Review Article

The Four Pillars for Successful Regenerative Therapy in Endodontics: Stem Cells, Biomaterials, Growth Factors, and Their Synergistic Interactions

Table 3

Published randomized clinical trials.

Authors and number of citeStudy titleInstitutionSample size (teethAgeEtiology/type toothIntracanal irrigationIntracanal medicationGroupsFollow-up timeRadiographic evaluationSuccess/survivalMain findingsVitality test

Brizuela et al.“Cell-Based Regenerative Endodontics for Treatment of Periapical Lesions: A Randomized, Controlled Phase I/II Clinical Trial”Centro “Activa Biosilicate Technology™” de Investigación en Biología y Regeneración Oral (CIBRO), Faculty of Dentistry, Universidad de los Andes, Santiago, Chile36p (36 Mt)16-58 yTrauma 96.7% (A) Dens evaginatus 3.3% (A)25% NaOCl 17% EDTACalcium hydroxideExp (13p/13t): REP/BC-UC-MSCs in PPP-biodentine Control (13p/13t): RC/GP6-12 m2D x-ray and 3D-CBCT6 m: 94.4% (100%) 12 m: 100% (100%)No difference between groups except for the anterior posterior healing improved for the exp. group. Increase positives vitality responses for exp groupCold 56%, hot test 28%, EPT 50% at 12 m
ElSheshtawy et al.“The Effect of Platelet-Rich Plasma as a Scaffold in Regeneration/Revitalization Endodontics of Immature Permanent Teeth Assessed Using 2-Dimensional”Department of Endodontics, Faculty of Dentistry, Cairo University, Cairo, Egypt26p (31 It)8.3-12.1 yTrauma 96.7% (A) Dens evaginatus 3.3% (A)5.25% NaOCl 2.5% NaOCl 17% EDTATAP 1:1:1Exp (13p/13t): PRP/MTA Control (13p/13t): BC/MTA3-6-9-12 m2D x-ray and 3D-CBCT87% (100%)No difference between groups except for the influence of the diameter of the periapical lesion100% negative response
Xuan et al.“Deciduous Autologous Tooth Stem Cells Regenerate Dental Pulp after Implantation into Injured Teeth”Department of Endodontics, Faculty of Dentistry, Health Sciences University, İstanbul, Turkey MS-State Key Laboratory, School of Stomatology, Fourth Military Medical University, Xi’an, China36p (36 It)18-30 yTrauma 100% (A)3% NaOCl 5% EDTACalcium hydroxide/iodoformExp (26t): RET/hDPSC/MTA Control (10t): Apx/Ca(OH)1-2-3-6-9-12-24 m2D x-ray and 3D-CBCT100% (100%)Significant difference in root lengthNegative EPT test at 6 and 12 m but increase blood vessels formation
Ulusoy et al.“Evaluation of Blood Clot, Platelet-Rich Plasma, Platelet-Rich Fibrin, and Platelet Pellet as Scaffolds in Regenerative Endodontic Treatment: A Prospective Randomized Trial”Department of Pediatric Dentistry, Hacettepe University, Ankara Hacettepe University, Istanbul Okan University, Turkey Louisiana State University Health Sciences Center, New Orleans, Louisiana88p (88t)8-11 yTrauma 100% (A)5.25% NaOCl 2.5% NaOCl 17% EDTATAP 1:1:1Exp1 (18t): PRP scaffold Exp2 (17t): PRF scaffold Exp3 (17t): PP scaffold Control (21t): BC scaffold1-3-6-9-12-15-18 m2D x-ray95.6%/100%There was no statistically significant difference in periapical healing, apical closure, but dentinal wall thickening and root length were significant for the BC group86% positive response to EPT in all groups
Lin et al.“Regenerative Endodontics Versus Apexification in Immature Permanent Teeth with Apical Periodontitis: A Prospective Randomized Controlled Study”Dentistry, Operative Dentistry and Endodontics, Department of Radiology, Department of Medical Statistics and Epidemiology, Sun Yat-sen University, Guangzhou, Guangdong, China Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou1036-16 yDens evaginatus 67% (P) Trauma 33% (A)1.5% NaOCl 0.9% saline 17% EDTATAP 0.1 mg/ml with clindamycinExp: 67t REP (21t T-A, 48t DE-P)
Control: 34t apex MTA (13t T-A, 21t DE-P)
3-6-9-12 m2D x-ray and 3D-CBCTRET 89.8% (100%) Apex MTA 97% (100%)There was statistically significant difference in success rate for the RET group between the DE and trauma cases. The etiology is considered an important factor for successN/A
Jiang et al.“Clinical and Radiographic Assessment of the Efficacy of a Collagen Membrane in Regenerative Endodontics: A Randomized, Controlled Clinical Trial”Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China40p (43t)8.3-12.1yTrauma 24% (A) Dens evaginatus 76% (P)1.5% NaOCl 17% EDTACalcium hydroxideExp (20p/22t): Bio-Gide collagen membrane at mid root/MTA Control (20p/21t): no membrane/MTA6 months2D x-ray100%No difference between groups except for the increase in the mid third wall thickness on experimental groupExperiment group 33% (+ EPT) Control group 18% (+ EPT)
Bezgin et al.“Efficacy of Platelet-Rich Plasma as a Scaffold in Regenerative Endodontic Treatment”Department of Pedodontics, Faculty of Dentistry, Ankara University, Ankara, Turkey20p (22t)7-13 yTrauma 70% (A) Caries 30% (P)2.5% NaOCl 0.12% CHX 5% EDTA Sterile salineTAP 1:1:1 with cefaclorExp (11t): PRP scaffold Control (11t): BC scaffold1-3-6-9-12-15-18 m2D x-ray95.6%/100%There was no statistically significant difference in periapical healing, apical closure, but dentinal wall thickening between groupsExperiment group 50% (+ EPT and + cold) Control group 20% (+ EPT and cold test)
Nagata et al.“Traumatized Immature Teeth Treated with 2 Protocols of Pulp Revascularization”Department of Restorative Dentistry, Endodontics Area, State University of Campinas-UNICAMP, Piracicaba, São Paulo, Brazil23p (23t)7-17 yTrauma 100% (A)6% NaOCl 5% sodium thiosulfate 2% chlorhexidine 17% EDTA 5% Tween 80 0.07% soy lecithinCHP 2% or TAP 1:1:1Exp (11p/11t): CHP calcium hydroxide and 2% chlorhexidine Control (12p/12t): TAP1-3-6-9-12-15-19 m2D x-ray95.6%/100%There was no statistically significant difference in periapical healing, apical closure, and dentinal wall thickening between groups but CHP show less discolorationIn both groups no recovery of sensitivity
Nagy et al.“Regenerative Potential of Immature Permanent Teeth with Necrotic Pulps after Different Regenerative Protocols”Department of Endodontics, Faculty of Dentistry, Ain Shams University, Cairo, Egypt36p (36t)9-13 yN/A, 100% (A)2.6% NaOClTAP 1:1:1Exp (12p/12t): hydrogel bFGF Control (12p/12t): blood clot Control (12p/12t): MTA apical plug3-6-12-18 m2D x-ray80%/100%There was no statistically significant difference in periapical healing, apical closure, and dentinal wall thickeningN/A
Jadhav et al.“Revascularization with and without Platelet-Rich Plasma in Nonvital, Immature, Anterior Teeth: A Pilot Clinical Study”Department of Conservative Dentistry and Endodontics, Institute of Medical Sciences, New Delhi, India20p (20t)15-28 yN/A2.5% NaOClTAP 1:1:1Exp (10p/10t): PRP and metronidazole collagen (Metrogene) Control (10p/10t): blood clot6-12 m2D x-ray100%/80%There was a statistically significant difference in periapical healing, apical closure, and dentinal wall thickeningN/A