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Mazor et al
Background: Adequate vital bone volume (BV) is
essential for successful dental implant placement
with satisfactory esthetic results. Calcium sulfate
(CS) has osseoconductive, angiogenic, biocompatible
and barrier properties. As CS dissolves it
leads to formation of biological apatite and causes
a local release of growth factors. NanoGen (nCS)
is a granular material comprised of tightly compressed
nanocrystalline CS that undergoes controlled
degradation. This case report uses nCS for
the regeneration of bone in an extraction socket.
Methods: A 55 year-old female patient required
extraction of tooth #31. Following socket debridement,
nCS was mixed with saline, packed into the
extraction defect and contained with a non-resorbable
membrane. After flap elevation, 6-months
following grafting, a bone core was collected for
histological and histomorphometrical analysis. A
dental implant was placed and restored 4-months
later. The patient was monitored clinically and
radiographically over the subsequent 2 years.
Results: Clinical, radiographic and CT scan
inspection at 6-months following grafting
revealed keratinized soft tissue and ideal BV for
implant placement. Histomorphometric analysis
of core extracted from the regenerated socket
showed 47% vital BV, with osteoclasts and
osteoblasts, remodeling trabecular bone. Radiographs
obtained at 5-months following implant
placement showed alveolar bone height and
soft tissue retained around the implant. Prosthetic
restoration was then completed. Radiographs
showed minimal marginal bone loss and
intimate BIC 1-year after implant placement.
Conclusions: nCS could become an alternative
to other graft materials in treating extraction
sockets. The combination between the
nano-crystalline structure and angiogenic
potential of CS adequately supported bone
regeneration and implant osseointegration.
The Use of a Novel Nano-Crystalline Calcium Sulfate
for Bone Regeneration in Extraction Socket
Ziv Mazor, DDS1 • Robert Horowitz, DDS2 • John Ricci, PhD4
Harold Alexander, PhD3 • Ioana Chesnoiu-Matei. DDS, MS4
Sachin Mamidwar, MBBS, MS3
Abstract
KEY WORDS: Calcium sulfate, bone graft, tooth extraction, socket bone regeneration,
wound healing, ridge preservation
The Journal of Implant & Advanced Clinical Dentistry • XX
1. Private Practice, Ra’anana, Israel • 2. Private Practice, Scarsdale, NY, USA • 3. Orthogen LLC, Springfield, NJ, USA
4. New York University College of Dentistry, New York, NY, USA
XX • Vol. 3, No. X • XX 2011
Mazor et al
Introd uctio n
Tooth replacement by different materials has
been a common practice since ancient times.1,2
Tooth loss can be due to many causes. Left
untreated, periodontal disease leads to tooth
loss due to diminished periodontal ligament
and bone support. Factors such as smoking,3
genetic disorders,4 and other coexisting systemic
diseases5 may hasten the effects of periodontitis,
causing the loss of affected portions
of the dentition. Non-restorable teeth, owing to
carious lesions, failed endodontic treatment or
other reasons are extracted.6 As other studies
have mentioned, defects resulting from extractions
require grafting so that the adequate
bone levels for implant placement and optimal
support for gingival tissues are maintained.7,8
When restoring partially or completely edentulous
patients with dental implants, vital bone
volume is a key factor.9 Following tooth extraction,
alveolar bone decreases in height and
width, a fact that poses a problem in implant
dentistry. The esthetic function of the implant
can be affected by the inadequate volume of
bone and soft tissue, endangering the treatment
outcome.8 The buccal plate, especially in
the maxilla, is the thinnest and weakest alveolar
wall, which gives it the highest resorption rate.10
In order to overcome these drawbacks, atraumatic
extractions and subsequent bone grafting
are used to achieve socket volume preservation.
Studies have reported that grafting the sockets
with bone graft materials does preserve the
ridge post-extraction.11-13 As reported by several
clinicians and researchers,7,14 fibrous tissue
invades the grafted socket when no barrier
is used, which compromises bone quality, volume
and subsequent implant osseointegration.
Alloplast materials have been frequently used
in dentistry to increase or maintain bone volume
for over 100 years.15 While autografts are
considered the gold standard for bone grafting,
several drawbacks, such as the need for a
second surgery site and limited graft availability,
make clinicians less inclined to use them. Alternate
grafting materials were attempted, such as
allografts (DFDBA, FDBA). They are biocompatible
and do not require a second surgery.
Bovine bone grafts are among the most commonly
used bone grafts in dentistry. However,
reports have shown the presence of residual
xenograft material at the site 8 years after grafting.
16 This fact indicates that xenografts are
neither resorbed nor replaced by bone.17 Ridge
height and width were maintained with minimal
bone loss when allografts were used for socket
preservation.13,18 However, in these studies, the
quality of bone was compromised. The quality
of bone at the grafted socket is of maximal
importance due to its effect on primary implant
stability. In sites grafted with DFDBA, onestage
implant placement was not possible in
more sites than control sites18 due to lack of primary
stability. Furthermore, histological assessments
of sockets grafted with allografts showed
entrapment of the implanted particles by dense
connective tissue,7,19 which may interfere with
the healing process around an inserted implant.7
When grafting with allografts and xenografts,
non-vital bone was reported at the healed site
over a period ranging from 9 months17 to 8+
years.16 New bone regenerates primarily at
the periphery of the defect, where the graft
comes in contact with the host bone.20 However,
recently, there has been a trend towards
development of bone graft materials that proThe
Journal of Implant & Advanced Clinical Dentistry • XX
Mazor et al
mote bone regeneration throughout the entire
defect at a quicker rate than was seen with earlier
bone replacement grafts. These materials
degrade after implantation in the bone defect,
provide stimulus for bone formation and are
eventually replaced by newly regenerated bone.
Considering the disadvantages of autografts,
allografts and xenografts in certain defect
sites, and the inability to utilize some of these
materials in numerous countries, alternative
materials have received renewed interest:
alloplasts. Use of calcium sulfate (CS) as a
successful bone graft material has been documented
for 119 years.21 It is biocompatible
and it dissolves completely, leaving new bone
behind. This can be attributed to the increase
in the concentration of Ca+ ions as CS dissolves.
The released Ca+ ions react with the
PO4 ions in the body, re-precipitating as calcium
phosphate, which stimulates osteoblastic
activity.22,23 Other studies suggested the
angiogenic potential of CS24 and its anti-inflammatory
potential. In their study, Strocchi et al.
compared the growth of blood vessels in bone
defects grafted with CS and autograft. They
found that significantly more blood vessels grew
in defects grafted with CS compared to those
grafted with autograft. Blood vessels provide
nutrition for growing bone and hence further
promote bone formation inside the defect.
A possible reason for the anti-inflammatory
properties of CS is that it dissolves rapidly
and is washed away before infection can
occur.25 The oral cavity is exposed to bacteria,
so a material that can resist infection such
Figure 1: SEM image showing nanocrystalline structure of
nCS (NanoGen, Orthogen, Springfield, NJ).
Figure 2: Periapical radiograph showing periapical
involvement of the mesial root of tooth #31.
Figure 3: nCS granules and saline mixture.
XX • Vol. 3, No. X • XX 2011
Mazor et al
as CS can be successfully used as a graft for
socket preservation26,27 or as a barrier for the
prevention of soft-tissue infiltration,25 especially
in cases when primary closure cannot
be achieved. CS has also been used in
combination with other bone grafts materials.
The combination of CS with allograft or
xenograft worked better compared to the same
grafts used alone.28 In spite of these unique
properties, CS degrades quickly in the body,
which limits its use as a bone graft material. It
degrades over a period of 4 to 6 weeks and
hence has limited success as a bone graft for
large defects (like molar extraction sites or
sinus augmentation site) unless special techniques
are followed.29 To address this prob-
Figure 4a: Clinical picture showing the barrier on the
lingual wall and nCS graft packed to ideal contour.
Figure 4b: Grafted socket is covered with barrier and the
site is closed with single-interrupted suture.
Figure 5: Periapical radiograph of socket filled with nCS
granules.
Figure 6: Clinical image of regenerated ridge 6-months
after grafting. There is no evidence of graft or infection.
The Journal of Implant & Advanced Clinical Dentistry • XX
Mazor et al
lem, a unique nanocrystalline version of CS
was developed. Using a proprietary technology,
the nanocrystalline CS was compressed
into granules (nCS). The present study is a
case report on the preservation of socket volume
using nCS granules as bone-graft material
and a non-resorbable PTFE membrane
for the prevention of soft-tissue in-growth.
Materia ls and Methods :
This report presents clinical and histologic evaluation
of a case where a defect resulting from the
extraction of a molar tooth was grafted with granules
of nanocrystalline CS (NanoGen, Orthogen,
Springfield, NJ) (Figure 1). A 55-year-old
female presented to a private dental office with
a complaint of pain in the lower right posterior
quadrant. After clinical examination, tooth #31
was shown to be the cause of the pain due to
advanced carious lesion and periapical involvement
(Figure 2). Since it was deemed nonrestorable,
the recommended treatment plan was
extraction of tooth #31 followed by socket bone
regeneration with granules of nanocrystalline CS
protected by a barrier, and prosthetic restoration
through implant surgery. After patient consent,
local anesthesia was administered and the tooth
was extracted using the atraumatic technique.
After socket debridement, granules of nanocrystalline
CS were mixed with saline (Figure 3) and
packed into the defect, filling it to ideal contour
Figure 7a: Cone-beam volumetric panoramic scan of the
extraction site 6-months after grafting shows good healing
of the socket.
Figure 7b: Periapical radiograph showing extraction
site 6-months after grafting. Bone has similar density as
surrounding, native bone.
Figure 8: Periapical radiograph of implant immediately
after placement.
XX • Vol. 3, No. X • XX 2011
Mazor et al
(Figure 4a). A non-resorbable barrier (Cytoplast
® Ti-250 Titanium-Reinforced, Osteogenics,
Lubbock, Tx) was positioned over the
grafted material in order to assist in augmentation
of the buccal plate and for better graft containment
(Figure 4b). It was placed under the
buccal periosteum, on the lingual side of the
alveolus and the gingival tissues, extending 2
– 3 mm beyond the defects. The gingival tissues
were repositioned with a single interrupted
resorbable suture, but no attempt was made to
obtain primary closure. A radiograph was taken
to record socket fill with the nCS granules (figure
5). The membrane was removed after 3
weeks and the site was allowed to heal for 6
months (Figure 6). Six months following grafting,
after flap elevation, a bone core was collected
for histological and histomorphometrical
analysis. A cone beam volumetric tomographic
scan was performed at 6 months after socket
grafting, immediately prior to implant placement
(Figure 7a). A periapical radiograph was
also taken at this time demonstrating similar
findings (figure 7b). A single two-stage den-
Figure 9a: Histological evaluation of core obtained
6 months after grafting demonstrates robust bone
formation.
Figure 9b: High-magnification histology picture showing
active osteoblasts and osteoclasts.
The Journal of Implant & Advanced Clinical Dentistry • XX
Mazor et al
tal implant (Intra-Lock, Boca Raton, FL) was
placed to restore the site to function and was
restored 4 months later. (Figure 8). The patient
was monitored, clinically and by periapical digital
radiographic inspection, for two years following
surgery. Radiographs were taken at 1,
2, 6, 12 and 15 months after socket grafting.
His tologica l Analysis
The core was fixed in 10% formalin and then
transferred to different gradients of alcohol
concentrations (70% Ethanol for 24hrs,
95% Ethanol for 24hrs, 100% Ethanol (x2)
48hrs). After dehydration, the sample was infiltrated
and embedded in PMMA. Sectioning
was performed with a low-speed saw (Isom-
Figure 10a: Clinical photograph of prosthetic restoration,
4-months after implant placement.
Figure 10b: Periapical radiograph showing implant,
abutment and crown 4-months after implant placement.
Good bone density and height observed.
Figure 11a: Periapical radiograph showing stable implant,
abutment and crown10-months after implant placement.
Figure 11b: Clinical photograph of the restored site with
crown: 10-months after implant placement.
XX • Vol. 3, No. X • XX 2011
Mazor et al
etTM, Buehler, Lake Bluff, IL). The slide was
ground and polished to a thickness of 100μm
and then stained with Stevenel’s blue and Van
Gieson’s picro fuchsine stain. A slide scanner
(ScanScope GL, Aperio, Vista, CA) was
used to image the sample and Leica QWin
software was used for the histomorphometrical
assessment of bone formation. Histomorphometrical
analysis was conducted to quantify the
amount of total vital bone present in the core.
Res ults
Immediate post-grafting radiographs showed
the defect was completely filled with granules
of nanocrystalline CS. Wound margins
presented as clean and almost adjoined
at the coronal part with no sign of inflammation
one month post-grafting. Radiographic
analysis over the next few months
showed graft resorption and the appearance
of new bone formation in the treated site.
At 6 months post-grafting, clinical inspection
revealed a healed site with fully keratinized soft
tissue. The clinical examination of the newly
formed bone showed a ridge with bone suitable
to support the placement of a single two-stage
implant; there was no sign of grafted material or
granulation tissue remaining. CT scan and additional
radiographic examination of the extraction
area at the 6-month time-point showed a fully
healed socket with suitable bone height and
bone density similar to the surrounding bone.
Histological analysis of the core extracted
from the healed socket showed formation
of new trabecular bone and osteoid
tissue (Figure 9a) with marked bone turnover,
evidently due to the presence of osteoclasts,
and also active osteoblasts (Figure
9b). Quantitative analysis of the bone core
collected 6 months following socket grafting
revealed a 47% vital bone content.
At 4 months following implant placement,
clinical inspection and radiographs showed
that alveolar bone height and soft tissue was
retained around the implant (Figures 10a,
10b). Prosthetic restoration was then completed.
Radiographs 10 months after the
implant was placed, showed minimal marginal
bone loss and intimate contact between the
bone and implant surface (Figures 11a, 11b).
Disc ussio n
A satisfactory esthetic profile in implant dentistry
depends on several factors, such as the
thickness of the underlying bone and the gingival
biotype.30 However, determining the
adequate thickness of the buccal plate and
biotype is difficult. Due to the anatomical characteristics
of the alveolar bone, the thin labial
walls of the alveoli resorb the fastest; more
so in the maxilla than the mandible.31 Gingival
soft tissue contour is strictly dependent
on the underlying bone. A 12-month prospective
study by Schropp et al.32 reported
a decrease of 50% in bone width following
single-tooth extraction when the alveolar site
was not grafted. In order to prevent future tissue
loss, most clinicians opt for grafting in
extraction sockets before placing implants.
Vital bone-to-implant contact (BIC) is one criterion
affected by vital bone content in a site,
and used for selecting different bone-grafting
materials. Becker et al,. showed that 36 months
after implanting xenografts or DFDBA in extraction
sockets, minimal vital bone formation was
achieved.7 A different study looking at healing
The Journal of Implant & Advanced Clinical Dentistry • XX
Mazor et al
of an extraction socket grafted with bioactive
glass showed that the material was present at
the site for up to 2–3 years.33 Synthetic materials
such as Ca3(PO4)2 and CaSO4-based
materials have been successfully used for bone
regeneration. They degrade completely at a
faster rate and can influence bone remodeling.
34 The use of CS for bone grafting purposes
showed better results than other graft materials
used alone.35 As CS dissolves, it leads to formation
of calcium phosphate and also causes
a local release of growth factors from the surrounding
bone. Both of these mechanisms
help in bone regeneration in the extraction site.
CS is the only bone graft known to have barrier,
hemostatic and angiogenic properties and
possibly effect a local release of growth factors.
23 This novel version of CS was developed
to preserve these unique properties of
CS while overcoming its fast degradation rate.
This case shows that using novel CS, in the
form of granules made up of nano-crystals of
CS, to regenerate extraction socket can offer
an alternative to other currently investigated
graft materials in treating dental bone defects.
The final goal when using any bone graft material
should be the complete resorption of the
grafted material and bone regeneration in the
defect site prior to, or at the time of implant
placement. As reported by others,7,33,36 materials
such as DFDBA, xenografts, and bioactive
glass render a smaller amount of vital bone and
the resorption rate is more than 6 months, if
they resorb at all. In contrast, CS pre-hardened
particles grafted in fresh extraction sockets
were shown to allow for full material resorption
and vital bone regeneration has been observed
as early as 3 months after placement.26 CS
has been documented extensively for different
procedures such as socket grafting,26
sinus augmentation,37 and as a membrane.25
The microscopic structure of nCS is nanocrystalline
CS. The nano-crystals are tightly
compressed together forming a granule. This
structural pattern results in controlled degradation
of the CS granules. Rapid degradation
of traditional forms of CS was a limiting factor
for its use in bone grafting applications. The
unique nanocrystalline structure of CS granules
used in this study allows the material to have
a controlled degradation over 10 to 12 weeks
(compared to traditional CS, which degrades
in 4 to 6 weeks). Radiographic and histological
investigations showed that the extraction
socket grafted with nCS had fully regenerated
with vital bone by 6 months. Therefore,
it helped provide the ideal bone volume for
implant placement. The combination between
the controlled degradation of nCS and the
excellent properties of CS adequately supports
graft resorption and bone remodeling. nCS can
be a suitable dental bone-grafting option when
a shorter healing time is desired. Its properties
to generate vital bone and to completely resorb
are qualities much needed in the clinical field.
Conclusio n
The material investigated in this case report,
nCS, is calcium sulfate (CS) with a unique
nanocrystalline granular structure that allows
for a controlled dissolution that leads to complete
graft resorption. The granules that form
the material consist of smaller, agglomerated
particles that increase the surface area of
the material. As the calcium sulfate granules
undergo controlled degradation, the formation
XX • Vol. 3, No. X • XX 2011
Mazor et al
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of a calcium phosphate layer on their surface
stimulates bone regeneration. An extraction
socket grafted with this granular material prevented
the resorption of the alveolar bone and
provided an ideal vital bone volume for implant
placement. At the one-year follow-up the
patient presents good implant osseointegration
with esthetically satisfactory gingival profile.
This case demonstrates clinical success
when using nCS and a dense PTFE barrier for
extraction socket alveolar regeneration procedures.
Future studies will be undertaken to follow
alveolar volume preservation and vital bone
formation in similar extraction socket defects. ●
Correspondence:
Sachin Mamidwar
505 Morris Avenue, Suite 104
Springfield, NJ, 07081
P: 973-467-2404
F: 973-467-1218
e-mail:
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
The Journal of Implant & Advanced Clinical Dentistry • XX
Mazor et al
Disclosure:
Drs. Alexander and Mamidwar are employees of Orthogen.
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