F1000Research F1000Research 2046-1402 F1000 Research Limited London, UK 10.12688/f1000research.144522.2 Study Protocol Articles How effective is dentin autograft for socket preservation and implant site preparation: A systematic review protocol.

[version 2; peer review: 2 approved]

 Sivaraman Karthik Conceptualization Data Curation Formal Analysis Investigation Methodology Project Administration Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 1 Rajwar Eti Data Curation Investigation Methodology Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0002-8339-218X 2 3 Chopra Aditi Conceptualization Data Curation Formal Analysis Methodology Resources Software Supervision Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0003-4805-5943 a 4 Cherukara George Conceptualization Data Curation Formal Analysis Methodology Resources Supervision Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0001-6014-4290 5 Mehrotra Shubhankar Data Curation Methodology Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing 4 Datta Namrata Conceptualization Formal Analysis Methodology Resources Software Visualization Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0001-5609-5481 4 Koshy Bindhu Methodology Supervision Validation Writing – Original Draft Preparation Writing – Review & Editing 6 Department of Prosthodontics, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India The George Institute for Global Health India, New Delhi, Delhi, 110025, India Public Health Evidence South Asia, Department of Health Information, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India Department of Periodontology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India School of Dentistry, University of Dundee, Dundee, Scotland, UK Specialist Referral Practice, Regents Street, BUPA Dental Care, Bristol, UK aditi.chopra@manipal.edu

No competing interests were disclosed.

 1 8 2024 2024 13 204 29 7 2024 Copyright: © 2024 Sivaraman K et al. 2024 This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background

Socket preservation is a surgical procedure aimed at preserving the dimensions of the alveolar bone following tooth extraction. It is performed by filling the extraction socket with bone graft material with or without a barrier membrane. Recently, dentine obtained from extracted teeth has been tried as an autograft for socket preservation. Studies have compared the use of dentin to other bone grafts, however, systematic reviews evaluating the efficacy of dentin for socket preservation are limited. Hence, this systematic review protocol is proposed to generate evidence on the efficacy of dentin as a viable alternative to other bone graft materials for socket preservation.

 Methods

This systematic review protocol was prepared according to the Methodological Expectations of the Cochrane Intervention Reviews (MECIR) guidelines. It will be conducted using the Cochrane Handbook for Systematic Review of Interventions. PubMed, Scopus, Web of Science, EMBASE, Epistemonikos, Cochrane Central, and EBSCO databases and clinical trial registries, will be searched for all randomized controlled trials (RCTs) and non-randomized studies that have used autologous dentin graft (either in particulate/putty, or/matrix form) for socket preservation. The radiographic and clinical assessment of bone and soft tissue healing of the preserved sockets along with patient-related outcomes following surgery will be assessed. The risk of bias assessment of the RCTs and Non-RCTs will be assessed using the ‘Cochrane Risk of Bias assessment tool (ROB II) and ROBINS-I respectively. The certainty of evidence will be assessed by the GRADE approach.

 Discussion

This evidence is important for dental clinicians and the public to make an informed decision when choosing graft material for socket preservation. The extracted teeth are considered biological waste; however, this evidence provides scope for using a less invasive autograft for bone regenerative procedures.

 Systematic review registration

PROSPERO: CRD42021201958 (Registered on 15/02/2021).

 Dentin Bone Bone graft Implants Tooth Extraction Socket preservation Regeneration Healing Autograft Periodontal surgery The author(s) declared that no grants were involved in supporting this work. Amendments from Version 1

The new version contains the following changes: 1. As suggested by the reviewers, the inclusion of studies where implants are placed in patients with medically compromised conditions (such as Diabetes) or smokers has been mentioned in the eligibility criteria. 2. The year of published articles (2000 and above) to be included in the review has been added.  3. We have also included the subgroup analysis which can be performed based on the age, gender, systemic/ medical condition of the patient, and clinical condition of the site of socket preservation.

 List of abbreviations BMP

Bone morphogenic protein

 CI

Confidence interval

 DDM

Demineralized dentin matrix

 ECM

Extracellular matrix proteins

 GF

Growth factors

 GRADE

Grading of Recommendations, Assessment, Development, and Evaluation

 NRS

Numeric Rating Scale

 OR

Odds ratio

 POWF

Pulsed oscillation waveform

 PRISMA P

Preferred Reporting Items for Systematic Review and Meta-analysis Protocols

 RCT

Randomized controlled trial

 RFA

Radiofrequency analysis

 RR

Risk ratio

 TGF-β

Transforming growth factor

 VAS

Visual Analog Scale

 Introduction

Dental implants are increasingly being used as a promising modality for replacing missing teeth with superior biological, functional, and aesthetic properties. 1 However, one of the important requirements for placing implants is the presence of favorable volume and architecture of the available bone at the time of placement. Many times, adequate bone height and width may not be present to place an implant owing to resorption of the alveolar ridge following extraction. 2 – 5 Approximately 29 to 63% of horizontal bone loss and 11 to 22% of vertical bone loss occur within the first six months following tooth extraction. 6 The crest of the alveolar ridge also shifts lingually with more bone loss occurring in the buccolingual dimension (4.5 to 6.1 mm) compared to mesiodistal dimensions. 7 – 14 This reduction in bone volume and thinning of the buccal cortical plates affects the overlying soft tissues, and in turn affects the esthetic, phonetic, and functional outcomes after prosthetic rehabilitation. 10 – 14 Studies have noted that a loss of 2.46 to 4.56 mm ridge width occurs at sites without socket preservation compared to a reduction of 1.14 to 2.5 mm in preserved socket sites. 15 – 25 Additionally, preserving sockets immediately following extraction reduces the need for additional ridge augmentation procedures at the time of implant placement by five times when compared to unassisted socket healing. 26 – 28 Studies have also noted that approximately 20.8 % of non-preserved sockets need additional grafting for implant placement compared to only 9.9 % of preserved sockets. 28 – 35 Thus, to prevent the inevitable resorption of the alveolar ridge, reduce the physiologic bone loss, and retain the volume and quality of bone and associated soft tissue profile, sockets are preserved with bone grafts with and without barrier membranes. 15 – 24

Sockets can be preserved with either an autograft, xenograft, allograft, or alloplasts. Among all these bone grafts, autografts have the highest bone regenerative potential. 20 – 22 Autografts can be harvested from edentulous ridges, extraction sockets, mandibular ramus, symphysis, maxillary tuberosity, tibia, iliac crest, and calvarium. 20 However, procuring autograft is difficult and requires superior clinical skills. Additionally, many patient-related complications, such as post-operative infection, root resorption, ankylosis, and increased patient morbidity have been noted with the use of autografts. 20 – 24 To overcome these limitations novel bone graft materials with osteogenic potential are being researched.

Recently, whole tooth, enamel, and dentin have been tried as autograft material for various surgical procedures. 23 – 42 Among these dentin autografts are being used owing to their high osteoinductive potential. The composition, physical, and chemical properties of dentin are also similar to that of alveolar bone. 30 Dentin also contains insulin-like growth factor, bone morphogenetic protein (BMP), and transforming growth factor-beta (TGF-β) which promotes bone regeneration. 25 – 29 It is available in three forms: demineralized dentin matrix, partially demineralized dentin matrix, and un-demineralized dentin. Dentin bone graft is used for various periodontal and oral surgical procedures such as sinus lift, periodontal defects, ridge augmentation, socket preservation for implant placement, and the treatment of peri-implantitis. 26 – 42 However, there are still various uncertainties and limited systematic reviews related to its use for socket preservation compared to other bone graft materials. The PubMed search with the keyword dentin bone graft yielded only six systematic reviews, with none comparing dentin to other bone graft materials for socket preservation. There is limited data that quantitatively substantiate whether sockets preserved with dentin bone graft are better than those preserved with other bone graft material. Additionally, the understanding of the effect of dentin bone graft on the nature of bone healing and soft tissue healing around the preserved sockets, stability of implants placed in the sockets preserved with dentin, and postoperative complications after using dentin are limited. Thus, this systematic review aims to synthesize evidence on the effectiveness and efficacy of dentin autograft as a graft material for socket preservation compared to allograft, alloplast, and xenograft materials. This evidence is crucial for clinicians, patients, and other stakeholder groups in making evidence-based choices regarding the use of dentin as a bone graft material.

Focus question

How effective is dentin autograft compared to other bone graft material (autograft, allograft, xenograft, and alloplast) for socket preservation?

 Objectives Primary objective

To assess the clinical and radiographic changes in the height and width (in mm) of the extraction sockets preserved with dentin autograft (particulate/putty) compared to allograft, alloplast, and xenograft materials.

 Secondary objectives

To evaluate and compare the clinical and radiographic change in the quality of bone and soft tissue healing in sockets preserved with dentin bone graft compared to sockets preserved with other bone grafts (allograft, alloplast, or xenograft).

To assess and compare the details of the type of dentin bone graft used, method of application, duration of surgical procedure, patient’s compliance, and time of surgery with dentin bone graft compared to sockets preserved with other bone graft (allograft, alloplast or xenograft).

To assess and report prognosis and any adverse events/effects or postoperative complications associated with the use of dentin autografts for sockets preservation.

Methods

The proposed systematic review will be conducted according to the Cochrane Handbook for the Systematic Review of Interventions, 43 Methodological Expectations of the Cochrane Intervention Reviews (MECIR) guidelines 44 and the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) checklist. 45 , 48 The systematic review protocol has been registered in the International Prospective Register of Systematic Review PROSPERO with registration number - CRD42021201958 on 15/02/2021. Differences between the protocol and the final review, if any, because of the methodological alterations due to the unavailability of data, will be reported in the final review.

Criteria for considering studies for the proposed systematic review

The eligibility criteria are described using the Participant-Intervention-Comparison-Outcome-Study Design (PICOS) framework, which also indicates the key components of the research question.

Types of participants

For the proposed systematic review, studies with participants who are above 18 years of age and have undergone a socket preservation procedure following tooth extraction will be included. Any studies where implants were placed in patients with systemic diseases such as controlled diabetes, smokers, and cardiovascular, renal, respiratory, and neurological disorders, etc. will be included.

Studies with participants who have or have not received any dental implants, either at the time of socket preservation or following socket preservation will also be included. Participants who have undergone tooth extraction because of any of the following reasons will be included: unrestorable tooth due to caries or fracture; avulsion of a tooth following trauma; root resorption (internal or external); tooth fracture that cannot be restored; endodontic infection or periodontal disease that cannot be addressed with endodontic and periodontal therapy; failure of root canal treatment, a tooth with grade III mobility and more than 50% bone loss, Grade IV furcation defect (based on Glickman classification) with through and through bone defect that cannot be regenerated and needs an extraction.

Following exclusion criteria will be followed:

Studies with participants suffering from conditions or diseases that might impair bone healing or metabolism, for example, osteoporosis, vitamin D deficiency, and use of anti-resorptive therapy such as bisphosphonates.

Studies with participants who use tobacco products, areca nut, gutka, or supari, as smoking. The above factors may influence the uptake of the graft material and or dental implants and hence have been used as exclusion criteria.

Studies with participants undergoing chemotherapy or radiation therapy as these treatment modalities compromise angiogenesis and impair bone healing.

Types of interventions

Studies, where the extraction sockets are preserved with any form of dentin bone graft (demineralized, partially demineralized, or not demineralized) in any form (particulate/putty/matrix/gel), size, or application method with or without a barrier membrane will be included. Studies, where the extraction sockets are preserved with dentin (any particle size) and compared to other bone grafts such as other autografts, alloplasts, allografts, and xenografts with a minimum follow-up of three months will be included. Since bone healing requires a minimum of three months, studies providing a three-month follow-up will be included. Studies where implants are placed immediately following socket preservation will also be included. Studies with both infected and non-infected sockets will be included. Studies where the whole tooth was used as a graft material, will not be considered.

Types of comparators

Studies, where dentin bone graft is compared with any of the following bone graft material, will be included: autografts (enamel; autologous bone graft from any anatomic site such as chin, ramus, maxillary tuberosity; fresh socket, bone chips, osseous coagulum, bone blend); allograft (Demineralized freeze-dried bone graft and freeze-dried bone graft); xenograft (bovine, porcine, coral-based xenograft); and alloplast (hydroxyapatite; plaster of Paris; tricalcium phosphate; calcium phosphosilicate; calcium phosphate; calcium silicate, etc.).

Types of outcomes

The following outcomes will be considered in the proposed review: 1) Clinical and radiographic changes in the height and width (in mm) of the socket before and after socket preservation with dentin bone graft compared to other bone graft; 2) Changes in quality of bone following socket preservation; 3) clinical assessment of soft tissue (in terms of gain in the width of keratinized gingiva) following socket preservation; 4) details of the type of dentin bone graft used, method of application, duration of surgical procedure 5) occurrence of any immediate and delayed post-operative complications following socket preservation surgery.

Types of studies

In the proposed systematic review, randomized controlled trials (RCTs), the gold standard study design for assessing the effectiveness of an intervention will be used as the preferred study design for inclusion. RCTs with parallel-group, individual participant, or cluster-allocation designs comparing the independent effects of the intervention on the comparison group will all be included. Non-randomized trials such as pre-post (controlled before-after) and quasi-experimental studies will also be included. Case series with more than 10 subjects and a follow of at least three months would be included. Animal studies, case series with fewer than 10 subjects, letters to the editor, and case reports will all be excluded from inclusion. The proposed systematic review will only include manuscripts published in English and published in 2000 or later.

Context or setting

Studies conducted in hospitals, dental clinics, university hospitals, and other relevant healthcare facilities, dependent on the country where the study was conducted, will be included in the review. Studies, where treatment was provided by specialists and non-specialists, will be included in the review.

 Search strategy and information sources

A search strategy was developed using keywords identified from the preliminary search and following agreement between the research team (KS, AC, ER) and a search expert (GC, BK). It included Medical Subject Headings (Mesh) terms, free text terms, and Boolean (AND, OR), as well as the components of the PICO framework. The advanced search strategy for PubMed, one of the databases to be searched is given in Table 1. An electronic search for English language publications in PubMed, Scopus, Web of Science, EMBASE, Epistemonikos, EBSCO (Dentistry and Open Access), and Cochrane CENTRAL databases will be conducted. Additionally, ProQuest, World Clinical Trial Registry, and Clinical Trials Registry of India (CTRI) will be searched for ongoing clinical trials. The corresponding authors for the ongoing clinical trials will be requested to share the results (if available). In addition, the bibliography section of the following journals will be searched for any articles in press: Journal of Periodontology, Journal of Dental Research, Journal of Periodontal Research, Journal of Clinical Periodontology, Journal of Clinical Oral Implant Research, Journal of Implantology, Journal of Clinical Implants and Related Research. We will also check references of the included studies for other relevant articles. Preprint servers such as BioRxiv, Research Square, and MedRxiv will be screened for relevant articles on dentin as bone graft material used in socket preservation. Doctoral theses, conference proceedings, and industry studies published in company publications will also be screened for relevant literature.

Search strategy (PubMed).
(“dental implants”[MeSH Terms] OR “Autogenous tooth bone graft”[Title/Abstract] OR “Autogenous demineralized dentin graft”[Title/Abstract] OR “Tooth derived bone graft”[Title/Abstract] OR “dentin”[MeSH Terms] OR “dentin”[Title/Abstract] OR “Autogenous dentin graft”[Title/Abstract] OR “Particulate dentin”[Title/Abstract]) AND (“transplantation, autologous”[MeSH Terms] OR “autografts”[MeSH Terms] OR “allografts”[MeSH Terms] OR “Alveolar ridge augmentation”[MeSH Terms] OR “autograft*”[Title/Abstract] OR “allograft*”[Title/Abstract] OR “heterograft*”[Title/Abstract] OR “xenograft*”[Title/Abstract] OR “autologous graft*”[Title/Abstract] OR “allogenic bone graft*”[Title/Abstract] OR “autogenous graft*”[Title/Abstract] OR “bone graft*”[Title/Abstract] OR “autogenous bone graft*”[Title/Abstract] OR “Alveolar ridge augmentation”[Title/Abstract]) AND (“peri-implantitis”[MeSH Terms] OR “paresthesia”[MeSH Terms] OR “pain, postoperative”[MeSH Terms] OR “guided tissue regeneration”[MeSH Terms] OR “peri-implantitis”[Title/Abstract] OR “periimplantitis”[Title/Abstract] OR “post-operative pain*”[Title/Abstract] OR “postoperative pain*”[Title/Abstract] OR “guided tissue regeneration”[Title/Abstract] OR “bone regeneration”[Title/Abstract] OR “peri implant infection*”[Title/Abstract] OR “peri implant infection*”[Title/Abstract] OR “paresthesia*”[Title/Abstract] OR “Dysesthesia”[Title/Abstract] OR “socket-length”[Title/Abstract] OR “socket-length”[Title/Abstract] OR “Socket-height”[Title/Abstract] OR “Socket preservation”[Title/Abstract] OR “Implant mobility”[Title/Abstract] OR “post-operative complication*”[Title/Abstract] OR “post-operative complication*”[Title/Abstract] OR “post-operative adverse effects”[Title/Abstract] OR “post-operative adverse effect*”[Title/Abstract] OR “post-operative healing”[Title/Abstract] OR “post-operative healing”[Title/Abstract] OR “post-operative wound management”[Title/Abstract] OR “post-operative wound management”[Title/Abstract] OR “Post-surgical pain”[Title/Abstract] OR “Postsurgical pain”[Title/Abstract] OR “implant survival”[Title/Abstract] OR “implant stability”[Title/Abstract] OR “implant prognosis”[Title/Abstract]) AND (“humans”[MeSH Terms] AND “english”[Language]) AND “humans”[MeSH Terms] AND “english”[Language]) AND (“humans”[MeSH Terms] AND “english”[Language])) AND ((humans [Filter]) AND (AND (english [Filter]))
Study selection (screening process)

The search results will be managed using the Microsoft Office (MS) Excel software. After the removal of duplicates, four reviewers (KS, AC, SM, ND) will independently select studies using the inclusion and exclusion criteria. The screening process will be performed in two stages. In the first stage, the titles, and abstracts of the studies will be independently screened. Studies that do not qualify according to the eligibility criteria and those with inadequate data or information will be excluded at the title/abstract (Ti/Ab) screening stage. In the second stage, full-text screening of the included studies will be performed independently by the four reviewers (KS, AC, SM, ND). They will also perform hand-searching of the journals listed above and screen the potential articles for inclusion. Any disagreements regarding inclusion will be resolved initially by discussion between the reviewers (GC) and if unresolved the other reviewers (BK, KS) will be consulted for agreement; a majority decision will be adopted. A pre-designed screening protocol will be used to select studies ( Table 2).

Screening protocol.
1. Title and abstract screening
A. Is the study published in English? And is it published in the year 2000 or later? If the answer to both the components is ‘yes’, Go to B. If it is non-English or published before 2000 then exclude the study
B. Does the study involve one of the following designs or analysis: Randomized controlled trials and non-randomized clinical trials including pre-post analysis and quasi-experimental studies If the answer is ‘yes’ OR it is not clearly stated in the abstract, Go to C. If the publication is a commentary, perspective, editorial, review, conference abstract, OR policy paper that does not provide details of the implementation of the intervention: exclude the study
C. Does the study describe the intervention in the form of dentin autografts in comparison to other types of bone grafts for socket preservation about implant treatment? If the answer is ‘yes’ OR it is not clearly stated in the abstract, Go to D. If the answer is ‘no’ then exclude
2. Full-text screening
D. Did the study involve the adult population i.e. 18 yrs. And above? If it is ‘yes’, Go to E If no, or if the study involves participants with any systemic disease that might impair bone metabolism, anti-resorptive therapy such as bisphosphonates, pregnancy, psychiatric conditions, and heavy smokers (>10 cigarettes), including the use of smokeless or chewing form of tobacco, areca nut or supari. If the study includes participants undergoing chemotherapy or radiation therapy, in such cases, exclude the study
E. Does the study involve one of the following designs or analyses: Randomized controlled trials and non-randomized clinical trials including pre-post analysis and quasi-experimental studies? If it is ‘yes’, Go to F If ‘no’, exclude the study
F. Does the study describe the intervention in the form of dentin autografts in comparison to other types of bone grafts for socket preservation about implant treatment? If the answer is ‘yes’ Go to G OR If you are in doubt, then flag it for discussion If ‘no’, exclude the study
G. Did the study measure outcomes of our interest e.g. radiographic and clinical assessment of the bone and soft tissue healing in the preserved socket, type of dentin bone graft and nature of the processing of the graft; post-operative complications, etc.? If ‘yes’, including the study for data analysis If ‘no’, exclude the study
Data extraction

Three reviewers (KS, AC, ND, SM) will perform data extraction independently, using a pre-designed pilot-tested data extraction sheet. Any disagreements during the extraction process will be resolved initially by discussion between three reviewers, and if still unresolved BK and GC will be consulted. A majority decision will be adopted as final. In case of unpublished and missing information/data, the study authors will be contacted to request the required information. If adequate data are available, the review team will perform additional relevant statistical analysis.

 Outcomes assessed

The outcomes considered in the proposed review are:

Primary outcomes:

Clinical and radiographic assessment of the overall bone volume gain or otherwise, following socket preservation as measured by the gain or otherwise, in the mesiodistal, buccolingual, and apicocoronal dimensions of the socket before and after the intervention (in mm) will be measured. This can be measured by bone-sounding/trans-gingival probing or any radiographic assessment. The changes in the proximal/interdental bone levels at teeth-bounding extraction sites will also be noted.

The nature of bone, and quality of bone as assessed by any clinical or radiographic method will be considered. Radiographic assessment of bone volume or quality as measured by changes in the density of the trabecular pattern (no/mm 2); changes in the trabecular pattern; ratio of cortical to cancellous bone in terms of Hounsfield unit (HU) in the extraction socket pre- and post-intervention (mm 2); or any other techniques reported in respective studies will be considered. The stability of implants in sockets preserved with dentin bone graft compared to other bone grafts is of interest.

If the clinical method is not used and the radiographic method is used in the studies to provide the change in the dimension of the socket and it does not provide three-dimensional information, the two-dimensional measurement will be recorded. The method of assessment will also be recorded. These outcomes have been chosen as the primary outcomes because the quality and quantity of bone and soft tissue following socket preservation are the most crucial outcomes to define success.

Secondary outcomes:

The health of soft tissue around the socket preserved, as measured by the health of the gingival tissues, and gain in the amount of keratinized tissue after socket preservation at baseline and post-treatment, as measured by any histomorphometric analysis or manually by any periodontal probe will be noted.

The percentage/amount of bone graft remaining in the socket post-intervention (at each recall) reported by surgical re-entry, histology, or radiographic imaging technique will be considered.

The presence or absence of any postoperative complications at the time of surgery, immediately after surgery; within 24 hours, or delayed after socket preservation will be considered. Presence or absence of non-healed sockets, delayed socket healing, exposure of barrier membrane, loss of graft material, presence and presence of soft tissue defects on the alveolar ridge; presence or absence of any suppuration, pus discharge, excessive bleeding, dehiscence and opening of the wound, fenestration on the buccal or lingual aspect of the closed wound, recession of soft tissue following surgery, postoperative pain, persistent pain or dysesthesia following treatment as measured by any pain scale such as Visual Analog Scale (VAS), Numeric Rating Scale (NRS), and The Wong-Baker face pain scale following socket preservation are other will be considered.

Time required between socket preservation and implant placement; nature of osseointegration if implants were placed at the time of socket preservation will be considered.

Health of the tooth used for procurement of dentin; type of dentine used, method of processing of dentin; time of utilization of tooth following extraction; method of storage of dentin, mode of application of dentin (with or without any device) and particle size of dentin graft (if mentioned); use of dentin with or without a barrier membrane will be considered.

Risk of bias (ROB) assessment

The risk of bias will be assessed using the revised Cochrane Risk of Bias Assessment Tool (ROB2). 46 , 47 Two review authors (KS, AC) will independently assess the risk of bias in the included studies. Any disagreements will be resolved via discussion, if consensus cannot be reached, then a majority decision will be adopted after consulting the other two reviewers (BK, GC). The following domains will be assessed for risk of bias: 1. Randomization process; 2. Bias resulting from deviations from intended interventions; 3. Bias resulting from missing outcome data; 4. Bias resulting from measurement of the outcome; 5. Bias resulting from selection of the reported result; 6. Bias in the identification or recruitment of individual participants within clusters. If cluster-RCTs are included, whether the reported data analysis had appropriately taken account of the aggregate nature of the data will be determined. The identified risks shall be categorized as low risk, high risk, and risk with some concern. The ‘effects of assignment’ will be considered as the effect of principal interest to assess the risk of bias.

Quality assessment of non-randomized studies will be performed using the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I). 47 As per this tool, bias in a non-randomized trial will be assessed for the following seven domains: 1) Bias due to confounding, 2) Bias in the selection of participants into the study, 3) Bias in the classification of interventions, 4) Bias due to deviations from intended interventions, 5) Bias due to missing data, 6) Bias in measurement of outcomes, 7) Bias in selection of the reported result. The assessed risk will be categorized as low risk, moderate risk, serious risk, and critical risk.

 Measures of effects

In the case of continuous data, Mean Difference (MD) and Standard Mean Difference (SMD) with 95% Confidence Interval (CI) will be used to estimate the effects of the intervention. Odds Ratio (OR) and Risk Ratio (RR) with 95% CI will be used for categorical data.

 Unit of analysis

The participant will be the unit of analysis for individual randomized trials, however, a study cluster will be considered as the unit of analysis for cluster-randomized trials. The impact of data clustering will be considered and the unit of analysis will be adjusted accordingly during analysis.

 Data synthesis

Meta-analysis will be performed in case homogenous data is obtained from the included studies. I 2 statistic will be used to assess statistical heterogeneity, describing the percentage of the variability in effect estimates that is due to heterogeneity rather than chance. Based on the I 2 statistic, the level of heterogeneity will be categorized as follows:

0% to 40%: might not be important

30% to 60%: may represent moderate heterogeneity

50% to 90%: may represent substantial heterogeneity

75% to 100%: considerable heterogeneity

A fixed-effects model will be used for meta-analysis. A forest plot will be used to report the results of the meta-analysis. A narrative synthesis, with tables and figures for explanation, will be performed when meta-analysis is not possible in case of more than 50% ‘clinical,’ ‘methodological,’ and ‘statistical’ heterogeneity.

 Sub-group analysis

If possible, sub-group analysis will be performed based on the height and width of the socket before and after socket preservation; quality of bone formed before and after socket preservation in dentin compared to other bone grafts; nature of soft tissue before and after socket preservation in dentin compared to other bone graft; post-operative complications following socket preservation. The comparison of healing of sockets in healthy patients compared to those with the systemic condition will done (based on the article retrieved). The comparison of healing based on age and gender analysis can also be analysed.

 Assessment of reporting bias

Funnel plots will be used for the identification of reporting bias. The identification of reporting bias will be done based on the visual assessment of the funnel plot, where a symmetrical funnel plot will be interpreted as the absence of reporting bias and an asymmetrical plot will indicate the presence of reporting bias.

 Sensitivity analysis

If sufficient data is available, a sensitivity analysis will be performed to assess the robustness of the results. This will be done using studies with a ‘low risk of bias’.

 Assessment of certainty of evidence

The certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. This approach grades evidence for five domains 1) risk of bias, 2) indirectness, 3) inconsistency, 4) imprecision, and 5) publication bias. The level of certainty of evidence will be classified as high, moderate, low, and very low, using the GRADE Pro GDT software, independently by three of the review authors (KS, AC, and ER). Disagreements will be resolved by discussion and in case of non-consensus, the two other authors (BK and GC) will be consulted, and a majority decision taken. The certainty of evidence will be reported for the following seven outcomes 1) Changes in the dimensions (height and width) of the alveolar ridge following grafting; 2) Nature of bone and soft tissue healing following socket preservation; 3) Postoperative complications (presence and absence of pain, dysesthesia, suppuration, marginal bone loss or loss of graft material.

 Study status

The review is currently in the full-text screening stage.

 Discussion

The proposed systematic review will assess the quality of the evidence base available regarding the efficacy and efficiency of using dentine bone graft material in socket preservation. The review will help to understand whether dentin has a superior osteogenic potential than other bone grafts and what future complications one should note when using dentin. This will help to understand if dentin is a good alternative to conventional autografts like ramus graft and chin graft which involve many patient-related complications and morbidity. 18 – 20 Since many times the tooth is discarded as a biological waste, the utilization of the same tooth for regeneration of bone defect would preclude the need for additional bone graft material. This would help patients to obtain a cheaper, affordable, and relatively easier option compared to other autografts. Hence the evidence is crucial for the patients and clinicians who wish to make informed decisions about choosing dentin autograft, in resource-constrained settings. 23 – 32 We have involved relevant stakeholders such as clinicians, patients, and researchers for the identification of research uncertainties and the formulation of the research question. After consultation with the stakeholders, the need for a non-invasive, cheaper, and more comfortable option for procuring autografts was deemed necessary. We also took feedback from patients in our clinics regarding their experience following surgery where autograft was procured from the chin and ramus. There is a need to explore this research knowledge and explore the efficacy of dentin as bone graft material for socket preservation and at the same it is important to understand the clinical outcomes and patient-related outcomes after surgery using dentin as a bone graft material. The review will also cue the dentist to understand the probable complications associated with dentin bone graft. Thus, the comprehensive evaluation of research and the resulting consolidated up-to-date evidence will help clinicians make evidence-informed decisions while choosing graft material. Additionally, the review will also propose further studies required to address gaps identified in the knowledge created so far on dentine as a graft material. It is hoped that collaborative research with clinicians, scientists, and the industry will be promoted as a result of the planned review. However, one should note that one of the limitations of the proposed review is that the evidence will be based on English language literature only. Although this review aims to explore, the role of dentin as graft material for socket preservation, we would not be able to provide strong evidence on the stability, prognosis, and long-term survival of the implants as these factors have many confounding variables that cannot be addressed and is not within the scope of this review. However, future studies should explore the prognosis and survival rate of implants in sockets preserved in the dentin compared to other bone grafts.

 Data availability Underlying data

No data are associated with this article.

 Reporting guidelines

Figshare: PRISMA-P checklist for ‘How effective is dentin autograft for socket preservation and implant site preparation: A systematic review protocol.’ https://doi.org/10.6084/m9.figshare.25195910. 48

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

 Acknowledgments

We would like to acknowledge Manipal Academy of Higher Education, Manipal, Karnataka, for logistic and technical support.

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Anat. 2023;246:152024. 36396018 10.1016/j.aanat.2022.152024 Higgins JPT Thomas J Chandler J : Cochrane Handbook for systematic reviews of interventions version 6.1 (updated September 2020). London: Cochrane;2020. Higgins JPT Lasserson T Chandler J : Methodological Expectations of Cochrane Intervention Reviews. London: Cochrane;February 2021. Version. MECIR Version February 2021 clean final_1.pdf Reference Source Moher D Liberati A Tetzlaff J : Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. 19621072 10.1371/journal.pmed.1000097 PMC2707599 Sterne JAC Savović J Page MJ : RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ (Clinical research ed.). 2019;366:l4898. 10.1136/bmj.l4898 Sterne JA Hernán MA Reeves BC : ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ (Clinical research ed.). 2016;355:i4919. 27733354 10.1136/bmj.i4919 PMC5062054 Chopra A : PRISMA-P checklist for dentin bone graft for socket preservation: systematic review.[Dataset]. Figshare. 2024. 10.6084/m9.figshare.25195910 10.5256/f1000research.169766.r309907 Reviewer response for version 2 Melek Lydia N. 1 Referee https://orcid.org/0000-0001-6379-3800 Alexandria University, Alexandria, Egypt

Competing interests: No competing interests were disclosed.

 7 8 2024 Copyright: © 2024 Melek LN 2024 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve

Comments have been adequately addressed by the authors.

Is the study design appropriate for the research question?

Yes

Is the rationale for, and objectives of, the study clearly described?

Yes

Are sufficient details of the methods provided to allow replication by others?

Yes

Are the datasets clearly presented in a useable and accessible format?

Not applicable

Reviewer Expertise:

Oral and Maxillofacial surgery with a special interest in dental implantology and grafts. I have several publications on the use of dentin graft.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

 10.5256/f1000research.158329.r295742 Reviewer response for version 1 Madi Marwa 1 Referee Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

Competing interests: No competing interests were disclosed.

 22 7 2024 Copyright: © 2024 Madi M 2024 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve

The study is well written and the methodology is explained in a detailed and organized manner. Since the objective of the review is clinical and radiographic findings as well as soft tissue healing following socket preservation using dentin allograft I think the authors need to exclude all animal studies and include only clinical studies.

Strength of the proposal:

The proposal addresses a novel approach by investigating the use of dentin autografts for socket preservation, which is an emerging area in dental research. This originality is relevant and significant for students at this level. The proposal is grounded in a well-established scientific premise, highlighting the importance of alveolar ridge preservation and the potential benefits of using dentin as a graft material. The background information provided is comprehensive and supports the rationale for the study.

The methodology is robust, following the Cochrane Handbook for Systematic Reviews and adhering to PRISMA-P guidelines. The use of multiple databases for literature search, clear inclusion and exclusion criteria, and detailed data extraction and analysis plan demonstrate feasibility and rigor.

The weakness of the proposal: Focus  on Specific Population:

The study focuses on healthy adults, potentially overlooking how dentin autografts might perform in populations with comorbidities or different age groups.

Limited Scope of Comparative Studies: While the proposal compares dentin autografts with other types of grafts, it does not account for potential variations in outcomes based on patient demographics or specific clinical conditions.

Is the study design appropriate for the research question?

Yes

Is the rationale for, and objectives of, the study clearly described?

Yes

Are sufficient details of the methods provided to allow replication by others?

Yes

Are the datasets clearly presented in a useable and accessible format?

Yes

Reviewer Expertise:

Periodontology; implant dentistry

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Chopra Aditi Periodontology, Manipal College of Dental Sciences, Manipal, Manipal, India

Competing interests: Nil

 29 7 2024

Reviewer 2

Comment 1: Since the review's objective is clinical and radiographic findings and soft tissue healing following socket preservation using dentin allograft, I think the authors need to exclude all animal studies and include only clinical studies.

Response: We agree with the reviewer, We have added these points to the eligibility criteria.

Comment 2: The study focuses on healthy adults, potentially overlooking how dentin autografts might perform in populations with comorbidities or different age groups.

Response: We thank the reviewer for their valuable insight. We agree that the effect of dentin should be checked in diverse populations to establish its validity and efficacy. Hence, we would like to highlight that we would not exclude studies where dentin was used in populations with co-morbidities. This would even help us to do a subgroup analysis and check. We have added these points to our eligibility criteria.

Comment 3: While the proposal compares dentin autografts with other types of grafts, it does not account for potential variations in outcomes based on patient demographics or specific clinical conditions.

Response: We agree with the reviewer for this valuable suggestion. Based on the articles we retrieved, we can analyze the clinical outcomes based on variation in variations in demographic and clinical conditions.

 10.5256/f1000research.158329.r295738 Reviewer response for version 1 Melek Lydia N. 1 Referee https://orcid.org/0000-0001-6379-3800 Alexandria University, Alexandria, Egypt

Competing interests: No competing interests were disclosed.

 8 7 2024 Copyright: © 2024 Melek LN 2024 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve

The systematic review protocol is very well-designed with sufficient feedback about the topic and adequately addresses the current knowledge gap in utilizing the dentin graft as an autograft alternative. The study aim is clear and the methods are reproducible. 

The authors are advised to add a separate subtitle with the research question of the systematic review stated clearly and concisely for the reader.

Also, the authors are advised to add the time frame for the studies included in the review. It's mentioned in Table 2 "year 2000 or after" but it's better to add it in the manuscript too.

Is the study design appropriate for the research question?

Yes

Is the rationale for, and objectives of, the study clearly described?

Yes

Are sufficient details of the methods provided to allow replication by others?

Yes

Are the datasets clearly presented in a useable and accessible format?

Not applicable

Reviewer Expertise:

Oral and Maxillofacial surgery with a special interest in dental implantology and grafts. I have several publications on the use of dentin graft.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Chopra Aditi Periodontology, Manipal College of Dental Sciences, Manipal, Manipal, India

Competing interests: Nil

 29 7 2024

Firstly I would like to thank the editor and all the reviewers for their valuable suggestions and insightful comments. It has helped us in improving our work. We have tried our best to revise the manuscript as per the comments. The changes are highlighted in yellow.

Reviewer 1

Comment 1: The systematic review protocol is very well-designed with sufficient feedback about the topic and adequately addresses the current knowledge gap in utilizing the dentin graft as an autograft alternative. The study aim is clear and the methods are reproducible. The authors are advised to add a separate subtitle with the research question of the systematic review stated clearly and concisely for the reader.

Response: We have now added a separate subtitle as the focus question as suggested.

Comment 2: Also, the authors are advised to add the time frame for the studies included in the review. It's mentioned in Table 2 "year 2000 or after" but it's better to add it in the manuscript too.

Response: We have now added the study duration in the text.