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Alveolar ridge dimensional changes following ridge preservation procedure: CBCT linear analysis in non-human primate model

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Alveolar ridge dimensional changes following ridge preservation procedure: CBCT linear analysis in non-human primate model

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Content 1
Alveolar ridge dimensional changes following ridge
preservation procedure: CBCT linear analysis in non-human
primate model

by

Seong Hong Min

__________________________________________________

A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CRANIOFACIAL BIOLOGY)

December 2014
2
TABLE OF CONTENTS

Acknowledgement 3

List of Figures 4

List of Tables 6

List of Symbols & Abbreviations 7

Abstract 8

Introduction 10

Materials & Methods
1. Animals 13
2. Material 13
3. Defect Models Following Extractions 16
4. CBCT analysis 17
5. Statistics 19

Results 21

Supplementary data 35

Discussion 41

Conclusion 45

Bibliography 46

3
ACKNOWLEDGEMENT

I would like to express the deepest appreciation to my committee chair,
Professor Homayoun Zadeh, for his guidance, encouragement, and patience
over the last two years. You have been a tremendous mentor for me. In
addition, I would like to thank my committee members, Professor Michael
Paine and Professor Kian Kar for serving as my committee members and
your brilliant comments and suggestions during my defense. I also
acknowledge to Professor Robert Keim, University of Southern California
Orthodontic department and Professor Michael Walker, Stanford University
for assistance with statistical analysis.
A special thanks to my family, words cannot express how grateful I am to
mother-in law, father-in-law, my sisters, and my uncle for all of the
sacrifices that you have made on my behalf. At the end, I would like to
express appreciation to my beloved wife, Nao Min, who spent sleepless
nights with and was always my support in the moments when there was no
one to answer my queries.

4
LIST OF FIGURES

Figure 1: Extraction devices 14
Figure 2: Clinical images of extraction socket devices 15
Figure 3: The radiographic landmarks used for measurement of bone width and
bone height on CBCT images. 18
Figure 4: Representative CBCT images at baseline, 6, and 12 weeks after
extraction 26
Figure 5A: The dimensional changes at 6 weeks following treatment of extraction
sockets of teeth with intact alveolar bone 27
Figure 5B: The dimensional changes at 12 weeks following treatment of extraction
sockets of teeth with intact alveolar bone 28
Figure 6A: The dimensional changes in height at 6 weeks following treatment of
extraction sockets of teeth with intact alveolar bone 29
Figure 6B: The dimensional changes in height at 12 weeks following treatment of
extraction sockets of teeth with intact alveolar bone 30
Figure 7A: The dimensional changes at 6 weeks following treatment of extraction
sockets of teeth with facial dehiscence 31
Figure 7B: The dimensional changes at 12 weeks following treatment of extraction
sockets of teeth with facial dehiscence 32
5
Figure 8A: The dimensional changes in height at 6 weeks following treatment of
extraction sockets of teeth with facial dehiscence 33
Figure 8B: The dimensional changes in height at 12 weeks following treatment of
extraction sockets of teeth with facial dehiscence 34

6
LIST OF TABLES

TABLE 1: The ANOVA results for the model with the dependent variable rank of
absolute change from baseline, and the independent variables treatment, location,
and week, with 2-way and 3-way interaction terms. 20

LIST OF SUPPLIMENTARY DATA TABLES

Table 1A: Alveolar bone width and height (mm) of teeth in 6 intervention groups
(A, B, C, D, E, F) prior to tooth extraction and at 6 and 12 weeks following tooth
extraction. 35
Table 1B: The percentage of alveolar bone width and height of teeth in 6
intervention groups (A, B, C, D, E, F) prior to tooth extraction and at 6 and 12
weeks following tooth extraction. 37
Table 2A: Statistical significance of the absolute values of the alveolar bone width
and height (mm) comparisons among the 6 intervention groups (A, B, C, D, E, F).
39
Table 2B: Statistical significance of the percentage change of the alveolar bone
width and height relative to baseline among the 6 intervention groups (A, B, C, D,
E, F). 40

7
LIST OF SYMBOLS AND ABBREVIATIONS

ABBM Anorganic Bovine Bone Mineral
CBCT Cone Beam Computed Tomography
rh recombinant human
BMP Bone Morphogenetic Protein
IACUC Institutional Animal Care and Use Committee
PLLA Poly Lactic Acid
DICOM Digital Imaging and Communications in Medicine
HU Hounsfield Units

8
ABSTRACT

Aim: The aims of the present study were to: 1) Investigate dimensional changes to the
alveolar bone following tooth extraction in the non-human primate model using serial
CBCT studies, and 2) Examine the efficacy of two novel devices, SocketKAP™ and
SocketKAGE™, for ridge preservation and augmentation procedures following tooth
extraction in intact sockets and in sockets with large facial/buccal wall bony defects.
Material & Methods: Six 8-12 year old Macaca fascicularis had 6 teeth each (incisors,
premolars or molars) removed, 3 with intact socket walls and 3 with large facial
dehiscence defects. In each animal, Anorganic Bovine Bone Mineral (ABBM), non-
resorbable SocketKAP™ and resorbable SocketKAGE™ devices were used for the
following intervention groups:
Group A: Intact Socket Unfilled and Uncovered (Negative Control)
Group B: Intact Socket, the orifice of which was sealed with SocketKAP™
Group C: Intact Socket Filled with ABBM and covered with SocketKAP™
Group D: Facial Dehiscence Socket Unfilled and Uncovered (Negative Control)
Group E: Facial Dehiscence Socket reconstructed with SocketKAGE™ and covered with
SocketKAP™
Group F: Facial Dehiscence Socket reconstructed with SocketKAGE™, ABBM and
Covered with SocketKAP™
At four weeks, SocketKAP™, which had been sutured in place was removed from all
sockets. At pre-op, as well as 6 and 12 weeks post-extraction, CBCT imaging was
performed and used for measurement of socket width and height at multiple points.
9
Results: Without therapeutic intervention, intact sockets exhibited significant reduction
in width at the crestal 2 mm of the ridge crest within 6 weeks. Compared with the
negative control sites which lost up to 81% of crestal bone width, sites treated with
SocketKAP™ + ABBM lost at most 15% of bone width at the crestal 2 mm. Similar
results were seen in the dehiscence groups, with the combination of SocketKAP™ +
SocketKAGE™ + ABBM maintaining the greatest socket width and height dimensions
compared to the other two cohorts.
Conclusions: Results from the current non-human primate study suggest that the
SocketKAP™ and SocketKAGE™ devices, when used in conjunction with xenograft
proved effective in minimizing post-extraction socket width loss and height seen in both
intact sockets and sockets with facial dehiscence defects.

10
INTRODUCTION

The alveolar process is a dynamic structure whose integrity and function are to a
large extent tooth dependent. Loss of teeth predictably leads to resorption of the tooth-
bearing alveolus, a process that has been extensively studied in both animal models
(Lekovic et al. 1997, Camargo et al. 2000, Botticelli et al. 2004, Elian et al. 2007,
Hammerle et al. 2012) and humans (Schropp et al. 2003, Chen et al. 2005, Kan et al.
2007, Valentini et al. 2010). These studies have shown that most of the resorption occurs
during the first 3 months of healing, although dimensional changes can be observed up to
1 year or more after tooth extraction. Such changes result in approximately 50%
reduction of the bucco-lingual dimension of the alveolar ridge (Schropp et al. 2003),
mainly due to the resorption of the buccal bone plate (Araujo and Lindhe 2005). In spite
of predictable negative post-extraction resorption, no non-human primate split-mouth
designed studies currently exist that examine both the efficacy of ridge preservation
procedures and the ongoing dynamics of alveolar ridge dimensional changes following
tooth removal.
Post-extraction ridge resorption imposes significant limitations on subsequent
efforts to restore lost dentition, both in terms of compromised implant placement, or less
than ideal esthetic results obtained with traditional fixed prosthetic restorations. In
response to predictable post-extraction ridge remodeling, multiple ridge preservation
procedures have evolved to preserve alveolar ridge volume and morphology. These
include careful flapless tooth extraction designed to achieve undisturbed socket healing
(Chen et al. 2005, Chen et al. 2007), immediate implant placement (Chen et al. 2005,
Chen et al. 2007), grafting the post-extraction socket with bone graft substitute materials,

11
with or without barrier membranes (Fickl et al. 2008, Fickl et al. 2008), and placement of
tissue engineered growth factors, i.e. rhPDGF-BB or rhBMP-2, following tooth removal
(Sigurdsson et al. 1997, Paolantonio et al. 2001, Devlin and Sloan 2002, Schropp et al.
2003, Fickl et al. 2008, Fickl et al. 2008, Trombelli et al. 2008). However, to date there
has been no consensus verifying superior efficacy among these ridge preservation
procedures. A systematic review by Vignoletti et al (Vignoletti et al. 2012) concluded
that different ridge preservation techniques can significantly reduce post-extraction
alveolar ridge resorption, but was unable to conclude superiority of one technique over
another.
Multiple materials and techniques have been used in ridge preservation
procedures, including xenograft (Araujo and Lindhe 2009, Mardas et al. 2010, Favero et
al. 2013), allograft (Araujo and Lindhe 2011, Wallace 2013), and alloplastic materials.
An important objective of ridge preservation procedures is the protection of the graft
material from the oral environment during the healing process. A variety of both
resorbable (Scheyer et al. 2012, Favero et al. 2013) and non-resorbable (Lekovic et al.
1997) membranes have been used for this purpose. It remains controversial, however,
whether it’s best to achieve primary soft tissue closure over the grafted socket and
membrane, or to leave the membrane exposed without changing the position of the
gingival margin.
A common challenge in current ridge preservation procedures is the application of
flat shaped membranes to the complex geometric configurations of extraction sockets. In
an attempt to respond to limitations inherent in post-extraction membrane placement,
preformed novel devices have been fabricated as an alternative to membrane positioning

12
in ridge preservation procedures. A dome-shaped non-resorbable device has been devised
with different sizes to readily adapt to socket orifice in different oral sites. The purpose of
this “socket cap” is to seal access to the underlying residual socket following tooth
removal.
Additional post-extraction challenge is the management of labial or buccal
alveolar wall dehiscence defects. Currently, the most common technique designed for
reconstruction of the missing facial plate is the “socket repair technique” (Elian et al.
2007), also known as the “ice cream cone technique”. A resorbable cage device has been
designed to maintain the space within socket in the absence of such function normally
played by the facial alveolar bone. The “socket cage” device functions to support and
maintain normal 3-dimensional volume of the socket in sites with facial wall dehiscence
defects to prevent tissue collapse following tooth removal. The aims of the present study
were to: 1) Investigate the dimensional changes occurring to the alveolar bone following
tooth extraction in the non-human primate animal model using serial CBCT studies, and
2) Examine the efficacy of Socket cap and Socket cage for ridge preservation and
augmentation procedures following tooth extraction.

13
MATERIALS & METHODS

1. Animals
This animal study was carried out in accordance with the guidelines of the Institutional
Animal Care and Use Committee (IACUC) of the Capital Medical University, Beijing, China. A
total of six young adult male crab-eating macaque (Macaca fascicularis), 8–12 years old and
weighing between 4.0 and 5.0 kg were included in this study. Before surgery, the animals were
maintained in individual cages with water and food ad libitum.

2. Materials
Extraction socket devices. Preformed socket devices were used to seal the orifice of
sockets (SocketKAP
™
) or to provide structural stability to sockets with loss of facial alveolar
bone (SocketKAGE
™
) (Figures 1A & 1B & 1C). SocketKAP
™
(Regenimmune, Woodland Hills,
CA) was composed of polypropylene and SocketKAGE
™
(Regenimmune, Woodland Hills, CA)
was produced from poly D,L-lactic acid co-polymer (PLLA; 5%D and 95% L-lactite). In sockets
with facial dehiscence, SocketKAGE
™
was placed in order to maintain normal 3-dimensional
residual socket geometry (Figure 2). When called for by the study protocol, anorganic bovine
bone mineral (ABBM), (Bio-Oss
®
Geistlich Pharma, AB, Wolhusen, Switzerland) was the bone
graft substitute material placed within residual sockets following tooth removal.

14
Figure 1.

Figure 1. Extraction devices utilized in the present study. SocketKAP
™
consists of a dome-
shaped device composed of polypropylene with channels on the superior surface for passage of
suture (A). The SocketKAP
™
was used for obturation of the extraction socket orifice and
protection from the oral environment. Facial (B) and lateral (C) views of the SocketKAGE
™

illustrate a device consisting of a rigid series of inter-connected ribs composed of PLLA utilized
for support of sockets with facial dehiscence. The conical projections on ribs are intended as
spacers to prevent direct contact with facial and lingual alveolar plates, to allow better blood
circulation.

15
Figure 2.
Figure 2. Clinical images of extraction socket devices utilized for treatment of extraction sockets.
Placement of SocketKAP™ in situ (a). Teeth with intact alveolar bone were extracted with
flapless approach and the SocketKAP™ was secured to the opening of sockets with aid of PTFE
sutures. Surgically induced facial dehiscence (b) A mucoperiosteal flap was elevated to expose
the facial alveolar bone. Following tooth extraction, the entire facial plate was surgically
removed from crest to apex, extending to interproximal line angles. Placement of
SocketKAGE™ in situ.

16
3. Defect Models Following Extractions
In order to examine device effectiveness, two defect models were utilized in this study
following tooth removal: 1) Intact extraction socket wall model (SocketKAP™); or 2) Facial
dehiscence defect model (SocketKAP™ + SocketKAGE™), each with or without ABBM. Prior
to surgery each animal received a dental prophylaxis followed by a 0.12% Chlorhexidine
Gluconate solution surgical site wash. Maxillary incisors, premolars and molars and mandibular
premolars and molars were atraumatically extracted in each monkey, followed by thorough
degranulation of any soft tissue remnants. For the dehiscence defect model facial bony plates
were removed from the alveolar crest to the tooth apex. (Figure 2)
Following tooth removal, the following Defect Groups were created, with each animal
contributing one of each of the 6 defect types:
Group A: Intact Socket Unfilled and Uncovered (Negative Control)
Group B: Intact Socket Covered with SocketKAP™
Group C: Intact Socket Filled with ABBM and Covered with SocketKAP™
Group D: Facial Dehiscence Socket Unfilled and Uncovered (Negative Control)
Group E: Facial Dehiscence Socket reconstructed with SocketKAGE™ and covered with
SocketKAP™
Group F: Facial Dehiscence Socket reconstructed with SocketKAGE™ and ABBM and Covered
with SocketKAP™
At four weeks, the non-resorbable SocketKAP™ device, which had been sutured in place
with PTFE sutures, was removed from all defect sites.

17
4. CBCT analysis
Live animals were scanned with CBCT-scan at baseline and then at 6 and 12 weeks after
surgery, followed by quantitative analysis to measure new bone formation at defined locations
within the grafted sites. In addition, three-dimensional reconstruction of bone and soft tissues
was performed. Each specimen was placed in a sample holder and scanned using high-resolution.
After scanning, the 2D image data was stored in Digital Imaging and Communications in
Medicine (DICOM) format and then transferred to a computer for 3D reconstruction and
analysis. The bone tissues were segmented using a global thresholding procedure. Threshold
equaled to -360 HU was used to investigate bone tissues within the defects. The proportion of
bone volume occupying the defect virtual spaces was measured, allowing quantitative
comparisons among Groups A – F. Bone volume within any defect area was measured using
Simplant
®
software (Dentsply Implants, Waldham, MA, USA). Simplant® software is capable of
aligning the images so that it was able to slice the same point for direct comparison. 3
dimensional images were rotated until marginal bone level of subject site match to those of
adjacent tooth site. Then, for each bucco-lingual cross-sectional images were obtained using
adjacent tooth axis as a reference. CBCT linear measurements at baseline, 6, and 12 weeks post-
surgery using Simplant® software were as follows: 1) Bone width at different levels (1, 2, 3, and
5 mm) relative to the alveolar bone crest at baseline; and 2) Bone height at the buccal, middle,
and lingual thirds of the examined alveolus relative to the bone crest and root apex at baseline
(Figure 3). The baseline CBCT images were superimposed with the corresponding 6 weeks and
12 weeks CBCT images to verify the measurement sites were matched with different time point
images using anatomic repeatable landmarks such as maxillary sinus floor, mandibular canal,
and outline of alveolar bone. When the bone width at 1, 2, 3, and 5 mm below the baseline crest

18
and bone height, from bone crest to tooth apex, were measured, adjacent marginal bone level and
tooth apex level were used as a reference object of baseline marginal bone crest and a baseline
tooth apex at subject sites. All radiographic measurements were conducted by the primary
author. The reliability of measurement were made by 10% of repeated measurement and the
variance between two measures was less than 5%.

Figure 3.

Figure 3. The radiographic landmarks used for measurement of bone width and bone height on
CBCT images. The bone crest and tooth apex were demarcated as dotted lines. Bone width was
measured at 1, 2, 3, and 5mm relative to the alveolar bone crest (A). Bone height was measured
at facial/buccal, middle and lingual third of the alveolar bone relative to bone crest and root apex
(B).

19
5. Statistical Analysis
Statistical analysis was performed using SPSS v. 18, IBM, Chicago, IL and R v. 3.0.2.
We examined the effects of treatment (A, B, C, D, E, and F), location (widths or heights), and
week in analysis of variance models, using (i) absolute change from baseline or (ii) percent
change from baseline as the dependent variable, with or without interaction terms. To deal with
possible non-normality of distributions, we repeated the analyses using (iii) rank of absolute
change from baseline and (iv) rank of percent change from baseline (comparable to a Wilcoxon
or Kruskal-Wallis analysis, but allowing use of covariates). For all these models, there were
significant differences between treatments and significant differences between locations. Week
was significant in some but not all models. Interaction terms were significant in some but not all
models. Table 1 shows the ANOVA results for the model with the dependent variable rank of
absolute change from baseline, and the independent variables treatment, location, and week, with
2-way and 3-way interaction terms. The p-value for treatment in other models was in some cases
better than and in some cases worse than in this example, but in all models, treatment was
significant. The hypothesis tests indicate that the treatment groups differed significantly in
absolute change, percent change, and ranked change from baseline. To further examine the
treatment effects, we performed separate pairwise t-tests for all combinations of week, treatment
group (pairwise for treatments {A, B, C} or {D, E, F}), and location (widths and heights). These
post-hoc tests have low power because of the small number of observations in each comparison.
In addition, unlike the global hypothesis tests described above, these post-hoc t-tests require
adjustment for multiple comparisons. Of 48 post-hoc t-tests for treatment effect on width, 21 are
significant (p<0.05) without correction for multiple comparisons, while 7 are significant after
Bonferroni correction for multiple comparison. Of 36 post-hoc t-tests for treatment effect on

20
height, 6 are significant (p<0.05) without correction for multiple comparisons, while one is
significant after Bonferroni correction. These results are expected due to the large number of
tests performed, the small number of observations used in each test, and the conservative nature
of the Bonferroni test. The p-values for all comparisons are listed in Supplemental Table 2.

Table 1.
Table 1. The ANOVA results for the model with the dependent variable rank of absolute change
from baseline, and the independent variables treatment, location, and week, with 2-way and 3-
way interaction terms.

21
RESULTS

1. Clinical Observation
Throughout the study all surgical sites healed uneventfully with minimal inflammation
and no signs of infection.

2. Radiographic CBCT Measurements
-Bone Width at 6 Weeks: Intact Sockets (Figures 4 and 5A)
Group A Negative Control: Significant loss of bone width occurred, especially at 1 and 2 mm
apical to the alveolar crest. At 6-weeks post-surgery, the percentage of remaining bone width
were 18.9±23.2%, 48.2±10.6%, 84.4±13.2%, 91.5±7.2% at 1, 2, 3 and 5mm from the crest,
respectively. (Figure 5A)
Group B SocketKAP™ Only: When SocketKAP™ was used to seal sockets without a bone
filler, approximately 23.1±24.3%, 56.1±10.6%, 89.2±11.3%, 95.2±4.8% remained at 1, 2, 3 and
5mm from the crest, respectively. At 6 weeks, the bone widths of groups A and B were not
statistically significantly different. (Figure 5A)
Group C SocketKAP™ + ABBM: When sockets were filled with ABBM and covered with
SocketKAP™, approximately 87.9±8.7%, 96.2±3%, 98.1±1.6%, 97±2.4% bone width remained
at 1, 2, 3 and 5mm from the crest, respectively. At 1 and 2mm from the bone crest, the
percentage of bone width remaining in group C was statistically significantly higher than the
remaining bone width in groups A or B. (Figure 5A)

22
-Bone Width at 12 Weeks: Intact Sockets (Figures 4 and 5B)
Group A Negative Control: Significant loss of bone width persisted, especially at 1 mm apical to
the alveolar crest. After 12 weeks, the percentages of bone width remaining were 33.5±30%,
64.4±13.7%, 77.7±6.3%, 89.8±5.1% at 1, 2, 3 and 5mm from the crest, respectively.(Figure 5B)
Group B SocketKAP™ Only: Approximately 39.3±22.2%, 67.7±27.2%, 76.7±21.7%,
86.4±11.5% remained at 1, 2, 3 and 5mm from the crest, respectively at 12 weeks.(Figure 5B)
Group C SocketKAP™ + ABBM: When sockets were filled with ABBM and covered with
SocketKAP™85.3±6.4%, 90.6±5.2%, 94.5±5.5%, 96±3.6% of the original bone width remained
at 1, 2, 3 and 5mm from the crest, respectively. At 1 and 2mm from the bone crest, the
percentage of bone width remaining in group C was statistically significantly higher than the
remaining bone width in groups A or B and statistically significantly greater than Group A at 3
mm from the ridge crest. (Figure 5B)

-Bone height at 6 Weeks: Intact Sockets (Figures 4 and 6A)
Group A Negative Control: Significant loss of bone height occurred, most notably at the buccal
aspects of the ridge. At 6-weeks post-surgery, the percentages of bone height remaining were
52.8±17.9%, 77.2±17.6%, 85.6±10.8%at the buccal, middle, and lingual aspects, respectively.
Group B SocketKAP™ Only: No statistically significant differences in height at 6 weeks were
observed between Group B and Groups A and C at any measured location. (Figure 6A)
Group C SocketKAP™ + ABBM: When sockets were filled with ABBM and covered with
SocketKAP™, most of the loss of vertical bone height was avoided, i.e. 92.5±8.1%, 97.1±1.2%,
92.4±4.5% remained at buccal, middle, and lingual aspects, respectively. The difference between

23
the loss of vertical height between groups A and C was significant in the buccal aspect (p<0.05).
(Figure 6A)

-Bone height at 12Weeks: Intact Sockets (Figures 4 and 6B)
Group A Negative Control: Significant loss of bone height occurred, most notably at the buccal
aspects of the ridge. At 12-weeks post-surgery, the percentages of bone height remaining were
49.3±18.9%, 86.5±9.1%, 84.2±9.2% in the buccal, middle and lingual aspects, respectively.
Group B SocketKAP™ Only: Vertical bone height at the buccal aspect was significantly greater
compared with the negative control group (p<0.05).
Group C SocketKAP™ + ABBM: Most of the loss of vertical bone height was avoided with
85.0±12.71%, 93.4±4.1%, 90.4±6.6 bone height remaining in the buccal, middle, and lingual
aspects, respectively. At 12 weeks, in intact sockets, significantly greater percentages of bone
height remained in Group C compared to the negative control Group A (p<0.01).
-Bone Width at 6 Weeks: Facial Dehiscence Sockets (Figures 4 and 7A)
Group D Negative Control: Significant loss of width occurred at 6 weeks, with the majority of
bone width loss occurring at 1, 2, and 3 mm from the crest. At 6 weeks,5.5±6.9%, 13.4±13.4%,
36.6±12.3%, 64.6±10.6% remained at 1, 2, 3, 5mm from crest respectively.
Group E SocketKAP™ + SocketKAGE™ Only: At 6 weeks, the bone width remaining was
significantly greater than in negative control sites at 1, 2 and 3mm from the crest, with
35.3±6.3%, 47.9±9.4%, 66.3±17.9%, 75.5±10.6% remaining at 1, 2, 3 and 5mm from crest
respectively.

24
Group F: SocketKAP™ + SocketKAGE™ +ABBM: At 6 weeks, the remaining bone width was
statistically significantly greater than Groups D and E at 2 and 3 mm from the alveolar crest and
significantly greater than Group D negative control at 5 mm.

-Bone Width at 12 Weeks: Facial Dehiscence Sockets (Figures 4 and 7B)
Group D Negative Control: At 12 weeks, improvement in remaining width was seen compared to
week six findings, with 25.6±17.7%, 52.5±24.8%, 56.3±27.8%, 79.5±16.2% remaining at 1, 2, 3,
and 5mm from the crest respectively.
Group E SocketKAP™ + SocketKAGE™ Only: At 12 weeks, 43.4±12.1%, 48±13.5%,
59±14.2%, 82±8.6% bone width remained at 1, 2, 3, and 5mm from the crest respectively. No
significant differences in bony width were seen between Group D and Group E at any level from
the alveolar crest at 12 weeks.
Group F: SocketKAP™ + SocketKAGE™ +ABBM: At 12 weeks, the bone width remaining
was significantly greater in group F compared with both other groups at 2 and 3 mm from the
alveolar bone crest. At 5mm from the bone crest, group F also demonstrated significantly greater
bone width compared to group E.

-Bone Height at 6 Weeks: Facial Dehiscence Sockets (Figures 4 and 8A)
Group D Negative Control: At six weeks, sites with facial dehiscence lost a significant degree of
bone height, with 40.3±12.2%, 77.2±24%, 87.1±11.5% of bone height remaining at the buccal,
middle, and lingual aspects respectively when no device or grafting material were placed.
Group E SocketKAP™ + SocketKAGE™ Only: At six weeks, no significant differences in
height were observed at any location between Group E and the negative control Group D sites.

25
Group F: SocketKAP™ + SocketKAGE™ +ABBM: Significant differences in height in favor of
Group F were noted at six weeks compared with Group D at the buccal aspect and Group E at
the middle aspect of the treated sockets.

-Bone Height at 12 Weeks: Facial Dehiscence Sockets (Figures 4 and 8B)
Group D Negative Control: At 12 weeks, the remaining bone height of Group D remained similar to the
height observed at 6 weeks. At 12 weeks, 44.1±29.7%, 62.3±25.6%, 88.3±8.5% bone height in this
facial dehiscence treated group were noted at buccal, middle, and lingual aspects respectively.
Group E SocketKAP™ + SocketKAGE™ Only: No statistically significant differences in height
were observed at any measured location between Group E and Group D and between Group E
and Group F at the middle and lingual aspects. There was, however, a statistically significant
difference seen at the buccal aspect, between Group E and Group F, in favor of Group F.
Group F: SocketKAP™ + SocketKAGE™ +ABBM: At 12 weeks, the only statistically
significant finding was a greater percentage of bone height of Group F sites compared with
Group E sites at the buccal aspect (p<0.01).

26
Figure 4.

Figure 4. Representative CBCT images at baseline, 6, and 12 weeks after extraction. Groups A-C
had intact alveolar socket walls. Facial bony dehiscence was created for groups D - F. Group A
(negative control), Group B (SocketKAP
™
), Group C (SocketKAP
™
plus anorganic bovine bone
mineral), Group D (negative control), Group E (SocketKAP
™
and SocketKAGE
™
), Group F
(SocketKAP
™
, SocketKAGE
™
plus anorganic bovine bone mineral).

27
Figure 5A.

Figure 5A. The dimensional changes at 6 weeks following treatment of extraction sockets of
teeth with intact alveolar bone is shown in Figure 5A. Results revealed significant differences in
remaining percentage of bone width at 1 and 2 mm from the crest among the treatment groups,
with statistically significantly greater percentages of bone noted for SocketKAP™ + ABBM
versus SocketKAP™ alone or the unfilled negative control (**p<0.01).

28
Figure 5B.

Figure 5B. At 12 weeks results revealed the percentage of bone width in intact sockets present at
1, 2 and 3 mm relative to the bone crest were significantly different among the 3 treatment
groups. Ridge width was maintained best (~85%) for sockets filled with ABBM and covered
with SocketKAP
TM
relative to other groups. SocketKAP™ +ABBM group also demonstrated
greater bone width at 3mm compared to the negative control (*p<0.05). No significant
differences in bone width were seen between the negative control and SocketKAP™ alone
groups.

29
Figure 6A.

Figure 6A. The dimensional changes in height at 6 weeks following treatment of extraction
sockets of teeth with intact alveolar bone is shown in Figure 6A. At the buccal aspect ABBM
+SocketKAP
TM
exhibited significantly greater bone height compared to the negative control
(*p<0.05).

30
Figure 6B.

Figure 6B. Dimensional bone height changes at 12 weeks following treatment of extraction
sockets of teeth with intact alveolar bone is shown in Figure 6B. At the buccal aspect, Group B
(SocketKAP™ alone) and Group C (ABBM + SocketKAP™) exhibited significantly greater
bone height when compared to the negative control (*p<0.05, **p<0.01).

31
Figure 7A.
Figure7A. The dimensional changes at 6 weeks following treatment of extraction sockets of teeth
with facial dehiscence are shown in Figure 7A. Group F (SocketKAP™ + SocketKAGE™ +
ABBM)exhibited significantly greater bone width at 2, 3, and 5 mm from the alveolar bone crest
compared to other groups (*p<0.05, **p<0.01). Group E(SocketKAP
TM
+ SocketKAGE™)
demonstrated greater bone width than the negative control group at 1, 2, and 3 mm from the
crest. (*p<0.05, **p<0.01).

32
Figure 7B.
Figure 7B. The dimensional width changes at 12 weeks following treatment of extraction sockets
of teeth with facial dehiscence are shown in Figure 7B.Significant differences were seen among
the 3 groups at 2, 3, and 5 mm from the alveolar crest. Group F (SocketKAP™ +
SocketKAGE™ + ABBM) exhibited significantly greater bone width at 2 and 3 mm relative to
the alveolar bone crest compared to Groups D and E (*p<0.05, **p<0.01) and significantly
greater bone width at 5 mm compared to Group E (SocketKAP™ + SocketKAGE™). No
significant differences were seen between Groups D and E at any distance from the alveolar
crest.

33
Figure 8A.

Figure 8A. The dimensional changes in height at 6 weeks following treatment of extraction
sockets of teeth with facial dehiscence are shown in Figure 8A. Statistically significant
differences in bone height are noted between Group F (SocketKAP™ + SocketKAGE™ +
ABBM) and Group D negative control at the buccal aspect and between Group F and Group E
(SocketKAP™ + SocketKAGE™) at the middle aspect of the treated sockets.

34
Figure 8B.
Figure 8B. The dimensional changes in height at 12 weeks following treatment of extraction
sockets of teeth with facial dehiscence are shown in Figure 8B. At 12 weeks the only statistically
significant difference among the 3 groups was noted at the buccal aspect between Group F
(SocketKAP™ + SocketKAGE™ + ABBM) and Group E (SocketKAP™ + SocketKAGE™)
(**p<0.01).

35
SUPPLEMENTARY DATA
Table 1A. Alveolar bone width and height (mm) of teeth in 6 intervention groups (A, B, C, D, E,
F) prior to tooth extraction and at 6 and 12 weeks following tooth extraction. Statistical
significance using Student t-test: A vs. B: *P<0.05, **P<0.01, A vs. C:
✝
P<0.05,
✝✝
P<0.01, B vs.
C:
✤
P<0.05,
✤✤
P<0.01, D vs. E:
#
P<0.05,
##
P<0.01, D vs. F:
§
P<0.05,
§§
P<0.01, E vs. F:
¶
P<0.05,
¶¶
P<0.01

Bone width at
1mm
Extraction sockets of teeth with intact alveolar bone Extraction sockets of teeth with facial dehiscence
Negative control
(A)
(Median)
Socket cap (B)
(Median)
Socket cap +
ABBM (C)
(Median)
Negative
control (D)
(Median)
Socket cap +
Socket cage (E)
(Median)
Socket cap +
Socket cage +
ABBM (F)
(Median)
Baseline (mm) 8.3 ±0.7 (8.2) 8.5 ±0.3 (8.5) 8.4 ±0.1 (8.3) 7.3 ±1.8 (6.8) 7.2 ±0.6 (7.2) 7.0 ±0.8 (7.0)
6 week (mm) 1.5 ±2.0 (0) 1.9 ±2.3 (1.4)
7.3 ±0.7
✝✝,
✤✤

(7.2)
0.3 ±0.6 (0)
2.6 ±0.7
##

(2.7)
2.4 ±2.6 (1.1)
12 week (mm) 2.2 ±2.6 (1.4) 4.0 ±3.2 (3.4) 7.0 ±0.7
✝✝

(6.7)
2.2 ±1.5 (1.9) 2.7 ±1.3 (2.9) 3.0 ±2.5 (2.7)

Bone width at
2mm
Extraction sockets of teeth with intact alveolar bone Extraction sockets of teeth with facial dehiscence
Negative control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
Baseline (mm) 9.0 ±0.7 (9.0) 9.4 ±0.8 (9.5) 8.8 ±0.2 (8.9) 7.0 ±0.7 (6.9) 7.6 ±0.9 (7.4) 7.3 ±0.7 (7.5)
6 week (mm) 4.2 ±0.9 (4.2) 5.3 ±1.5 (5.7)
8.5 ±0.2
✝✝,
✤✤

(8.5)
0.9 ±0.9 (0.6)
3.5 ±0.8
##

(3.2)
5.9 ±2.4
§§

(6.6)
12 week (mm) 5.7 ±1.2 (5.9) 6.5 ±2.9 (6.3) 8.0 ±0.4
✝✝

(8.0)
3.8 ±2.2 (3.9) 3.6 ±0.8 (3.8)
6.7 ±1.1
¶¶,§

(6.9)

Bone width at
3mm
Extraction sockets of teeth with intact alveolar bone Extraction sockets of teeth with facial dehiscence
Negative control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
Baseline (mm) 9.8 ±1.0 (10.3) 10.3 ±0.7
✤✤

(10.7)
8.9 ±0.2 (8.9) 7.4 ±0.7 (7.3) 7.8 ±0.7 (7.6) 8.0 ±0.9 (8.0)
6 week (mm) 8.1 ±1.8 (8.0) 9.1 ±1.5 (9.6) 8.8 ±0.2 (8.8) 2.7 ±1.1 (2.6)
5.0 ±1.6
#
(4.9) 7.6 ±1.0
§§,¶¶

(7.5)
12 week (mm) 7.5 ±1.0 (7.6) 8.3 ±2.5 (9.9) 8.4 ±0.5 (8.3) 4.5 ±2.4 (4.8) 4.8 ±1.4 (4.9)
7.6 ±1.2
§,¶¶

(7.6)

36

Bone width at
5mm
Extraction sockets of teeth with intact alveolar bone Extraction sockets of teeth with facial dehiscence
Negative control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
Baseline (mm) 10.3 ±1.6 (11.0) 11.3 ±0.4
✤✤

(11.2)
8.8 ±0.6

(8.8) 8.0 ±0.8 (8.1) 7.9 ±0.7 (7.8) 8.3 ±1.2 (8.8)
6 week (mm) 9.3 ±1.9 (8.8) 10.9 ±1.0
✤✤

(11.1)
8.7 ±0.5 (8.7) 6.6 ±1.3 (6.2) 6.5 ±1.1 (6.7) 8.2 ±1.3 (8.7)
12 week (mm) 9.2 ±1.6 (9.5) 9.8 ±1.7 (10.5) 8.4 ±0.4 (8.3) 6.4 ±1.6 (6.4) 6.5 ±1.0 (6.4) 7.8 ±1.1 (8.1)

Bone height at
buccal point
Extraction sockets of teeth with intact alveolar bone Extraction sockets of teeth with facial dehiscence
Negative control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socketcap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
Baseline (mm) 8.7 ±2.4 (8.2) 8.4 ±2.7 (9.7) 8.6 ±0.7 (8.5) 8.2 ±1.5 (8.4) 8.7 ±2.1 (8.3) 8.8 ±0.7 (9.0)
6 week (mm) 4.7 ±2.2 (4.6) 6.8 ±2.5 (6.7) 8.1 ±1.1
✝
(8.4) 3.5 ±1.7 (3.3) 4.2 ±2.4 (4.8)
6.9 ±1.5
§
(7.7)
12 week (mm) 4.5 ±2.6 (3.4) 6.0 ±1.7 (5.7) 7.4 ±1.8 (6.9) 3.5 ±2.7 (2.1) 3.8 ±2.2 (3.2) 6.2 ±1.6 (5.8)

Bone height at
middle point
Extraction sockets of teeth with intact alveolar bone Extraction sockets of teeth with facial dehiscence
Negative control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
Baseline (mm) 8.1 ±2.3 (7.9) 7.7 ±2.7 (8.0) 8.4 ±0.9 (8.2) 7.7 ±1.9 (7.8) 8.7 ±2.3 (8.5) 7.4 ±0.9 (7.6)
6 week (mm) 6.5 ±2.9 (5.0) 6.5 ±2.6 (6.4) 8.3 ±1.0 (8.4) 4.6 ±1.8 (4.8) 5.3 ±2.2 (5.5)
6.9 ±1.1
§
(7.5)
12 week (mm) 6.8 ±1.8 (6.6) 7.0 ±1.9 (6.8) 7.7 ±1.3 (7.7) 5.2 ±2.5 (5.5) 6.6 ±3.1 (7.4) 6.5 ±1.1 (6.6)

Bone height at
lingual point
Extraction sockets of teeth with intact alveolar bone Extraction sockets of teeth with facial dehiscence
Negative control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
Baseline (mm) 7.9 ±2.8 (8.1) 6.7 ±2.3 (6.8) 10.0 ±0.6
✤

(10.1)
7.0 ±2.5 (7.3) 9.5 ±2.8 (9.3)
6.2 ±0.8
¶
(6.4)
6 week (mm) 6.8 ±2.2 (6.8) 5.9 ±2.4 (5.9) 9.2 ±1.1
✤
(9.3) 6.1 ±3.0 (4.8) 9.2 ±1.9 (9.6)
5.8 ±1.1
¶¶

(6.1)
12 week (mm) 6.4 ±2.5 (6.0) 5.9 ±1.8 (6.0) 8.5 ±1.4
✤
(9.1) 5.4 ±2.8 (5.2) 8.5 ±2.2 (9.1)
5.5 ±1.2
¶
(6.0)

37
Table 1B. The percentage of alveolar bone width and height of teeth in 6 intervention groups (A,
B, C, D, E, F) prior to tooth extraction and at 6 and 12 weeks following tooth extraction.
Statistical significance using Student t-test: A vs. B: *P<0.05, **P<0.01, A vs. C:
✝
P<0.05,
✝✝
P<0.01, B vs. C:
✤
P<0.05,
✤✤
P<0.01, D vs. E:
#
P<0.05,
##
P<0.01, D vs. F:
§
P<0.05,
§§
P<0.01, E
vs. F:
¶
P<0.05,
¶¶
P<0.01

Bone width at
1mm
Extraction sockets of teeth with intact alveolar
bone
Extraction sockets of teeth with facial dehiscence
Negative
control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
6 week (mm) 18.9 ±23.3 (0) 23.1 ±24.3
(17.8)
87.8 ±
8.7
✝✝,
✤✤

(86.6)
5.5 ±6.9
(6.3)
35.3 ±6.3
##

(36.6)
36.3 ±39.2
(18.8)
12 week (mm) 33.5 ±30.0
(33.6)
39.2 ±22.2
(39.9)
85.3 ±
6.4
✝✝,
✤✤

(85.4)
25.6 ±17.6
(28.8)
43.4 ±12.1
(42.7)
29.6 ±17.7
(33.3)

Bone width at
2mm
Extraction sockets of teeth with intact alveolar
bone
Extraction sockets of teeth with facial dehiscence
Negative
control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
6 week (mm) 48.2 ±10.6
(52.1)
56.1 ±10.6
(59.7)
96.2 ±
3.0
✝✝,
✤✤

(96.5)
13.4 ±13.4
(8.2)
47.8 ±9.4
##

(44.4)
83.2 ±29.4
§§

(97.6)
12 week (mm) 64.4 ±13.7
(69.3)
67.7 ±27.2
(63.0)
90.6 ±5.2
✝,
✤

(91.5)
52.5 ±24.8
(57.9)
48.0 ±13.5
(48.1)
91.3 ±
8.8
§§,¶¶

(92.4)

Bone width at
3mm
Extraction sockets of teeth with intact alveolar
bone
Extraction sockets of teeth with facial dehiscence
Negative
control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
6 week (mm) 84.4 ±13.2
(91.6)
89.2 ±11.3
(93.7)
98.1 ±1.6
(98.4)
36.6 ±12.3
(40.0)
66.3 ±17.9
#

(66.3)
97.7 ±
2.2
§§,¶¶

(98.8)
12 week (mm) 77.7 ±6.3
(75.9)
76.7 ±21.7
(82.1)
94.5 ±5.5
✝

(96.4)
56.3 ±27.8
(70.2)
59.0 ±14.2
(67.5)
93.6 ±4.7
§,¶¶

(95.7)

38
Bone width at
5mm
Extraction sockets of teeth with intact alveolar
bone
Extraction sockets of teeth with facial dehiscence
Negative
control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
6 week (mm) 91.5 ±7.2
(95.8)
95.2 ±4.8
(96.9)
97.0 ±2.4
(97.4)
83.2 ±10.6
(82.8)
84.8 ±10.6
(85.7)
99.6 ±0.4
§

(99.7)
12 week (mm) 89.8 ±5.1
(92.8)
86.4 ±11.5
(93.6)
96.0 ±3.6
(96.3)
79.5 ±16.2
(88.0)
82.2 ±8.6
(81.2)
93.9 ±3.5
¶

(94.8)

Bone height at
buccal point
Extraction sockets of teeth with intact alveolar
bone
Extraction sockets of teeth with facial dehiscence
Negative
control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socketcap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
6 week (mm) 52.8 ±17.9
(46.1)
76.2 ±14.6
(82.9)
92.5 ±8.1
✝

(95.6)
40.4 ±12.0
(36.6)
48.1 ±28.0
(39.6)
77.7 ±13.8
§

(82.0)
12 week (mm) 49.2 ±18.9
(46.0)
76.4 ±19.0*
(77.0)
85.0 ±12.7
✝✝

(85.6)
44.1 ±29.7
(32.4)
41.5 ±17.0
(42.8)
70.7 ±14.4
¶

(65.2)

Bone height at
middle point
Extraction sockets of teeth with intact alveolar
bone
Extraction sockets of teeth with facial dehiscence
Negative
control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
6 week (mm) 77.2 ±17.6
(88.7)
79.8 ±16.6
(85.4)
97.1 ±1.4
(97.3)
63.8 ±24.0
(68.9)
59.1 ±21.2
(52.1)
90.7 ±8.2
¶

(94.8)
12 week (mm) 86.5 ±9.1
(90.1)
88.7 ±6.7
(88.5)
93.4 ±4.1
(93.5)
62.3 ±25.6
(53.9)
82.8 ±21.0
(92.6)
84.0 ±13.2
(91.7)

Bone height at
lingual point
Extraction sockets of teeth with intact alveolar
bone
Extraction sockets of teeth with facial dehiscence
Negative
control
(Median)
Socket cap
(Median)
Socket cap +
ABBM
(Median)
Negative
control
(Median)
Socket cap +
Socket cage
(Median)
Socket cap +
Socket cage +
ABBM
(Median)
6 week (mm) 85.6 ±10.7
(91.4)
84.1 ±18.1
(90.6)
92.4 ±
4.5

(93.5)
87.1 ±11.5
(94.3)
90.1 ±3.7
(91.4)
91.1 ±8.6
(92.1)
12 week (mm) 84.2 ±9.2
(87.1)
84.3 ±11.5
(88.0)
90.4 ±
6.6

(92.3)
88.3 ±8.5
(90.5)
90.0 ±7.5
(89.3)
84.8 ±14.2
(90.4)

39
Table 2A. Statistical significance of the absolute values of the alveolar bone width and height
(mm) comparisons among the 6 intervention groups (A, B, C, D, E, F). Student’s t-test was used
for pair-wise comparisons.
1mm 2mm 3mm 5mm B M L
Baseline A vs B N.S N.S N.S N.S N.S N.S N.S
A vs C N.S N.S N.S N.S N.S N.S N.S
B vs C N.S N.S 0.00488 0.00005 N.S N.S 0.01454
6 week A vs B N.S N.S N.S N.S N.S N.S N.S
A vs C 0.00097 0.00005 N.S N.S 0.02724 N.S N.S
B vs C 0.00436 0.00596 N.S 0.00958 N.S N.S 0.04657
12 week A vs B N.S N.S N.S N.S N.S N.S N.S
A vs C 0.00312 0.00364 N.S N.S N.S N.S N.S
B vs C N.S N.S N.S N.S N.S N.S 0.0398

1mm 2mm 3mm 5mm B M L
Baseline D vs E N.S N.S N.S N.S N.S N.S N.S
D vs F N.S N.S N.S N.S N.S N.S N.S
E vs F N.S N.S N.S N.S N.S N.S 0.01868
6 week D vs E 0.0012 0.00125 0.02577 N.S N.S N.S N.S
D vs F N.S 0.00217 0.00007 N.S 0.01135 0.04552 N.S
E vs F N.S 0.06520 0.00345 N.S N.S N.S 0.00868
12 week D vs E N.S N.S N.S N.S N.S N.S N.S
D vs F N.S 0.01507 0.01802 N.S N.S N.S N.S
E vs F N.S 0.00019 0.00349 N.S N.S N.S 0.01357

40
Table 2B. Statistical significance of the percentage change of the alveolar bone width and height
relative to baseline among the 6 intervention groups (A, B, C, D, E, F). Student’s t-test was used
for pair-wise comparisons.

1mm 2mm 3mm 5mm B M L
6 week A vs B N.S N.S N.S N.S N.S N.S N.S
A vs C 0.00073 0.0004 N.S N.S 0.021209 N.S N.S
B vs C 0.00479 0.0007 N.S N.S N.S N.S N.S
12 week A vs B N.S N.S N.S N.S 0.014348 N.S N.S
A vs C 0.00945 0.0103 0.01692 N.S 0.000656 N.S N.S
B vs C 0.04615 0.0472 N.S N.S N.S N.S N.S

1mm 2mm 3mm 5mm B M L
6 week D vs E 0.00019 0.0004 0.02582 N.S N.S N.S N.S
D vs F N.S 0.0025 0.000001 0.0151 0.00356 N.S N.S
E vs F N.S N.S 0.00841 N.S N.S 0.02381 N.S
12 week D vs E N.S N.S N.S N.S N.S N.S N.S
D vs F N.S 0.0081 0.02939 N.S N.S N.S N.S
E vs F N.S 0.0001 0.00169 0.0181 0.01502 N.S N.S

41
DISCUSSION

Regeneration of bone is often necessitated for treatment of congenital anomalies,
traumatic injuries and infections such as periodontal disease which destroy jaw bone. Repair and
regeneration of these defects have traditionally been achieved with autologous bone grafting as a
gold standard due to its osteogenic property. Currently more than 500,000 bone grafts are
performed in US, with the global numbers estimated to be double, at a cost, projected to reach
$3.18 billion by 2015. Therefore, development of novel cost-effective bone regenerative material
can potentially obviate the need for bone harvesting and make this therapy accessible to a wider
number of patients. Since the alveolar process is a dynamic structure that is tooth-dependent
whereby the loss of teeth is followed by resorption of the tooth-bearing alveolus, proper
management of post-extraction ridge resorption is critical to the development of sites with
adequate bone volume and shape needed for implant placement or for conventional fixed
prostheses designed for optimal function and esthetics. A variety of current ridge preservation
protocols attempt to reduce the magnitude of negative ridge remodeling that invariably occurs
following tooth removal. In an attempt to respond to limitations inherent in post-extraction
membrane placement, preformed test devices have been fabricated as an alternative to membrane
positioning in ridge preservation procedures. The results of present study showed that the
combination of ABBM and extraction socket devices preserve better than other groups.
In addition, the present study was undertaken to better understand the magnitude and
kinetics of post-extraction ridge remodeling using serial CBCT analysis. Since there was not
enough evidence to conclude that which ridge preservation technique is superior than others
when dehiscence defect are present, the result of this study can provide better understanding to

42
the clinician in terms of wound healing and the efficacy of extraction socket devices and bone
graft for of dehiscence defect. The non-human primate model was chosen as the study vehicle
because of its closeness to humans and therefore its potential ability to extrapolate results
relevant to clinical practice and as a guide for future human clinical trials. In addition, the
effectiveness of newly developed extraction socket devices was also evaluated in the present
study using CBCT with linear measurement outcomes.
The present data demonstrated that without therapeutic intervention, post-extraction
remodeling in this non-human primate model leads to predictable alveolar bone width reduction
within 6 weeks in intact sockets within the first 2 mm apical to the ridge crest. These results are
consistent with those observations noted in human clinical (Camargo et al. 2000, Schropp et al.
2003) and canine (Cardaropoli et al. 2003, Araujo and Lindhe 2005) models. The SocketKAP™
device examined in this study, when used in conjunction with a xenograft material proved
effective in reducing the magnitude of crestal ridge width loss. Compared with the negative
control sites which lost up to 81% of crestal bone width, sites treated with SocketKAP™ +
xenograft lost at most 15% of bone width within the 2 mm zone apical to the ridge crest. Similar
statistically significant results were seen when comparing buccal height loss experienced in the
untreated negative controls to those intact sockets treated with SocketKAP™ + ABBM at both 6
and 12 weeks. In a recent systematic review, Hammerle, et al (Hammerle et al. 2012) concluded
that the alveolar ridge undergoes a mean horizontal width reduction of 3.8 mm and a mean
vertical height reduction of 1.24 mm within 6 months after tooth extraction. Vignoletti, et al.
(Vignoletti et al. 2012) in their meta-analyses of data demonstrated a statistically significant
greater ridge reduction in bone height of 1.4mm and bone width of 1.8mm for control sockets
without intervention as compared to test sites with ridge preservation.

43
Unlike intact sockets, little data is currently available for extraction sockets with facial
dehiscence, nor have the reconstruction protocols treating facial dehiscence been validated with
experimental data. Therefore, the present data are an important first step in leading to a more
comprehensive understanding of the trajectories of healing that occur when attempting to
reconstruct the missing facial bony plate. The results in this study, both for alveolar width and
height at both time periods, suggest that a protocol using SocketKAP™ + SocketKAGE™ +
ABBM following tooth removal in sockets with severe labial dehiscence defects will likely be
more effective in restoring normal dimensional anatomy when compared to the other groups in
this non-human primate study. However, the facial dehiscence data exhibited larger standard
deviations than seen for data derived from intact sockets. In view of the small number of sites
investigated in the present study, it is impossible to determine whether treatment with
SocketKAP™ + SocketKAGE™, without additional bone filler, will be effective in restoration
of bone height and width in the presence of significant labial dehiscence defects. Moreover, due
to limited number of sites, the efficacy of SocketKAP™ and SocketKAGE™ for bone
regeneration wasn’t able to be demonstrated. Further studies will be necessary to verify the effect
of SocketKAP™ and SocketKAGE™ in bone regeneration compare to other devices, such as
resorbable, non-resorbable membrane and autogenous soft tissue when those extraction devices
were used in conjunction with ABBM.
Previous canine animal model studies have demonstrated that placement of implants in
sites with facial dehiscence is accompanied with only partial restoration of lost facial bone
(Botticelli et al. 2004). Moreover, implants placed into human sites with facial dehiscence tend
to lead to higher early failure (Valentini et al. 2010), more mucosal recession (Kan et al. 2007),
fewer sites with bone fill , and greater peri-implant horizontal bone resorption (Chen et al. 2005,

44
Chen et al. 2007). Evidence therefore suggests that it may be clinically important to reconstruct
the missing facial plate prior to implant placement.
Since the current study’s outcome parameters looked at linear ridge dimensions using
serial CBCT, further studies examining the quality of regenerated bone through histologic
observation will be required in further determining the efficacy of the devices under present
examination. Such studies are currently being conducted.
Although important, the results derived from the current non-human primate model need
to be verified with comprehensive, randomized controlled human clinical trials. There is
presently an ongoing human clinical trial, which seeks to investigate the efficacy of ridge
preservation and reconstructive techniques using the SocketKAP™ and SocketKAGE™ devices.
It is anticipated that results from this human study will be useful in validating the utility of these
extraction socket devices in the clinical post-extraction management of extraction sockets.

45
CONCLUSION

In conclusion, results from the current non-human primate study suggest that the
SocketKAP™ and SocketKAGE™ devices, when used in conjunction with an appropriate bone
filler, may prove effective in treating post-extraction socket width loss and height seen in both
intact sockets and sockets with significant labial dehiscence defects.

46

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Abstract (if available)

Abstract Aim: The aims of the present study were to: 1) Investigate dimensional changes to the alveolar bone following tooth extraction in the non-human primate model using serial CBCT studies, and 2) Examine the efficacy of two novel devices, SocketKAP™ and SocketKAGE™, for ridge preservation and augmentation procedures following tooth extraction in intact sockets and in sockets with large facial/buccal wall bony defects. ❧ Material & Methods: Six 8-12 year old Macaca fascicularis had 6 teeth each (incisors, premolars or molars) removed, 3 with intact socket walls and 3 with large facial dehiscence defects. In each animal, Anorganic Bovine Bone Mineral (ABBM), non-resorbable SocketKAP™ and resorbable SocketKAGE™ devices were used for the following intervention groups: ❧ Group A: Intact Socket Unfilled and Uncovered (Negative Control) ❧ Group B: Intact Socket, the orifice of which was sealed with SocketKAP™ ❧ Group C: Intact Socket Filled with ABBM and covered with SocketKAP™ ❧ Group D: Facial Dehiscence Socket Unfilled and Uncovered (Negative Control) ❧ Group E: Facial Dehiscence Socket reconstructed with SocketKAGE™ and covered with SocketKAP™ ❧ Group F: Facial Dehiscence Socket reconstructed with SocketKAGE™, ABBM and Covered with SocketKAP™ ❧ At four weeks, SocketKAP™, which had been sutured in place was removed from all sockets. At pre-op, as well as 6 and 12 weeks post-extraction, CBCT imaging was performed and used for measurement of socket width and height at multiple points. ❧ Results: Without therapeutic intervention, intact sockets exhibited significant reduction in width at the crestal 2 mm of the ridge crest within 6 weeks. Compared with the negative control sites which lost up to 81% of crestal bone width, sites treated with SocketKAP™ + ABBM lost at most 15% of bone width at the crestal 2 mm. Similar results were seen in the dehiscence groups, with the combination of SocketKAP™ + SocketKAGE™ + ABBM maintaining the greatest socket width and height dimensions compared to the other two cohorts. ❧ Conclusions: Results from the current non-human primate study suggest that the SocketKAP™ and SocketKAGE™ devices, when used in conjunction with xenograft proved effective in minimizing post-extraction socket width loss and height seen in both intact sockets and sockets with facial dehiscence defects.

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Asset Metadata

Creator Min, Seong Hong (author)

Core Title Alveolar ridge dimensional changes following ridge preservation procedure: CBCT linear analysis in non-human primate model

School School of Dentistry

Degree Master of Science

Degree Program Craniofacial Biology

Publication Date 09/12/2014

Defense Date 07/08/2014

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag bone regeneration,CBCT analysis,dehiscence defect,non human primate model,OAI-PMH Harvest,wound healing

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Zadeh, Homayoun H. (committee chair), Kar, Kian (committee member), Paine, Michael L. (committee member)

Creator Email 3inseiko@gmail.com,seonghom@usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c3-475249

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