Bluteau G, Magne D, Lieubeau B, Guicheux J, Alliot-Licht B (2006) Culture medium modulates the behaviour of human dental pulp-derived cells: technical note. Europ Cell Mater 17:35–42Google Scholar
  38. 38.
    Mizuno M, Banzai Y (2008) Calcium ion release from calcium hydroxide stimulated fibronectin gene expression in dental pulp cells and the differentiation of dental pulp cells to mineralized tissue forming cells by fibronectin. Int Endod J 41:933–938CrossRefPubMedGoogle Scholar
  39. 39.
    Schmalz G (2009) Calcium hydroxide cements. In: Schmalz G, Arenholt-Bindslev D (eds) Biocompatibility of dental materials, vol Chapter 6.5. Springer, Verlag Berlin, pp 166–176Google Scholar
  40. 40.
    Pitt Ford TR, Torabinejad M, Abedi HR, Bakland LK, Kariyawasam SP (1996) Using mineral trioxide aggregate as a pulp-capping material. J Am Dent Assoc 127:1491–1494CrossRefGoogle Scholar
  41. 41.
    Mente J, Geletneky B, Ohle M, Koch MJ, Ding PGF, Wolff D, Dreyhaupt J, Martin N, Staehle HJ, Pfefferle T (2010) Mineral trioxide aggregate or calcium hydroxide direct pulp capping: an analysis of the clinical treatment outcome. J Endod 36:806–813CrossRefPubMedGoogle Scholar
  42. 42.
    Rashid F, Shiba H, Mizuno N, Mouri Y, Fujita T, Shinohara H, Ogawa T, Kawaguchi H, Kurihara H (2003) The effect of extracellular calcium ion on gene expression of bone-related proteins inhuman pulp cells. J Endod 29:104–107CrossRefPubMedGoogle Scholar
  43. 43.
    Clapham DE (1995) Calcium signaling. Cell 80:259–268CrossRefPubMedGoogle Scholar
  44. 44.
    Okabe T, Sakamoto M, Takeuchi H, Matsushima K (2006) Effects of pH on mineralization ability of human dental pulp cells. J Endod 32:198–201CrossRefPubMedGoogle Scholar
  45. 45.
    Takagi S, Chow LC, Ishikawa K (1998) Formation of hydroxyapatite in new calcium phosphate cements. Biomaterials 19:1593–1599CrossRefPubMedGoogle Scholar
  46. 46.
    Chow LC, Eanes ED (2001) Solubility of calcium phosphates. In: Chow LC, Eanes ED (eds) Octacalcium phosphate. Monogr Oral Sci. Karger, Basel, pp 94–111CrossRefGoogle Scholar
  47. 47.
    Gandolfi MG, Taddei P, Tinti A, Prati C (2010) Apatite-forming ability of ProRoot MTA. Int Endod J 43:917–929CrossRefPubMedGoogle Scholar
  48. 48.
    Collepardi MM (1995) Water reducers/retarders, chapter 6 in Concrete admixtures handbook. Properties, science and technology. Ed. Ramachandran VS, pp 286-409Google Scholar
  49. 49.
    Ma W, Brown PW (1994) Effect of phosphate additions on the hydration of Portland cement. Adv Cem Res 6:1–12CrossRefGoogle Scholar
  50. 50.
    Hakki SS, Bozkurt SB, Hakki EE, Belli S (2009) Effects of Mineral Trioxide Aggregate on cell survival, gene expression associated with mineralized tissues, and biomineralization of cementoblasts. J Endod 35:513–519CrossRefPubMedGoogle Scholar
  51. 51.
    Sun J, Wei L, Liu X, Li J, Li B, Wang G, Meng F (2009) Influences of ionic dissolution products of dicalcium silicate coating on osteoblastic proliferation, differentiation and gene expression. Acta Biomater 5:1284–1293CrossRefPubMedGoogle Scholar
  52. 52.
    Jung GY, Park YJ, Han JS (2010) Effects of HA released calcium ion on osteoblast differentiation. J Mater Sci Mat Med 21:1649–1654CrossRefGoogle Scholar
  53. 53.
    Nakamura S, Matsumoto T, Sasaki J, Egusa H, Lee KY, Nakano T, Sohmura T, Nakahira A (2010) Effect of calcium ion concentrations on osteogenic differentiation and hematopoietic stem cell niche-related protein expression in osteoblasts. Tissue Eng Part A 16:2467–2473CrossRefPubMedGoogle Scholar
  54. 54.
    Matsumoto S, Hayashi M, Suzuki Y, Suzuki N, Maeno M, Ogiso B (2013) Calcium ions released from mineral trioxide aggregate convert the differentiation pathway of C2C12 Cells into osteoblast lineage. J Endod 39:68–75CrossRefPubMedGoogle Scholar
  55. 55.
    Shie MY, Ding SJ, Chang HC (2011) The role of silicon in osteoblast-like cell proliferation and apoptosis. Acta Biomater 7:2604–2614CrossRefPubMedGoogle Scholar
  56. 56.
    Shie MY, Chang HC, Ding SJ (2012) Effects of altering the Si/Ca molar ratio of a calcium silicate cement on in vitro cell attachment. Int Endod J 45:337–345CrossRefPubMedGoogle Scholar
  57. 57.
    Accorinte MLR, Holland R, Reis A, Bortoluzzi MC, Murata SS, Dezan E, Souza V, Loguercio Dourado A (2008) Evaluation of Mineral Trioxide Aggregate and Calcium Hydroxide cement as pulp-capping agents in human teeth. J Endod 34:1–6CrossRefGoogle Scholar
  58. 58.
    Chaung HM, Hong CH, Chiang CP, Lin SK, Kuo YS, Lan WH, Hsieh CC (1996) Comparison of calcium phosphate cement mixture and pure calcium hydroxide as derect pulp-capping. J Formos Med Assoc 95:545–550PubMedGoogle Scholar
  59. 59.
    Yoshimine Y, Maeda K (1995) Histologic evaluation of tetracalcium phosphate-based cement as a direct pulp-capping agent. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 79:351–358CrossRefPubMedGoogle Scholar
  60. 60.
    Chohayeb AA, Adrian JC, Salamat K (1991) Pulpal response to tricalcium phosphate as a capping agent. Oral Surg, Oral Med, Oral Pathol Endod 71:343–345CrossRefGoogle Scholar
  61. 61.
    Lee JB, Park SJ, Kim HH, Kwon YS, Lee KW, Min KS (2014) Physical properties and biological/odontogenicy effects of and experimentally developed fast-setting alpha-tricalcium phosphate-based pulp capping material. BMC Oral Health 14:87–97PubMedCentralCrossRefPubMedGoogle Scholar
  62. 62.
    Boone ME, Kafrawy AH (1979) Pulp reaction to a tricalcium phosphate ceramic capping agent. Oral Surg Oral Med Oral Pathol Endod 47:369–371CrossRefGoogle Scholar
  63. 63.
    Estrela C, Bammann LL, Estrela CR, Silva RS, Pécora JD (2000) Antimicrobial and chemical study of MTA, Portland cement, calcium hydroxide paste, Sealapex and Dycal. Braz Dent J 11:3–9PubMedGoogle Scholar
  64. 64.
    McHugh CP, Zhang P, Michalek S, Eleazer PD (2004) pH required to kill Enterococcus faecalis in vitro. J Endod 30:218–219CrossRefPubMedGoogle Scholar
  65. 65.
    Al-Hezaimi K, Al-Hamdan K, Naghshbandi J, Oglesby S, Simon JHS, Rotstein I (2005) Effect of white-colored Mineral Trioxide Aggregate in different concentrations on Candida albicans in vitro. J Endod 31:684–686CrossRefPubMedGoogle Scholar
  66. 66.
    Siqueira JF Jr, Lopes HP (1999) Mechanisms of antimicrobial activity of calcium hydroxide: a critical review. Int Endod J 32:361–369CrossRefPubMedGoogle Scholar
  67. 67.
    Ding S-J, Shie M-Y, Wang C-Y (2009) Novel fast-setting calcium silicate bone cements with high bioactivity and enhanced osteogenesis in vitro. J Mater Chem 19:1183–1190CrossRefGoogle Scholar
  68. 68.
    An S, Gao Y, Ling J, Wei X, Xiao Y (2012) Calcium ions promote osteogenic differentiation and mineralization of human dental pulp cells: implications for pulp capping materials. J Mater Sci: Mater Med 23:789–795Google Scholar
  69. 69.
    Wu BC, Huang SC, Ding SJ (2013) Comparative osteogenesis of radiopaque dicalcium silicate cement and white-colored mineral trioxide aggregate in a rabbit femur model. Materials 6:5675–5689CrossRefGoogle Scholar
  70. 70.
    Min KS, Kim HI, Park HJ, Pi SH, Hong CU, Kim EC (2007) Human pulp cells response to Portland cement in vitro. J Endod 33:163–166CrossRefPubMedGoogle Scholar
  71. 71.
    Shen Q, Sun J, Wu J, Liu C, Chen F (2010) An in vitro investigation of the mechanical-chemical and biological properties of calcium phosphate/calcium silicate/bismutite cement for dental pulp capping. J Biomed Mater Res B Appl Biomater 94:141–148PubMedGoogle Scholar
  72. 72.
    Eleniste PP, Huang S, Wayakanon K, Largura HW, Bruzzaniti A (2014) Osteoblast differentiation and migration are regulated by dynamin GTPase activity. Int J Biochem Cell Biol 46:9–18PubMedCentralCrossRefPubMedGoogle Scholar
  73. 73.
    Lim WH, Liu B, Cheng D, Hunter DJ, Zhong Z, Ramos DM, Williams BO, Sharpe PT, Bardet C, Mah SJ, Helms JA (2014) Wnt signaling regulates pulp volume and dentin thickness. J Bone Miner Res 29:892–901PubMedCentralCrossRefPubMedGoogle Scholar
  74. 74.
    Min KS, Lee S-I, Lee Y, Kim E-C (2009) Effect of radiopaque Portland cement on mineralization in human dental pulp cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108:e82–e86CrossRefPubMedGoogle Scholar
  75. 75.
    Schmalz G, Smith AJ (2014) Pulp development, repair, and regeneration: challenges of the transition from the traditional dentistry to biologically based therapies. J Endod 40:S2–S5CrossRefPubMedGoogle Scholar
  76. 76.
    Cooper PR, Holder MJ, Smith AJ (2014) Inflammation and regeneration in the dentin-pulp complex: a double-edged sword. J Endod 40:S46–S51CrossRefPubMedGoogle Scholar
  77. 77.
    Simon SRJ, Tomson PL, Berdal A (2014) Regenerative endodontics: regeneration or repair? J Endod 40:S70–S75CrossRefPubMedGoogle Scholar
  78. 78.
    Prati C, Gandolfi MG (2015) Calcium silicate bioactive cements: biological perspectives and clinical applications. Dent Mater 31:351–370Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • M. G. Gandolfi
    • 1
    Email author
  • G. Spagnuolo
    • 2
  • F. Siboni
    • 1
  • A. Procino
    • 2
  • V. Rivieccio
    • 2
  • G. A. Pelliccioni
    • 1
  • C. Prati
    • 1
  • S. Rengo
    • 2
  1. 1.Dental School (Laboratory of Biomaterials and Oral Pathology), Department of Biomedical and NeuroMotor SciencesUniversity of BolognaBolognaItaly
  2. 2.Department of Neurosciences, Reproductive and Odontostomatological SciencesUniversity of Naples “Federico II”NapoliItaly

Personalised recommendations