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Article
Peer-Review Record

Histomorphometric and Clinical Analysis of Ridge Preservation Procedures in Extraction Sockets with Buccal Bone Defects (>5mm) Using an In Situ Hardening Biphasic Calcium Phosphate (HA/β-TCP) Graft and a Bioresorbable Matrix: A Human Study at 6 Months

Appl. Sci. 2020, 10(9), 3034; https://doi.org/10.3390/app10093034
by Fortunato Alfonsi 1,†, Niccolò Baldi 2,*,†, Stefano Romeggio 1, Paolo Tonelli 2, Giovanna Iezzi 3, Eugenio Velasco-Ortega 4 and Antonio Barone 5
Reviewer 1: Anonymous
Reviewer 2:
Appl. Sci. 2020, 10(9), 3034; https://doi.org/10.3390/app10093034
Submission received: 24 March 2020 / Revised: 21 April 2020 / Accepted: 22 April 2020 / Published: 27 April 2020
(This article belongs to the Special Issue Bio-Inspired Biodegradable Scaffold Constructs for Bone Tissue Repair)

Round 1

Reviewer 1 Report

The authors investigated the effects of HA/beta-TCP composite materials to bone regeneration in alveolar ridge loss. This paper clearly show the histological data in 6months after surgy, but the present manuscript lack the duscussion based on the observed bone cell activities. For exmaple, table 3 shows the difference between horizontal and vertical bone loss recovery after implantation, how come the difference between these two types of the loss? The authors describerd the frequency of each type of bone loss (horizontal>vertical), regarding to the topographical effects of bone materials. Discuss the findings regarding to the interaction between materials and bone cells, which can improve this manuscript. The relationship between surface topography and bone cells can be discussed by citing these current studies (For example, Biomaterials, 209 (2019) 103-110, Int J Stem Cells 12 (2019) 84-94, Journal of Biomedical Materials Research 107 (2019) 1031-1041 ). Discussion of histological evidence (Fig. 1-Fig. 5) is poor and further cellular understanding is necessary for acceptance in this journal. How come the osteocyte apoptosis (Fig.4) and how involved in the bone resorption? Discussion of the cellular mechanisms underlying the bone regeneration associated biomaterilas is mandatory.

Author Response

Dear Editor and Reviewers,

We have really appreciated your suggestions and comments.

First of all, we have rewritten the manuscript to reduce the repetition rate, mainly the “Introduction” and “Material and Methods”.

Subsequently, we have answered to reviewers explaining point-by-point the revisions.

We have modified the text accordingly with reviewer’s suggestions and integrated the discussion following the indications.

Thank you for your consideration of this manuscript.

We appreciate your time and look forward to your response Sincerely,
Dr. Niccolò Baldi

 

Author's Reply to the Review Report (Reviewer 1)

  1. Reviewer:

For exmaple, table 3 shows the difference between horizontal and vertical bone loss recovery after implantation, how come the difference between these two types of the loss? The authors describerd the frequency of each type of bone loss (horizontal>vertical), regarding to the topographical effects of bone materials.

Discuss the findings regarding to the interaction between materials and bone cells, which can improve this manuscript. The relationship between surface topography and bone cells can be discussed by citing these current studies (For example, Biomaterials, 209 (2019) 103-110, Int J Stem Cells 12 (2019) 84-94, Journal of Biomedical Materials Research 107 (2019) 1031-1041).

Author:

-Line 341-355: We modified the text accordingly with reviewer’s suggestion, the discussion was expanded.  We have added some references recommended by the reviewer. Moreover, we have discussed other histological studies in which a similar histological analysis as in our study was performed.

-Table3 and Line 390-396: In Table3, we reported the vertical and horizontal bone changes (between T0 and T1, expressed in mm and %) after ridge preservation procedures on horizontal and vertical dimension.

We modified the text accordingly with reviewer’s suggestion and we added and discussed the effect of spontaneous healing on bone remodeling after tooth extraction (references: Araujo 2005, Tan 2012) and we compared our outcomes with those from other studies in term of horizontal and vertical resorption.

 

  1. Reviewer:

Discussion of histological evidence (Fig. 1-Fig. 5) is poor and further cellular understanding is necessary for acceptance in this journal. How come the osteocyte apoptosis (Fig.4) and how involved in the bone resorption? Discussion of the cellular mechanisms underlying the bone regeneration associated biomaterilas is mandatory.

Author:

-Figure 2-6: We modified the text accordingly with reviewer’s suggestion and we added further details to the Figure Legends.

Regarding  the osteocyte apoptosis, we have better specified that  the large osteocyte lacunae were typical of newly formed bone, as reported in several papers.

(Giovanna Iezzi, Carlo Mangano, Antonio Barone, Federico Tirone, Luigi Baggi Giuliana Tromba, Adriano Piattelli, Alessandra Giuliani . Jawbone Remodeling: A Conceptual Study Based on Synchrotron High-resolution Tomography.Sci Rep  2020 Mar 2;10(1):3777.)

(Michele Cassetta, Vittoria Perrotti, Sabrina Calasso, Adriano Piattelli, Bruna Sinjari, Giovanna Iezzi. Bone formation in sinus augmentation procedures using autologous bone, porcine bone, and a 50 : 50 mixture: a human clinical and histological evaluation at 2 months. Clin. Oral Impl. Res. 26, 2015 / 1180–1184)

Reviewer 2 Report

This manuscript examined the reliability and efficacy of the ridge preservation using GUIDOR easy-graft and bioresorbable matrix barrier. 

 

There are some issues or questions to be discussed.

Line 144 The authors only mentioned custom acrylic template was used with no other information. Exact measuring location should be described as well as some figure or diagram of custom acrylic template. 

Line 156 The authors did not tell the product brand name of collagen sponge. 

Line 118~120, 211 According the exclusion criteria, smokers (more than 10 cigarettes per day) were excluded. However, three of them smoked of more than 10-cigarette/day and included for this study. You should described the reason why they were included. Also, the authors mentioned that compliance was not monitored. Is it reliable??

Line 225 What is the exact cause of infection? smoking? 

Line 264 There is no (NB) annotation in the figure.

Line 324 It is recommended to add the percent change of either AHB or AVB compared to the initial measurement. 

 

Author Response

Dear Editor and Reviewers,

We have really appreciated your suggestions and comments.

First of all, we have rewritten the manuscript to reduce the repetition rate, mainly the “Introduction” and “Material and Methods”.

Subsequently, we have answered to reviewers explaining point-by-point the revisions.

We have modified the text accordingly with reviewer’s suggestions and integrated the discussion following the indications.

Thank you for your consideration of this manuscript.

We appreciate your time and look forward to your response

Sincerely,
Dr. Niccolò Baldi

 

 

Author's Reply to the Review Report (Reviewer 2)

 

  1. Reviewer:

Line 144 The authors only mentioned custom acrylic template was used with no other information. Exact measuring location should be described as well as some figure or diagram of custom acrylic template. 

Author:

-Line 140-143, Figure 1: We modified the text accordingly with reviewer’s suggestion. We have added a figure to better illustrate the surgical template (Figure1). The surgical template was stabilized on the adjacent teeth to allow reproducible horizontal and vertical measurements at the different time points of the study. The vertical measurements were performed taking the surgical stent as reference point as shown in Figure1.

 

  1. Reviewer:

Line 156 The authors did not tell the product brand name of collagen sponge. 

Author:

-Line 156: We modified the text accordingly with reviewer’s suggestion and we added the brand name: Collafleece, Botiss Biomaterials, Berlin, Germany.

 

  1. Reviewer:

Line 118~120, 211 According the exclusion criteria, smokers (more than 10 cigarettes per day) were excluded. However, three of them smoked of more than 10-cigarette/day and included for this study. You should described the reason why they were included. Also, the authors mentioned that compliance was not monitored. Is it reliable??

Author:

-Line 213: We modified the text accordingly with reviewer’s suggestion as follows. there was a typing error made by the authors:  ”three of them smoked less than 10-cigarette/day”.

We removed from the text: “Subjects smoking <10 cigarettes per day were requested to stop smoking before and after surgery; however, their compliance was not monitored” because it was not possible for the author to evaluate patient’s compliance.

 

  1. Reviewer:

Line 225 What is the exact cause of infection? smoking? 

Author:

In 2 cases, an infection of the surgical site with prominent signs of inflammation was observed. The main responsable for surgical site infection was not attributable to any specific factor. However, the two infected sites received 0,2% chlorhexidine mouthwash therapy for the following 6 weeks after surgery, instead of 2 weeks as for the rest of experimental population.

 

  1. Reviewer:

Line 264 There is no (NB) annotation in the figure.

Author:

-Line 269: We modified the text accordingly with reviewer’s suggestion. (NB) was removed from the text.

 

  1. Reviewer:

Line 324 It is recommended to add the percent change of either AHB or AVB compared to the initial measurement. 

Author:

-Line 398, 407, Table3: We modified the text and the Table.

 A percentage of bone loss between initial and reentry values was reported: 7,4% for AHB, 14,8% for AVB.

Round 2

Reviewer 1 Report

Most of the comments I pointed out are reflected in the revised manuscript. However, some of the references I suggested are not included in the revised manuscript. (For example, Biomaterials, 209 (2019) 103-110). Pease confirm.

Author Response

Reviewer: Most of the comments I pointed out are reflected in the revised manuscript. However, some of the references I suggested are not included in the revised manuscript. (For example, Biomaterials, 209 (2019) 103-110). Pease confirm.

Author: We added the references, accordingly with reviewer’s suggestion

[24] Zhang, B.; Kasoju, N.; Li, Q.; Ma, J.; Yang, A.; Cui, Z.; Wang, H.; Ye, H. Effect of Substrate Topography and Chemistry on Human Mesenchymal Stem Cell Markers: A Transcriptome Study International Journal of Stem Cells 2019;12:84-94.

[26] Nakanishi, Y.; Matsugaki, A.; Kawahara, K; Ninomiya, T; Sawada, H; Nakano, T. Unique arrangement of bone matrix orthogonal to osteoblast alignment controlled by Tspan11-mediated focal adhesion assembly. Biomaterials 2019; 209: 103-110.

Reviewer 2 Report

Thanks for the revision.

All the points the reviewer recommended were corrected.

This manuscript is now suitable for publication.

Author Response

Reviewer Thanks for the revision. All the points the reviewer recommended were corrected.

This manuscript is now suitable for publication.

Author: Thank you for the comments and the time spent for the revision.

 

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