Does Apical Papilla Survive and Develop in Apical Periodontitis Presence after Regenerative Endodontic Procedures?
, João Martins 1, Patrícia Diogo 1, Diana Sequeira 1,2,3,4, João Carlos Ramos 5, Aníbal Diogenes 6 and João Miguel Santos 1Round 1
Reviewer 1 Report
The case reports have been described well, with the support of CBTC and periapical endoral radiographs with controls up to 5 years. Moreover in the second case report the authors report the histological images in support of their thesis.
Only a few additions are recommended
1) Add a subchapter on endodontic apical regeneration procedures, present in the scientific literature with the results obtained.
-Expand with a sub-chapter what is written from the 66-70 line, adding more information in the literature on clinical cases with the results obtained from the different case reports.
- describe in detail the Regenerative endodontic procedures present in the scientific literature
- Specify if the procedure (Regenerative endodontic procedures) adopted by the authors differs from the other clinical cases present in the literature, specify how it differs, justifying the relative modifications of the method with bibliographic references.
2) discussion : Add a sentence on how the results obtained from the 2 case reports differ or are confirmed by the different clinical studies in the literature; if there have been changes in the procedures(Regenerative endodontic procedures), justify the different or equal results by providing a coherent motivation with the data present in the literature ( Yang et al, . Gibson et al)
Author Response
The case reports have been described well, with the support of CBTC and periapical endoral radiographs with controls up to 5 years. Moreover in the second case report the authors report the histological images in support of their thesis.
Only a few additions are recommended
1) Add a subchapter on endodontic apical regeneration procedures, present in the scientific literature with the results obtained.
-Expand with a sub-chapter what is written from the 66-70 line, adding more information in the literature on clinical cases with the results obtained from the different case reports.
- describe in detail the Regenerative endodontic procedures present in the scientific literature
Authors: We added more information at the beginning of the introduction. “The clinical protocol of regenerative endodontic procedures for immature permanent teeth with noninfected and infected necrotic pulps in humans varies considerably mostly in terms of concentrations of sodium hypochlorite irrigant and intracanal medication in all published studies. There is no standard protocol of REPs thus the American Association of Endodontists, as well as the European Society of Endodontics, suggests Clinical Guidelines for a regenerative procedure which was adapted in both case reports hereby described (1, 2).”
- Specify if the procedure (Regenerative endodontic procedures) adopted by the authors differs from the other clinical cases present in the literature, specify how it differs, justifying the relative modifications of the method with bibliographic references.
Authors: Thank you for the valuable suggestions provided. We expect to be able to fulfil your concerns. We did include the rationale for this option in the new document.
2) discussion : Add a sentence on how the results obtained from the 2 case reports differ or are confirmed by the different clinical studies in the literature; if there have been changes in the procedures(Regenerative endodontic procedures), justify the different or equal results by providing a coherent motivation with the data present in the literature ( Yang et al, . Gibson et al)
Authors: We accepted the suggestion and reformulated the reference to the figures in the text, trying to make a better connection between both.
Please see the attachment of the new manuscript.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Significant English correction is required. The abstract-alone had the following concerns. Consider grammar correction software such as Grammarly as some of these errors are basic.
Page 1, line 2: could you make sure the title is formatted correctly – it breaks lines prematurely.
Line 18. Regenerative shouldn’t be in bold.
Line 20. Consider comma after WHICH and comma after DEVELOPMENT
Line 21. The goal of THESE?
Line 24. 11 YEAR old
Line 25. AN intra canal medication followed by A blood clot
Line 25. The 5-year follow-up.
Line 27. Please reword.
Line 29. Please correct grammar – it’s in abbreviated english
Line 30. Not a complete sentence
Line 31. THE presence
Line 32. THE present report.
Page 1, line 2: could you make sure the title is formatted correctly – it breaks lines prematurely.
Line 18. Regenerative shouldn’t be in bold.
Line 20. Consider comma after WHICH and comma after DEVELOPMENT
Line 21. The goal of THESE?
Line 24. 11 YEAR old
Line 25. AN intra canal medication followed by A blood clot
Line 25. The 5-year follow-up.
Line 27. Please reword.
Line 29. Please correct grammar – it’s in abbreviated english
Line 30. Not a complete sentence
Line 31. THE presence
Line 32. THE present report.
Please consider quoting systematic reviews on success and complications such as staining.
When you say “confirmed with paper points at 15mm”, is that the working length or the location of vital tissue within the root canal?
If you don’t discuss it later, please discuss why you chose 3% NaOCl
Probably a good idea to include the CaOH concentration as you say the concentration of everything else.
“17mm into the root canal and placed 2mm..” implies you placed it 17mm into the tooth, and then 2mm further. But you possibly said the working length was 15mm so I’m guessing you mean that the 17mm includes the 2mm past the apex. Please reword.
Please include TM and ® where product names are named
Line 109 – what was the temporary restoration material?
Line 111 – Figure 1E is ABSENT, please add.
Line 122 – 2.5% or 3% NaOCl – the % seems to have changed.
Line 151 – bioceramic
Was there no instrumentation or irrigant activation ? Upon reflection, do you believe this could have contributed to the failure of the apical barrier?
Line 160 – why did you use naocl to remove medicament, not edta ?
Please note that the procedure is , as defined by the AAE, an MTA apical plug, rather than apexification. You haven’t ‘created an apex’ with MTA.
Please explain why you waited 12 minutes - the so called setting time of MTA, yet decided to used a cotton pellet. And why a dry one instead of a damp one? What was the temporary material?
Line 176. The composite was used to build what?
Line 189. Are you sure it’s a failed previous REP? the radiopacity on figure 3b extends to the apex so it looks like a failed obturation – possibly with a bioceramic material – but not a REP.
Line 194 – I’m unable to see the descriptor for image H.. G needs to be bold.
Figure 4. consider changing the letters in the pictures. You have letters to describe the sequence of pictures AND the reference
Line 225. Is a cyst, an example of a PARL, also a ‘highly vascularised granulomatous tissue’ ?
**If the patient had the dental trauma when she was 14, the central incisor should have already had full root development. You may be looking at a horizontal root fracture that lead to the apical portion forming. Not an immature tooth that later had apical formation despite failed REP. Please check this.
Do you know the type of dental trauma?
-apical surgery performed after some time after orthograde MTA placement is novel. This can be discussed further as it makes the paper more unique.
Author Response
Significant English correction is required. The abstract-alone had the following concerns. Consider grammar correction software such as Grammarly as some of these errors are basic.
Page 1, line 2: could you make sure the title is formatted correctly – it breaks lines prematurely.
Authors: The formatting was performed by the journal itself, in which case a formatting problem occurred. This will be addressed in the next formatting by this Journal.
Line 18. Regenerative shouldn’t be in bold.
Authors: The same problem, and it is now corrected in the manuscript.
Line 20. Consider comma after WHICH and comma after DEVELOPMENT
Authors: This is now corrected in the manuscript.
Line 21. The goal of THESE?
Authors: This is now corrected in the manuscript.
Line 24. 11 YEAR old
Authors: This is now corrected in the manuscript.
Line 25. AN intra canal medication followed by A blood clot
Authors: This is now corrected in the manuscript.
Line 25. The 5-year follow-up.
Authors: This is now corrected in the manuscript.
Line 27. Please reword.
Authors: This phrase was reworded in the manuscript “Case 2, a 16-year-old girl was referred for endodontic treatment of tooth 21. Parents mention a previous dental trauma (non-specified on the patient records) on tooth 21 at age 7. The dental historic show a previous attempt of REPs and presence of a long-standing sinus tract”.
Line 29. Please correct grammar – it’s in abbreviated English
Authors: This grammar error was corrected in the manuscript.
Line 30. Not a complete sentence
Authors: This sentence was corrected in the manuscript.
Line 31. THE presence
Authors: This is now corrected in the manuscript.
Line 32. THE present report.
Authors: This is now corrected in the manuscript.
Please consider quoting systematic reviews on success and complications such as staining.
Authors: We appreciate this consideration, and we include the systematic reviews of the Kahler et al. JOE 2017, Tong et al. JOE 2017, and He et al. Scientific Reports 2017 and inserted new details at the discussion.
When you say “confirmed with paper points at 15mm”, is that the working length or the location of vital tissue within the root canal?
Authors: It is the location of the vital tissue inside the canal.
If you don’t discuss it later, please discuss why you chose 3% NaOCl
Authors: Already inserted at the discussion “The European Society of Endodontology position statement about revitalization procedures advise the use of 1.5 – 3% sodium hypochlorite. The choice of 3% sodium hypochlorite concentration reflects the need for adequate disinfection and at the same time the preservation of the apical tissue allowing the further development of the root depicting the success of the clinical procedure in case report 1.
Probably a good idea to include the CaOH concentration as you say the concentration of everything else.
Authors: Thank you for the suggestion, it was inserted “45% Calcium Hydroxide” on the manuscript.
“17mm into the root canal and placed 2mm..” implies you placed it 17mm into the tooth, and then 2mm further. But you possibly said the working length was 15mm so I’m guessing you mean that the 17mm includes the 2mm past the apex. Please reword.
Authors: Thank you for the suggestion, it was reworded on the manuscript “Subsequently, a manual sterilized k-file (size #25, Dentsply-Maillefer, Balaigues, Switzerland) was introduced until reaching the 15 mm working length and then, deliberately pushed 2 mm beyond the working length to induce bleeding into the canal. After blood canal filling up to 2 mm short of cementoenamel junction (JAC), an absorbable hemostatic gelatin matrix (Spongostan DentalTM, MS0005, Ethicon Inc, New Jersey, EUA) was placed inside the root canal.”
Please include TM and ® where product names are named
Authors: We include these (TM and ®)products names in the manuscript.
Line 109 – what was the temporary restoration material?
Authors: The temporary restoration material was Cavit(3M, Neuss, Germany, and is now included in the manuscript.
Line 111 – Figure 1E is ABSENT, please add.
Authors: This is now correct in the manuscript
Line 122 – 2.5% or 3% NaOCl – the % seems to have changed.
Authors: Thanks for this information, this is now correct in the manuscript.
Line 151 – bioceramic
Authors: This is now correct in the manuscript.
Was there no instrumentation or irrigant activation ? Upon reflection, do you believe this could have contributed to the failure of the apical barrier?
Authors: In case 2, we used an ultrasonic tip for removal of the material inside the canal, and to active the irrigant. Also, minimal instrumentation of the canal walls with k-file was performed. This information was updated on the manuscript “ultrasonic tip (size #3, Start-XTM, Dentsply Sirona, Ballaigues Switzerland) was used to remove the hard material from the canal walls, which was similar to a bioceramic material (Figure 3C) and made activation the irrigant. After minimal manual instrumentation with K-file (size #50, Dentsply-Maillefer, Balaigues, Switzerland)”.
Line 160 – why did you use naocl to remove medicament, not edta ?
Authors: In case 2 had a history of the presence of an apical lesion with years of evolution, there was the possibility of biofilm in the apical zone. As we used ultrassonics to activate the NaOCl, we believe this action would dislodge the biofilm and remove the smear layer.
Please note that the procedure is , as defined by the AAE, an MTA apical plug, rather than apexification. You haven’t ‘created an apex’ with MTA.
Authors: We only made a one-visit apexification (Rafter JOE 2005), using a bioceramic material in the apical plug. We thank for the suggestion and we modified that on the manuscript.
Please explain why you waited 12 minutes - the so called setting time of MTA, yet decided to used a cotton pellet. And why a dry one instead of a damp one?
Authors: You're right the text is not clear so what we rewrote in the text“The excess of material from the walls was removed with paper points, a moist cotton pellet was added, and the access cavity was temporarily closed (CavitTM, 3M, Neuss, Germany). Intraoperative and postoperative radiographs were made to confirm the apical plug position”.
What was the temporary material?
Authors: In this case was used Cavit, this information was added to the manuscript.
Line 176. The composite was used to build what?
Authors: In both cases was used a resin composite (SDRTM flow and Spectrum®, DentsplyDetrey GmgH, Konstanz, Germany), we also complete in the manuscript.
Line 189. Are you sure it’s a failed previous REP? the radiopacity on figure 3b extends to the apex so it looks like a failed obturation – possibly with a bioceramic material – but not a REP.
Authors: Thanks for the suggestion, what we know was reported by the parents, they described the previous treatment as like a new treatment biological with new material…so we supposed the REPs treatment. We change in the manuscript from “REPs failure” to “endodontic treatment failure”.
Line 194 – I’m unable to see the descriptor for image H.. G needs to be bold.
Authors: It was inserted on the manuscript.
Figure 4. consider changing the letters in the pictures. You have letters to describe the sequence of pictures AND the reference
Authors: Thanks for the suggestion, we made the suggested changes in the manuscript.
Line 225. Is a cyst, an example of a PARL, also a ‘highly vascularised granulomatous tissue’ ?
Authors: This lesion is a periradicular granuloma, so we made the changes in the manuscript.
**If the patient had the dental trauma when she was 14, the central incisor should have already had full root development. You may be looking at a horizontal root fracture that lead to the apical portion forming. Not an immature tooth that later had apical formation despite failed REP. Please check this.
Do you know the type of dental trauma?
Authors: The history of trauma occurred when the patient was 7-year-old, and for that the root with very thin canal walls and wide canal. We do not know the type of trauma in this case. But our rationale is that the total separation may be because of the fact that apical papilla and HERS are loosely attached to the apex so they can be easily detached by infection, mechanical trauma, iatrogenic factors, or as a result of the anterior treatment (Palma, P. 2017 JOE).
-apical surgery performed after some time after orthograde MTA placement is novel. This can be discussed further as it makes the paper more unique.
Authors: Thanks for the suggestion, we add more information on the manuscript.
Description of Case 2 “After root-end resection (~2 mm), the previous Biodentineplug was inspected under magnification - nor voids nor chromogenic pigmentation or discoloration detected - as well as mechanically tested with a probe to evaluate its resistance and the lack of voids.”
Discussion“ It is important to refer that even after the apexification procedure there was no signs of periapical healing - pain, swelling as well as a fistula were present after 2 weeks of the apical plug. The persistence of apical infection might be explained by the presence of an extraradicular biofilm - as shown by the histologic slides after the apical surgery - which was not removed by the intraradicular disinfection procedures (19). As reported by Siqueira et al. (36)biofilms adhered to the apical root surface (extraradicular biofilms) have been a possible cause of post-treatment apical periodontitis.”
Please see the attachment of the new version of the manuscript.
Author Response File: Author Response.pdf
Reviewer 3 Report
Interesting two case reports,
Minor concerns
Check for typos, especially in Title and abstract.
Check reference’s format.
Why different materials (MTA, Biodentine) in the case reports?
What is the novelty of this paper? Please clarify in the appropriate section
Author Response
Check for typos, especially in Title and abstract.
Authors: Thank you for the valuable suggestions provided. We expect to be able to fulfil your concerns in the new manuscript, the changes are highlighted.
Check reference’s format.
Authors: We made the changes in the manuscript.
Why different materials (MTA, Biodentine) in the cases reports?
Authors: There was no particular reason, just the availability at that time. Knowing the current indications and our studies (Ramos JOE 2016, Palma JFB 2019), we recommend the use of Biodentine, mainly for medium-term colour stabilization. “ However, it is known that Biodentinehas significant potential to stimulate TGF-b1 release from the root dentin with similar effects to the irrigation with EDTA which explains our material choice of Biodentine over MTA (34). These high levels of TGF-b1 were explained by alkaline property (high pH levels of Biodentine) on solubilize of dentin matrix. On the clinical case 2, an apexification procedure with an apical plug of Biodentine was the treatment of choice. Furthermore, Biodentine can enable restore in the same session (Palma, Materials 2018), however, in this case, the restoration was performed in a second appointment.”
What is the novelty of this paper? Please clarify in the appropriate section
Authors: Thanks for the question, we described in the manuscript “The present case reports support survival and continued potential differentiation of the apical papilla after endodontic infection” and“The literature documenting follow-up of REPs teeth beyond 18 months is limited, and its long-term effects and full impact in a young patient remain unknown (20). In this case report, we show the follow up of 2 cases at 5 years and their respectively radiographic and clinical success. Despite the loss of pulp vitality with the development of a chronic abscess in both presented clinical cases, a successful outcome with the resolution of the symptoms and tooth survival was achieved.”
Please see the attachment of the new manuscript.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The authors have made the suggested changes in the manuscript.
Author Response
The authors have made the suggested changes in the manuscript.
Authors: Thank you for your valuable review and help to improve the quality of the manuscript.
Reviewer 2 Report
Abstract: Would be good to fully state what SCAP stands for
*May be better to change sentence to The apical papilla (SCAPs) plays an important role in physiologic root development and may also contribute to further root development during REPs.
You can use “REP” as a singular term. So in the sentence beginning with “In the first case…” you can change REPs to REP.
“Parents mentions..” Should be “The parents of the patient recalled..”
What is “dental historic” - and are you sure it’s an REP and not a bioceramic obturation.. Possibly a full bioceramic obturation.
“..can be seen on the preoperative x-ray” should be “could be seen on the preoperative X-ray”
What is a “control appointment”?
“The surgical procedure was performed” should be “Apical surgery was performed”.
The subsequence sentence does not need to state apical surgery. Ie. “root fragment collected showed the presence..”
“The clinical protocol of REPs differs mostly in terms of concentrations of sodium hypochlorite irrigant and intracanal medication in human published studies.” This may be better stated after listing the AAE and ESE guidelines and to clarify that the AAE and ESE guidelines (possibly) differ.
“One of the goals of this approach..” replace “this” with REP because the reader cannot be 100% sure that you are referring to REP approach in general or only specific to your case.
“HERS together with the apical papilla are..” Should be ““HERS, together with the apical papilla, are..”
Should be ‘Sensibility tests’ , not sensitivity tests.
‘Positive vertical and lateral percussion’ should be ‘pain with vertical and lateral percussion’.
‘Radigraphically Figure 1A..’ Should be “Radiographically, the root canal..” With Figure 1A referenced at the end of the sentence.
I don’t understand what is “intracanal retention”
No need for ‘a’ before ‘REP was performed’.
Replace accomplished with achieved.
Don’t need to say a before rubber dam. If you used Grammarly - it can sometimes be incorrect when referring to technical things.
Replaced access cavity was achieved to accesss cavity was prepared.
Use a full stop after ‘inside the root canal’. Start a new sentence and explain what was confirmed. I am assuming the working length but initially I thought you meant that you confirmed there was pulp tissue present using a paperpoint (and I don’t know how you would do that).
No need to say ‘a’ rubber dam - can just say rubber dam.
After blood filled the canal up to 2mm
Cementoenamel junction should be CEJ.
… was placed into the root canal, forming a blood clot.
Once you list the details of a product once, eg. Cavit TM (3M etc). In all remaining text you can just say Cavit. You don’t need to state the full details.
Did you place Cavit directly onto the MTA? Did you wet the cavit before placement? Did you place a cotton pellet?
Better to not say apexification and go straight to stating an apical plug with biodentine (brand details) was elected. Biodentine doesn’t create an apex. It creates an apical plug. Please refer to the AAE glossary to clarify.
-historic papers did call MTA apical barrier as apexification but it’s commonly not accepted to call it MTA apexifcation.
After accessing the pulp chamber
“..made activation the irrigant.” does not make sense.
Are you sure you only placed 3mm? A lot of biodentine appears to be remaining after the apical surgery.
Postoperative radiographs were taken to confirm
“..same Endodontist” should be ‘same endodontist’
I believe it’s an ‘air impact’ handpiece, not ‘air impacted’.
Replace ‘was built’, with ‘was placed’. Was it placed into the root canal structure above the apical barrier all the way to the incisal edge??
Legends shouldn’t be in the text. (a) to (f) and (gt) don’t need to be stated as it’s already clarified in Figure 4’s information.
In Figure 4 (A) - I cannot see (p) in the figure. Dont’ mention a letter if you’re not listing the letter.
You can still say there’s pulp in the foramina, but don’t have the letter unless the figure is actually in the figure.
I noticed you spelt “hematoxilin” - did you mean hematoxylin?
Discussion
When you say Kahler et al (21) e He et al (22) - please note that the English word for ‘and’ is ‘and’ and not ‘e’.
Please correct your paragraphing for ‘In case 1’
“Control in a supplement” does not make sense
Consider using a different word instead of ‘besides’.
Did you expand what ERM stands for? I didn’t spot it.
If you don’t mention PDLSCs more than once, there’s no need to abbreviate it.
Don’t say and/.or. Just say and
You can just say ‘our research group showed 79%’. No need to say ‘in an experimental study’. Having a reference makes it obvious that a study was performed and published.
Correct the paragraphing starting with ‘concerning..’ And the paragraphs after.
Please correct the grammar for the sentence starting with ‘in the first case report’. Especially around ‘is possible once MTA show even greater colour change’..
Studies that used MTA directly on blood clots..
You can abbreviate the European Society of Endo earlier as ESE as you list it more than once. But also make sure you show the abbreviation next to the first instance of its use.
The paragraph that says ‘it should be emphasised’.. is confusing. You are not performing a REP. So there’s no need discuss EDTA and REP here. You are performing an apical barrier. Please consider removing the discussion of EDTA for the second case.
No need to say biodentine can be restored in the same session as some papers show MTA can be restored in the same session too. It doesn’t add to the article
confirm not conform the results observed in a study BY Yang
conclusion: Are you sure you can make this conclusion?
It is possible that your 2nd case was a horizontal root fracture where the apex stayed vital and hence continued to develop. While the coronal section was necrotic. The necrosis of the coronal section is separate to the vital apical fragment. It may not be associated with any REP attemps.
References
You can find a better link to the AAE regenerative endo document
Check reference 6,11 regarding sentence case capitalisation
:
—
Other things,
I don’t understand why you call radiographs “control radiographs”. Just call it a radiograph.
I noticed there’s an inconsistent italicisation of et al. Please make sure it’s consistent and correct with the journal.
Would be good to make sure the red arrow in figure 3 isn’t on the root tip as it makes it harder to see that it grew
Actually, you should call it MTA apical barrier - rather than MTA apical plug. I checked the AAE glossary.
Author Response
Authors: Thanks a lot for the valuable suggestions provided and help to improve the quality of the manuscript. We expect to be able to fulfil your concerns. We did include the rationale for these options in the new document. the new changes are highlighted in blue.
Abstract: Would be good to fully state what SCAP stands forMay be better to change sentence to The apical papilla (SCAPs) plays an important role in physiologic root development and may also contribute to further root development during REPs.
Authors: This sentence is now corrected in the manuscript.
You can use “REP” as a singular term. So in the sentence beginning with “In the first case…” you can change REPs to REP.
Authors: This is now corrected in the manuscript.
“Parents mentions..” Should be “The parents of the patient recalled..”
What is “dental historic”
Authors: Dental historyis now corrected in the manuscript.
- and are you sure it’s an REP and not a bioceramic obturation. Possibly a full bioceramic obturation.
Authors:Dental history here is used as the patient files sent by the general dentist through the parents. Even though its not mentioned on the file which material was used, the general dentist state he had “attempt to do a regenerative procedure”.
“..can be seen on the preoperative x-ray” should be “could be seen on the preoperative X-ray”
Authors: This is now corrected in the manuscript.
What is a “control appointment”?
Authors: This is now corrected in the manuscript.“After 2-weeks, the patient was recalled for a follow-upappointment presenting spontaneous pain, swelling, and sinus tract.”
“The surgical procedure was performed” should be “Apical surgery was performed”.
Authors: This is now corrected in the manuscript.
The subsequence sentence does not need to state apical surgery. Ie. “root fragment collected showed the presence..”
Authors: This is now corrected in the manuscript.
“The clinical protocol of REPs differs mostly in terms of concentrations of sodium hypochlorite irrigant and intracanal medication in human published studies.” This may be better stated after listing the AAE and ESE guidelines and to clarify that the AAE and ESE guidelines (possibly) differ.
Authors: There is no considerable differences between both of the guidelines except for the NaOCl concentration - AAE advise 1,5% and ESE 1,5-3% - and the type of file used to induce bleeding into the canal - H40 or K file - 2mm over the WL. So we add this sentence the manuscript “There is no standard protocol of REPs hence the American Association of Endodontists (AAE) as well as the European Society of Endodontology (ESE), suggests Quality Clinical Guidelines for a regenerative procedure which was adapted in both of the cases reports hereby described (1, 2). The clinical protocol of REPs differs mostly in terms of concentrations of sodium hypochlorite irrigant, intracanal medication, the method to induce the bleeding and the use of biological matrices (Table 1)”.
“One of the goals of this approach..” replace “this” with REP because the reader cannot be 100% sure that you are referring to REP approach in general or only specific to your case.
Authors: This is now corrected in the manuscript.
“HERS together with the apical papilla are..” Should be ““HERS, together with the apical papilla, are..”
Authors: This is now corrected in the manuscript.
Should be ‘Sensibility tests’ , not sensitivity tests.
Authors: This is now corrected in the manuscript.
‘Positive vertical and lateral percussion’ should be ‘pain with vertical and lateral percussion’.
Authors: This is now corrected in the manuscript.
‘Radigraphically Figure 1A..’ Should be “Radiographically, the root canal..” With Figure 1A referenced at the end of the sentence.
Authors: This is now corrected in the manuscript.
“I don’t understand what is “intracanal retention”
Authors: We mean possibility of restoring the tooth without intracanal post. This correction was added to the text.
No need for ‘a’ before ‘REP was performed’.
Authors: This is now corrected in the manuscript.
Replace accomplished with achieved.
Authors: This is now corrected in the manuscript.
Don’t need to say a before rubber dam. If you used Grammarly - it can sometimes be incorrect when referring to technical things.
Authors: This is now corrected in all manuscript.
Replaced access cavity was achieved to access cavity was prepared.
Authors: This is now corrected in the manuscript.
Use a full stop after ‘inside the root canal’. Start a new sentence and explain what was confirmed. I am assuming the working length but initially I thought you meant that you confirmed there was pulp tissue present using a paperpoint (and I don’t know how you would do that).
Authors: This is now corrected in the manuscript as follows: “After access, the wide-open canal was observed by dental microscope (Leica M320 F12, Leica Microsystems, Heerbrugg Switzerland) with 10x magnification depicting that some vital pulp tissue remained inside the root canal. The working length was confirmed with paper points (size #80, Dentsply-Maillefer, Balaigues, Switzerland) by the presence of bleeding at 15 mm inside the canal.”
No need to say ‘a’ rubber dam - can just say rubber dam.
Authors: This is now corrected in the manuscript.
After blood filled the canal up to 2mm
Authors: This is now corrected in the manuscript.
Cementoenamel junction should be CEJ.
Authors: This is now corrected in the manuscript.
… was placed into the root canal, forming a blood clot.
Authors: This is now corrected in the manuscript.
was placed over the blood clot.
Once you list the details of a product once, eg. Cavit TM (3M etc). In all remaining text you can just say Cavit. You don’t need to state the full details.
Authors: This is now corrected in all manuscript.
Did you place Cavit directly onto the MTA? Did you wet the cavit before placement? Did you place a cotton pellet?
Authors: We add to the manuscript this sentence “After placing a moist cotton pellet over the MTA”.
Better to not say apexification and go straight to stating an apical plug with biodentine (brand details) was elected. Biodentine doesn’t create an apex. It creates an apical plug. Please refer to the AAE glossary to clarify.
-historic papers did call MTA apical barrier as apexification but it’s commonly not accepted to call it MTA apexifcation.
Authors: This is now corrected in the manuscript.
After accessing the pulp chamber
Authors: This is now corrected in the manuscript.
“..made activation the irrigant.” does not make sense.
Authors: This is now corrected in the manuscript.
Are you sure you only placed 3mm? A lot of biodentine appears to be remaining after the apical surgery.
Authors: You are right, was 5 mm, and on the surgery we only adjusted the apical portion contour, minimizing the removal of apical root structure.
Postoperative radiographs were taken to confirm
Authors: This is now corrected in the manuscript.
“..same Endodontist” should be ‘same endodontist’
Authors: This is now corrected in the manuscript.
I believe it’s an ‘air impact’ handpiece, not ‘air impacted’.
Authors: This is now corrected in the manuscript.
Replace ‘was built’, with ‘was placed’. Was it placed into the root canal structure above the apical barrier all the way to the incisal edge??
Authors: Thanks for the improvement, this “was placed” and is now corrected in the manuscript.
Legends shouldn’t be in the text. (a) to (f) and (gt) don’t need to be stated as it’s already clarified in Figure 4’s information.
Authors: This is now corrected in the manuscript.
In Figure 4 (A) - I cannot see (p) in the figure. Dont’ mention a letter if you’re not listing the letter.
You can still say there’s pulp in the foramina, but don’t have the letter unless the figure is actually in the figure.
Authors: This is now corrected in the manuscript.
I noticed you spelt “hematoxilin” - did you mean hematoxylin?
Authors: This was a misspelling. It is corrected now.
Discussion
When you say Kahler et al (21) e He et al (22) - please note that the English word for ‘and’ is ‘and’ and not ‘e’.
Authors: This is now corrected in the manuscript. We also correct the order of the references, to cite first the firstly published papers.
Please correct your paragraphing for ‘In case 1’
Authors: This is now corrected in the manuscript.
“Control in a supplement” does not make sense
Authors: This is sentence is now corrected “investigators affirmed that HERS cells are essential for controlling stem cell differentiation in a complement to cementum”.
Consider using a different word instead of ‘besides’.
Authors: This is now corrected for “Furthermore”.
Did you expand what ERM stands for? I didn’t spot it.
Authors: This is now corrected in the introduction.
If you don’t mention PDLSCs more than once, there’s no need to abbreviate it.
Authors: This is now corrected.
Don’t say and/.or. Just say and
Authors: This is now corrected.
You can just say ‘our research group showed 79%’. No need to say ‘in an experimental study’. Having a reference makes it obvious that a study was performed and published.
Authors: This is now corrected in the manuscript.
Correct the paragraphing starting with ‘concerning..’ And the paragraphs after.
Authors: This is now corrected in the manuscript.
Please correct the grammar for the sentence starting with ‘in the first case report’. Especially around ‘is possible once MTA show even greater colour change’..
Authors: This is now corrected for “In the first case-report, where REP was performed, even though there is no discoloration at the 5 years follow-up a higher risk of discoloration is still possible to occur in a longer-term follow-up”.
Studies that used MTA directly on blood clots..
Authors: This is now corrected in the manuscript.
You can abbreviate the European Society of Endo earlier as ESE as you list it more than once. But also make sure you show the abbreviation next to the first instance of its use.
Authors: This is now corrected in the manuscript.
The paragraph that says ‘it should be emphasised’.. is confusing. You are not performing a REP. So there’s no need discuss EDTA and REP here. You are performing an apical barrier. Please consider removing the discussion of EDTA for the second case.
No need to say biodentine can be restored in the same session as some papers show MTA can be restored in the same session too. It doesn’t add to the article
Authors: This is now corrected in the manuscript.
confirm not conform the results observed in a study BY Yang
Authors: These findings confirm the results observed in a study by Yang.
conclusion:
Are you sure you can make this conclusion?
Authors: Yes, we intend to keep the same conclusion, as this has already been rectified according to the first revision by the other reviewers.
It is possible that your 2nd case was a horizontal root fracture where the apex stayed vital and hence continued to develop. While the coronal section was necrotic. The necrosis of the coronal section is separate to the vital apical fragment. It may not be associated with any REP attemps.
Authors: As we had already answered in the first review, the history of trauma occurred when the patient was 7-year-old, and for that the root with very thin canal walls and wide canal. We do not know the type of trauma in this case. But our rationale is that the total separation maybe because of the fact that apical papilla and HERS are loosely attached to the apex so they can be easily detached by infection, mechanical trauma, iatrogenic factors, or as a result of the anterior treatment (Palma, P. 2017 JOE).
References
New changes are highlighted in blue.
Authors: This is now corrected in the references.
Check reference 6,11 regarding sentence case capitalisation
Authors: This is now corrected in the manuscript.
—
Other things,
I don’t understand why you call radiographs “control radiographs”. Just call it a radiograph.
Authors: This is now corrected in all manuscript.
I noticed there’s an inconsistent italicisation of et al. Please make sure it’s consistent and correct with the journal.
Authors: This is now corrected in all manuscript.
Would be good to make sure the red arrow in figure 3 isn’t on the root tip as it makes it harder to see that it grew
Authors: Thanks for the recommendation, we changed the arrow by an asterisk and its location as well.
Actually, you should call it MTA apical barrier - rather than MTA apical plug. I checked the AAE glossary.
Authors: Thank you very much, for indications you gave us for article improvement.
Author Response File: Author Response.pdf
Round 3
Reviewer 2 Report
Abstract: 37: Do you have a clinical photograph? You state there’s no discolouration with no clinical image.
39: You state previous REP here but in the main paper it talks about previous endo?
62: you can abbreviate MSCs here
Table 1: ESE first point: replace “e” with “and”
add ‘the’ before apical papilla. You can’t really say Figure 1E shows no discoloration if the figure is a radiograph and not a clinical photograph.159: check the formatting of the hyphen at A) 12 -month
188: you can say ‘Intra canal medication of 45% calcium hydroxide (Calcicur…
195: did you forget to irrigate with EDTA? (looking at line 335 it seems you can ignore this comment)
203: check your formatting – should there be a tab to start the new paragraph
231: don’t need to state the brand details on the 2ndmention of Calcicur.
334: If you say that an apical barrier was the treatment of choice, you need to clarify why.
335: the sentence regarding why EDTA was not used is difficult to understand. It seems the statement is just that EDTA was not used. Did you have a specific reason for not using it? Did you want to say that, because you used Biodentine and it helps TGF, that it was thought that EDTA was not needed ?
348, remove ‘that’ after ‘Furthermore’.
reword: change “…papilla and HERS cells…” to “papilla, HERS cells..” and change ‘several damages’ to something scientifically specific.355: reword “attributable to injure to HERS”
Also, could you replace all incidences of ‘apexification’ with apical barrier placement?
Discussion: It’s worth mentioning that you didn’t feel you need to do a retrograde filling in case 2 because you found it well condensed. Some people think that all apical surgery need a retrograde root end filling but it depends on your diagnosis – and your case had a good obturation with the disease being outside of the canal.
Author Response
Authors: Thank you for your valuable review and help to improve the quality of the manuscript.
Abstract: 37: Do you have a clinical photograph? You state there’s no discolouration with no clinical image.
Authors: In case 1 we decided do not put the clinical photograph, for this reason, we remove the sentence “no discolouration” from the abstract.
39: You state previous REP here but in the main paper it talks about previous endo?
Authors: We correct it accordingly to the main document.
62: you can abbreviate MSCs here
Authors: This is now corrected in the manuscript.
Table 1: ESE first point: replace “e” with “and”
Authors: This is now corrected in the manuscript.
add ‘the’ before apical papilla.
Authors: This is now corrected in the manuscript.
You can’t really say Figure 1E shows no discoloration if the figure is a radiograph and not a clinical photograph.
Authors: Thank you for the observation. We agree and this is now corrected in the manuscript.
159: check the formatting of the hyphen at A) 12 -month
Authors: we accepted the suggestion, this is now corrected in the manuscript.
188: you can say ‘Intra canal medication of 45% calcium hydroxide (Calcicur…
Authors: we accepted the suggestion, this is now corrected in the manuscript “45% CH - Calcicur” once it was used previously on line 116.
195: did you forget to irrigate with EDTA? (looking at line 335 it seems you can ignore this comment)
Authors: This will be answered together with line 355.
203: check your formatting – should there be a tab to start the new paragraph
Authors: This is now corrected in the manuscript.
231: don’t need to state the brand details on the 2ndmention of Calcicur.
Authors: This is now corrected in the manuscript.
334: If you say that an apical barrier was the treatment of choice, you need to clarify why.
Authors: This indication was due to the presence of wide root canal and open apex ( blunderbuss). This sentence was included in the manuscript line 334.
335: the sentence regarding why EDTA was not used is difficult to understand. It seems the statement is just that EDTA was not used. Did you have a specific reason for not using it? Did you want to say that, because you used Biodentine and it helps TGF, that it was thought that EDTA was not needed ?
Authors: Thank you for the question. This is now explained in the manuscript.
We didn’t have any specific reason to not use EDTA, we modified the sentence for “Despite this wasn’t performed by the time the case report 2 was carried out which seemed not to impact the outcome of the treatment. However, it is known that Biodentine has significant potential to stimulate TGF-b1 release from the root dentin with similar effects to the irrigation with EDTA which might have helped the successful outcome achieved”.
348, remove ‘that’ after ‘Furthermore’.
Authors: This is now corrected in the manuscript.
reword: change “…papilla and HERS cells…” to “papilla, HERS cells..” and change ‘several damages’ to something scientifically specific.
Authors: This is now corrected in the manuscript. Several damages were described in line 264. “Trauma, infection or iatrogenic factors can be responsible for apical papilla and HERS dislodgement from the main root walls”, but we can refer it again.
355: reword “attributable to injure to HERS”
Authors: This is now corrected in the manuscript.
Also, could you replace all incidences of ‘apexification’ with apical barrier placement?
Authors: This is now corrected in the manuscript.
Discussion: It’s worth mentioning that you didn’t feel you need to do a retrograde filling in case 2 because you found it well condensed. Some people think that all apical surgery need a retrograde root end filling but it depends on your diagnosis – and your case had a good obturation with the disease being outside of the canal.
Authors: we accepted the suggestion, but we prefer to add a sentence in the description of the apical surgery of the case 2. “And because this barrier was well condensed no retrograde root-end filling was done.”
Author Response File: Author Response.pdf
Round 4
Reviewer 2 Report
Page 5
Furthermore, the Endo Z is a side cutting bur. So it seems incorrect to say the access was prepared using the EndoZ. If anything, it was refined using the EndoZ and separate bur was created using a different bur. Otherwise, there’s probably no need to type the bur as endodontic access is somewhat standard.
There is mention of a vertical barrier case 1. It should be a coronal barrier
Page 7
Should the diagnosis be chronic apical abscess as there was a sinus tract?
https://www.aae.org/specialty/wp-content/uploads/sites/2/2017/07/endodonticdiagnosisfall2013.pdf
Page 8
45% CH, Calcicur – the R is missing in calcicur
Page 11
In the discussion, no need to expand SCAPs if you already define the term in the introduction.
Page 13
Create a space between (blunderbuss)(32) so it is (blunderbuss) (32)
Should say ‘Despite this, EDTA irrigation wasn’t performed when performing case report 2 as the irrigation of EDTA did not seem like it would impact the outcome of treatment.
When you say “However, it is known that Biodentine has significant potential to stimulate TGF-b1 release from the root dentin with similar effects to the irrigation with EDTA which might have helped the successful outcome achieved.” It's confusing because the case had problems after the barrier was placed. Should you really say it was a successful outcome?
“It is important to refer” Please reword.
Page 14
“HERS can survive several damages” - consider “HERS can survive several types of damage”
“associated with injury to HERS”
Last sentence of the discussion – please reword the last sentence as it’s hard to understand. Also, I believe Yang’s case is an apexification. Not an MTA barrier placement.
Fix paragraphing in conclusion
A paper you may find interesting is:
https://www.ncbi.nlm.nih.gov/pubmed/29336522
Also, did you do any pulp testing for Case 1? The case looks great on radiographs. However, it is disappointing not to know if the pulp had any responses during the healing.
Author Response
Reviewer 2
Authors: Thank you for your valuable review and help to improve the quality of the manuscript.
Furthermore, the Endo Z is a side cutting bur. So it seems incorrect to say the access was prepared using the EndoZ. If anything, it was refined using the EndoZ and separate bur was created using a different bur. Otherwise, there’s probably no need to type the bur as endodontic access is somewhat standard.
Authors: we accepted the suggestion, this is now corrected in the manuscript as “After isolation with rubber dam, restorative material and carious lesions were removed and the access cavity was performed.”
There is mention of a vertical barrier case 1. It should be a coronal barrier
Authors: This is now corrected in the manuscript.
Page 7
Should the diagnosis be chronic apical abscess as there was a sinus tract?
https://www.aae.org/specialty/wp-content/uploads/sites/2/2017/07/endodonticdiagnosisfall2013.pdf
Authors: Thank you for the observation. We agree and this is now corrected in the manuscript.
Page 8
45% CH, Calcicur – the R is missing in calcicur
Authors: This is now corrected in the manuscript.
Page 11
In the discussion, no need to expand SCAPs if you already define the term in the introduction.
Authors: This is now corrected in the manuscript.
Page 13
Create a space between (blunderbuss)(32) so it is (blunderbuss) (32)
Authors: This is now corrected in the manuscript.
Should say ‘Despite this, EDTA irrigation wasn’t performed when performing case report 2 as the irrigation of EDTA did not seem like it would impact the outcome of treatment.
Authors: Thank to improve the quality of the manuscript and this is now adding in the manuscript.
When you say “However, it is known that Biodentine has significant potential to stimulate TGF-b1 release from the root dentin with similar effects to the irrigation with EDTA which might have helped the successful outcome achieved.” It's confusing because the case had problems after the barrier was placed. Should you really say it was a successful outcome?
Authors: Thank you for the suggestion. We agree and this is now corrected in this sentence “However, it is known that Biodentine has significant potential to stimulate TGF-b1 release from the root dentin with similar effects to the irrigation with EDTA”.
“It is important to refer” Please reword.
Authors: This sentence is now corrected in the manuscript. “We should stress out, that even after the apical barrier placement there were no signs of periapical healing - pain, swelling as well as a fistula were present after 2 weeks of the apical barrier”
Page 14
“HERS can survive several damages” - consider “HERS can survive several types of damage”
“associated with injury to HERS”
Authors: Thank you for the suggestion we change the sentence for “Thus, according to our findings, it is reasonable to suggest that even when partially or completely detached from the main root, the apical papilla with HERS can survive several types of damage and preserve their potential of continuing root development”.
Last sentence of the discussion – please reword the last sentence as it’s hard to understand. Also, I believe Yang’s case is an apexification. Not an MTA barrier placement.
Authors: Thanks for the comment. And we change to the initial form submitted.
Fix paragraphing in conclusion
Authors: This is now corrected in the manuscript.
A paper you may find interesting is:
https://www.ncbi.nlm.nih.gov/pubmed/29336522
Also, did you do any pulp testing for Case 1? The case looks great on radiographs. However, it is disappointing not to know if the pulp had any responses during the healing.
Authors: We understand, but we still don't think it's a disappointment with an increase in the length and thickness of the root walls. We achieved the second goal of AAE. So far it has not been possible to have a pulp positive response to the sensitivity / electrical tests performed throughout the controls. There is a great difficulty in performing these tests when we have a large coronary restoration and a cervical barrier.
Author Response File: Author Response.pdf
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
