Int J Stomatol

Int J Stomatol ›› 2025, Vol. 52 ›› Issue (6): 738-747.doi: 10.7518/gjkq.2025065

• Cariology and Endodontics • Previous Articles     Next Articles

Research progress in regenerative endodontics for traumatized immature permanent teeth

Shuyang Zhang1(),Shunjiayi Hu2,Linlong Qi1,Xiaoyao Liang1,Shuli Deng1()   

  1. 1.Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China
    2.School of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, China
  • Received:2024-06-30 Revised:2025-02-24 Online:2025-11-01 Published:2025-10-23
  • Contact: Shuli Deng E-mail:22218752@zju.edu.cn;dengshuli@zju.edu.cn
  • Supported by:
    Grants from "Pioneer" and "Leading Goose" Research and Development Program in Zhejiang Province(2022C03060)

RichHTML

5

PDF (PC)

24

Abstract:

Trauma can easily lead to pulp necrosis and periapical periodontitis in immature permanent teeth, and the roots then stop developing. At this time, immature permanent teeth are characterized by open apical foramina, thin root canal walls, and short roots that affect their retention and function in the oral cavity. Regenerative endodontics is a treatment that can promote the continuous development of the roots of immature permanent teeth. This procedure has significant clinical significance in the healing of periapical lesions and the closure of apical foramina as well as in increasing the length of the roots and the thickness of the root canal walls. Although most studies reported a high success rate for this procedure, failure may occur, including persistent root resorption and persistent periapical inflammation. In this paper, we provide a systematic review of regenerative endodontics for traumatized immature permanent teeth in terms of the treatment process, biological rationale, clinical outcomes, and analysis of cases of treatment failure to provide theoretical basis for clinicians.

Key words: dental trauma, immature permanent teeth, pulp necrosis and periapical periodontitis, regenerative endodontics procedure

CLC Number: 

  • R781.05

TrendMD: 
[1] Hargreaves KM, Diogenes A, Teixeira FB. Treatment options: biological basis of regenerative en-dodontic procedures[J]. J Endod, 2013, 39(3 ): S30-S43.
[2] Kallel I, Douki N, Amaidi S, et al. The Incidence of complications of dental trauma and associated factors: a retrospective study[J]. Int J Dent, 2020, 2020: 2968174.
[3] Andreasen JO, Kristerson L, Andreasen FM. Da-mage of the Hertwig’s epithelial root sheath: effect upon root growth after autotransplantation of teeth in monkeys[J]. Endod Dent Traumatol, 1988, 4(4): 145-151.
[4] Andreasen JO. Pulp and periodontal tissue repair- regeneration or tissue metaplasia after dental trauma. A review[J]. Dent Traumatol, 2012, 28(1): 19-24.
[5] Lin S, Moreinos D, Wisblech D, et al. Regenerative endodontic therapy for external inflammatory lateral resorption following traumatic dental injuries: evidence assessment of best practices[J]. Int Endod J, 2022, 55(11): 1165-1176.
[6] Andreasen JO, Andreasen FM, Andersson L. Textbook and color atlas of traumatic injuries to the teeth[M]. 5th ed. New Jersey: Wiley-Blackwell, 2018.
[7] Fuss Z, Tsesis I, Lin S. Root resorption-diagnosis, classification and treatment choices based on stimulation factors[J]. Dent Traumatol, 2003, 19(4): 175-182.
[8] Andreasen JO, Hjorting-Hansen E. Replantation of teeth. Ⅰ. Radiographic and clinical study of 110 human teeth replanted after accidental loss[J]. Acta Odontol Scand, 1966, 24(3): 263-286.
[9] Hammarström L, Blomlöf L, Lindskog S. Dynamics of dentoalveolar ankylosis and associated root resorption[J]. Endod Dent Traumatol, 1989, 5(4): 163-175.
[10] Filippi A, Pohl Y, von Arx T. Treatment of replacement resorption with Emdogain-preliminary results after 10 months[J]. Dent Traumatol, 2001, 17(3): 134-138.
[11] Fouad AF. Microbiological aspects of traumatic injuries[J]. J Endod, 2019, 45(12S): S39-S48.
[12] Souza BDM, Dutra KL, Kuntze MM, et al. Incidence of root resorption after the replantation of avulsed teeth: a meta-analysis[J]. J Endod, 2018, 44(8): 1216-1227.
[13] Fouad AF. Microbial factors and antimicrobial stra-tegies in dental pulp regeneration[J]. J Endod, 2017, 43(9S): S46-S50.
[14] Andreasen FM, Pedersen BV. Prognosis of luxated permanent teeth-the development of pulp necrosis[J]. Endod Dent Traumatol, 1985, 1(6): 207-220.
[15] Antunes LS, Salles AG, Gomes CC, et al. The effectiveness of pulp revascularization in root formation of necrotic immature permanent teeth: a systematic review[J]. Acta Odontol Scand, 2016, 74(3): 161-169.
[16] Cehreli ZC, Sara S, Uysal S, et al. MTA apical plugs in the treatment of traumatized immature teeth with large periapical lesions[J]. Dent Traumatol, 2011, 27(1): 59-62.
[17] Damle SG, Bhattal H, Loomba A. Apexification of anterior teeth: a comparative evaluation of mineral trioxide aggregate and calcium hydroxide paste[J]. J Clin Pediatr Dent, 2012, 36(3): 263-268.
[18] Możyńska J, Metlerski M, Lipski M, et al. Tooth discoloration induced by different calcium silicate-based cements: a systematic review of in vitro stu-dies[J]. J Endod, 2017, 43(10): 1593-1601.
[19] Wei X, Yang M, Yue L, et al. Expert consensus on regenerative endodontic procedures[J]. Int J Oral Sci, 2022, 14(1): 55.
[20] Bourguignon C, Cohenca N, Lauridsen E, et al. International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 1. Fractures and luxations[J]. Dent Traumatol, 2020, 36(4): 314-330.
[21] Lin LM, Huang GT, Sigurdsson A, et al. Clinical cell-based versus cell-free regenerative endodontics: clarification of concept and term[J]. Int Endod J, 2021, 54(6): 887-901.
[22] Sonoyama W, Liu Y, Yamaza T, et al. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study[J]. J Endod, 2008, 34(2): 166-171.
[23] Huang GT. Pulp and dentin tissue engineering and regeneration: current progress[J]. Regen Med, 2009, 4(5): 697-707.
[24] Sonoyama W, Seo BM, Yamaza T, et al. Human Hertwig’s epithelial root sheath cells play crucial roles in cementum formation[J]. J Dent Res, 2007, 86(7): 594-599.
[25] Zeichner-David M, Oishi K, Su Z, et al. Role of Hertwig’s epithelial root sheath cells in tooth root development[J]. Dev Dyn, 2003, 228(4): 651-663.
[26] Seo BM, Miura M, Gronthos S, et al. Investigation of multipotent postnatal stem cells from human perio-dontal ligament[J]. Lancet, 2004, 364(9429): 149-155.
[27] Priya MH, Tambakad PB, Naidu J. Pulp and pe-riodontal regeneration of an avulsed permanent mature incisor using platelet-rich plasma after delayed replantation: a 12-month clinical case study[J]. J Endod, 2016, 42(1): 66-71.
[28] Tobias Duarte PC, Gomes-Filho JE, Ervolino E, et al. Histopathological condition of the remaining tissues after endodontic infection of rat immature teeth[J]. J Endod, 2014, 40(4): 538-542.
[29] Chrepa V, Pitcher B, Henry MA, et al. Survival of the apical papilla and its resident stem cells in a case of advanced pulpal necrosis and apical perio-dontitis[J]. J Endod, 2017, 43(4): 561-567.
[30] Diogenes A, Hargreaves KM. Microbial modulation of stem cells and future directions in regenerative endodontics[J]. J Endod, 2017, 43(9S): S95-S101.
[31] Lovelace TW, Henry MA, Hargreaves KM, et al. Evaluation of the delivery of mesenchymal stem cells into the root canal space of necrotic immature teeth after clinical regenerative endodontic procedure[J]. J Endod, 2011, 37(2): 133-138.
[32] Sharpe PT. Dental mesenchymal stem cells[J]. Development, 2016, 143(13): 2273-2280.
[33] Cui D, Yu S, Zhou X, et al. Roles of dental mesenchymal stem cells in the management of immature necrotic permanent teeth[J]. Front Cell Dev Biol, 2021, 9: 666186.
[34] Huang GT, Gronthos S, Shi S. Mesenchymal stem cells derived from dental tissues vs. those from o-ther sources: their biology and role in regenerative medicine[J]. J Dent Res, 2009, 88(9): 792-806.
[35] Liu Y, Gan L, Cui DX, et al. Epigenetic regulation of dental pulp stem cells and its potential in regene-rative endodontics[J]. World J Stem Cells, 2021, 13(11): 1647-1666.
[36] Xuan K, Li B, Guo H, et al. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth[J]. Sci Transl Med, 2018, 10(455): eaaf3227.
[37] Sanz JL, Forner L, Almudéver A, et al. Viability and stimulation of human stem cells from the apical papilla (hscaps) induced by silicate-based materials for their potential use in regenerative endodontics: a systematic review[J]. Materials (Basel), 2020, 13(4): 974.
[38] Trubiani O, Pizzicannella J, Caputi S, et al. Perio-dontal ligament stem cells: current knowledge and future perspectives[J]. Stem Cells Dev, 2019, 28(15): 995-1003.
[39] Ding RY, Cheung GS, Chen J, et al. Pulp revascularization of immature teeth with apical perio-dontitis: a clinical study[J]. J Endod, 2009, 35(5): 745-749.
[40] Keswani D, Pandey RK. Revascularization of an immature tooth with a necrotic pulp using platelet-rich fibrin: a case report[J]. Int Endod J, 2013, 46(11): 1096-1104.
[41] Koç S, Del Fabbro M. Does the etiology of pulp necrosis affect regenerative endodontic treatment outcomes? A systematic review and meta-analyses[J]. J Evid Based Dent Pract, 2020, 20(1): 101400.
[42] Huang F, Cheng L, Li J, et al. Nanofibrous scaffolds for regenerative endodontics treatment[J]. Front Bioeng Biotechnol, 2022, 10: 1078453.
[43] Galler KM, Buchalla W, Hiller KA, et al. Influence of root canal disinfectants on growth factor release from dentin[J]. J Endod, 2015, 41(3): 363-368.
[44] Smith AJ, Duncan HF, Diogenes A, et al. Exploiting the bioactive properties of the dentin-pulp complex in regenerative endodontics[J]. J Endod, 2016, 42(1): 47-56.
[45] Cameron R, Claudia E, Ping W, et al. Effect of a residual biofilm on release of transforming growth factor β1 from dentin[J]. J Endod, 2019, 45(9): 1119-1125.
[46] Galler KM, D’Souza RN, Federlin M, et al. Dentin conditioning codetermines cell fate in regenerative endodontics[J]. J Endod, 2011, 37(11): 1536-1541.
[47] Meza G, Urrejola D, Saint Jean N, et al. Persona-lized cell therapy for pulpitis using autologous dental pulp stem cells and leukocyte platelet-rich fibrin: a case report[J]. J Endod, 2019, 45(2): 144-149.
[48] Swaikat M, Faus-Matoses I, Zubizarreta-Macho Á, et al. Is revascularization the treatment of choice for traumatized necrotic immature teeth? A systematic review and meta-analysis[J]. J Clin Med, 2023, 12(7): 2656.
[49] Tong HJ, Rajan S, Bhujel N, et al. Regenerative en-dodontic therapy in the management of nonvital immature permanent teeth: a systematic review-outcome evaluation and meta-analysis[J]. J Endod, 2017, 43(9): 1453-1464.
[50] Friedman S, Mor C. The success of endodontic the-rapy-healing and functionality[J]. J Calif Dent Assoc, 2004, 32(6): 493-503.
[51] Conde MCM, Chisini LA, Sarkis-Onofre R, et al. A scoping review of root canal revascularization: relevant aspects for clinical success and tissue formation[J]. Int Endod J, 2017, 50(9): 860-874.
[52] Yoshpe M, Einy S, Ruparel N, et al. Regenerative endodontics: a potential solution for external root resorption (case series)[J]. J Endod, 2020, 46(2): 192-199.
[53] Kahler B, Lu J, Taha NA. Regenerative endodontic treatment and traumatic dental injuries[J]. Dent Traumatol, 2024, 40(6): 618-635.
[54] Zeng Q, Zhang J, Guo J, et al. Preoperative factors analysis on root development after regenerative endo-dontic procedures: a retrospective study[J]. BMC Oral Health, 2022, 22(1): 374.
[55] Alobaid AS, Cortes LM, Lo J, et al. Radiographic and clinical outcomes of the treatment of immature permanent teeth by revascularization or apexification: a pilot retrospective cohort study[J]. J Endod, 2014, 40(8): 1063-1070.
[56] Lin LM, Shimizu E, Gibbs JL, et al. Histologic and histobacteriologic observations of failed revascula-rization/revitalization therapy: a case report[J]. J Endod, 2014, 40(2): 291-295.
[57] Santiago CN, Pinto SS, Sassone LM, et al. Revascularization technique for the treatment of external inflammatory root resorption: a report of 3 cases[J]. J Endod, 2015, 41(9): 1560-1564.
[58] Nagata JY, Gomes BP, Rocha Lima TF, et al. Traumatized immature teeth treated with 2 protocols of pulp revascularization[J]. J Endod, 2014, 40(5): 606-612.
[59] Almutairi W, Yassen GH, Aminoshariae A, et al. Regenerative endodontics: a systematic analysis of the failed cases[J]. J Endod, 2019, 45(5): 567-577.
[60] Mittmann CW, Kostka E, Ballout H, et al. Outcome of revascularization therapy in traumatized immature incisors[J]. BMC Oral Health, 2020, 20(1): 207.
[61] Lin J, Zeng Q, Wei X, et al. Regenerative endodontics versus apexification in immature permanent teeth with apical periodontitis: a prospective randomized controlled study[J]. J Endod, 2017, 43(11): 1821-1827.
[62] Nazzal H, Duggal MS. Regenerative endodontics: a true paradigm shift or a bandwagon about to be derailed[J]. Eur Arch Paediatr Dent, 2017, 18(1): 3-15.
[63] Lee C, Song M. Failure of regenerative endodontic procedures: case analysis and subsequent treatment options[J]. J Endod, 2022, 48(9): 1137-1145.
[64] Torabinejad M, Faras H. A clinical and histological report of a tooth with an open apex treated with regenerative endodontics using platelet-rich plasma[J]. J Endod, 2012, 38(6): 864-868.
[65] Yadav P, Pruthi PJ, Naval RR, et al. Novel use of platelet-rich fibrin matrix and MTA as an apical barrier in the management of a failed revascularization case[J]. Dent Traumatol, 2015, 31(4): 328-331.
[66] Boukpessi T, Cottreel L, Galler KM. External inflammatory root resorption in traumatized immature incisors: MTA plug or revitalization? A case series[J]. Children (Basel), 2023, 10(7): 1236.
[67] Farhad Mollashahi N, Saberi E, Karkehabadi H. Evaluation of cytotoxic effects of various endodontic irrigation solutions on the survival of stem cell of human apical papilla[J]. Iran Endod J, 2016, 11(4): 293-297.
[68] Martin DE, De Almeida JF, Henry MA, et al. Concentration-dependent effect of sodium hypochlorite on stem cells of apical papilla survival and differentiation[J]. J Endod, 2014, 40(1): 51-55.
[69] Casagrande L, Demarco FF, Zhang Z, et al. Dentin-derived BMP-2 and odontoblast differentiation[J]. J Dent Res, 2010, 89(6): 603-608.
[70] Marending M, Luder HU, Brunner TJ, et al. Effect of sodium hypochlorite on human root dentine-mechanical, chemical and structural evaluation[J]. Int Endod J, 2007, 40(10): 786-793.
[71] Ring KC, Murray PE, Namerow KN, et al. The comparison of the effect of endodontic irrigation on cell adherence to root canal dentin[J]. J Endod, 2008, 34(12): 1474-1479.
[72] Taweewattanapaisan P, Jantarat J, Ounjai P, et al. The effects of EDTA on blood clot in regenerative endodontic procedures[J]. J Endod, 2019, 45(3): 281-286.
[73] 黄定明, 杨懋彬, 周学东. 牙髓再生治疗的临床操作管理及疗效评价[J]. 中华口腔医学杂志, 2019, 54(9): 584-590.
Huang DM, Yang MB, Zhou XD. Clinical management and prognosis evaluation of pulp regeneration therapy[J]. Chin J Stomatol, 2019, 54(9): 584-590.
[74] Diogenes AR, Ruparel NB, Teixeira FB, et al. Translational science in disinfection for regenerative en-dodontics[J]. J Endod, 2014, 40(4 ): S52-S57.
[75] Takushige T, Cruz EV, Asgor Moral A, et al. Endo-dontic treatment of primary teeth using a combination of antibacterial drugs[J]. Int Endod J, 2004, 37(2): 132-138.
[76] Ruparel NB, Teixeira FB, Ferraz CC, et al. Direct effect of intracanal medicaments on survival of stem cells of the apical papilla[J]. J Endod, 2012, 38(10): 1372-1375.
[77] Berkhoff JA, Chen PB, Teixeira FB, et al. Evaluation of triple antibiotic paste removal by different irrigation procedures[J]. J Endod, 2014, 40(8): 1172-1177.
[78] Yassen GH, Vail MM, Chu TG, et al. The effect of medicaments used in endodontic regeneration on root fracture and microhardness of radicular dentine[J]. Int Endod J, 2013, 46(7): 688-695.
[79] Akcay M, Arslan H, Yasa B, et al. Spectrophotome-tric analysis of crown discoloration induced by va-rious antibiotic pastes used in revascularization[J]. J Endod, 2014, 40(6): 845-848.
[80] Gelman R, Park H. Pulp revascularization in an immature necrotic tooth: a case report[J]. Pediatr Dent, 2012, 34(7): 496-499.
[81] Lei L, Chen Y, Zhou R, et al. Histologic and immunohistochemical findings of a human immature permanent tooth with apical periodontitis after regene-rative endodontic treatment[J]. J Endod, 2015, 41(7): 1172-1179.
[82] Vieira AR, Siqueira JF Jr, Ricucci D, et al. Dentinal tubule infection as the cause of recurrent disease and late endodontic treatment failure: a case report[J]. J Endod, 2012, 38(2): 250-254.
[83] Ricucci D, Siqueira JF Jr. Fate of the tissue in late-ral canals and apical ramifications in response to pathologic conditions and treatment procedures[J]. J Endod, 2010, 36(1): 1-15.
[84] Verma P, Nosrat A, Kim JR, et al. Effect of residual bacteria on the outcome of pulp regeneration in vivo [J]. J Dent Res, 2017, 96(1): 100-106.
[85] Ward CL, Sanchez CJ Jr, Pollot BE, et al. Soluble factors from biofilms of wound pathogens modulate human bone marrow-derived stromal cell differen-tiation, migration, angiogenesis, and cytokine secretion[J]. BMC Microbiol, 2015, 15: 75.
[86] Huang GT. Dental pulp and dentin tissue enginee-ring and regeneration: advancement and challenge[J]. Front Biosci (Elite Ed), 2011, 3(2): 788-800.
[87] Chen MY, Chen KL, Chen CA, et al. Responses of immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures[J]. Int Endod J, 2012, 45(3): 294-305.
[88] Cymerman JJ, Nosrat A. Regenerative endodontic treatment as a biologically based approach for non-surgical retreatment of immature teeth[J]. J Endod, 2020, 46(1): 44-50.
[89] Wang N, Liu H, Shen Y. Endodontic microsurgery for failed regenerative endodontic procedures[J]. Asian J Surg, 2023, 46(12): 6093-6094.
[90] Shimizu E, Ricucci D, Albert J, et al. Clinical, radiographic, and histological observation of a human immature permanent tooth with chronic apical abscess after revitalization treatment[J]. J Endod, 2013, 39(8): 1078-1083.
[91] Austah O, Joon R, Fath WM, et al. Comprehensive characterization of 2 immature teeth treated with regenerative endodontic procedures[J]. J Endod, 2018, 44(12): 1802-1811.
[1] Xiaoju Jiang,Jing Chen,Qin Su. Dental trauma: biological responses of pulp tissue, diagnosis, and treatment strategies [J]. Int J Stomatol, 2025, 52(5): 586-593.
[2] Jiaojiao Li,Jun Liu. Research progress on early fixed orthodontic treatment of traumatic teeth [J]. Int J Stomatol, 2024, 51(4): 498-504.
[3] Gao Huihui,Deng Shuli,He Xinmin,Hu Ji,an. Evaluation of pulp status and selection of treatment in young permanent teeth after trauma [J]. Int J Stomatol, 2021, 48(6): 675-682.
[4] Liao Wenxiao,Ma Xindi,Hong Zhiwei,Wu Xinyu,Xing Yundi,Liu Jingwei,Chen Lei. Clinical effect of surgical extrusion in the treatment of complicated crown-root fracture of anterior teeth [J]. Int J Stomatol, 2021, 48(5): 541-548.
[5] Yidi Jiang,Chenglin Wang,Ling Ye. Complications of regenerative endodontics [J]. Inter J Stomatol, 2019, 46(1): 73-77.
[6] Zhu Yuanbing, Wang Jun. Factors affecting the variation of incisor sheet thickness of a custom-made mouthguard during fabrication [J]. Inter J Stomatol, 2017, 44(5): 583-586.
[7] Lei Qiyin, Chen Ke.. Research progress on the clinical treatment of regenerative endodontics in immature permanent teeth [J]. Inter J Stomatol, 2017, 44(3): 267-272.
[8] LUO Gang, WANG Jun. The public's knowledge of children's dental trauma [J]. Inter J Stomatol, 2008, 35(6): 678-678～680.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!