Current and Future Views on Biomaterial Use in Regenerative Endodontics

  • Eliseu A. Münchow
  • Marco C. BottinoEmail author


Regeneration of the pulp-dentine complex depends on satisfactory disinfection of the root canal system followed by the wise application of scaffolds, stem cells and growth factors. Hence, the purpose of this chapter is to discuss the latest discoveries on biocompatible strategies of root canal disinfection and the use of scaffolds and tissue engineering strategies in regenerative endodontics. Traditionally, root canal disinfection of necrotic permanent immature teeth has been done using antibiotic pastes, but although effective, these can be extremely toxic to stem cells, preventing reliable regenerative outcomes. Alternatively, nanofibrous constructs have been demonstrated able to function as drug delivery systems for a range of antibiotics, showing comparable antimicrobial effects to antibiotic pastes but using minimal drug concentration. After disinfection, pulp-dentine complex regeneration may be encouraged by cell-free or cell transplantation approaches. While the former approach comprises a cell-free strategy in which no exogenous cells are used, the latter approach induces regenerative outcomes by transplanting cells into the root canal. To conclude, the clinical translation of reliable and predictable regenerative therapeutics to treat teeth with necrotic pulps will involve the use of advanced scaffolds, loaded or not with stem cells, and/or growth factors to predictably foster pulp and dentine regeneration.


Scaffolds Dental pulp Regeneration Biomaterials Endodontics Disinfection 



M.C.B. acknowledges funding from the NIH/NIDCR (Grants K08DE023552 and R01DE026578). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


  1. Akbari T, Pourhajibagher M, Hosseini F, Chiniforush N, Gholibegloo E, Khoobi M, Shahabi S, Bahador A (2017) The effect of indocyanine green loaded on a novel nano-graphene oxide for high performance of photodynamic therapy against Enterococcus faecalis. Photodiagnosis Photodyn Ther 20:148–153CrossRefGoogle Scholar
  2. Albuquerque MT, Valera MC, Nakashima M, Nor JE, Bottino MC (2014a) Tissue-engineering-based strategies for regenerative endodontics. J Dent Res 93:1222–1231CrossRefGoogle Scholar
  3. Albuquerque MT, Junqueira JC, Coelho MB, de Carvalho CA, Valera MC (2014b) Novel in vitro methodology for induction of Enterococcus faecalis biofilm on apical resorption areas. Indian J Dent Res 25:535–538CrossRefGoogle Scholar
  4. Albuquerque MT, Ryan SJ, Munchow EA, Kamocka MM, Gregory RL, Valera MC, Bottino MC (2015a) Antimicrobial effects of novel triple antibiotic paste-mimic scaffolds on Actinomyces naeslundii biofilm. J Endod 41:1337–1343CrossRefGoogle Scholar
  5. Albuquerque MT, Valera MC, Moreira CS, Bresciani E, de Melo RM, Bottino MC (2015b) Effects of ciprofloxacin-containing scaffolds on enterococcus faecalis biofilms. J Endod 41:710–714CrossRefGoogle Scholar
  6. Albuquerque MT, Evans JD, Gregory RL, Valera MC, Bottino MC (2016) Antibacterial TAP-mimic electrospun polymer scaffold: effects on P. gingivalis-infected dentin biofilm. Clin Oral Investig 20:387–393CrossRefGoogle Scholar
  7. Althumairy RI, Teixeira FB, Diogenes A (2014) Effect of dentin conditioning with intracanal medicaments on survival of stem cells of apical papilla. J Endod 40:521–525CrossRefGoogle Scholar
  8. American Association of Endodontics (2016). Accessed on 2 May 2016.
  9. Andreasen FM, Kahler B (2015) Diagnosis of acute dental trauma: the importance of standardized documentation: a review. Dent Traumatol 31:340–349CrossRefGoogle Scholar
  10. Athirasala A, Lins F, Tahayeri A, Hinds M, Smith AJ, Sedgley C, Ferracane J, Bertassoni LE (2017) A novel strategy to engineer pre-vascularized full-length dental pulp-like tissue constructs. Sci Rep 7:3323CrossRefGoogle Scholar
  11. Banchs F, Trope M (2004) Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol? J Endod 30:196–200CrossRefGoogle Scholar
  12. Becerra P, Ricucci D, Loghin S, Gibbs JL, Lin LM (2014) Histologic study of a human immature permanent premolar with chronic apical abscess after revascularization/revitalization. J Endod 40:133–139CrossRefGoogle Scholar
  13. Bertassoni LE, Cardoso JC, Manoharan V, Cristino AL, Bhise NS, Araujo WA, Zorlutuna P, Vrana NE, Ghaemmaghami AM, Dokmeci MR, Khademhosseini A (2014a) Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels. Biofabrication 6:024105CrossRefGoogle Scholar
  14. Bertassoni LE, Cecconi M, Manoharan V, Nikkhah M, Hjortnaes J, Cristino AL, Barabaschi G, Demarchi D, Dokmeci MR, Yang Y, Khademhosseini A (2014b) Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip 14:2202–2211CrossRefGoogle Scholar
  15. Bose R, Nummikoski P, Hargreaves K (2009) A retrospective evaluation of radiographic outcomes in immature teeth with necrotic root canal systems treated with regenerative endodontic procedures. J Endod 35:1343–1349CrossRefGoogle Scholar
  16. Bottino MC, Thomas V, Schmidt G, Vohra YK, Chu TM, Kowolik MJ, Janowski GM (2012) Recent advances in the development of GTR/GBR membranes for periodontal regeneration--a materials perspective. Dent Mater 28:703–721CrossRefGoogle Scholar
  17. Bottino MC, Kamocki K, Yassen GH, Platt JA, Vail MM, Ehrlich Y, Spolnik KJ, Gregory RL (2013) Bioactive nanofibrous scaffolds for regenerative endodontics. J Dent Res 92:963–969CrossRefGoogle Scholar
  18. Bottino MC, Yassen GH, Platt JA, Labban N, Windsor LJ, Spolnik KJ, Bressiani AH (2015) A novel three-dimensional scaffold for regenerative endodontics: materials and biological characterizations. J Tissue Eng Regen Med 9:E116–E123CrossRefGoogle Scholar
  19. Bottino MC, Pankajakshan D, Nör JE (2017) Advanced scaffolds for dental pulp and periodontal regeneration. Dent Clin N Am 61:689–711CrossRefGoogle Scholar
  20. Bunyaratavej P, Wang HL (2001) Collagen membranes: a review. J Periodontol 72:215–229CrossRefGoogle Scholar
  21. Cehreli ZC, Isbitiren B, Sara S, Erbas G (2011) Regenerative endodontic treatment (revascularization) of immature necrotic molars medicated with calcium hydroxide: a case series. J Endod 37:1327–1330CrossRefGoogle Scholar
  22. Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, Smith AJ, Nor JE (2008) Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 34:962–969CrossRefGoogle Scholar
  23. Cvek M (1972) Treatment of non-vital permanent incisors with calcium hydroxide. I. Follow-up of periapical repair and apical closure of immature roots. Odontol Revy 23:27–44PubMedGoogle Scholar
  24. Cvek M (1973) Treatment of non-vital permanent incisors with calcium hydroxide. II. Effect on external root resorption in luxated teeth compared with effect of root filling with guttapucha. A follow-up. Odontol Revy 24:343–354PubMedGoogle Scholar
  25. Cvek M (1992) Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha. A retrospective clinical study. Endod Dent Traumatol 8:45–55CrossRefGoogle Scholar
  26. Damle SG, Bhattal H, Loomba A (2012) Apexification of anterior teeth: a comparative evaluation of mineral trioxide aggregate and calcium hydroxide paste. J Clin Pediatr Dent 36:263–268CrossRefGoogle Scholar
  27. Diogenes A, Hargreaves KM (2017) Microbial modulation of stem cells and future directions in regenerative endodontics. J Endod 43:S95–S101CrossRefGoogle Scholar
  28. Diogenes A, Henry MA, Teixeira FB, Hargreaves KM (2013) An update on clinical regenerative endodontics. Endod Topics 28:2–23CrossRefGoogle Scholar
  29. Diogenes AR, Ruparel NB, Teixeira FB, Hargreaves KM (2014) Translational science in disinfection for regenerative endodontics. J Endod 40:S52–S57CrossRefGoogle Scholar
  30. Diogenes A, Ruparel NB, Shiloah Y, Hargreaves KM (2016) Regenerative endodontics: a way forward. J Am Dent Assoc 147:372–380CrossRefGoogle Scholar
  31. Dye B, Thornton-Evans G, Li X, Iafolla T (2015) Dental caries and tooth loss in adults in the United States, 2011-2012. NCHS Data Brief 197:1Google Scholar
  32. Ertem E, Gutt B, Zuber F, Allegri S, Le Ouay B, Mefti S, Formentin K, Stellacci F, Ren Q (2017) Core-shell silver nanoparticles in endodontic disinfection solutions enable long-term antimicrobial effect on oral biofilms. ACS Appl Mater Interfaces 9:34762–34772CrossRefGoogle Scholar
  33. Galler KM (2016) Clinical procedures for revitalization: current knowledge and considerations. Int Endod J 49:926–936CrossRefGoogle Scholar
  34. Galler KM, Widbiller M (2017) Perspectives for cell-homing approaches to engineer dental pulp. J Endod 43:S40–S45CrossRefGoogle Scholar
  35. Galler KM, Buchalla W, Hiller KA, Federlin M, Eidt A, Schiefersteiner M, Schmalz G (2015) Influence of root canal disinfectants on growth factor release from dentin. J Endod 41:363–368CrossRefGoogle Scholar
  36. Galler KM, Widbiller M, Buchalla W, Eidt A, Hiller KA, Hoffer PC, Schmalz G (2016) EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells. Int Endod J 49:581–590CrossRefGoogle Scholar
  37. Glendor U (2009) Aetiology and risk factors related to traumatic dental injuries--a review of the literature. Dent Traumatol 25:19–31CrossRefGoogle Scholar
  38. Gomes BP, Pinheiro ET, Gade-Neto CR, Sousa EL, Ferraz CC, Zaia AA, Teixeira FB, Souza-Filho FJ (2004) Microbiological examination of infected dental root canals. Oral Microbiol Immunol 19:71–76CrossRefGoogle Scholar
  39. Gomes-Filho JE, Duarte PC, Ervolino E, Mogami Bomfim SR, Xavier Abimussi CJ, Mota da Silva Santos L, Lodi CS, Penha De Oliveira SH, Dezan E Jr, Cintra LT (2013) Histologic characterization of engineered tissues in the canal space of closed-apex teeth with apical periodontitis. J Endod 39:1549–1556CrossRefGoogle Scholar
  40. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A 97:13625–13630CrossRefGoogle Scholar
  41. Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S (2002) Stem cell properties of human dental pulp stem cells. J Dent Res 81:531–535CrossRefGoogle Scholar
  42. Hoshino E, Kurihara-Ando N, Sato I, Uematsu H, Sato M, Kota K, Iwaku M (1996) In-vitro antibacterial susceptibility of bacteria taken from infected root dentine to a mixture of ciprofloxacin, metronidazole and minocycline. Int Endod J 29:125–130CrossRefGoogle Scholar
  43. Huang GT (2011) Dental pulp and dentin tissue engineering and regeneration: advancement and challenge. Front Biosci 3:788–800CrossRefGoogle Scholar
  44. Huang GT, Yamaza T, Shea LD, Djouad F, Kuhn NZ, Tuan RS, Shi S (2010) Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng Part A 16:605–615CrossRefGoogle Scholar
  45. Huang GT, Al-Habib M, Gauthier P (2013) Challenges of stem cell-based pulp and dentin regeneration: a clinical perspective. Endod Topics 28:51–60CrossRefGoogle Scholar
  46. Iohara K, Imabayashi K, Ishizaka R, Watanabe A, Nabekura J, Ito M, Matsushita K, Nakamura H, Nakashima M (2011) Complete pulp regeneration after pulpectomy by transplantation of CD105+ stem cells with stromal cell-derived factor-1. Tissue Eng Part A 17:1911–1920CrossRefGoogle Scholar
  47. Ishizaka R, Iohara K, Murakami M, Fukuta O, Nakashima M (2012) Regeneration of dental pulp following pulpectomy by fractionated stem/progenitor cells from bone marrow and adipose tissue. Biomaterials 33:2109–2118CrossRefGoogle Scholar
  48. Iwaya SI, Ikawa M, Kubota M (2001) Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dent Traumatol 17:185–187CrossRefGoogle Scholar
  49. Jeeruphan T, Jantarat J, Yanpiset K, Suwannapan L, Khewsawai P, Hargreaves KM (2012) Mahidol study 1: comparison of radiographic and survival outcomes of immature teeth treated with either regenerative endodontic or apexification methods: a retrospective study. J Endod 38:1330–1336CrossRefGoogle Scholar
  50. Kahler B, Rossi-Fedele G (2016) A review of tooth discoloration after regenerative endodontic therapy. J Endod 42:563–569CrossRefGoogle Scholar
  51. Kamocki K, Nor JE, Bottino MC (2015a) Effects of ciprofloxacin-containing antimicrobial scaffolds on dental pulp stem cell viability-In vitro studies. Arch Oral Biol 60:1131–1137CrossRefGoogle Scholar
  52. Kamocki K, Nor JE, Bottino MC (2015b) Dental pulp stem cell responses to novel antibiotic-containing scaffolds for regenerative endodontics. Int Endod J 48:1147–1156CrossRefGoogle Scholar
  53. Kappes UP, Luo D, Potter M, Schulmeister K, Runger TM (2006) Short- and long-wave UV light (UVB and UVA) induce similar mutations in human skin cells. J Invest Dermatol 126:667–675CrossRefGoogle Scholar
  54. Karczewski A, Feitosa SA, Hamer EI, Pankajakshan D, Gregory RL, Spolnik KJ, Bottino MC (2018) Clindamycin-modified triple antibiotic nanofibers: a stain-free antimicrobial intracanal drug delivery system. J Endod 44:155–162CrossRefGoogle Scholar
  55. Khayat A, Monteiro N, Smith EE, Pagni S, Zhang W, Khademhosseini A, Yelick PC (2017) GelMA-encapsulated hDPSCs and HUVECs for dental pulp regeneration. J Dent Res 96:192–199CrossRefGoogle Scholar
  56. Kim JY, Xin X, Moioli EK, Chung J, Lee CH, Chen M, Fu SY, Koch PD, Mao JJ (2010) Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing. Tissue Eng Part A 16:3023–3031CrossRefGoogle Scholar
  57. Kuang R, Zhang Z, Jin X, Hu J, Gupte MJ, Ni L, Ma PX (2015) Nanofibrous spongy microspheres enhance odontogenic differentiation of human dental pulp stem cells. Adv Healthc Mater 4:1993–2000CrossRefGoogle Scholar
  58. Kuang R, Zhang Z, Jin X, Hu J, Shi S, Ni L, Ma PX (2016) Nanofibrous spongy microspheres for the delivery of hypoxia-primed human dental pulp stem cells to regenerate vascularized dental pulp. Acta Biomater 33:225–234CrossRefGoogle Scholar
  59. Larsen T, Fiehn NE (2017) Dental biofilm infections - an update. Acta Pathol Microbiol Immunol Scand 125:376–384CrossRefGoogle Scholar
  60. Latham J, Fong H, Jewett A, Johnson JD, Paranjpe A (2016) Disinfection efficacy of current regenerative endodontic protocols in simulated necrotic immature permanent teeth. J Endod 42:1218–1225CrossRefGoogle Scholar
  61. Li CH, Liao PL, Yang YT, Huang SH, Lin CH, Cheng YW, Kang JJ (2014) Minocycline accelerates hypoxia-inducible factor-1 alpha degradation and inhibits hypoxia-induced neovasculogenesis through prolyl hydroxylase, von Hippel-Lindau-dependent pathway. Arch Toxicol 88:659–671PubMedGoogle Scholar
  62. Lin J, Shen Y, Haapasalo M (2013) A comparative study of biofilm removal with hand, rotary nickel-titanium, and self-adjusting file instrumentation using a novel in vitro biofilm model. J Endod 39:658–663CrossRefGoogle Scholar
  63. Mandras N, Roana J, Allizond V, Pasqualini D, Crosasso P, Burlando M, Banche G, Denisova T, Berutti E, Cuffini AM (2013) Antibacterial efficacy and drug-induced tooth discolouration of antibiotic combinations for endodontic regenerative procedures. Int J Immunopathol Pharmacol 26:557–563CrossRefGoogle Scholar
  64. Martin G, Ricucci D, Gibbs JL, Lin LM (2013) Histological findings of revascularized/revitalized immature permanent molar with apical periodontitis using platelet-rich plasma. J Endod 39:138–144CrossRefGoogle Scholar
  65. Martin DE, De Almeida JF, Henry MA, Khaing ZZ, Schmidt CE, Teixeira FB, Diogenes A (2014) Concentration-dependent effect of sodium hypochlorite on stem cells of apical papilla survival and differentiation. J Endod 40:51–55CrossRefGoogle Scholar
  66. Monteiro N, Thrivikraman G, Athirasala A, Tahayeri A, Franca CM, Ferracane JL, Bertassoni LE (2018) Photopolymerization of cell-laden gelatin methacryloyl hydrogels using a dental curing light for regenerative dentistry. Dent Mater 34:389CrossRefGoogle Scholar
  67. Mooney DJ, Powell C, Piana J, Rutherford B (1996) Engineering dental pulp-like tissue in vitro. Biotechnol Prog 12:865–868CrossRefGoogle Scholar
  68. Nagata JY, Soares AJ, Souza-Filho FJ, Zaia AA, Ferraz CC, Almeida JF, Gomes BP (2014) Microbial evaluation of traumatized teeth treated with triple antibiotic paste or calcium hydroxide with 2% chlorhexidine gel in pulp revascularization. J Endod 40:778–783CrossRefGoogle Scholar
  69. Nakashima M, Iohara K (2011) Regeneration of dental pulp by stem cells. Adv Dent Res 23:313–319CrossRefGoogle Scholar
  70. Nakashima M, Iohara K, Murakami M, Nakamura H, Sato Y, Ariji Y, Matsushita K (2017) Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study. Stem Cell Res Ther 8:61CrossRefGoogle Scholar
  71. Niu X, Liu Z, Hu J, Rambhia KJ, Fan Y, Ma PX (2016) Microspheres assembled from chitosan-graft-poly(lactic acid) micelle-like core-shell nanospheres for distinctly controlled release of hydrophobic and hydrophilic biomolecules. Macromol Biosci 16:1039–1047CrossRefGoogle Scholar
  72. Nosrat A, Li KL, Vir K, Hicks ML, Fouad AF (2013) Is pulp regeneration necessary for root maturation? J Endod 39:1291–1295CrossRefGoogle Scholar
  73. Owens KW, Yukna RA (2001) Collagen membrane resorption in dogs: a comparative study. Implant Dent 10:49–58CrossRefGoogle Scholar
  74. Palasuk J, Kamocki K, Hippenmeyer L, Platt JA, Spolnik KJ, Gregory RL, Bottino MC (2014) Bimix antimicrobial scaffolds for regenerative endodontics. J Endod 40:1879–1884CrossRefGoogle Scholar
  75. Petrino JA, Boda KK, Shambarger S, Bowles WR, McClanahan SB (2010) Challenges in regenerative endodontics: a case series. J Endod 36:536–541CrossRefGoogle Scholar
  76. Porter ML, Munchow EA, Albuquerque MT, Spolnik KJ, Hara AT, Bottino MC (2016) Effects of novel 3-dimensional antibiotic-containing electrospun scaffolds on dentin discoloration. J Endod 42:106–112CrossRefGoogle Scholar
  77. Radomska-Lesniewska DM, Skopinska-Rozwska E, Malejczyk J (2010) The effect of clindamycin and lincomycin on angiogenic activity of human blood mononuclear cells. C Eur J Immunol 35:217–222Google Scholar
  78. Ruparel NB, Teixeira FB, Ferraz CC, Diogenes A (2012) Direct effect of intracanal medicaments on survival of stem cells of the apical papilla. J Endod 38:1372–1375CrossRefGoogle Scholar
  79. Saghiri MA, Asatourian A, Sorenson CM, Sheibani N (2015) Role of angiogenesis in endodontics: contributions of stem cells and proangiogenic and antiangiogenic factors to dental pulp regeneration. J Endod 41:797–803CrossRefGoogle Scholar
  80. Selwitz RH, Ismail AI, Pitts NB (2007) Dental caries. Lancet 369:51–59CrossRefGoogle Scholar
  81. da Silva LA, Nelson-Filho P, da Silva RA, Flores DS, Heilborn C, Johnson JD, Cohenca N (2010) Revascularization and periapical repair after endodontic treatment using apical negative pressure irrigation versus conventional irrigation plus triantibiotic intracanal dressing in dogs’ teeth with apical periodontitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:779–787CrossRefGoogle Scholar
  82. Sousa FF, Luzardo-Alvarez A, Perez-Estevez A, Seoane-Prado R, Blanco-Mendez J (2010) Development of a novel AMX-loaded PLGA/zein microsphere for root canal disinfection. Biomed Mater 5:055008CrossRefGoogle Scholar
  83. Verma P, Nosrat A, Kim JR, Price JB, Wang P, Bair E, Xu HH, Fouad AF (2017) Effect of residual bacteria on the outcome of pulp regeneration in vivo. J Dent Res 96:100–106CrossRefGoogle Scholar
  84. Vishwanat L, Duong R, Takimoto K, Phillips L, Espitia CO, Diogenes A, Ruparel SB, Kolodrubetz D, Ruparel NB (2017) Effect of bacterial biofilm on the osteogenic differentiation of stem cells of apical papilla. J Endod 43:916–922CrossRefGoogle Scholar
  85. Wang X, Thibodeau B, Trope M, Lin LM, Huang GT (2010) Histologic characterization of regenerated tissues in canal space after the revitalization/revascularization procedure of immature dog teeth with apical periodontitis. J Endod 36:56–63CrossRefGoogle Scholar
  86. Wang Z, Shen Y, Haapasalo M (2012) Effectiveness of endodontic disinfecting solutions against young and old Enterococcus faecalis biofilms in dentin canals. J Endod 38:1376–1379CrossRefGoogle Scholar
  87. Widbiller M, Eidt A, Lindner SR, Hiller KA, Schweikl H, Buchalla W, Galler KM (2018) Dentine matrix proteins: isolation and effects on human pulp cells. Int Endod J 51:e278CrossRefGoogle Scholar
  88. Windley W 3rd, Teixeira F, Levin L, Sigurdsson A, Trope M (2005) Disinfection of immature teeth with a triple antibiotic paste. J Endod 31:439–443CrossRefGoogle Scholar
  89. Zaleckiene V, Peciuliene V, Brukiene V, Drukteinis S (2014) Traumatic dental injuries: etiology, prevalence and possible outcomes. Stomatologija 16:7–14PubMedGoogle Scholar
  90. Zhu W, Zhu X, Huang GT, Cheung GS, Dissanayaka WL, Zhang C (2013) Regeneration of dental pulp tissue in immature teeth with apical periodontitis using platelet-rich plasma and dental pulp cells. Int Endod J 46:962–970CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Dentistry, Health Science InstituteFederal University of Juiz de ForaGovernador ValadaresBrazil
  2. 2.Department of Cariology, Restorative Sciences, and EndodonticsUniversity of Michigan School of DentistryAnn ArborUSA

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