Comparison of d-PTFE Membrane With Titanium-mesh in Vertical Ridge Augmentation: A Split Mouth, Randomized Controlled Clinical Trial
Phase: NA
Conditions: Vertical Alveolar Bone Loss
Sponsor: Tufts University

 
 
 
 
 
 
 
 
 
Comparing the Efficacy and Morbidity of Two Vertical Ridge 
Augmentation Techniques 
 
 
 
 
 
 
    
 
                             
                                      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                      
NCT number:             02703480  
  
  
 
 
 
 
Document  Date:       12/1/2020  
 
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I) Introduction 
 
The aim of the randomized prospective controlled clinical trial, a split mouth design, 
is to compare the efficacy and morbidity of the two vertical ridge augmentation 
techniques: Titanium mesh (Ti-mesh) technique and Guided Bone Regeneration 
(GBR) technique using a high-density polytetrafluoroethylene (d-PTFE) membrane. 
The efficacy will be measured by the height gain (Aim 1) and the bone core 
histology/histomorphometry (Aim 3). The morbidity will be assessed by the 
incidence of post-operative complications (Aim 2).   
 
Aim 1: Compare the height gain obtained in vertical ridge augmentation procedures 
using intrasurgical clinical measurement in millimeter. 
We hypothesize that the height gain obtained after the six months healing period 
following vertical augmentation using Ti-mesh will be more, compared with that of 
a d-PTFE membrane.  
 
Aim 2: Identify and compare the rate of post-operative complications following 
vertical ridge augmentation procedures using a complication case report form 
(CRF).   
We hypothesize the incidence of surgical complications occurring in vertical ridge 
augmentation procedures with Ti-mesh will be less frequent, compared with a d-
PTFE membrane.  
 
Aim 3: Evaluate and compare bone core histology by quantifying new bone 
formation using histomorphometric analysis.  
We hypothesize that the new bone formation using vertical ridge augmentation 
procedures with a Ti-mesh membrane will be greater, compared with d-PTFE 
membrane.  
 
II) Background and Rationale 
 
Background: 
 
Vertical ridge augmentation is challenging, but an important treatment modality 
for patients with severely deficient edentulous ridges usually from being 
edentulous in these areas for an extended period of time. A successful 
procedure will make implant placement possible by providing new bone 
formation with improved functional and aesthetic outcomes. Vertical ridge 
augmentation can be achieved through different methods including Guided Bone 
Regeneration (GBR) with non-resorbable membrane, onlay autogenous block 
bone graft, distraction osteogenesis (DO) and Titanium mesh (Ti-mesh) 
technique.1-3 Currently, GBR and Ti-mesh techniques are commonly used in the 
clinical practice because of their less-invasive characteristics compared to other 
techniques. GBR using non-resorbable membrane with particulated bone graft is 
supported by a wide range of scientific evidence.4 In particular, an expanded-
polytetrafluoroethylene (e-PTFE) membrane with particulate graft was 
considered the gold standard of GBR procedure in vertical augmentation.5-8 
However, recently, the traditionally used e-PTFE membrane was discontinued in 
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the market. A newer non-resorbable membrane, a high-density 
polytetrafluoroethylene (d-PTFE) membrane has been introduced as an 
alternative. The main characteristic of the d-PTFE membrane is lower porosity, 
which is less than 0.2 micrometer pore size on the membrane surface, 
compared with the e-PTFE. This feature may provide resistance to the 
membrane against bacteria, and low risk of infection compared with the e-PTFE 
membrane. The d-PTFE membrane has been used widely for procedures such as 
ridge preservation after tooth extraction. However there is limited scientific data 
available evaluating the performance of the d-PTFE membrane in vertical ridge 
augmentation at the present time. Only a few studies are available with a small 
number of subjects.9,10 
 
Titanium mesh technique with particulate graft is also used for vertical ridge 
augmentation. The stiffness of the titanium mesh can provide better space 
maintenance ability compared to a non-resorbable membrane. However, some 
drawbacks have been reported such as an increased number of mesh exposures 
and soft tissue ingrowth, which result in less bone regeneration. Only a few 
studies are available with a small number of subjects to support its applications 
for vertical augmentation at this time.11-14 
 
Rationale: 
The proposed study will be the first randomized controlled clinical trial that will 
investigate the use of d-PTFE membrane compared to Ti-mesh in vertical 
augmentation. The study will be able to provide scientific evidence that will help 
clinicians in the decision-making process for vertical ridge augmentation. The 
split-mouth study design will support a direct comparison between the two 
surgical techniques. Additionally, this project will benefit TUSDM educationally by 
creating more interest in the vertical ridge augmentation procedure among the 
residents, dental students and faculty members. Ultimately, it may improve the 
quality of care for the patients at TUSDM. 
 
The current literature does not provide evidence-based criteria that indicate one 
of the two techniques currently used in the clinic. The primary goal of this study 
is to compare the efficacy by measuring clinical height gain between the two 
techniques. The secondary goal of the study is to compare the morbidity with 
patient-centered outcomes research design. The proposed study will help make 
more informed treatment decisions of patients by providing evidence on the risks 
and benefits between the treatment options. 
 
TUSDM Periodontology Clinic Standard of Care 
 
A patient who requires vertical ridge augmentation receives either of the two 
surgical materials, d-PTFE membrane or Ti-mesh, based on the dentist’s 
preference. It is the surgeon’s discretion to choose one or the other material based 
on their experience. The two materials are considered equally effective and no 
additional risk of one over the other has been reported at TUSDM.    
 
 
 
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III) Research Plan 
 
A) Experimental Design 
 
 
The proposed study design is a randomized controlled trial, split mouth 
 
design, to compare the two different vertical augmentation procedures: 
 
Titanium mesh (Ti-mesh) technique and Guided Bone Regeneration (GBR) 
 
technique with a high-density polytetrafluoroethylene (d-PTFE) membrane. 
 
B) Sample Size and Statistical Analysis 
 
 
Sample Size: 
 
 
We have used the available data (mean, standard deviation) for the height 
gain with an anorganic bovine bone (Bio-oss) with e-PTFE membrane or Ti-
mesh for the sample size calculation.6,15 We anticipate that the property of a 
d-PTFE membrane is similar to an e-PTFE membrane, and the amount of the 
height gain to be similar between these two membranes.10  
 
A power calculation was performed in nQuery Advisor (version 7.0) with the 
following assumptions: a type I error of 5%; a type II error of 7%; the titanium 
mesh group has a mean (SD) height gain of 5.2 (0.79) mm (Artzi 2003)15; the e-
PTFE group has a mean (SD) height gain of 3.15 (1.12) mm (Simion 2007) 6. The 
minimum sample size necessary was determined to be 7 subjects.  To account for 
potential dropout, the study population will be increased to include 10 subjects. Up 
to 15 subjects will be consented (and considered enrolled) into the study to achieve 
these goals.  
 
 
Statistical Analysis: 
Counts and percentages, will be reported for categorical data. Mean and 
standard deviations will be reported for continuous data.  
1. For the Aim 1, the height gain will be measured in millimeters (mm) and 
considered to be continuous data. The paired t-test will be used to compare 
the height gain after the healing following vertical ridge augmentation between 
the d-PTFE membrane group and the Ti-mesh group. 
 
2. For the Aim 2, the mean incidence of post-operative complication in each 
group will be measured in percentage as categorical data. The Mann-Whitney 
U test will be used to compare the incidence of post-operative complications 
occurred in vertical ridge augmentation procedures between the d-PTFE 
membrane group and the Ti-mesh group. 
 
3. For the Aim 3, the new bone formation will be measured in percentage as 
categorical data. The paired t-test will be used to compare the percentage of 
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new bone formation after the healing following vertical ridge augmentation 
between the d-PTFE membrane group and the Ti-mesh group. 
 
All analyses will be performed using Stata (version 13.1) 
 
Randomization: 
Randomization will be performed in a 1:1 ratio using a balanced design based 
on a computer-generated randomization scheme, both for the location of the 
procedure, but also for the performed technique. Randomization will occur 
during visit 2.  
 
Blinding: 
The subjects will be blinded for the randomization assignment (Single-
blinded). We will blind subjects by not informing them of their treatment 
allocation (d-PTFE membrane or Ti-mesh).  If subjects do not see the 
preparation of the materials (d-PTFE or Ti-mesh), they will not be able to tell 
which procedure they receive.  The preparation of d-PTFE membrane and Ti-
mesh will be performed and delivered to the surgical site out of sight of 
participants during surgery.  
 
 
C) Products 
 
Group 
Product 1 
Product 2 
d-PTFE 
membrane 
Cytoplast™ Barrier 
Membranes, Osteogenics 
Biomedical 
Bone graft material: 
Deproteinized bovine bone 
material (DBBM) 
 
Bio-Oss GeistlichPharma 
North America, Inc.  
Ti-mesh 
Titanium Mesh, BioHorizons  
Bone graft material: 
Deproteinized bovine bone 
material (DBBM) 
 
Bio-oss GeistlichPharma 
North America, Inc. 
 
Cytoplast™ Barrier Membranes, Osteogenics Biomedical: Cytoplast has been FDA-
approved for use in a space-making barrier.  The material will be used in this study for 
its approved indication. 
 
Titanium Mesh, BioHorizons: Ti-mesh is regulated as a minimally manipulated product.  
Titanium products such as mesh and screws are commonly used as adjunctive materials 
in periodontal or oral surgeries. As such, there is no FDA approval process or 
documentation to be had. Currently, Ti-mesh from BioHorizon is used in the TUSDM clinic.  
 
Deproteinized bovine bone material (DBBM) Bio-oss GeistlichPharma 
North America, Inc.: Bio-oss has been FDA-approved as a bone grafting material.  The 
material will be used in this study for its approved indication. 
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D) Subject Characteristics 
 
Subjects referred to the postgraduate clinic in the Department of Periodontology at 
Tufts University School of Dental Medicine, that were previously diagnosed with 
severely deficient edentulous ridges in the bilateral posterior mandible (Seibert Class 
III) and treatment planned for vertical ridge augmentation and implant placement 
procedure, will be included in the study. The diagnosis and  
treatment plan will 
be established by the undergraduate or postgraduate clinics. 
 
 
1) Inclusion Criteria 
 
All patients will be required to meet the following inclusion criteria. 
(1) 18 years of age or older 
(2) Non-smokers  
(3) Existence of bilateral vertical/horizontal ridge deformities (Seibert 
Class III)  
(4) The length of the edentulous span is from two or more teeth 
 
2) Exclusion Criteria 
 
The patients will not be admitted in the study if any of the following 
exclusion criteria are met:  
  
(1) Patients who have an infectious disease (self reported - HIV, 
tuberculosis or hepatitis) 
(2) Known allergies to the research-related materials 
(3) Patients who have compromised healing potential: 
- bone metabolic disease e.g., Paget's disease, osteoporosis, 
osteomalacia 
- uncontrolled diabetes: HbA1c >=7, values measured within six months 
(using the existing record in AxiUm or if the subject has the condition, but 
there is no report in AxiUm – a blood test record will be requested) 
- patient currently taking steroid medication 
- history of oral bisphosphonate intake greater than 3 years or any IV 
administration   
(4) Pregnant or lactating patients (self-reported), as part of TUSDM 
standard of care not to treat for non-emergency surgical procedures  
(5) Presence of surgical scar tissue from previous surgical procedure in 
the posterior mandible 
(6) Pathology present within the alveolar ridges in the posterior mandible, 
determined clinically or radiographically 
(7) History of radiation therapy to the mandible 
(8) Smokers 
 
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Elective periodontal procedures are postponed during pregnancy, active 
infectious disease, bisphosphonate intake or uncontrolled diabetes as 
standard of care in the TUSDM department of periodontology. Diseases or 
conditions which have been shown to affect healing are excluded for 
research. Vertical ridge augmentation is not contraindicated with pregnancy 
and there is no known safely issues associated with it. 
 
3) Subject Withdrawal/Termination Criteria 
 
(1)  Non-compliance. 
(2)  Unwillingness to further participate. 
 
The Principal Investigator will determine whether withdrawn subjects are in 
need of additional treatment and/or follow-up observation as a result of 
participation in this trial. These treatment and/or follow-up appointments 
will follow standard clinic guidelines of the TUSDM periodontology clinic 
dependent upon which point the subject was withdrawn from the study.  
 
 
D) Assessment 
 
1) Risk 
The present study has no additional risks to the subjects beyond the normal 
risks for the surgical procedure as the study involves standard clinical 
procedures performed at TUSDM periodontology clinic. However, subjects 
may experience more discomfort and longer surgery time because two 
surgeries will be done in one day for this study. Usually, either of one 
augmentation techniques is used at a time for one side from standard 
clinical practice at TUSDM, because vertical augmentation is technically 
demanding procedure. However, occasionally, we perform two vertical 
augmentation procedures at a time for both sides depending on cases in 
the practice or at TUSDM. 
 
The present study presents various complications that are possible with the 
vertical ridge augmentation procedures, both with a d-PTFE and titanium 
mesh. The common complications that can occur are: exposure of d-PTFE 
membrane or titanium mesh, infection, paresthesia, postoperative pain, 
swelling and bleeding. However, there is no additional risk participating in 
the study compared to the standard of care of vertical ridge augmentation. 
d-PTFE membrane cannot be used under load bearing conditions, which is 
not related to the study procedure.   
 
As with surgeries involving metallic implants there is a chance for foreign 
body sensitivity. Where material sensitivity is suspected appropriate tests 
should be made to rule out this possibility prior to implantation. 
 
Risk of bone core biopsy 
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In the bone core biopsy, a trephine will be used and a bone core sample of 
the hard tissue will be collected and finalized with standard bur prior to 
implant  placement.  No  more  than  the  standard  amount  of  bone  will  be 
removed for this study. There is no additional risk related to this procedure.  
The risk associated with bone biopsy is over-drilling of bone (create a bigger 
hole than the size of hole that is necessary for bone core) when harvesting 
a bone piece. However, the risks associated with bone biopsy are minimal 
because a bone core drill is smaller than a standard implant drill, which is 
necessary to place an implant. 
 
2)  Benefits 
There is no medical benefit to the subject for participating in this study. 
         
3)  Alternatives 
Study subjects will be informed that they have the right to withdraw from 
the study at any time for any reason, without prejudice to their dental care. 
The alternative is not to participate in the study. Patients may receive the 
standard  care  for  vertical  augmentation  procedures  from  postgraduate 
students of the TUSDM periodontology clinic at standard clinic fees. 
 
E)  Study Procedures 
Visit 1: Screening  
Informed  consent  will  be  obtained  by  the  principal  investigator  or  a  co- 
investigator. The subjects will be instructed to read the informed consent form 
(ICF), given ample time to have any questions answered, and then instructed 
to sign the ICF. Subject will be given a copy of the ICF. 
 
Subject  will  be  asked  to  complete  demographic  information  and  a  medical 
history. 
 
Inclusion/exclusion criteria will be evaluated. 
 
The pre-operative height of the bony crest will be evaluated on the pre-existing 
radiographs  from  the  referring  clinic  if  they  are  less  than  6 months old.  If 
recent  radiographs  do  not  exist,  radiographs  will  be  taken  at  this  visit. 
Regardless of the subject’s involvement in the study,  it is standard of care to 
have radiographs taken within the past 6 months prior to surgery.  
 
Visit 2: Surgery 
Medical history will be reviewed as standard of care.  
 
     Eligibility and subject withdrawal criteria will be reviewed to ensure the              
     subject still qualifies for the study.  
 
Surgeries will be performed by either of two investigators. 
 
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The use of d-PTFE for vertical ridge augmentation will be randomly assigned 
to one side of the mouth of each subject (randomization is for research 
purposes) and Ti-mesh to the other side of mouth, and therefore, subjects will 
receive both of the following procedures: 
 
*Guided Bone regeneration (GBR) procedure using a d-PTFE: (standard of 
care excluding clinical measurements)  
The following steps will be performed following standard of care procedures: 
local anesthesia, muco-periosteal incision, full thickness flap reflection, de-
cortication of the alveolar ridge, bone harvesting using bone scrapers, 
tenting screw placement, clinical measurements, DBBM graft material 
placement, the placement and stabilization of the d-PTFE membrane 
according to manufacturer’s instructions, sutures.  
 
* Guided Bone regeneration (GBR) procedure using Ti-mesh: (standard of 
care excluding clinical measurements) 
The following steps will be performed following standard of care procedures: 
local anesthesia, muco-periosteal incision, full thickness flap reflection, de-
cortication of the alveolar ridge, bone harvesting using bone scrapers, 
tenting screw placement, clinical measurements, DBBM graft material 
placement, the placement and stabilization of the titanium mesh according 
to manufacturer’s instructions, sutures. 
 
Bone harvesting using bone scrapers will be performed during GBR procedures with 
both techniques (d-PTFE and Ti-mesh). Bone harvesting using bone scrapers is for 
harvesting particulate autogeneous bone graft material. We will use a mixture of 
50:50 DBBM and autogenous bone graft material for all vertical augmentation 
procedures in the study. Particulate autogenous bone graft will be harvested from 
the retromolar region of the mandible. This area is just next to the area of GBR 
procedures (posterior mandible) and will be visible after flap elevation for vertical 
augmentation. Therefore, we do not need any additional steps except harvesting 
autogenous bone graft. Intraoral harvesting by bone scrapers from the retromolar 
region is a simple and safe method for collecting cortical bone chips. 
 
The intrasurgical clinical measurements of the ridge height will be taken 
during surgery. The distance between the top of the tenting screw and bone 
crest will be measured with a periodontal probe during the procedure. 
Duration of each procedure and surgical complications including flap tear and 
bleeding will be collected. All outcome measurements will be performed by a 
Co-I who did not perform the surgery. 
 
The subject will be asked to complete a pain/discomfort survey using VAS 
scale from zero to ten. A medication log will be given to the patient to track 
the number of pills of the prescribed painkiller they have taken in order to 
examine the amount of pain after the surgical procedures. The mean number 
of pills used after surgical procedures will be analyzed. 
 
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Post-operative medication will be prescribed following TUSDM standard of 
care guidelines.  
 
Visit 3 (7±3 days after procedure): Post-operative Follow-up  
Visit 4 (21±3 days after procedure): Post-operative Follow-up 
 
Medical history will be reviewed as standard of care. Eligibility and subject 
withdrawal criteria will be reviewed to ensure the subject still qualifies for 
the study.  
 
Each subject will have a post-operative visit, which is standard practice at 
TUSDM periodontology clinic. Standard of care procedures including suture 
removal and evaluation of surgical site will be performed.  
 
For research, information regarding bleeding, presence of infection, bruising, 
and/or other complications will be collected. Each subject will complete a 
survey to evaluate the level of pain/discomfort, bleeding, and swelling 
following the surgical procedure for each side – each classified on a VAS 
scale from zero to ten. In addition, the subject will return his or her 
completed medication log. 
 
 
 
Medical history will be reviewed as standard of care. Eligibility and subject 
withdrawal criteria will be reviewed to ensure the subject still qualifies for the 
study.  
 
Each subject will have a post-operative visit, which is standard practice at 
TUSDM periodontology clinic. Standard of care procedures including suture 
removal and evaluation of surgical site will be performed.  
 
For research, information regarding bleeding, presence of infection, bruising, 
and/or  other  complications  will  be  collected.  Each  subject  will  complete  a 
survey  to  evaluate  the  level  of  pain/discomfort,  bleeding,  and  swelling 
following the surgical procedure for each side – each classified on a VAS scale 
from zero to ten.  
Follow-up  visits  during  the  six  month  post-operative  period  of  the  vertical 
ridge augmentation surgery will be scheduled. Standard of care procedures 
and evaluations will be completed during follow-up visits. The surgical sites 
will be evaluated after the vertical ridge augmentation procedures, in order to 
assess the presence of postoperative complications, such as the exposure of 
a d-PTFE membrane or Ti-mesh, infection, swelling, paresthesia or any other 
complications. All will be noted in the subject’s axiUm record and reviewed at 
the time of Visit 4. 
 
Visit 5 (6±1 months after Visit 4): Evaluation visit 
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Medical history will be reviewed as standard of care. Eligibility and subject 
withdrawal criteria will be reviewed to ensure the subject still qualifies for the 
study.  
 
Surgical sites will be evaluated and the subject’s axiUm record will be reviewed 
for any complications. 
 
Each subject will complete a survey to evaluate the level of pain/discomfort, 
bleeding, and swelling following the surgical procedure for each side – each 
classified on a VAS scale from zero to ten, as at Visit 3.  
 
Radiographs will be taken. It is standard of care to have radiographs taken 
prior to implant placement. The post-operative (after the vertical GBR 
augmentation procedure) height of the bony crest will be evaluated on the 
radiographs taken as part of standard of care.  
 
Visit 6 (Up to 1 month after Visit 5): Bone core harvesting, implant placement 
visit  
Medical history will be reviewed as standard of care. Eligibility and subject 
withdrawal criteria will be reviewed to ensure the subject still qualifies for the 
study.  
 
The subject will present for their regularly scheduled implant placement. The 
following steps will be performed following standard of care procedures: local 
anesthesia, muco-periosteal incision, full thickness flap reflection, membrane 
(Ti-mesh/d-PTFE) removal, clinical measurements, tenting screws removal, 
bone core harvesting, implant osteotomy, implant placement, and sutures.  
 
The intrasurgical clinical measurements of the ridge height will be taken at 
during implant placement surgery. The distance between the top of the 
tenting screw and bone crest will be measured with a periodontal probe 
during the procedure. The bone height gain will be calculated by subtracting 
the second measurement form the first measurement (taken during initial 
surgery).  
 
At the time of the implant placement a bone core will be harvested from 
each site of the implant locations for histological analysis. For the bone 
samples in this study, a hollow (trephine) bur, rather than solid bur, will be 
used to allow for sampling.  A trephine bur with 3-4 mm diameter will be 
used.  The core size will not exceed the amount of bone removal required for 
designated implants. Removal of bone is standard during implant placement 
in order to create space for the fixture.  
 
The bone core biopsies will be placed in fixative and labeled with subject ID. 
The collected bone samples will be placed in alcohol for storage and stored in 
a basic science laboratory DHS-635. 
 
The implant placement will not be considered a part of this study. 
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After Visit 6 - Laboratory analysis of bone core sample 
Histological  slides  will  be  prepared  and  histomorphometric  analysis  will  be 
performed by the commercial laboratory. The samples will be coded as subje
ct numbers and histological analysis will be blinded. All collected bone core sa
mples will be shipped to the laboratory by PI or Co-I.  
 
Histomorphometric measurements of the tissue fractions (DBBM, autogenous 
bone,  newly  formed  bone  and  marrow  and/or  connective  tissue)  will  be 
performed for the grafted area. The sections will be digitally photographed 
with computerized software.  
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Table 1. Subject Timeline 
 
 
 
  
 
 
 
 
V1 
 
V2 
 
 
V3 
 
V4 
V5 
V6 
 
Screening 
 
Surgery  
 
1 week  
Evaluation 
 
 
3 week  
Evaluation 
 
6 month 
Evaluation 
 
Bone Core 
Biopsy 
 
Consent 
 
X 
 
 
 
 
 
 
 
Evaluation of 
eligibility 
X 
X 
 
X 
X 
X 
X 
Medical History 
X 
X 
 
X 
X 
X 
X 
Pre-operative 
Radiograph 
Evaluation  
(radiographs taken 
if necessary) 
 
 
X 
 
 
 
 
 
 
 
 
Randomization 
 
 
 
 
X 
 
 
 
 
 
Surgery 
 
X 
 
 
 
 
 
Clinical 
Measurements  
 
 
 
X 
 
 
 
 
 
 
X 
Patient VAS 
Scoring 
 
X 
 
X 
X 
X 
 
Medication Log 
Given/Collected 
 
X 
 
X 
 
 
 
Complication 
Evaluation  
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
X 
 
 
 
 
Post-operative 
Radiographic 
Evaluation 
(radiographs 
taken) 
 
 
 
 
 
X 
 
Bone Core 
Harvesting  
 
 
 
 
 
 
 
 
X 
Adverse Event 
Assessment 
 
X 
 
X 
X 
X 
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F) Subject Safety  
 
1) Adverse Event Reporting 
 
Adverse Events 
An adverse event is any untoward or unfavorable medical occurrence in a 
human subject, including any abnormal physical exam or laboratory 
finding, symptom, or disease, temporally associated with a subject’s 
participation in the research.  
 
Adverse events will be recorded in source documents and on case report 
forms. All adverse events and non-serious situations will be recorded, 
monitored, and reported to the IRB at time of continuing review and at the 
time of the study’s termination. Subjects experiencing an adverse event 
will be evaluated by the PI to determine if it is safe for them to continue in 
the study.  If continuation in the study poses any additional risks, the 
subject will be withdrawn from the study. 
 
Serious Adverse Events  
A serious adverse event is one that results in death, or is life-threatening, 
or results in hospitalization or prolongation of existing hospitalization, or 
results in a persistent or significant disability/incapacitation, or results in a 
congenital anomaly/birth defect, or may jeopardize the subject’s health and 
may require medical or surgical intervention to prevent one of the other 
outcomes listed above. 
 
Serious adverse events will be recorded in source documents and on case 
report forms. Serious Adverse Events will be reported to the IRB within 15 
business days. 
 
Unanticipated Problems 
An unanticipated problem is an incident, experience, or outcome that meets 
all of the following criteria: 1) The nature, severity, or frequency is 
unexpected for the subject population or research activities as described in 
the current IRB approved protocol, supporting documents, and the ICF(s); 
2) it is related or possibly related to participation in the research; 3) it 
suggests the research may place the subject or others at a greater risk of 
harm then was previously recognized.  
 
Unanticipated problems will be recorded in source documents and on case 
report forms. Unanticipated problems will be reported to the IRB within 5 
business days. An initial report will be submitted to the IRB no later than 2 
business days after the PI/study team become aware of the problem, as 
well. 
 
 
 
 
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2) Reporting 
Notification of the IRB of any protocol deviation, including to protect the life or 
physical well being of a subject in an emergency, shall be given to the IRB as 
they occur throughout the course of the study. 
 
Progress reports on the investigation shall be submitted to the IRB at regular 
intervals, but in no event less often than yearly. 
 
A final study report shall be submitted to the IRB following termination or 
completion of the study. Study completion will be defined as completing 
assessments on the last subject. 
 
G) Subject Participation 
 
1) Screening 
The principal investigator or her representative will conduct screening 
examinations to identify subjects who meet the inclusion/exclusion criteria 
for enrollment into the study.  
 
2) Informed Consent 
The principal investigator or her representative will introduce the study.   
 
Consenting will take place in a private clinic bay area and the patient will 
be given as much time as he/she needs to consider participation. The 
participant will be invited to include or exclude any associates (e.g., loved 
ones) in the consent process.  
 
Patients will be asked to read the consent form and given ample 
opportunity to have their questions answered.  To avoid coercion, the 
consenting investigator will read through the copy of the consent form with 
the participant section by section, making sure the participant understands 
each section and has an opportunity to ask questions.  If at any time the 
participant indicates s/he is not interested in participation, the meeting will 
end.   
 
If after going through the consent form, the participant indicates s/he 
would like to discuss the study with associates or think about participating, 
then the meeting will be ended and the participant will be asked to contact 
the study when s/he makes her decision. If the participant contacts the 
study in the future for participation, s/he will be invited back to the clinic, 
and if informed consent is given at that time, study activities will begin 
then. 
 
If the participant indicates s/he may be interested in participating after 
going through the consent form with the investigator, and the investigator 
determines the participant has the capacity to provide informed consent, 
the participant will be asked to provide informed consent at that time. 
Patients will certify their willingness to participate in the study by signing 
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and dating the IRB approved informed consent document.  The subject will 
be given a copy of the consent form.    
 
If any new finding requires any change to the informed consent form, the 
subject will be reconsented. 
 
Non-English speaking subjects will not be enrolled in the study because 
study staff at this time are not certified, prepared, or trained to translate 
or communicate in any language other than English. The study budget does 
not allow for the payment of translation services at this time. 
 
3) Study Location 
TUSDM 
 
4) Personnel 
The PI will be responsible for ongoing communication with the IRB.  
 
PI or Dr. Co­I will perform all surgical procedures including bone 
biopsy.  The Co-I will perform clinical measurements, surveys and follow- 
up visits. 
  
 
PI or Co-I will be responsible for obtaining informed consent. The 
consent process will be begun by PI, medical Co-I, or a research 
coordinator. If a research coordinator begins the consent process, PI or 
medical Co-I will complete it. 
PI or medical Co-I will be available to answer any medical questions.                       
PI, Co-I, or a research coordinator will be responsible for 
maintaining records. 
 
The research coordinating team at TUSDM have worked on numerous 
clinical studies and have a history of performing the consent process with 
subjects and assessing competency. They are CITI education certified and 
GCP trained. In addition, they have attended multiple trainings related to 
these tasks. 
 
 
5) Payment for Participation 
(a) Compensation 
Subject will not be charged a fee of $738 for each bone augmentation 
surgery.  
 
If re-do of the procedure is necessary due to infection or additional need 
for bone grafting, the second procedure will be provided at no cost. 
 
Subject will not be charged surgical fee of $1,165 for one implant.  
 
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The reduction in surgical fees (both the bone augmentation surgery and 
implant surgery) will go into effect at the time of the visit. The subject 
will pay the reduced surgical fees at the time of the visit. 
 
 
If the subject is in need of placement of any additional implants, he/she 
and/or their insurance will be responsible for the cost. 
 
Subject will be responsible for covering the fees for the later implant 
crown procedures (which are not a part of this study).   
 
If a subject withdraws or is withdrawn from the study, the reduction in 
fees will only apply for the time prior to the withdrawal. 
 
(b) Transportation 
No travel reimbursement and transportation costs will be provided.   
 
(c) Payment and Insurance 
If  the  patient  has  insurance  policy  that  covers  the  fee  of  additional 
implants, he or she will be responsible for the co-payment only. 
 
6)  Study Results 
 If interested, study results will be presented to a subject upon his/her 
 request.  Study results will be given to a subject in person or via mail,  
 according to the subject’s preference, upon completion of the study. A log 
will be kept of the participants who are interested in receiving study 
results. Identifying screen failure data will be retained by the PI. Data 
from screen failures will be retained in the locked cabinet in the PI’s office 
at TUSDM. 
 
7)  Confidentiality 
To ensure confidentiality of subject information, each subject enrolled in 
the study will be assigned a unique alphanumeric code. Subjects’ files will 
be kept in a secure, locked cabinet, within a locked room (DHS-1256) 
when the files are not reviewed. The information will only be shared 
between the researchers. All HIPAA requirements will be followed. All 
electronic files will be kept on a password protected computer in a secure, 
locked office. 
a) Coding 
 Each  subject  will  be  assigned  a  subject  identification  number.  
Alphanumeric identification numbers will be assigned sequentially.  This 
will  be  accessible  by  study  personnel  only.  Dental  records  and  case 
reports  used  in  this  study  will  be  coded  and  will  not  include  subject 
names.  
 
 
 
 
b)  Access 
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Only study personnel will have access to data.  Investigators will  
 
 
permit monitoring, audits, and regulatory inspections and will provide  
 
 
direct access to study related documentation. 
 
 
 
c) Publication 
If any publication results from this study, subjects will not be identified 
by name without their written consent.  
 
8) Data Safety Monitoring Plan: 
Study personnel will monitor this trial for all safety related issues to 
determine whether an unreasonable risk to subjects develops. Quality 
control measures include routine inspection of case report forms, source 
documents, data tabulations, and tracking of adverse events. 
 
 
9) New Findings 
The subject will be informed of any significant new findings discovered 
during the course of this study that might influence the subject’s 
continuation and participation in the study.  Subjects will be told at a study 
appointment or via telephone of new findings during the study.   
 
If new findings require revisions to the ICF, the subject will be re-
consented. 
 
H) Record Retention 
1) Study Records 
The investigators will maintain all study records and documents during the 
study period.  All paper files and documents will be kept in a locked file 
cabinet, within a locked room (DHS-1256).  Electronic records will be kept 
on a password protected computer will only be accessible to study 
personnel. 
 
2) Long Term Retention 
The investigator will maintain all study records following completion or 
termination of this study in accordance to state law and institutional policy (at 
least 7 years after the study is completed or terminated). 
 
I) Reporting 
Unanticipated problems and adverse events will be reported per the Tufts 
MC/TUHS IRB Unanticipated Problem and Adverse Event Reporting Policy.  
The IRB will be notified of any deviations from the protocol in cases of medical 
emergencies when the change is necessary to eliminate an apparent 
immediate hazard to the subject  
Progress reports on the investigation shall be submitted to the IRB at regular 
intervals, but in no event less often than yearly, e.g., at continuing review. 
 
J) Protocol Deviations 
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No protocol changes or deviations will be made without prior agreement by the 
IRB unless implemented to prevent an immediate hazard to subjects.  All other 
protocol changes or deviations will be made by a formal amendment subject 
to IRB approval.  All such changes or deviations will be reported to the IRB as 
they occur and included in the final study report. 
 
K) Study Termination 
This study may be terminated for the following reasons:  
Discovery of unforeseen risk that could jeopardize the dental/physical 
well being of subjects. 
 
Enrollment or recall rates that are not likely to produce sufficient data 
for evaluation of safety and efficacy 
 
Non-compliance with the clinical investigational plan, the Investigator 
Agreement, applicable FDA regulations or conditions of approval 
imposed by the reviewing IRB 
 
Withdrawal of IRB approval  
 
In the event of study termination, the Principal Investigator will 
determine whether subjects are in need of additional treatment and/or 
follow-up observation as a result of participation in this trial. 
 
 
L) Subject Recruitment/Advertising  
Paper flyers will be posted throughout TUSDM. Permission is not required for 
these posting locations. Flyers will remain posted until enrollment goals are 
met. Subjects will be recruited through responding to posted study 
advertisements.   
Investigators may also inform clinic patients about the study.  
Investigators may send messages to colleagues via axiUm asking for their help 
in recruiting eligible subjects.  
Likewise, e-mails and/or newsletters that alert the TUSDM community to 
ongoing studies may include information on this study for recruiting purposes.  
Forms of electronic media such as twitter, university websites, Facebook, 
Craigslist, etc. may also be used to recruit.  
All of the forms of recruitment will be submitted for IRB approval prior to use.  
A screening interview/questionnaire or screening script will be used for 
recruitment.  
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Screen failure data will be retained by PI. Screening ID number and 
demographic information will be recorded.  Identifiable information will not be 
recorded in the screening log. 
 
M) References/Bibliography 
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2007;78(3):377-396. 
2. Rocchietta I, Fontana F, Simion M. Clinical outcomes of vertical bone augmentation to 
enable dental implant placement: a systematic review. J Clin Periodontol. 2008;35(8 
Suppl):203-215. 
3. Tonetti MS, Hammerle CH, European Workshop on Periodontology Group C. Advances 
in bone augmentation to enable dental implant placement: Consensus Report of the 
Sixth European Workshop on Periodontology. J Clin Periodontol. 2008;35(8 
Suppl):168-172. 
4. Hammerle CH, Jung RE. Bone augmentation by means of barrier membranes. 
Periodontol 2000. 2003;33:36-53. 
5. Ogata Y, Griffin TJ, Ko AC, Hur Y. Comparison of double-flap incision to periosteal 
releasing incision for flap advancement: a prospective clinical trial. The International 
journal of oral & maxillofacial implants. 2013;28(2):597-604. 
6. Simion M, Fontana F, Rasperini G, Maiorana C. Vertical ridge augmentation by 
expanded-polytetrafluoroethylene 
membrane 
and 
a 
combination 
of 
intraoral 
autogenous bone graft and deproteinized anorganic bovine bone (Bio Oss). Clinical 
oral implants research. 2007;18(5):620-629. 
7. Simion M, Trisi P, Piattelli A. Vertical ridge augmentation using a membrane technique 
associated with osseointegrated implants. Int J Periodontics Restorative Dent. 
1994;14(6):496-511. 
8. Tinti C, Parma-Benfenati S, Polizzi G. Vertical ridge augmentation: what is the limit? 
Int J Periodontics Restorative Dent. 1996;16(3):220-229. 
9. Urban IA, Lozada JL, Jovanovic SA, Nagursky H, Nagy K. Vertical ridge augmentation 
with titanium-reinforced, dense-PTFE membranes and a combination of particulated 
autogenous bone and anorganic bovine bone-derived mineral: a prospective case 
series in 19 patients. The International journal of oral & maxillofacial implants. 
2014;29(1):185-193. 
10. Ronda M, Rebaudi A, Torelli L, Stacchi C. Expanded vs. dense polytetrafluoroethylene 
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11. Merli M, Migani M, Esposito M. Vertical ridge augmentation with autogenous bone 
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12. Misch CM. Bone augmentation of the atrophic posterior mandible for dental implants 
using rhBMP-2 and titanium mesh: clinical technique and early results. Int J 
Periodontics Restorative Dent. 2011;31(6):581-589. 
13. Pieri F, Corinaldesi G, Fini M, Aldini NN, Giardino R, Marchetti C. Alveolar ridge 
augmentation with titanium mesh and a combination of autogenous bone and 
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14. Rakhmatia YD, Ayukawa Y, Furuhashi A, Koyano K. Current barrier membranes: 
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applications. J Prosthodont Res. 2013;57(1):3-14. 
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15. Artzi Z, Dayan D, Alpern Y, Nemcovsky CE. Vertical ridge augmentation using 
xenogenic material supported by a configured titanium mesh: clinicohistopathologic 
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