Revascularization of an Immature Permanent Tooth with Periapical Periodontitis Using Concentrated Growth Factor Assisted by Erbium Laser (2940 nm) Irrigation: A Case Report

Round 1

Reviewer 1 Report

Dear Authors, your work is interesting and well organized. 
I suggest you describe, in the introduction, a new safe technique to perform active cleaning in teeth with an open apex. You can read this recent research and add this citation:

Iandolo A, Amato A, Pantaleo G, Dagna A, Ivaldi L, di Spirito F, Abdellatif D. An innovative technique to safely perform active cleaning in teeth with open apices: CAB technique.
J Conserv Dent. 2021 Mar-Apr;24(2):153-157. doi: 10.4103/jcd.jcd_42_21.

Author Response

Comments from Reviewer #1:

1.Dear Authors, your work is interesting and well organized.

Response: Thank you very much for your comments.

2. I suggest you describe, in the introduction, a new safe technique to perform active cleaning in teeth with an open apex. You can read this recent research and add this citation.

Iandolo A, Amato A, Pantaleo G, Dagna A, Ivaldi L, di Spirito F, Abdellatif D. An innovative technique to safely perform active cleaning in teeth with open apices: CAB technique.

J Conserv Dent. 2021 Mar-Apr;24(2):153-157. doi: 10.4103/jcd.jcd_42_21.

Response: Thank you very much for the suggestion. We have added this reference in our Introduction.

Author Response File: Author Response.docx

Reviewer 2 Report

The paper entitled “Revascularization of immature permanent teeth with periapical periodontitis using concentrated growth factor assisted by er4 bium laser (2940 nm) irrigation: a case report” is a contribute  that presents a case report about the effects of the revascularization of an immature permanent tooth with periapical periodontitis assisted by Er: YAG laser irrigation. Considering that there is no case report about the use of laser-assisted irrigation in revascularization, this paper, despite the low level of scientific evidence, can be of interest to the reader, as it proposes an original clinical protocol. However some corrections are required before it can be considered suitable for publication

INTRODUCTION

The introductory part of the paper is too general and brief; the revascularisation technique for treating immature apex teeth is addressed in a totally unsatisfactory manner as is the idea of applying the ER: Yag laser to improve individual response. This part of the work needs to be completely revised.

CASE REPORT

The clinical case is clearly and comprehensively described and the procedures applied are reported in detail. The supporting clinical and radiographic iconography is satisfactory.

The follow-up at 53 months is sufficient to demonstrate the success of the clinical procedure employed.

DISCUSSION

Overall, it is well structured, describes in a satisfactory manner the factors that may influence the success of the proposed clinical procedure and compares quite well with the evidence in the literature.

CONCLUSION

Conclusion section should be structured differently and report, preferably with a bulleted list, only the most relevant clinical results of the case reported.

Author Response

Comments from Reviewer #2:

1. Introduction

The introductory part of the paper is too general and brief; the revascularisation technique for treating immature apex teeth is addressed in a totally unsatisfactory manner as is the idea of applying the ER: Yag laser to improve individual response. This part of the work needs to be completely revised.

Response: Thank you very much for the suggestion. We have added more information about the revascularization technique, as well as Er: YAG laser in detail in the 2nd Paragraph of Introduction.

 

 

2. CONCLUSION

Conclusion section should be structured differently and report, preferably with a bulleted list, only the most relevant clinical results of the case reported.

Response: Thank you very much for the suggestion. We have restructured our Conclusion section. Besides, we have added the limitation and highlighted that further high-quality clinical studies are needed in our Conclusions.

Author Response File: Author Response.docx

Reviewer 3 Report

The description of the case speaks of a normal probe, however, taking into account figure 1b, this should not be the case.
In point 2.2, The pulpal diagnosis is understood, but should be specified.
Figure 1.a is very dark, would it be possible to clarify or improve it?
In line 74 the authors indicate: "The treatment plan was to use CGF to achieve revascularization", CFG is not a means of revascularization, it is an aid to it (scaffold), it should be better explained.
In line 79: "After two days, 79 under a rubber dam", the patient had two days with rubber dam???, this must be reviewed
Line 83: the method of use with the laser should be better specified: volume of NaOCl, penetration of the laser tip, irradiation time....
It is indicated that the radiation was "low energy (20 ml)," ml is not a measure of energy
The wording of the following sentence should be revised: "was applied to the middle and apical 88 thirds of the root canal for 2 weeks, and the access was restored with CavitTM."
Why was "NaOCl assisted by Er: YAG 100 laser irrigation with the PIPS procedure" performed on the second visit? should be justified. How was it controlled that the laser did not damage the cells of the apical papilla?
Figure 5b shows a very shaky X-ray plate, it is not acceptable for a publication.
On line 141: the statement: "The patient felt sensitivity 141 when we prepared the cavity, which may further indicate that this tooth had vital tissue." cannot be associated with a certainty, so it should be suppressed
Line 148 states: "The three key factors for successful revascularization are as follows: (a) an 148 effective coronal seal; (b) a matrix for tissue ingrowth; and (c) thorough disinfection of the root canal 7." This statement is based on reference 7, but it is false. Vijayaraghavan's article states the following: "The three key factors for successful revascularization are as follows: (a) an 148 effective coronal seal; (b) a matrix for tissue ingrowth;and (c) thorough disinfection of the 149 root canal 7.2 The matrix is ​​a part, but not a key factor.This part of the discussion should be rewritten.
Was the Er: YAG wavelength used together with water? (line 181), in which case a PIPS technique is not being performed.
line 195, if the smear layer is removed from the apical portion, how can it be ensured that the apical cells are not altered?
Line 201: "In our case, after 53 months, the patient responded 201 positively to not only pulp electrical testing but also cold testing." the sensitivity of the electrical test is greater than that of the cold test, so that statement cannot be accepted, that paragraph should be removed from the discussion.

There has been no correct justification for the use of laser in revascularization

One of the phases of revascularization is the induction of apical bleeding, it must be explained very well in the discussion why it was not performed in order to be able to publish the paper.

Author Response

Comments from Reviewer #3:

1. Case Report

1). The description of the case speaks of a normal probe, however, taking into account figure 1b, this should not be the case. Figure 1.a is very dark, would it be possible to clarify or improve it?

Response: Thank you very much for your kindly reminder. We checked the patient’s records and affirmed that figure 1b belonged to her. The description of the periodontal probing test was copied directly from her records in the previous manuscript. Considering this confusing point, now we have deleted the result of the periodontal probing test. Figure 1a has been revised.

 

2). In point 2.2, The pulpal diagnosis is understood, but should be specified.

Response: Thank you very much for the suggestion. Revision done.

 

3). In line 74 the authors indicate: "The treatment plan was to use CGF to achieve revascularization", CGF is not a means of revascularization, it is an aid to it (scaffold), it should be better explained

Response: Thank you very much for your reminder. We revised the description of the treatment plan and added more related information about CGF in the 2nd Paragraph of Discussion.

 

4). In line 79: "After two days, under a rubber dam", the patient had two days with rubber dam? this must be reviewed

Response: Thank you very much for the suggestion. Revision done.

 

5). Line 83: the method of use with the laser should be better specified: volume of NaOCl, penetration of the laser tip, irradiation time.... It is indicated that the radiation was "low energy (20 ml)," ml is not a measure of energy.

Response: Thank you very much for your reminder. We have specified the use of Er: YAG laser in the 2nd Paragraph of the Therapeutic Plan (2.3). Revision done.

 

6). The wording of the following sentence should be revised: "was applied to the middle and apical thirds of the root canal for 2 weeks, and the access was restored with CavitTM."

Response: Thank you very much. Revision done.

 

7). Why was "NaOCl assisted by Er: YAG 100 laser irrigation with the PIPS procedure" performed on the second visit? should be justified. How was it controlled that the laser did not damage the cells of the apical papilla? line 195, if the smear layer is removed from the apical portion, how can it be ensured that the apical cells are not altered?

Response: Thank you very much for your comments. With defined parameters, the safety of laser used in root canal disinfection with an open apex has been proved ¹, and we added this point in the 6th Paragraph of Discussion.

 

8). Figure 5b shows a very shaky X-ray plate, it is not acceptable for a publication. On line 141: the statement: "The patient felt sensitivity when we prepared the cavity, which may further indicate that this tooth had vital tissue." cannot be associated with a certainty, so it should be suppressed.

Response: Thank you very much. Revision done.

 

2. Discussion

1). Line 148 states: "The three key factors for successful revascularization are as follows: (a) an effective coronal seal; (b) a matrix for tissue ingrowth; and (c) thorough disinfection of the root canal 7." This statement is based on reference 7, but it is false. Vijayaraghavan's article states the following: "The three key factors for successful revascularization are as follows: (a) an effective coronal seal; (b) a matrix for tissue ingrowth; and (c) thorough disinfection of the root canal 7.2 The matrix is a part, but not a key factor. This part of the discussion should be rewritten.

Response: Thank you very much for your reminder. We have revised the statement about the part of the matrix and added more related information about CGF in the 2nd Paragraph of Discussion.

 

2). Was the Er: YAG wavelength used together with water? (line 181), in which case a PIPS technique is not being performed.

Response: Thank you very much for your reminder. Revision done. A PIPS technique is being performed when the fibre tip of Er:YAG is submerged in irrigant^1-3.

 

3). Line 201: "In our case, after 53 months, the patient responded positively to not only pulp electrical testing but also cold testing." the sensitivity of the electrical test is greater than that of the cold test, so that statement cannot be accepted, that paragraph should be removed from the discussion.

Response: Thank you very much for the suggestion. Revision done.

 

4). There has been no correct justification for the use of laser in revascularization

Response: Thank you very much for your reminder. We have corrected the justification for the use of laser in root canal disinfection and added the discussion about the safety of laser used in revascularization in the 6th Paragraph of Discussion.

 

5). One of the phases of revascularization is the induction of apical bleeding, it must be explained very well in the discussion why it was not performed in order to be able to publish the paper.

Response: Thank you very much for the suggestion. We failed to induce enough blood to fill the canal at first and we revised this in the 4th Paragraph of Therapeutic Plan (2.3).Besides, this point was elaborated in the 2nd Paragraph of Discussion.

References

1. Magni E, Jaggi M, Eggmann F, Weiger R, Connert T. Apical pressures generated by several canal irrigation methods: A laboratory study in a maxillary central incisor with an open apex. Int Endod J. Oct 2021;54(10):1937-1947. doi:10.1111/iej.13575
2. Kosarieh E, Bolhari B, Sanjari Pirayvatlou S, et al. Effect of Er:YAG laser irradiation using SWEEPS and PIPS technique on dye penetration depth after root canal preparation. Photodiagnosis Photodyn Ther. Mar 2021;33:102136. doi:10.1016/j.pdpdt.2020.102136
3. Jezesaek M, Jereb T, Lukb N, Tenyi A, Lukb  M, Fidler A. Evaluation of Apical Extrusion During Novel Er:YAG Laser-Activated Irrigation Modality. Photobiomodulation, photomedicine, and laser surgery. 2019;

 

Author Response File: Author Response.docx

Reviewer 4 Report

I would like to thank Authors for this interesting case report regarding the revascularization of immature permanent tooth using concentrated growth factor and erbium laser (2940 nm) irrigation.

Title

• Authors should change the terms teeth with tooth since the case report is on a single case and it is not a case series.

Introduction

• The introduction should be thoroughly revised since the background of the research has been roughly described. In my opinion it should be implemented adding some aspects such as: information about erbium laser and its functioning and application in endodontics; an in-depth description of regenerative endodontics (advantages and limitation) and the revascularization protocols; the use of concentrated growth factor (advantages, protocols and limitations).
• The cited references are not sufficient, they should be implemented.

Case Report

• Kindly provide the acceptation and the reference number of the ethic committee approval and specify in the manuscript the obtainment of the Informed Consent by patient or parents for sharing the case.
• Kindly specify at which classification the Authors were referring to “Tooth mobility 60 was categorized as class I.”.
• Was anaesthesia performed? If yes, kindly specify the used technique and molecule.
• “After two days, 79 under a rubber dam, the necrotic pulp tissue was chemically debrided using 30 ml 0.5% 80 sodium hypochlorite (NaOCl) assisted by Er: YAG laser irrigation with the photon-in-81 duced photoacoustic streaming (PIPS) procedure”. Why was not the WL established before irrigation protocol? At which depth from the coronal reference was the needle inserted?
• Kindly provide more information about the used centrifuge.
• “The tooth was restored using glass-ionomer cement” Why was the restoration performed immediately after MTA placement? Would not it be better to use “bioceramic” putty sealer?
• Was the canal instrumented? Why did the Authors decide to not stimulate the apical region to fill the canal with blood?

Results

Ok

Discussion

Kindly discuss the limitation of the current research, highlighting the possible future research (for example a RCT on the comparison between no laser and laser activation).

Author Response

Response to Reviewer 4 Comments

Comments from Reviewer #4:

1. I would like to thank Authors for this interesting case report regarding the revascularization of immature permanent tooth using concentrated growth factor and erbium laser (2940 nm) irrigation.

Response: Thank you very much for your comments.

 

2. Title

Authors should change the terms teeth with tooth since the case report is on a single case and it is not a case series.

Response: Thank you very much for the suggestion. Revision done.

 

3. Introduction

The introduction should be thoroughly revised since the background of the research has been roughly described. In my opinion it should be implemented adding some aspects such as: information about erbium laser and its functioning and application in endodontics; an in-depth description of regenerative endodontics (advantages and limitation) and the revascularization protocols; the use of concentrated growth factor (advantages, protocols and limitations).

The cited references are not sufficient, they should be implemented.

Response: Thank you very much for the suggestion. We have added related studies^1-4 in Introduction.

 

4. Case Report

1). Kindly provide the acceptation and the reference number of the ethic committee approval and specify in the manuscript the obtainment of the Informed Consent by patient or parents for sharing the case.

Response: Thank you very much for the suggestion. We have supplied the reference number of the ethic committee approval in the Informed Consent Statement.

 

2). Kindly specify at which classification the Authors were referring to “Tooth mobility was categorized as class I.”

Response: Thank you very much for the suggestion. Revision done.

 

3). Was anaesthesia performed? If yes, kindly specify the used technique and molecule.

Response: Thank you very much. We did not perform anesthesia during the whole procedure.

 

4). “After two days, under a rubber dam, the necrotic pulp tissue was chemically debrided using 30 ml 0.5% 80 sodium hypochlorite (NaOCl) assisted by Er: YAG laser irrigation with the photon-in- duced photoacoustic streaming (PIPS) procedure”. Why was not the WL established before irrigation protocol? At which depth from the coronal reference was the needle inserted?

Response: Thank you very much for your reminder. According to the guideline of European Society of Endodontology ⁵, the key points of revitalization procedures include minimal or no instrumentation of the dentinal walls. Therefore, we did not perform mechanical instrumentation and establish WL before the irrigation protocol. And we have added this point in the 2nd Paragraph of Therapeutic Plan (2.3).

 

5). Kindly provide more information about the used centrifuge.

Response: Thank you very much for the suggestion. Revision done.

 

6). “The tooth was restored using glass-ionomer cement” Why was the restoration performed immediately after MTA placement? Would not it be better to use “bio-ceramic” putty sealer?

Response: Thank you very much for the suggestion. It is better to use “bio-ceramic” putty sealer and not performed the restoration immediately after MTA placement. Meantime, it is acceptable to perform the restoration immediately after MTA placement ⁶. Unfortunately, MTA was the only available capping material at that time.

 

7) Was the canal instrumented? Why did the Authors decide to not stimulate the apical region to fill the canal with blood?

Response: Thank you very much. The root canal was only chemically debrided without mechanical instrumentation. We failed to induce enough blood to fill the canal at first. Revision done.

 

5. Discussion

Kindly discuss the limitation of the current research, highlighting the possible future research (for example a RCT on the comparison between no laser and laser activation).

Response: Thank you. Thank you very much for the suggestion. We have added the limitation and highlighted that further high-quality clinical studies are needed in our Conclusions.

 

 

 

 

References

1. Magni E, Jaggi M, Eggmann F, Weiger R, Connert T. Apical pressures generated by several canal irrigation methods: A laboratory study in a maxillary central incisor with an open apex. Int Endod J. Oct 2021;54(10):1937-1947. doi:10.1111/iej.13575
2. Cheng J, Yang F, Li J, Hua F, He M, Song G. Treatment Outcomes of Regenerative Endodontic Procedures in Traumatized Immature Permanent Necrotic Teeth: A Retrospective Study. J Endodont. 2022;
3. Ulusoy AT, Turedi I, Cimen M, Cehreli ZC. 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. May 2019;45(5):560-566. doi:10.1016/j.joen.2019.02.002
4. Iandolo A, Amato A, Pantaleo G, et al. An innovative technique to safely perform active cleaning in teeth with open apices: CAB technique. Journal of Conservative Dentistry : JCD. 2021;24:153 - 157.
5. Galler KM, Krastl G, Simon SRJ, et al. European Society of Endodontology position statement: Revitalization procedures. Int Endod J. 2016;49 8:717-23.
6. Staffoli S, Plotino G, Torrijos BGN, et al. Regenerative Endodontic Procedures Using Contemporary Endodontic Materials. Materials. Mar 19 2019;12(6)

 

Author Response File: Author Response.docx

Round 2

Reviewer 3 Report

The corrections have been well made, but in the description of the case it is still not explained why an induction of the apical bleeding was not performed.

Author Response

Response to Reviewer 3 Comments

Comments from Reviewer #3:

The corrections have been well made, but in the description of the case it is still not explained why an induction of the apical bleeding was not performed.

Response: Thank you very much for your kindly reminder.

We planned to induce apical bleeding at first but failed to invoke enough blood clots into canal system. Previous study indicated that unfavourable REPs outcomes were related to inducing inadequate bleeding ^1-4. Therefore, we applied CGF as scaffold materials to compensate for the lack of formation of high-quality blood clots.

We have revised this point in the description of the case in the 4th Paragraph (lines 120-122) of Therapeutic Plan (2.3): “After failing to induce enough blood into the canal system by over-instrumenting, a 9 ml sample of whole venous blood was drawn from the patient’s forearm (right median cubital vein)” . Besides, this point was elaborated in the 2nd Paragraph of Discussion (lines 168-174).

 

 

References

1. 1. Nosrat A, Seifi A, Asgary S. Regenerative Endodontic Treatment (Revascularization) for Necrotic Immature Permanent Molars: A Review and Report of Two Cases with a New Biomaterial. Journal of endodontics. 2011;37(4):562-7. doi: 10.1016/j.joen.2011.01.011.
2. 2. Ding RY, Cheung GSP, Chen J, Yin XZ, Wang QQ, Zhang CF. Pulp Revascularization of Immature Teeth with Apical Periodontitis: A Clinical Study. Journal of endodontics. 2009;35(5):745-9. doi: 10.1016/j.joen.2009.02.009.
3. 3. Cehreli ZC, Sara S, Aksoy B. Revascularization of immature permanent incisors after severe extrusive luxation injury. Journal (Canadian Dental Association). 2012;78:c4.
4. 4. Petrino JA, Boda KK, Shambarger S, Bowles WR, McClanahan SB. Challenges in regenerative endodontics: a case series. Journal of endodontics. 2010;36(3):536-41. doi: 10.1016/j.joen.2009.10.006.

 

 

Author Response File: Author Response.docx

Reviewer 4 Report

Thank for your correction. In my opinion the manuscript could be accepted for publication.

Author Response

Comments from Reviewer #4:

Thank for your correction. In my opinion the manuscript could be accepted for publication.

Response: Thank you very much for your comments.

Author Response File: Author Response.docx