Effect of intracanal scaffolds on the success outcomes of Regenerative Endodontic Therapy - A systematic review and meta-analysis

Published:November 18, 2022DOI:



      The scaffolds used in regenerative endodontic therapy (RET) provide structural support for cells so that they can adhere to the scaffolds and also are crucial for cellular proliferation and differentiation. The objective of this network meta-analysis was to compare effects of different intracanal scaffolds on success outcomes of RET.


      PubMed/Medline, EMBASE, Cochrane, CINAHL, Scopus, and Web of Science databases were searched. Studies evaluating and/or comparing clinical and/or radiographic success of RET using different scaffolds with a minimum of 12 months follow-up were included. The Cochrane Collaboration risk of bias (ROB) tool and appropriate tools from Joanna Brigg’s Institute were used for the assessment of ROB. A network meta-analysis was performed to compare the primary outcome (clinical success) and other success outcomes (root maturation, and pulpal sensibility) using different scaffolds.


      Twenty-seven studies fulfilled the desired inclusion criteria of which 25 had a low ROB whereas two had a moderate ROB. Clinical success of RET using platelet-rich plasma (PRP), blood clot (BC), and platelet-rich fibrin (PRF) scaffolds ranged between 91.66%-100%, 84.61-100%, and 77-100% respectively. The different scaffolds did not show any statistically significant difference in clinical success (PRF versus BC [p=1.000], PRP versus BC [p=1.000], and PRF versus PRP [p=0.999]), apical root closure (PRF versus BC [p=1.000], PRP versus BC [p=0.835], PRF versus PRP[p=0.956]), and pulp sensibility (PRF versus BC[p=0.980], PRP versus BC [p=0.520], and PRF versus PRP, p=0.990]).


      The intracanal scaffolds used during RET did not result in significant differences in regard to clinical success, root maturation, and pulpal sensibility.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Endodontics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Diogenes A.
        • Ruparel N.B.
        • Shiloah Y.
        • Hargreaves K.M.
        Regenerative endodontics: a way forward.
        J Am Dent Assoc. 2016; 147: 372-380
        • Andreasen J.O.
        • Farik B.
        • Munksgaard E.C.
        Long-term calcium hydroxide as a root canal dressing may increase risk of root fracture.
        Dent Traumatol. 2002; 18: 134-137
        • Parirokh M.
        • Torabinejad M.
        Mineral trioxide aggregate: A comprehensive literature review-part III: clinical applications, drawbacks, and mechanism of action.
        J Endod. 2017; 36: 400-413
        • Diogenes A.
        • Henry M.A.
        • Teixeira F.B.
        • Hargreaves K.M.
        An update on clinical regenerative endodontics.
        Endod Topics. 2013; 28: 2-23
        • Lee C.
        • Song M.
        Failure of Regenerative Endodontic Procedures: Case Analysis and Subsequent Treatment Options.
        J Endod. 2022; 48: 1137-1145
        • Koç S.
        • Del Fabbro M.
        Does the Etiology of Pulp Necrosis Affect Regenerative Endodontic Treatment Outcomes? A Systematic Review and Meta-analyses.
        J Evid Based Dent Pract. 2020; 20101400
        • Fang Y.
        • Wang X.
        • Zhu J.
        • Su C.
        • Yang Y.
        • Meng L.
        Influence of Apical Diameter on the Outcome of Regenerative Endodontic Treatment in Teeth with Pulp Necrosis: A Review.
        J Endod. 2018; 44: 414-431
        • Estefan B.S.
        • El Batouty K.M.
        • Nagy M.M.
        • Diogenes A.
        Influence of Age and Apical Diameter on the Success of Endodontic Regeneration Procedures.
        J Endod. 2016; 42: 1620-1625
        • Joshi S.R.
        • Palekar A.U.
        • Pendyala G.S.
        • Mopagar V.
        • Padmawar N.
        • Shah P.
        Clinical Success of Platelet-rich Fibrin and Mineral Trioxide Aggregate (MTA) or MTA-like Agents in Healing of Periapical Lesion in Nonsurgically Treated Pulpless Immature Permanent Teeth: A Systematic Review.
        J Int Soc Prev Community Dent. 2020; 10: 379-383
        • Nagata J.Y.
        • Soares A.J.
        • Souza-Filho F.J.
        • Zaia A.A.
        • Ferraz C.C.
        • Almeida J.F.
        • et al.
        Microbial evaluation of traumatized teeth treated with triple antibiotic paste or calcium hydroxide with 2% chlorhexidine gel in pulp revascularization.
        J Endod. 2014; 40: 778-783
        • Cui D.
        • Yu S.
        • Zhou X.
        • Liu Y.
        • Gan L.
        • Pan Y.
        • et al.
        Roles of Dental Mesenchymal Stem Cells in the Management of Immature Necrotic Permanent Teeth.
        Front Cell Dev Biol. 2021; 9666186
        • Banchs F.
        • Trope M.
        Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol?.
        J Endod. 2004; 30: 196-200
        • Trope M.
        Treatment of the immature tooth with a non-vital pulp and apical periodontitis.
        Dent Clin North Am. 2010; 54: 313-324
        • Shivashankar V.Y.
        • Johns D.A.
        • Maroli R.K.
        • Sekar M.
        • Chandrasekaran R.
        • Karthikeyan S.
        • et al.
        Comparison of the Effect of PRP, PRF and Induced Bleeding in the Revascularization of Teeth with Necrotic Pulp and Open Apex: A Triple Blind Randomized Clinical Trial.
        J Clin Diagn Res. 2017; 11: ZC34-ZC39
        • Sakthivel S.
        • Gayathri V.
        • Anirudhan S.
        • Roja R.J.S.
        Platelet-rich fibrin and collagen matrix for the regeneration of infected necrotic immature teeth.
        J Clin Transl Res. 2020; 6: 1-5
        • Jiang X.
        • Liu H.
        • Peng C.
        Clinical and Radiographic Assessment of the Efficacy of a Collagen Membrane in Regenerative Endodontics: A Randomized, Controlled Clinical Trial.
        J Endod. 2017; 43: 1465-1471
        • Altaii M.
        • Richards L.
        • Rossi-Fedele G.
        Histological assessment of regenerative endodontic treatment in animal studies with different scaffolds: A systematic review.
        Dent Traumatol. 2017; 33: 235-244
        • Song F.
        • Clark A.
        • Bachmann M.O.
        • Maas J.
        Simulation evaluation of statistical properties of methods for indirect and mixed treatment comparisons.
        BMC Med Res Methodol. 2012; 12: 138
        • Hutton B.
        • Salanti G.
        • Caldwell D.M.
        • Chaimani A.
        • Schmid C.H.
        • CameronC
        • et al.
        The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.
        Ann Intern Med. 2015; 162: 777-784
        • Žižka R.
        • Belák Š.
        • Šedý J.
        • Fačevicová K.
        • Voborná I.
        • Marinčák D.
        Clinical and Radiographic Outcomes of Immature Teeth Treated with Different Treatment Protocols of Regenerative Endodontic Procedures: A Retrospective Cohort Study.
        J Clin Med. 2021; 10: 1600
        • Chrepa V.
        • Joon R.
        • Austah O.
        • Diogenes A.
        • Hargreaves K.M.
        • Ezeldeen M.
        • et al.
        Clinical Outcomes of Immature Teeth Treated with Regenerative Endodontic Procedures-A San Antonio Study.
        J Endod. 2020; 46: 1074-1084
        • Pereira A.C.
        • Oliveira M.L.
        • Cerqueira-Neto A.C.C.L.
        • Vargas-Neto J.
        • Nagata J.Y.
        • et al.
        Outcomes of traumatised immature teeth treated with apexification or regenerative endodontic procedure: a retrospective study.
        Aust Endod J. 2021; 47: 178-187
        • Lv H.
        • Chen Y.
        • Cai Z.
        • Lei L.
        • Zhang M.
        • Zhou R.
        • Huang X.
        The efficacy of platelet-rich fibrin as a scaffold in regenerative endodontic treatment: a retrospective controlled cohort study.
        BMC Oral Health. 2018; 18: 139
        • Linsuwanont P.
        • Sinpitaksakul P.
        • Lertsakchai T.
        Evaluation of root maturation after revitalization in immature permanent teeth with nonvital pulps by cone beam computed tomography and conventional radiographs.
        Int Endod J. 2017; 50: 836-846
        • Peng C.
        • Yang Y.
        • Zhao Y.
        • Liu H.
        • Xu Z.
        • Zhao D.
        • Qin M.
        Long-term treatment outcomes in immature permanent teeth by revascularisation using MTA and GIC as canal-sealing materials: a retrospective study.
        Int J Paediatr Dent. 2017; 27: 454-462
        • Peng C.F.
        • Zhao Y.M.
        • Yang Y.
        • Liu H.
        • Qin M.
        Retrospective analysis of pulp revascularization in immature permanent teeth with diffuse pulpitis.
        Zhonghua Kou Qiang Yi Xue Za Zhi. 2017; 52: 10-15
        • Silujjai J.
        • Linsuwanont P.
        Treatment Outcomes of Apexification or Revascularization in Nonvital Immature Permanent Teeth: A Retrospective Study.
        J Endod. 2017; 43: 238-245
        • Chen S.J.
        • Chen L.P.
        Radiographic outcome of necrotic immature teeth treated with two endodontic techniques: A retrospective analysis.
        Biomed J. 2016; 39: 366-371
        • Jeeruphan T.
        • Jantarat J.
        • Yanpiset K.
        • Suwannapan L.
        • Khewsawai P.
        • Hargreaves K.M.
        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. 2012; 38: 1330-1336
        • Bose R.
        • Nummikoski P.
        • Hargreaves K.
        A retrospective evaluation of radiographic outcomes in immature teeth with necrotic root canal systems treated with regenerative endodontic procedures.
        J Endod. 2009; 35: 1343-1349
        • Nosrat A.
        • Kolahdouzan A.
        • Khatibi A.H.
        • Verma P.
        • Jamshidi D.
        • Nevins A.J.
        • et al.
        Clinical, radiographic, and histologic outcome of regenerative endodontic treatment in human teeth using a novel collagen-hydroxyapatite scaffold.
        J Endod. 2019; 45: 136-143
        • Neelamurthy P.S.
        • Kumar R.A.
        • Balakrishnan V.
        • Venkatesan S.M.
        • Narayan G.S.
        • Karthikeyan I.
        Revascularization in immature and mature teeth with necrotic pulp: a clinical study.
        J Contemp Dent Pract. 2018; 19: 1394-1400
        • Jin-hui Lu
        • Qian Jun
        • Liu He
        • Zhu Jun-Xia
        Clinical study on autologous platelet-rich fibrin aided revascularization of immature permanent teeth.
        Journal of pecking university (Health sciences). 2018; 50: 672-679
        • Li J.
        • Wang E.H.
        • Wang Y.
        Effectiveness and safety of pulp regeneration and revascularization therapy for pulp necrosis of the immature permanent tooth, study protocol single center, randomized, controlled clinical trial.
        Zhongguo zuzchi gongcheng yanjiu. 2017; 21: 3809-3814
        • Liu X.
        • Yao Y.F.
        • Xu X.Y.
        Application of Nd:YAP laser in dental pulp revascularization.
        Shanghai Kou Qiang Yi Xue. 2017; 26: 628-632
        • Huang Y.
        • Chen K.
        • Zhang Y.
        • Xiong H.
        • Liu C.
        Effect of revascularization treatment of immature permanent teeth with endodontic infection.
        Nan Fang Yi Ke Da Xue Xue Bao. 2013; 33: 776-778
        • Cai W.F.
        • Li S.
        • Xie L.
        • Yao L.L.
        • Wang C.H.
        • Ren Z.H.
        Influence of age on the effectiveness of revascularization in immature permanent teeth.
        Shanghai Kou Qiang Yi Xue. 2017; 26: 545-548
        • Yang Y.
        • Peng C.F.
        • Qin M.
        Pulp revascularization of immature teeth with apical periodontitis: a clinical study.
        Zhonghua Kou Qiang Yi Xue Za Zhi. 2013; 48: 81-85
        • Chen M.Y.
        • Chen K.L.
        • Chen C.A.
        • Tayebaty F.
        • Rosenberg P.A.
        • Lin L.M.
        Responses of immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures.
        Int Endod J. 2012; 45: 294-305
        • Ding R.Y.
        • Cheung G.S.
        • Chen J.
        • Yin X.Z.
        • Wang Q.Q.
        • Zhang C.F.
        Pulp revascularization of immature teeth with apical periodontitis: a clinical study.
        J Endod. 2009; 35: 745-749
        • Alexander A.
        • Torabinejad M.
        • Vahdati S.A.
        • Nosrat A.
        • Verma P.
        • Grandhi A.
        • et al.
        Regenerative endodontic treatment in immature noninfected ferret teeth using blood clot or Synoss putty as scaffolds.
        J Endod. 2020; 46: 209-215
        • Zhou R.
        • Wang Y.
        • Chen Y.
        • Chen S.
        • Lyu H.
        • Cai Z.
        • et al.
        Radiographic, histologic, and biomechanical evaluation of combined application of platelet-rich fibrin with blood clot in regenerative endodontics.
        J Endod. 2017; 43: 2034-2040
        • Tawfik H.
        • Abu-Seida A.M.
        • Hashem A.A.
        • Nagy M.M.
        Regenerative potential following revascularization of immature permanent teeth with necrotic pulps.
        Int Endod J. 2013; 46: 910-922
        • Nageh M.
        • Ahmed G.M.
        • El-Baz A.A.
        Assessment of regaining pulp sensibility in mature necrotic teeth using a modified revascularization technique with platelet-rich fibrin: a clinical study.
        J Endod. 2018; 44: 1526-1533
        • Arslan H.
        • Ahmed H.M.A.
        • Şahin Y.
        • Doğanay Yıldız E.
        • Gündoğdu E.C.
        • Güven Y.
        • et al.
        Regenerative endodontic procedures in necrotic mature teeth with periapical radiolucencies: a preliminary randomized clinical study.
        J Endod. 2019; 45: 863-872
        • Brignardello-Petersen R.
        Outcomes of platelet concentrates for treating immature permanent teeth are acceptable but do not seem to be better than those of other techniques.
        J Am Dent Assoc. 2019; 150: e56
        • Verma P.
        Evaluation of efficacy of platelet rich plasma as a scaffold in regenerative endodontic treatment: an in-vivo study.
        J Adv Med Dent Scie Res. 2018; 6: 1-4
        • Higgins J.P.
        • Altman D.G.
        • Gøtzsche P.C.
        • Jüni P.
        • Moher D.
        • Oxman A.D.
        • et al.
        The cochrane collaboration's tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
      1. Joanna Briggs Institute (JBI). Critical appraisal tools. South Australia: The university of adelaide; 2018. Available from: [Last accessed on 2022, 30 June].

        • Jayadevan V.
        • Gehlot P.M.
        • Manjunath V.
        • Madhunapantula S.V.
        • Lakshmikanth J.S.
        A comparative evaluation of advanced platelet-rich fibrin (A-PRF) and platelet-rich fibrin (PRF) as a scaffold in regenerative endodontic treatment of traumatized immature non-vital permanent anterior teeth: a prospective clinical study.
        J Clin Exp Dent. 2021; 13: e463-e472
        • Shetty H.
        • Shetty S.
        • Kakade A.
        • Mali S.
        • Shetty A.
        • Neelakantan P.
        Three-dimensional qualitative and quantitative analyses of the effect of periradicular lesions on the outcome of regenerative endodontic procedures: a prospective clinical study.
        Clin Oral Investig. 2021; 25: 691-700
        • De-Jesus-Soares A.
        • Prado M.C.
        • Nardello L.C.L.
        • Pereira A.C.
        • Cerqueira-Neto A.C.C.L.
        • Nagata J.Y.
        • et al.
        Clinical and molecular microbiological evaluation of regenerative endodontic procedures in immature permanent teeth.
        J Endod. 2020; 46: 1448-1454
        • ElSheshtawy A.S.
        • Nazzal H.
        • El Shahawy O.I.
        • El Baz A.A.
        • Ismail S.M.
        • Kang J.
        • et al.
        The effect of platelet-rich plasma as a scaffold in regeneration/revitalization endodontics of immature permanent teeth assessed using 2-dimensional radiographs and cone beam computed tomography: a randomized controlled trial.
        Int Endod J. 2020; 53: 905-921
        • Rizk H.M.
        • Salah Al-Deen M.S.
        • Emam A.A.
        Pulp revascularization/revitalization of bilateral upper necrotic immature permanent central incisors with blood clot vs platelet-rich fibrin scaffolds- a split-mouth double-blind randomized controlled trial.
        Int J Clin Pediatr Dent. 2020; 13: 337-343
        • Uppala S.
        A comparative evaluation of PRF, blood clot and collagen scaffold in regenerative endodontics.
        European Journal of Molecular & Clinical Medicine. 2022; 9: 817-827
        • Rizk H.M.
        • Salah Al-Deen M.S.M.
        • Emam A.A.
        Comparative evaluation of platelet rich plasma (PRP) versus platelet rich fibrin (PRF) scaffolds in regenerative endodontic treatment of immature necrotic permanent maxillary central incisors: a double blinded randomized controlled trial.
        Saudi Dent J. 2020; 32: 224-231
        • Mittal N.
        • Parashar V.
        Regenerative evaluation of immature roots using PRF and artificial scaffolds in necrotic permanent teeth: A clinical study.
        J Contemp Dent Pract. 2019; 20: 720-726
        • Ragab R.A.
        • Lattif A.E.A.E.
        • Dokky N.A.E.W.E.
        Comparative study between revitalization of necrotic immature permanent anterior teeth with and without platelet rich fibrin: a randomized controlled trial.
        J Clin Pediatr Dent. 2019; 43: 78-85
        • Ulusoy A.T.
        • Turedi I.
        • Cimen M.
        • Cehreli Z.C.
        Evaluation of blood clot, platelet-rich plasma, platelet-rich fibrin, and platelet pellet as scaffolds in regenerative endodontic treatment: a prospective randomized trial.
        J Endod. 2019; 45: 560-566
        • Alagl A.
        • Bedi S.
        • Hassan K.
        • AlHumaid J.
        Use of platelet-rich plasma for regeneration in non-vital immature permanent teeth: Clinical and cone-beam computed tomography evaluation.
        J Int Med Res. 2017; 45: 583-593
        • Botero T.M.
        • Tang X.
        • Gardner R.
        • Hu J.C.C.
        • Boynton J.R.
        • Holland G.R.
        Clinical evidence for regenerative endodontic procedures: immediate versus delayed induction?.
        J Endod. 2017; 43: S75-S81
        • Chan E.K.
        • Desmeules M.
        • Cielecki M.
        • Dabbagh B.
        • Ferraz Dos Santos B.
        Longitudinal cohort study of regenerative endodontic treatment for immature necrotic permanent teeth.
        J Endod. 2017; 43: 395-400
        • Jiang X.
        • Liu H.
        • Peng C.
        Clinical and radiographic assessment of the efficacy of a collagen membrane in regenerative endodontics: a randomized, controlled clinical trial.
        J Endod. 2017; 43: 1465-1471
        • Li L.
        • Pan Y.
        • Mei L.
        • Li J.
        Clinical and radiographic outcomes in immature permanent necrotic evaginated teeth treated with regenerative endodontic procedures.
        J Endod. 2017; 43: 246-251
        • Lin J.
        • Zeng Q.
        • Wei X.
        • Zhao W.
        • Cui M.
        • Gu J.
        • et al.
        Regenerative endodontics versus apexification in immature permanent teeth with apical periodontitis: a prospective randomized controlled study.
        J Endod. 2017; 43: 1821-1827
        • Shivashankar V.Y.
        • Johns D.A.
        • Maroli R.K.
        • Sekar M.
        • Chandrasekaran R.
        • Karthikeyan S.
        • et al.
        Comparison of the effect of PRP, PRF and induced bleeding in the revascularization of teeth with necrotic pulp and open apex: a triple blind randomized clinical trial.
        J Clin Diagn Res. 2017; 11: ZC34-Z39
        • El Ashiry E.A.
        • Farsi N.M.
        • Abuzeid S.T.
        • El Ashiry M.M.
        • Bahammam H.A.
        Dental pulp revascularization of necrotic permanent teeth with immature apices.
        J Clin Pediatr Dent. 2016; 40: 361-366
        • Estefan B.S.
        • El Batouty K.M.
        • Nagy M.M.
        • Diogenes A.
        Influence of age and apical diameter on the success of endodontic regeneration procedures.
        J Endod. 2016; 42: 1620-1625
        • Sharma S.
        • Mittal N.
        A comparative evaluation of natural and artificial scaffolds in regenerative endodontics: a clinical study.
        Saudi Endod J. 2016; 6: 9-15
        • Bezgin T.
        • Yilmaz A.D.
        • Celik B.N.
        • Kolsuz M.E.
        • Sonmez H.
        Efficacy of platelet-rich plasma as a scaffold in regenerative endodontic treatment.
        J Endod. 2015; 41: 36-44
        • Narang I.
        • Mittal N.
        • Mishra N.
        A comparative evaluation of the blood clot, platelet-rich plasma, and platelet-rich fibrin in regeneration of necrotic immature permanent teeth: a clinical study.
        Contemp Clin Dent. 2015; 6: 63-68
        • Kahler B.
        • Mistry S.
        • Moule A.
        • Ringsmuth A.K.
        • Case P.
        • Thomson A.
        • et al.
        Revascularization outcomes: a prospective analysis of 16 consecutive cases.
        J Endod. 2014; 40: 333-338
        • Nagy M.M.
        • Tawfik H.E.
        • Hashem A.A.
        • Abu-Seida A.M.
        Regenerative potential of immature permanent teeth with necrotic pulps after different regenerative protocols.
        J Endod. 2014; 40: 192-198
        • Saoud T.M.
        • Zaazou A.
        • Nabil A.
        • Moussa S.
        • Lin L.M.
        • Gibbs J.L.
        Clinical and radiographic outcomes of traumatized immature permanent necrotic teeth after revascularization/revitalization therapy.
        J Endod. 2014; 40: 1946-1952
        • Shah N.
        • Logani A.
        • Bhaskar U.
        • Aggarwal V.
        Efficacy of revascularization to induce apexification/apexogensis in infected, nonvital, immature teeth: a pilot clinical study.
        J Endod. 2008; 34: 919-925
        • Santhakumar M.
        • Yayathi S.
        • Retnakumari N.
        A clinicoradiographic comparison of the effects of platelet-rich fibrin gel and platelet-rich fibrin membrane as scaffolds in the apexification treatment of young permanent teeth.
        J Indian Soc Pedod Prev Dent. 2018; 36: 65-70
        • Simonpieri A.
        • Del Corso M.
        • Sammartino G.
        • Ehrenfest D.M.
        The relevance of Choukroun’s platelet-rich fibrin and metronidazole during complex maxillary rehabilitations using bone allograft Part I: a new grafting protocol.
        Implant Dent. 2009; 18: 102-111
        • Ulusoy A.T.
        • Turedi I.
        • Cimen M.
        • Cehreli Z.C.
        Evaluation of blood clot, platelet-rich plasma, platelet-rich fibrin, and platelet pellet as scaffolds in regenerative endodontic treatment: a prospective randomized trial.
        J Endod. 2019; 45: 560-566
        • Wigler R.
        • Kaufman A.Y.
        • Lin S.
        • Steinbock N.
        • Hazan-Molina H.
        • Torneck C.D.
        Revascularization: a treatment for permanent teeth with necrotic pulp and incomplete root development.
        J Endod. 2013; 39: 319-326