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Journal of Cranio-Maxillo-Facial Surgery 40 (2012) 485e493

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Journal of Cranio-Maxillo-Facial Surgery


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Jaw cysts e Filling or no lling after enucleation? A reviewq


Tobias Ettla, *, Martin Gosaua, Robert Saderb, Torsten E. Reicherta
a
b

Department of Oral and Maxillofacial Surgery (Chair: Prof. T.E. Reichert, MD, DMD, PhD), University of Regensburg, Germany
Department of Oral and Maxillofacial Surgery (Chair: Prof. R. Sader, MD, DMD, PhD), University of Frankfurt, Germany

a r t i c l e i n f o

a b s t r a c t

Article history:
Paper received 24 March 2011
Accepted 23 July 2011

Introduction: Jaw cysts are common lesions in the oral and maxillofacial region. Enucleation of the lesions
and primary closure of the defects, the so-called cystectomy, has evolved as the treatment of choice. In
order to reduce infections and to accelerate bone regeneration, different types of bone grafts are
increasingly investigated for defect lling.
Material and methods: The present review reects the most recent studies using autogenous, allogenic,
xenogenic and alloplastic bone grafts and compares the results to current investigations about conservative cyst enucleation without using any lling materials. Relevant studies with signicant patient
sample sizes were electronically searched in PubMed and Medline.
Results: Simple cyst enucleation and blood clot healing show low complication rates and sufcient bone
regeneration even in large defects. Prospective randomized trials comparing the additional use of lling
materials to the cystectomy are rare. Currently available data do not indicate the superiority of additional bone grafts.
Conclusion: Enucleation of jaw cysts and primary closure without bone substitutes remains state of the
art in most cases.
2011 European Association for Cranio-Maxillo-Facial Surgery.

Keywords:
Jaw cysts
Enucleation
Defect lling
Bone grafts
Ossication
Complications

1. Introduction
Human bone is characterized by the unique ability to regenerate
its original structure after defects or fractures through a programmed sequence of maturation steps closely resembling the
pattern of bone development and bone growth (Schenk et al., 1994;
Buser et al., 1998). Reliable bone healing depends on an adequate
blood supply, a solid basis for bone deposition and immobilization.
During the rst 4 weeks angiogenic and osteogenic cells originating
from the adjacent bone walls and the periosteum turn a blood clot
into granulation tissue and woven bone towards the centre of the
defect. This procedure is stimulated by various cytokines, growth
factors (e.g. PDGFs, IGFs, FGFs, TGF-b, BMPs) and stem cells (Schenk
et al., 1994; Buser et al., 1998; Schliephake, 2002; Ogunlewe et al.,
2006; Rodeo et al., 2010). Over the following 4 months desmoplastic bone is replaced by parallel-bred bone resembling the
original Haversian bone structure (Lemperle et al., 1998).
q Presented at the 59th Annual Meeting of the Academy of Oral and Maxillofacial Surgery (Arbeitsgemeinschaft fr Kieferchirurgie), Bad Homburg,
Germany, 13.05.2010e14.05.2010.
* Corresponding author. Klinik und Poliklinik fr Mund-, Kiefer- und
Gesichtschirurgie, Klinikum der Universitt Regensburg, Franz-Josef-Strau-Allee
11, 93053 Regensburg, Germany. Tel.: 49 941 9446361; fax: 49 941 9446302.
E-mail address: tobias.ettl@klinik.uni-regensburg.de (T. Ettl).

Odontogenic jaw cysts are common lesions in the maxillofacial


area. The preferred treatment of these lesions consists of enucleation of the cysts and watertight primary closure, which has been
described by Partsch as Cystectomy (Partsch II) in 1910 (Partsch,
1910). Especially cysts located in the mandible present an ideal
bone defect after enucleation as in most cases these defects are
completely surrounded by solid bone walls apart from the site of
approach. This facilitates a stable blood clot leading to a regular and
safe healing process. The enucleation of jaw cysts of different sizes
with safe closure of the wound has been the standard procedure to
the present day (van Doorn, 1972; Chiapasco et al., 2000; Bolouri
et al., 2001; Ihan Hren and Miljavec, 2008; Iatrou et al., 2009;
Yim and Lee, 2009; Kreusch et al., 2010).
Partsch was convinced that the cystectomy was restricted to
smaller cavities up to 2 cm and that this method, when applied to
larger cysts, would lead to infections and complications. In the
1960s Schulte stated that with increasing size of the cyst, the risk of
wound infection rises due to retraction of the blood clot from the
cyst wall (Schulte, 1960; Dickmeiss et al., 1985). For this reason he
inserted a gelatine sponge in combination with thrombin to
stabilize the blood clot (Schulte, 1965).
In the last decades there have been numerous investigations
into the treatment of jaw lesions using autogenous grafts, allogenous grafts, xenografts or alloplastic and synthetic grafts as lling

1010-5182/$ e see front matter 2011 European Association for Cranio-Maxillo-Facial Surgery.
doi:10.1016/j.jcms.2011.07.023

486

T. Ettl et al. / Journal of Cranio-Maxillo-Facial Surgery 40 (2012) 485e493

materials. Besides reduction of infections and healing disturbances


these materials have been applied for reasons such as accelerated
bone regeneration, prevention of soft tissue collapse into the defect
and improved bone strength.
This review reects the results for cyst enucleation and simple
closure in comparison to those using bone substitutes. Data of
complications and bone regeneration are particularly emphasized.
2. Materials and methods
Relevant studies were identied and retrieved by electronic
searches in PubMed and Medline up to January 15, 2010. The search
was supported by a senior librarian who specialized in health
sciences. Free text words were used for search with following
terms: jaw, mandible, maxilla, cysts, lesion, defect, critical size,
treatment, enucleation, cystectomy, blood clot, lling material,
bone graft, autologous, iliac spongiose, allogenous, alloplastic,
synthetic, tricalcium phosphate, hydroxyapatite, xenogenic,
collagen, bone regeneration, ossication, complication, infection,
fracture, histology, radiographic, periosteum, bone wall, localisation Reference lists of all articles retrieved from PubMed search
were selected for further relevant studies. Clinical and preclinical
studies with a sample size of N  5 were evaluated and included in
this review. The main focus was on data regarding complication
rates and bone regeneration. The most recent studies are shown in
Table 1 and Table 2.
3. Results
3.1. Enucleation and primary closure e cystectomy e without any
additional bone substitutes
Up to date, several studies have reported safe and regular bone
healing after enucleation and simple closure of jaw cysts without
using bone grafts even in cases of large defects (van Doorn, 1972;
Mitchell, 1992; Chiapasco et al., 2000; Bolouri et al., 2001; Ihan
Hren and Miljavec, 2008; Iatrou et al., 2009; Yim and Lee, 2009;
Kreusch et al., 2010) (see Table 1).
The complication rate for cyst enucleation, primary closure and
perioperative antibiotic treatment seems to be less than 5%, even in
defects measuring far more than 3 cm (van Doorn, 1972; Chiapasco
et al., 2000; Ihan Hren and Miljavec, 2008; Iatrou et al., 2009;
Kreusch et al., 2010). Infection going along with suppuration and
wound dehiscence presents the main complication. However, the
presence of suppuration at the moment of surgery does not inevitably lead to healing disturbances (van Doorn, 1972). An optimal
access incision e e.g. marginal incision e ensures a safe defect
closure on solid bone, which is mandatory for undisturbed organization of the blood clot (van Doorn, 1972; Chiapasco et al., 2000;
Kreusch et al., 2010).
Fractures after enucleation of mandibular cysts are extremely
rare (Chiapasco et al., 2000; Kreusch et al., 2010). The highest risk
exists for lesions affecting the angle of the mandible. Bolouri et al.
(2001) reported a fracture-rate of 3.1% in a study on 160 patients
presenting with follicular cysts of the mandibular angle with
a mean size of 31.5 mm.
With regard to bone regeneration after cystectomy extensive
ossication of defects up to 3e4 cm in diameter can be expected
after 12 months. Ihan Hren and Miljavec evaluated spontaneous
bone healing of large mandible bone defects in 33 patients by
computer-analyzed radiographs. Analysis revealed a mean gain of
bone density of 7%, 27% and 46% after 2, 6 and 12 months respectively. In smaller defects measuring 2e3 cm in diameter a nal bone
density of 97% in relation to normal surrounding bone was observed
after 12 months (Ihan Hren and Miljavec, 2008). Similar results were

reported by Yim and Lee on 74 patients after enucleation of jaw


cysts. In this study panoramic radiograph analysis showed
a recovery of radiopacity of more than 97% in defects smaller than
3  4 cm after 12 months. It has to be mentioned that only patients
without wound dehiscence were selected (Yim and Lee, 2009). In
mandibular defects exceeding 3 cm in size Ihan Hren and Miljavec
(2008) found a bone density of 84% of normal surrounding bone
after 12 months. In another study by Chiapasco et al. evaluating
spontaneous bone regeneration after enucleation of 27 cysts larger
than 4 cm computed analysis of panoramic radiographs showed
a mean reduction in size of 12.3%, 43.5% and 81.3% after 6, 12 and
24 months respectively. The increase of bone density was 37.0%,
48.2% and 91.0% after 6, 12 and 24 months. This investigation
demonstrated almost complete bone healing of defects exceeding
4 cm in diameter after 24 months (Chiapasco et al., 2000).
Young patients show better bone healing compared to older
patients, and monocortical defects result in higher ossication rates
than bicortical defects (Ihan Hren and Miljavec, 2008; Yim and Lee,
2009). Furthermore, the shape of the bone defect seems to be more
important for healing than the volume. Ihan Hren and Miljavec
(2008) observed that the minimal diameter of the lesion is the
crucial parameter, for which reason elliptic defects show a better
bone healing as circular defects of the same volume. The same
group described a superior bony regeneration for mandibular
defects of the angle and the symphysis compared to defects of the
body region. In a former publication examining radiographs of 38
patients by Laffers and Zimmer, bone healing after cystectomy was
most favourable in the anterior region of the mandible and least
favourable in the anterior region of the maxilla (Laffers and
Zimmer, 1977). The poor bone regeneration of the anterior
maxilla has also been described (Hemprich et al., 1989). Other
studies again report no difference in bone regeneration of maxillary
and mandibular defects (van Doorn, 1972; Yim and Lee, 2009).
Special attention should be paid to the preservation of the
periosteum, which has a large capacity for spontaneous ossication
and bone repair. Ma et al. (2009) determined a critical size defect of
6 cm for minipig mandibular segmental defects when the periosteum was preserved and a critical size defect of only 2 cm when the
periosteum was removed. Similar results were observed in canine
mandibles where defects greater than 15 mm failed to heal when
the periosteum was removed in contrast to spontaneous bone
healing in defects up to 50 mm when the periosteum was preserved
(Huh et al., 2005). One report showed spontaneous osteogenesis in
mandibular segmental defects even when the whole mandible was
resected with preservation of the periosteum (Ogunlewe et al.,
2006). The periosteum seems to have a higher osteogenic potential than the adjacent bone edges (Lemperle et al., 1998; Huh et al.,
2005). Guided bone regeneration with the use of resorbable or
non-resorbable membranes did not show any advantage over
primary periosteal wound closure in human mandibular monocortical defects (Santamaria et al., 1998). Even the additional
application of iliac cancellous bone grafts did not enhance bone
regeneration in mandibular segmental defects of mongrel dogs
with intact periosteum leading to the authors conclusion that
absorption and replacement of the bone grafts delayed the healing
process (Lemperle et al., 1998). However, if the periosteum is absent
spontaneous bone regeneration might benet from osteoconductive and osteogenic cancellous autografts protected by
macroporous meshs against the adjacent soft tissue prolaps
(Lemperle et al., 1998; Ma et al., 2009).
3.2. Additional bone substitutes
As mentioned above there have been many investigations into
the treatment of cystic jaw lesions using additional bone

Table 1
Studies investigating outcome after enucleation of jaw cysts and primary closure.
N

Defects, main subtypes (n), size

Location (n)

Filling (n)

Time of
follow-up
(months)

Analysis

Complication rate

Bone regeneration, outcome

Authors conclusion

van Doorn (1972)

209

Jaw cysts; 117 radicular (117),


residual (48), incisivus (6),
KZOT (4); size 1.1e12.5 cm

Maxilla (161),
mandible (48)

No

12e48

Radiograph

In 4.8% wound
dehiscences with
suppuration in 3.3%

Primary healing in 95.2% independent


of site and size of lesion. No details
on bone regeneration

Jaw cysts; radicular (16),


follicular (6), residual (2),
KZOT (3); size >4 cm

Mandible

No

6, 12, 24

Radiograph,
bone
densitometry

0%

Jaw cysts; follicular;


mean defect size of 3.15 cm

Mandible angle

No

Radiograph

30.6% overall, 23.1%


infections, 3.1%
fractures
0%

Cavity reduction of 12% after 6 m,


43% after 12 m, 81% after 24 m. Mean
relative bone density of 37% after 6 m,
48% after 12 m, 91% after 24 m
No details

Organization of blood
clot regardless of its
volume. Depends on
optimal primary closure
Spontaneous bone
regeneration of large
cysts without lling

Chiapasco
et al. (2000)

Bolouri et al. (2001)

27

160

Ihan Hren and


Miljavec (2008)

33

Jaw cysts; radicular (15),


KZOT (13), follicular (2);
size >2 cm

Mandible;
monocortical (19),
bicortical (14)

No

2, 6, 12

Radiograph,
relative bone
densitometry

Iatrou et al. (2009)

47

Mandible (29),
maxilla (16)

No

6e72

Radiograph

0%

Yim and Lee (2009)

74

Children jaw cysts,


follicular (20),
radicular (5), KZOT (5),
eruption cysts (5);
size up to 12 cm
Jaw cysts; size smaller and
larger than 3  4 cm

No details

No

3, 6, 9, 12

Radiograph,
densitometry

Only patients
without wound
dehiscence
selected

Jaw cysts; KZOT (75),


radicular (182),
follicular (160); max.
diameter 0.5e12 cm

Maxilla and
mandible

No

3, 12

Radiograph

1.5% (two fractures,


ve infections)

Kreusch
et al. (2010)

417

Gain of bone density of 7% after 2 m, 27%


after 6 m, 46% after 12 m. Mean relative
bone density of 88% after 12 m. Worse
healing in older patients, bicortical defects,
mandibular body
Sufcient bone healing in all cases. No
details on bone regeneration

Recovery of radiopacity of 97% in


defects <3  4 cm after 12 m. Partial bone
regeneration for defects >3  4 cm after
12 m. More signicant bone regeneration
in younger patients, no signicance of site
Bony healing in all cases. No details on
regeneration rate

No need for bone grafts

Spontaneous bone
regeneration of large
cysts without lling

No need for autologous


bone grafting in children,
even in cases of extended
cystic lesions
Acceptable spontaneous
bone regeneration after
12 months without bone
graft procedures

T. Ettl et al. / Journal of Cranio-Maxillo-Facial Surgery 40 (2012) 485e493

Author

No need for lling after


enucleation

cm centimetre, m months.

487

Author

488

Table 2
Studies investigating outcome after enucleation of jaw cysts and insertion of bone grafts.
Defects, main subtypes (n), size

Location (n)

Filling (n)

Time of
follow-up
(months)

Analysis

Complication rate

Bone regeneration,
outcome

Authors conclusion

Infect resistance.
Shortening of
treatment.
Accelerated bone
regeneration.
Reduced risk of
fracture
Tissue-engineered
bone as an
alternative cyst
lling material

14

Jaw cysts; residual (4),


follicular (5), radicular (4).
Large cysts, no details
on size

Maxilla and
mandible

Autologous
(iliac spongiosa)

No details,
regularly

Radiograph

Secondary wound healing


in 14.2%. No infection.
No loss of implant

Total ossication
after 3e13 months

Pradel et al.
(2006)

22

Jaw cysts; follicular (11),


radicular (6), KZOT (5);
no details on size

Mandible

3, 6, 12

Radiograph,
radiodensity

Wound dehiscences in
50% of both groups

Few differences in bone


density after 3, 6 m. After
12 m stronger ossication
for tissue-engineered bone

Buser and
Berthold
(1985)

65

Jaw cysts; size more


than 2 cm

Maxilla and
mandible

Autogenous
osteoblasts on
demineralized bone
matrix
(Osteovit, 11) vs
iliac crest (11)
Collagen
(Collagen eece)

Regularly,
no details

Radiograph

6.2% (infection with


loss of implant)

Mean regeneration time of


15 m for maxilla and 8.5 m
for mandible depending on
localization, size and age

Joos (1985)

71

Jaw cysts; mean size 4.2 cm2

No details

24

Radiograph

1.5% (secondary
wound healing)

Hemprich et al.
(1989)

56

Jaw cysts; mean size 5.4 cm2

Mandible and
maxilla

Collagen (n 71) vs
control group
without lling (n
not mentioned)
Matrix collagen
Type I

Up to 8

Radiograph

13% wound dehiscences


with partial or total
removal of the implant

Complete bone healing in


81.1% for collagen group
and 61.8% without collagen
after 2 years
Primary healing in 82%.
After 8 m complete
reossication in 36%,
reduced defect size in 57%

Mitchell (1992)

100

Jaw cysts, radicular (89),


residual (11); <1 cm (54),
1e2 cm (37), >2 cm (9),
equal in both groups

Maxilla (75),
mandible (25)

No lling (50) vs
Collagen paste (50)

3, 6, 12

Radiograph,
radiodensity

No adverse reactions
for collagen. Infection
rate <5% in both groups

Mostly jaw cysts (12),


no details on size

No details

b-TCP blood

Radiograph, CT in
12 cases; histology
in some cases

0%

Jaw cysts, radicular (22),


follicular (24), residual (1),
KZOT (5)

Mandible

post-OP, 6,
12,
18, 24, 30
e60
1, 4, 13

Radiograph,
histology
in 16 cases

9.2% wound-healing
disturbances, partial loss of
implant in 5.9%. Total
loss in 2%

Odontogenic cysts (33),


defects after wisdom tooth
osteotomy (8); mean
size 4.7 cm2

No details

3, 6, 12

Radiograph,
densitometry

Wound dehiscences (n not


mentioned). Supercial loss
of Ostim in ve cases

Bicsak et al.
(2006)

17

Horch et al.
(2006)

52

Gerlach and
Niehues
(2007)

44

b-TCP blood;
addition of
autogenous bone
for
defects of >2 cm

Nanoparticular
hydroxyapatite

Healing delay for collagen


after 3 months. Similar
bone deposition after
6e12 m. Complete healing
in 59.4% for collagen and
77.1% for control group.
Collagen replaced by host
brous tissue in some cases
Full bone healing of all
defects after 36e60 m.
Nearly complete resorption
of b-TCP
Radiographically extensive
bony regeneration after
12 m. Degradation of b-TCP
alone 65%. Histologically
almost complete resorption
of b-TCP after 12 m. 3%
residues after 20 m
Partial bony regeneration
after 3 m for defects <3 cm.
Bone regeneration for
defects >3 cm after 6e12 m

Accelerated bone
healing by collagen.
Indication for large
cysts. Collagen
superior to other
alloplastic
materials
Accelerated bone
healing by collagen
in comparison to
simple closure
Good clinical
healing and
ossication;
recommended for
cyst lling
Collagen is not
osteoinductive. No
advantage of
collagen

b-TCP facilitates
osteogenesis and
enables post-Op
implantation
Fast b-TCP
resorption and
bony substitution.
Suitable material
for lling of bone
defects
Safe resorption, low
complication rate,
rapid bone
regeneration

T. Ettl et al. / Journal of Cranio-Maxillo-Facial Surgery 40 (2012) 485e493

Holtgrave and
Spiessl
(1975)

Suitable bone
mineral substitute
for moderate-sized
defects of calvaria
and forehead bone
Partial replacement of
material by bone tissue
after 12e30 m. Complete
replacement after 30 m

3.3. Autologous grafts

Radiograph,
histology in two
cases
6e40
(average
29)

3%, Partial wound dehiscence


with exposed material

No difference in bone
density and volume
No details
Computed
tomography
3, 6

cm centimetre, m months.

Mandible,
viscerocranium
Posttraumatic defects
viscerocranium, mandibular
cysts, atrophic mandible
27
Wolff et al.
(2004)

489

substitutes in order to reduce infections and healing disturbances,


to accelerate bone regeneration, to prevent soft tissue collapse and
to improve bone strength (see Table 2). In the following, the
reported lling materials are categorized into autologous grafts,
allogenous grafts, xenografts as well as alloplastic and synthetic
grafts.

No membrane (10)
vs resorbable
membrane (10)
vs non-resorbable
membrane (10)
Carbonated
apatite cement
(Norian SRS)
Mandible (17),
maxilla (13)
30
Santamaria
et al. (1998)

Radicular cysts

Increased bone height and


bone density for allogenic
bone after 6 and 12 m. No
difference after 24 m
Radiograph, height
measurement,
densitometry
52
Bodner (1998)

Jaw cysts; size 3e8 cm

Mandible (32),
maxilla (20)

Gelatine sponge
(Gelfoam) (25)
vs allogenic bone
Dembone (27)

6, 12, 24

Healing without incident in


both groups

Full bone incorporation


after 12 months
In 20% graft removal due
to infection and exposed graft
Radiograph
6, 12,
24e54
Calf xenograft (Kiel
bone) aspirated
bone marrow
Mandible (11),
maxilla (9)
20
Horowitz and
Bodner
(1989)

Jaw cysts; size 2e8 cm,


average 3.7 cm

31
Dickmeiss et al.
(1985)

Jaw cysts, size 1.5e4 cm


and more

Maxilla (13),
mandible (18)

Humane brine
concentrate
(Tissucol)

2, 6, 12

Radiograph

Wound dehiscence in 9.7%.


Infection and loss of brin
clot in 9.7%

Primary healing in 80.6%.


Bone deposition and cavity
reducing after 2 m

Fast and
uncomplicated
regeneration also in
large cysts. Slower
bone regeneration
in older patients
Good bone
substitute for larger
defects, infection
main cause for
failure
Enhanced
osteogenesis and
prevention of
height loss by
allogenic bone
implants
No advantage for
guided bone
regeneration

T. Ettl et al. / Journal of Cranio-Maxillo-Facial Surgery 40 (2012) 485e493

Autologous bone is repeatedly reported to represent the golden


standard of bone grafting (Hall et al., 1971; Younger and Chapman,
1989; Giannoudis et al., 2005; Pradel et al., 2006). Iliac crest is the
most frequently chosen donor site, especially as the iliac spongiosa
provides osteoconductive, osteoinductive and osteogenic properties (Giannoudis et al., 2005). In 1924 Lexer described the use of
autologous spongiosa for bone transplantation (Lexer, 1924).
Reichenbach and Taege reported good results for lling jaw defects
with iliac crest spongiosa after cystectomy in 1958 (Reichenbach
and Taege, 1958), which was conrmed by others in the following
years (Heiple et al., 1963; Lindsay et al., 1966; Schroder and
Schwenzer, 1970; Hall et al., 1971). Holtgrave and Spiessl
described homogenous radiographic reossication of large jaw
cysts after 3e13 months using autologous iliac spongiosa. In
a cohort of 14 patients with cysts of the upper and lower jaw, only
two wounds healed secondary, while infection was absent in all
cases. The authors concluded a safe and accelerated defect ossication with reduced risk of infections and mandibular fractures for
iliac spongiosa grafting in contrast to simple enucleation. As
mentioned in the publication, the vital spongiose osteoblasts are
fed by diffusion and early revascularization from the defect
boundary starting immediately with proliferation and production
of woven bone (Holtgrave and Spiessl, 1975). In experimental
minipig studies on standardized mandibular defects (mean size
10  5 mm) autologous bone showed the highest osteogenic
properties and regeneration rate during the initial healing period in
comparison to simple blood clot healing and to the lling materials
Type-I-collagen, b-tricalcium phosphate (b-TCP), hydroxyapatite
(HA), biphasic calcium phosphate (BCP) and demineralized freezedried allografts (DFDBA) (Buser et al., 1998; Jensen et al., 2006;
Jensen et al., 2007; Jensen et al., 2009). After 12 months no difference of both density and quality of the newly formed bone was
obvious between the autograft group and spontaneous regeneration without any lling material.
Osteogenic function of the iliac spongiosa (Muschler and Lane,
1992) may fail in clinical practice, if the early progenitor cells do
not survive transplantation (Sandhu et al., 1999). Moreover, osteogenic impact of the spongiosa is decreasing with increasing age of
the patients (Marx and Garg, 1998). Disadvantages like donor site
morbidity, possible hospitalization, and the need for general
anaesthesia should be kept in mind (Wolfe, 1982; Arrington et al.,
1996; Eunger and Leppanen, 2000).
Current clinical reports about lling jaw defects with autogenous iliac bone after cyst enucleation are extremely rare. Pradel
et al. compared 11 cases of jaw defects lled with autogenous
spongiosa to 11 cases lled with tissue-engineered bone (autogenous osteoblasts on demineralized bone matrix Osteovit) and
found similar bone regeneration in both groups with stronger
radiographic ossication for the tissue-engineered bone after
12 months. In both groups wound dehiscences were found in 55%
(Pradel et al., 2006). Unfortunately we could nd no recent clinical
studies comparing the use of autogenous bone graft to simple
enucleation. An important aspect for the use of additional autografts seems to be the cortical boundary of the defect and the
presence of sound periosteum. In defects with more than one
cortical border missing or in defects with incomplete periosteal

490

T. Ettl et al. / Journal of Cranio-Maxillo-Facial Surgery 40 (2012) 485e493

covering, autografts may prevent collapse of the surrounding soft


tissue, preserve the defect volume, and provide osteogenic cells and
growth factors for regular bone healing (Lemperle et al., 1998).
3.4. Allogenic grafts
Allografts are prepared as fresh, frozen, freeze-dried, mineralized and demineralized grafts and are provided as chips, cortical
granules, wedges or cancellous powder (Kao and Scott, 2007). Fresh
allografts possess high osteoconductive and osteoinductive
potential, however they might induce an immune response or
transmit diseases (Friedlaender et al., 1999). Freeze-dried or
lyophilized grafts are less immunogenic. These grafts still have
osteoconductive function, while osteoinductive properties are lost
(Kao and Scott, 2007). Allogenic freeze-dried bone has been used
several times in the past for defect lling after cyst enucleation with
reported complication rates ranging from 17% to 25% (Marble, 1968;
Spengos, 1974; Constantinides and Zachariades, 1978). Bodner
(1998) compared the effect of decalcied freeze-dried bone allografts (DFDBA, Dembone) on the osteogenesis of jaw defects
(3e8 cm in size) after cyst enucleation to a control group in which
absorbable gelatine sponges (Gelfoam) were used. Radiographically, relative height of the alveolar process and density of the
regenerated bone structure were superior in the DFDBA group after
6 and 12 months. After 24 months bone density did not differ in
both groups. The author concluded an enhanced osteogenesis with
prevention of alveolar height loss in the mandible by DFDBA. There
is no data comparing DFDBA to simple enucleation and blood clot
healing.
In an experimental comparative study on mandibular defects in
minipigs, DFDBA showed histologically delayed bone regeneration
in comparison to autografts and simple blood clot healing (Buser
et al., 1998). In this study the above mentioned osteoconductive
properties of allogenic grafts could be conrmed whereas no
osteoinductive effects were detectable.
3.5. Xenogenic grafts
One of the rst xenogenic materials used for bone defects after
cyst enucleation was the so-called Kiel bone, a calf bone engineered
by Maatz and Bauermeister (1961). Weiss described 14 cases of cyst
lling with Kiel bone, resulting in 3 (21%) infections requiring
removal of the bone transplant. He postulated an acceleration of
bone regeneration and stabilization of the blood clot (Weiss, 1964).
In another investigation 20 cysts were treated by aspirated bone
marrow in conjunction with Kiel bone. Exudation and exfoliation of
the grafts occurred in four cases (20%) and necessitated graft
removal (Horowitz and Bodner, 1989).
In order to stabilize the blood clot and to prevent infection, Schulte
used a gelatine sponge in combination with thrombin in 1959
(Schulte, 1965). During the following years gelatine enjoyed great
popularity (Becker, 1971; Bodner, 1996; Bodner, 1998) and was
replaced by collagen in the 1980s (Buser and Berthold, 1985; Joos,
1985; Hemprich et al., 1989; Mitchell, 1992; Pradel et al., 2006).
Hemprich et al. achieved complete reossication after enucleation of
56 jaw cysts measuring up to 1600 mm2 and lling with bovine matrix
collagen Type I in 36% and a reduced defect size in 54% after 8 months.
Undisturbed wound healing was achieved in 87% of cases (Hemprich
et al.,1989). Exact correlations between reossication and defect sizes
were not reported. The authors considered these data to be superior to
the results of Becker et al., who described a reossication rate of 67%
after 3e6 years using gelatine sponges (Becker, 1971; Hemprich et al.,
1989). After lling jaw defects of a minimal size of 20 mm with
collagen, Buser and Berthold found a mean regeneration time of
15 months for the upper jaw and 8.5 months for the lower jaw, also

concluding there had been an acceleration of bone regeneration


(Buser and Berthold, 1985). Investigations comparing defect lling
with collagen to simple blood clot healing after cyst enucleation are
ambiguous. Joos described a superior complete bone regeneration
rate in 81.1% of his patients after 2 years treated by collagen lling in
comparison to conventionally treated jaw defects showing complete
regeneration in 61.8% after two years. Defects sizes of both groups
were comparable (4.32 cm2 to 4.08 cm2) (Joos, 1985). In a different
study of Mitchell on 100 patients with jaw defects, reduced bone
deposition after 3 months was observed for the defects lled with
collagen in comparison to the control group with no material
implanted. After 6e12 months bone healing appeared similar in both
groups. In contrast to Joos who described a stimulating effect on bone
regeneration by collagen (Joos et al., 1982; Joos, 1985) Mitchell
assumed that collagen acts as a biological space ller without any
osteoinductive properties and that it has to be degraded before bone
healing can take place (Mitchell, 1992). In an experimental comparative minipig study mandibular defects lled with Type-I-collagen
demonstrated the same histological and histomorphometrical healing pattern as the control sites with blood clots alone (Buser et al.,
1998). When combined with BMPs or a carrier such as hydroxyapatite, demineralized collagen may increase graft incorporation
(Giannoudis et al., 2005). This principle was performed by Pradel et al.
who lled mandibular cyst defects with autogenous osteoblasts
cultured on demineralized bone matrix (Osteovit) receiving similar
ossication rates as for the defects treated with spongiose iliac bone
(Pradel et al., 2006). Carter et al. (2008) described a successfully
regenerated large mandibular bone defect after cyst enucleation and
lling with recombinant human morphogenetic protein-2 (rhBMP-2)
absorbed onto collagen sponges.
Further xenogenic materials comprise deproteinized bovine
bone mineral (DBBM, Bio Oss) or coral-derived (Interpore) and
phycogenic (Algipore) hydroxyapatite grafts (HA) which have
been successfully applied for sinus oor augmentations (Ewers,
2005; Scarano et al., 2006). These materials are supposed to
supply osteoconductive properties. However, they should be
considered as non-resorbable with different degrees of foreign
body reactions (Piecuch et al., 1990; Buser et al., 1998; Piattelli et al.,
1999; Jensen et al., 2009).
There are no reports of using these materials for defect lling
after cyst enucleation.
3.6. Alloplastic e synthetic grafts
Synthetic grafting materials can provide osteoconduction and
osteointegration. They should be biocompatible with minimal
brotic changes. Available synthetic materials include bioactive
glasses, glass ionomers, aluminium oxide, calcium sulphate,
calcium phosphates, a- and b-tricalcium phosphate (TCP), and
synthetic hydroxyapatite (HA) (Kao and Scott, 2007). The main
disadvantages of these materials in clinical settings may be low or
unpredictable resorption and occasional inammatory foreign
body reactions (Cornell, 1999; Giannoudis et al., 2005).
Concerning the treatment of jaw defects after cyst enucleation,
clinical experience exists for tricalcium phosphate and hydroxyapatite (Horch and Steegmann, 1985; Kohler et al., 1986; Thieme
et al., 1988; Velich et al., 2004; Horch et al., 2006; Gerlach and
Niehues, 2007). The idea of using these osteoconductive materials
is to stabilize the blood clot in the defect avoiding infections and to
advance bone regeneration by enhancing the migration of osteoprogenitor cells (Horch et al., 2006). Furthermore superior biomechanical properties should provide early implantation.
While traditional hydroxyapatite is generally considered as nonresorbable (Buser et al., 1998; Jensen et al., 2009), resorbability is
supposed to occur for novel nano-sized hydroxyapatite based on

T. Ettl et al. / Journal of Cranio-Maxillo-Facial Surgery 40 (2012) 485e493

greater solubility. In a preclinical animal study on adult domestic


pigs the nanoparticular hydroxyapatite Ostim was compared to
autogenous bone and to Ostim combined with 25% autogenous
bone as a lling material for articial bone defects of at least 1 cm.
Microradiography and histology indicated similar mineralization
rates for the three groups. Complete resorption of the nanoparticular hydroxyapatite had taken place after 12 weeks
(Thorwarth et al., 2005). In a recent prospective clinical investigation, jaw defect lling with Ostim was reported to show bony
regeneration after 3 months for defect sizes up to 3 cm and after
6e12 months for defects larger than 3 cm (Gerlach and Niehues,
2007). In ve cases supercial loss of the implanted material was
observed. The authors recommended Ostim because of its low
complication rate and its safe resorption observed by radiographs.
On closer examination of the gures in this publication, the
radiographs presented still demonstrate the opacity of the graft
after 12 months, although the authors describe complete ossication. This may point to a delayed or even missing resorption of the
used hydroxyapatite material. In a Russian study on 92 patients,
cyst lling with 33% Ostim-100 in combination with lincomycin
(n 49) was compared to simple enucleation (n 43). In the
available abstract the authors reported a more rapid ossication
and a lower complication rate for the Ostim-group (Bezrukov
et al., 1998), but interpretation of these results is difcult without
knowledge of the complete manuscript.
Tricalcium phosphates (TCPs), especially pure-phase b-TCPs are
regarded as being biocompatible, osteoconductive and resorbable
(Buser et al., 1998; Gaasbeek et al., 2005; Xin et al., 2005; Horch
et al., 2006). Recently, Cerasorb, a pure-phase, microporous
b-TCP with a grain size of 500e2000 mm, was repeatedly used for
lling of bone defects after cyst enucleation (Zerbo et al., 2001; Palti
and Hoch, 2002; Bicsak et al., 2006; Horch et al., 2006). In all these
studies with radiographic and partly histological follow-up investigations the b-TCP was widely resorbed after 12 months. In
a recent clinical study by Horch et al. 52 odontogenic cysts were
enucleated and lled with Cerasorb and blood alone, when the
diameter of the cyst was smaller than 2 cm, and with Cerasorb
combined with locoregional cancellous bone (ratio 1:1), when the
cysts diameter was larger than 2 cm (Horch et al., 2006). Healing
disturbances occurred in 9.2% of cases with partial loss of b-TCP
granulates in 5.9% and total loss in 2% of cases requiring surgical
defect lling with autogenous bone of the iliac crest. Radiographic
examination after 12 months revealed a density loss of 65% of the
b-TCP graft without admixture of spongiosa and a density loss of
85% of b-TCP with admixture of spongiosa indicating an accelerated
degradation of b-TCP when combined with autogenous bone. The
16 biopsied cases showed almost complete resorption of b-TCP
with regular trabecular bone formation and absence of foreign
body reactions (Horch et al., 2006). This study lacked a control
group and that Cerasorb alone was not applied to cysts larger than
2 cm in diameter.
Referring to comparative preclinical animal studies with
contained-type bone defects similar to jaw cysts, b-TCP leads to
faster bone regeneration in comparison to HA-based grafts. This is
explained by the fast resorption of b-TCP promoting complete
substitution with new bone (Buser et al., 1998; Artzi et al., 2004;
Jensen et al., 2006; Jensen et al., 2007). In a study of Jensen et al.
however, b-TCP (Ceros-TCP) decelerated bone regeneration during
early healing phase in defects of 9 mm diameter and 5 mm depth as
compared with autografts (Jensen et al., 2006).
Promising experimental results for mandibular bone regeneration have also been observed, when porous b-TCP was combined
with bone marrow stromal cells in order to combine osteoconduction and osteoinduction (Wu et al., 2006; He et al., 2007;
Yuan et al., 2007).

491

Mixtures of hydroxyapatite and b-tricalcium phosphate, known


as biphasic calcium phosphates (BCPs), have also been investigated
in different ratios as bone substitutes at the moment. They should
combine possible osteoconductive and osteogenic properties of
both materials and consider different defect morphologies
requiring adapted resorption rates (Giannoudis et al., 2005;
Habibovic et al., 2008). An HA/b-TCP ratio of 20/80 is reported to
resemble most the properties of autografts in bone formation and
degradation (Jensen et al., 2009). Clinical application of BCPs after
cyst enucleation has not reported to date.
4. Discussion
Objective evaluation of cystectomy and simple closure of jaw
cysts in contrast to procedures using additional bone grafts is
difcult, as clinical comparative studies are rare and criteria for
complications, bone regeneration and bone quality are dened
inconsistently. Most evaluations are based on radiographic techniques measuring bone density and boundary during regeneration.
Different bone grafts, for example alloplastic and certain synthetic
grafts, present with radiographic opacity, which aggravates analysis
of the newly formed bone quality. By means of radiographs it is
difcult to differentiate between regenerated physiological jaw
bone and persisting bone substitute.
Primary mucoperiosteal closure of the defects on solid margins
with simultaneous antibiotic treatment achieves a complication
rate of less than 5% even in defects measuring far more than 3 cm in
diameter (van Doorn, 1972; Chiapasco et al., 2000; Ihan Hren and
Miljavec, 2008; Kreusch et al., 2010). Infections present the main
complications while fractures are rare with a maximal risk of 3%
when located in the mandibular angle (Bolouri et al., 2001).
Currently there is no clinical data that the additional use of autografts, allogenous grafts (DFDBA), xenografts (gelatine, collagen) or
synthetic grafts (HA, b-TCP) signicantly reduces the risk of infections during primary wound healing. The previously used calf grafts
(Kiel bone) bear an increased risk for infections of 20% (Horowitz
and Bodner, 1989; Bodner, 1998) and should not be used any
more. The reported infection rates of modern synthetic grafts, e.g.
fast resorbing b-TCP, are comparable to simple blood clot or
collagen healing (Bicsak et al., 2006; Horch et al., 2006).
Considering bone regeneration, complete jaw ossication takes
about 12 months after enucleation and simple mucoperiosteal
closure for defects up to 3 cm. For larger defects almost complete
bone healing can be expected after 24 months (Chiapasco et al.,
2000; Ihan Hren and Miljavec, 2008; Yim and Lee, 2009). Preservation of periosteum and bone walls is the most important criteria
for regular bone healing (Lemperle et al., 1998; Huh et al., 2005; Ma
et al., 2009). Spontaneous bone regeneration can be delayed in
older patients, in bicortical or circular defects or in defects of the
anterior maxilla (Laffers and Zimmer, 1977; Hemprich et al., 1989;
Ihan Hren and Miljavec, 2008; Yim and Lee, 2009).
Autologous spongiosa shows the highest ossication rate during
the initial healing period (Holtgrave and Spiessl, 1975; Buser et al.,
1998), ending up in bone density and quality similar to simple
blood clot healing after 12 months. Interestingly there is no current
clinical study comparing iliac spongiosa grafting to simple
enucleation for large jaw cysts. Autologous bone from the iliac crest
still represents the rst alternative in extremely large defects with
partial absence of periosteum or loss of more than one cortical
margin, although donor site morbidity, possible hospitalization and
the need for general anaesthesia have to be taken into consideration. A stable membrane additionally prevents collapse of the
surrounding soft tissues (Lemperle et al., 1998; Blecher et al., 2000;
Ma et al., 2009). With regard to the patients satisfaction, iliac bone
grafting might reduce the duration from cyst enucleation to dental

492

T. Ettl et al. / Journal of Cranio-Maxillo-Facial Surgery 40 (2012) 485e493

implantation, leading to early prosthetic rehabilitation, although


data on this topic is absent in the literature.
Collagen has been very popular in recent times for stabilization
of the blood clot. Like the risk for infection, bone regeneration
seems also comparable to simple enucleation, although data is
inconsistent (Buser and Berthold, 1985; Joos, 1985; Hemprich et al.,
1989; Mitchell, 1992). The use of collagen is still justied in certain
circumstances, for example for patients with high risk of bleeding.
In future its clinical performance may be improved in combination
with engineered growth factors or osteoblasts (Pradel et al., 2006).
In preclinical animal studies, b-TCP alone or in combination with
autografts or hydroxyapatite (BCP) shows promising bone formation similar to autografts in contained-type defects, although ossication is delayed compared to autologous bone (Buser et al., 1998;
Jensen et al., 2006; Jensen et al., 2009). Clinically, defect lling with
b-TCP and blood results in almost complete radiographic bone
regeneration of defects up to 2 cm after 12 months with a resorption
rate of 65% of the used b-TCP. Degradation and substitution of b-TCP
is accelerated by the additional use of autologous grafts (Horch et al.,
2006). Clinical data for single b-TCP use in lesions exceeding 2 cm is
restricted to rare cases (Zerbo et al., 2001; Velich et al., 2004; Bicsak
et al., 2006). Further investigation is indicated as to whether b-TCPgrafting alone or in combination with regional autologous bone
enables early implantation when iliac bone grafting has to be avoided. For hydroxyapatite, also for nanoparticular modications,
delayed ossication due to decient resorption can be assumed.
There may be advances in the future using engineered osteoblasts, growth factors or mesenchymal stem cells for enhancing
bone regeneration. Different studies have been described in animal
models with BMPs, PRPs or mesenchymal stem cells (Boyne, 2001;
Srouji et al., 2005; Pradel et al., 2006; Carter et al., 2008; Pieri et al.,
2009; Miloro et al., 2010; Mooren et al., 2010; Kazakos et al., 2011).
At the moment however, these options are of experimental character and have to be further investigated in clinical trials.
5. Conclusion
Enucleation of jaw cysts e the so-called cystectomy e and
primary closure without the use of additional bone grafts represents the state of the art, even in large defects of 3 cm and more in
diameter. A safe mucoperiosteal ap on solid margins accompanied
by perioperative antibiotic treatment provides physiological organization of the blood clot and its transformation into regular bred
bone. The risk of infection or fracture complications is low. Followup investigations are not disturbed by bone graft artefacts. Loss of
periosteum or bone walls might require additional stabilization and
osteogenic induction by autogenous spongiosa. Xenogenic or
synthetic grafts do not indicate signicant advantages so far. The
use of engineered growth factors, osteoblasts or stem cells has to be
further investigated in the future.
Conict of interest
All authors disclose any nancial and personal relationships
with other people or organizations that could inappropriately
inuence their work.
References
Arrington ED, Smith WJ, Chambers HG, Bucknell AL, Davino NA: Complications of
iliac crest bone graft harvesting. Clin Orthop Relat Res: 300e309, 1996
Artzi Z, Weinreb M, Givol N, Rohrer MD, Nemcovsky CE, Prasad HS, et al: Biomaterial
resorption rate and healing site morphology of inorganic bovine bone and betatricalcium phosphate in the canine: a 24-month longitudinal histologic study and
morphometric analysis. Int J Oral Maxillofac Implants 19: 357e368, 2004
Becker R: Various methods of cyst surgery. Indications and results. ZWR 80:
106e112, 1971

Bezrukov VM, Grigoriants LA, Zuev VP, Pankratov AS: The surgical treatment of jaw
cysts using hydroxyapatite with an ultrahigh degree of dispersity. Stomatologiia
(Mosk) 77: 31e35, 1998
Bicsak A, Bogdan S, Barabas J, Szabo G: Medium-term study on lling large bone
defects with beta-tricalcium-phosphate (Cerasorb). J Craniomaxillofac Surg
34(Suppl. 1): 152, 2006
Blecher JC, Lemperle SM, Howaldt HP: Osteoplasty of extensive jaw defects by
protected bone regeneration using large pore resorbable implant. Mund Kiefer
Gesichtschir 4(Suppl. 2): S496eS500, 2000
Bodner L: Effect of decalcied freeze-dried bone allograft on the healing of jaw
defects after cyst enucleation. J Oral Maxillofac Surg 54: 1282e1286, 1996
Bodner L: Osseous regeneration in the jaws using demineralized allogenic bone
implants. J Craniomaxillofac Surg 26: 116e120, 1998
Bolouri S, Jonas S, Dunsche A: Die Komplikationen der Zystektomie ohne Fllung
der Knochenhhle. Deutsche Zahnrztliche Zeitschrift 56: 57e58, 2001
Boyne PJ: Application of bone morphogenetic proteins in the treatment of clinical
oral and maxillofacial osseous defects. J Bone Joint Surg Am 83-A(Suppl. 1):
S146eS150, 2001
Buser D, Berthold H: Promotion of bone regeneration using collagen eece after
defect management in voluminous jaw cysts. Dtsch Zahnarztl Z 40: 660, 1985
Buser D, Hoffmann B, Bernard JP, Lussi A, Mettler D, Schenk RK: Evaluation of lling
materials in membrane e protected bone defects. A comparative histomorphometric
study in the mandible of miniature pigs. Clin Oral Implants Res 9: 137e150, 1998
Carter TG, Brar PS, Tolas A, Beirne OR: Off-label use of recombinant human bone
morphogenetic protein-2 (rhBMP-2) for reconstruction of mandibular bone
defects in humans. J Oral Maxillofac Surg 66: 1417e1425, 2008
Chiapasco M, Rossi A, Motta JJ, Crescentini M: Spontaneous bone regeneration after
enucleation of large mandibular cysts: a radiographic computed analysis of 27
consecutive cases. J Oral Maxillofac Surg 58: 942e948, 2000 discussion 949
Constantinides J, Zachariades N: Homogenous bone grafts to the mandible. J Oral
Surg 36: 599e603, 1978
Cornell CN: Osteoconductive materials and their role as substitutes for autogenous
bone grafts. Orthop Clin North Am 30: 591e598, 1999
Dickmeiss B, Hauenstein H, Schettler D: Filling of bone defects with human brin
concentrate in large jaw cysts. Dtsch Zahnarztl Z 40: 653e656, 1985
Eunger H, Leppanen H: Iliac crest donor site morbidity following open and closed
methods of bone harvest for alveolar cleft osteoplasty. J Craniomaxillofac Surg
28: 31e38, 2000
Ewers R: Maxilla sinus grafting with marine algae derived bone forming material:
a clinical report of long-term results. J Oral Maxillofac Surg 63: 1712e1723, 2005
Friedlaender GE, Strong DM, Tomford WW, Mankin HJ: Long-term follow-up of
patients with osteochondral allografts. A correlation between immunologic
responses and clinical outcome. Orthop Clin North Am 30: 583e588, 1999
Gaasbeek RD, Toonen HG, van Heerwaarden RJ, Buma P: Mechanism of bone
incorporation of beta-TCP bone substitute in open wedge tibial osteotomy in
patients. Biomaterials 26: 6713e6719, 2005
Gerlach KL, Niehues D: Treatment of jaw cysts with a new kind of nanoparticular
hydroxylapatite. Mund Kiefer Gesichtschir 11: 131e137, 2007
Giannoudis PV, Dinopoulos H, Tsiridis E: Bone substitutes: an update. Injury
36(Suppl. 3): S20eS27, 2005
Habibovic P, Kruyt MC, Juhl MV, Clyens S, Martinetti R, Dolcini L, et al: Comparative
in vivo study of six hydroxyapatite-based bone graft substitutes. J Orthop Res
26: 1363e1370, 2008
Hall HD, Phillips RM, Chase DC: Bone grafts of large cystic defects in the mandible.
J Oral Surg 29: 146e150, 1971
He Y, Zhang ZY, Zhu HG, Qiu W, Jiang X, Guo W: Experimental study on reconstruction of segmental mandible defects using tissue engineered bone
combined bone marrow stromal cells with three-dimensional tricalcium
phosphate. J Craniofac Surg 18: 800e805, 2007
Heiple KG, Chase SW, Herndon CH: A comparative study of the healing process
following different types of bone transplantation. J Bone Joint Surg Am 45:
1593e1616, 1963
Hemprich A, Lehmann R, Khoury F, Schulte A, Hidding J: Filling cysts with type 1
bone collagen. Dtsch Zahnarztl Z 44: 590e592, 1989
Holtgrave E, Spiessl B: Die osteoplastische Behandlung groer Kieferzysten.
Schweiz Mschr Zahnheilk 85: 585, 1975
Horch HH, Sader R, Pautke C, Neff A, Deppe H, Kolk A: Synthetic, pure-phase betatricalcium phosphate ceramic granules (Cerasorb) for bone regeneration in the
reconstructive surgery of the jaws. Int J Oral Maxillofac Surg 35: 708e713, 2006
Horch HH, Steegmann B: Experience with resorbable TCP-ceramic granules for the
lling of large bone defects after cystectomy in the jaw. Dtsch Zahnarztl Z 40:
672e677, 1985
Horowitz I, Bodner L: Use of xenograft bone with aspirated bone marrow for
treatment of cystic defect of the jaws. Head Neck 11: 516e523, 1989
Huh JY, Choi BH, Kim BY, Lee SH, Zhu SJ, Jung JH: Critical size defect in the canine
mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100: 296e301, 2005
Iatrou I, Theologie-Lygidakis N, Leventis M: Intraosseous cystic lesions of the jaws
in children: a retrospective analysis of 47 consecutive cases. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 107: 485e492, 2009
Ihan Hren N, Miljavec M: Spontaneous bone healing of the large bone defects in the
mandible. Int J Oral Maxillofac Surg 37: 1111e1116, 2008
Jensen SS, Bornstein MM, Dard M, Bosshardt DD, Buser D: Comparative study of
biphasic calcium phosphates with different HA/TCP ratios in mandibular bone
defects. A long-term histomorphometric study in minipigs. J Biomed Mater Res
B Appl Biomater 90: 171e181, 2009

T. Ettl et al. / Journal of Cranio-Maxillo-Facial Surgery 40 (2012) 485e493


Jensen SS, Broggini N, Hjorting-Hansen E, Schenk R, Buser D: Bone healing and graft
resorption of autograft, anorganic bovine bone and beta-tricalcium phosphate.
A histologic and histomorphometric study in the mandibles of minipigs. Clin
Oral Implants Res 17: 237e243, 2006
Jensen SS, Yeo A, Dard M, Hunziker E, Schenk R, Buser D: Evaluation of a novel
biphasic calcium phosphate in standardized bone defects: a histologic and
histomorphometric study in the mandibles of minipigs. Clin Oral Implants Res
18: 752e760, 2007
Joos U: Bone regeneration after cyst surgery. Dtsch Zahnarztl Z 40: 661e663, 1985
Joos U, Mittermayer C, Schilli W, Kaden A: Effect of collagen, hydroxylapatite and
Geslastypt-S on a cell culture. Dtsch Zahnarztl Z 37: 22e24, 1982
Kao ST, Scott DD: A review of bone substitutes. Oral Maxillofac Surg Clin North Am
19: 513e521, vi, 2007
Kazakos K, Lyras DN, Thomaidis V, Agrogiannis G, Botaitis S, Drosos G, et al:
Application of PRP gel alone or in combination with guided bone regeneration
does not enhance bone healing process: an experimental study in rabbits.
J Craniomaxillofac Surg 39: 49e53, 2011
Kohler S, Berger G, Steinborn G: Calcium phosphate ceramics Mediceram-R e
a resorbable bioactive bone substitute for the treatment of odontogenous cysts.
Acta Chir Plast 28: 121e125, 1986
Kreusch T, Wittig J, Friedrich M, Geduhn A: Die Therapie von Kieferzysten. Vorgehen und Ergebnisse. Deutsche Zahnrztliche Zeitschrift 65, 2010
Laffers U, Zimmer H: Radiological interpretation of bone regeneration after cystectomy of odontogenic cysts. Stomatol DDR 27: 238e241, 1977
Lemperle SM, Calhoun CJ, Curran RW, Holmes RE: Bony healing of large cranial and
mandibular defects protected from soft-tissue interposition: a comparative
study of spontaneous bone regeneration, osteoconduction, and cancellous
autografting in dogs. Plast Reconstr Surg 101: 660e672, 1998
Lexer E. Die freien Transplantationen, vol. 2. Stuttgart: Enke Verlag, 1924
Lindsay JS, Martin WR, Green HG: Traumatic bone cyst treated with homogenous
bone graft. Report of a case. Oral Surg Oral Med Oral Pathol 21: 536e542, 1966
Ma JL, Pan JL, Tan BS, Cui FZ: Determination of critical size defect of minipig
mandible. J Tissue Eng Regen Med 3: 615e622, 2009
Maatz R, Bauermeister A: Clinical experiences with the Kiel graft. Langenbecks Arch
Klin Chir Ver Dtsch Z Chir 298: 239e244, 1961
Marble Jr HB: Homografts of freeze-dried bone in cystic defects of the jaws. A
survey of ninety-one cases. Oral Surg Oral Med Oral Pathol 26: 118e123, 1968
Marx RE, Garg AK: Bone structure, metabolism, and physiology: its impact on
dental implantology. Implant Dent 7: 267e276, 1998
Miloro M, Haralson DJ, Desa V: Bone healing in a rabbit mandibular defect using
platelet-rich plasma. J Oral Maxillofac Surg 68: 1225e1230, 2010
Mitchell R: An evaluation of bone healing in cavities in the jaws implanted with
a collagen matrix. Br J Oral Maxillofac Surg 30: 180e182, 1992
Mooren RE, Dankers AC, Merkx MA, Bronkhorst EM, Jansen JA, Stoelinga PJ: The
effect of platelet-rich plasma on early and late bone healing using a mixture of
particulate autogenous cancellous bone and Bio-Oss: an experimental study in
goats. Int J Oral Maxillofac Surg 39: 371e378, 2010
Muschler G, Lane J: Orthopedic surgery. In: Habal M, Reddi A (eds), Bone grafts and
bone substitutes. Philadelphia: WB Saunders, 1573e1589, 1992
Ogunlewe MO, Akinwande JA, Ladeinde AL, Adeyemo WL: Spontaneous regeneration of whole mandible after total mandibulectomy in a sickle cell patient. J Oral
Maxillofac Surg 64: 981e984, 2006
Palti A, Hoch T: A concept for the treatment of various dental bone defects. Implant
Dent 11: 73e78, 2002
Partsch C: Zur Behandlung der Kieferzysten. Dtsc Mschr Zahnheilkunde 28: 252, 1910
Piattelli M, Favero GA, Scarano A, Orsini G, Piattelli A: Bone reactions to anorganic
bovine bone (Bio-Oss) used in sinus augmentation procedures: a histologic longterm report of 20 cases in humans. Int J Oral Maxillofac Implants 14: 835e840,1999
Piecuch JF, Ponichtera A, Nikoukari H: Long-term evaluation of porous hydroxyapatite
blocks for alveolar ridge augmentation. Int J Oral Maxillofac Surg 19: 147e150, 1990
Pieri F, Lucarelli E, Corinaldesi G, Fini M, Aldini NN, Giardino R, et al: Effect of
mesenchymal stem cells and platelet-rich plasma on the healing of standardized bone defects in the alveolar ridge: a comparative histomorphometric study
in minipigs. J Oral Maxillofac Surg 67: 265e272, 2009

493

Pradel W, Eckelt U, Lauer G: Bone regeneration after enucleation of mandibular


cysts: comparing autogenous grafts from tissue-engineered bone and iliac
bone. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101: 285e290, 2006
Reichenbach E, Taege F. Dtsch Zahn-Mund-Kieferheilk 28: 121, 1958
Rodeo SA, Delos D, Weber A, Ju X, Cunningham ME, Fortier L, et al: Whats new in
orthopaedic research. J Bone Joint Surg Am 92: 2491e2501, 2010
Sandhu HS, Grewal HS, Parvataneni H: Bone grafting for spinal fusion. Orthop Clin
North Am 30: 685e698, 1999
Santamaria J, Garcia AM, de Vicente JC, Landa S, Lopez-Arranz JS: Bone regeneration
after radicular cyst removal with and without guided bone regeneration. Int J
Oral Maxillofac Surg 27: 118e120, 1998
Scarano A, Degidi M, Iezzi G, Pecora G, Piattelli M, Orsini G, et al: Maxillary sinus
augmentation with different biomaterials: a comparative histologic and histomorphometric study in man. Implant Dent 15: 197e207, 2006
Schenk RK, Buser D, Hardwick WR, Dahlin C: Healing pattern of bone regeneration
in membrane-protected defects: a histologic study in the canine mandible. Int
J Oral Maxillofac Implants 9: 13e29, 1994
Schliephake H: Bone growth factors in maxillofacial skeletal reconstruction. Int
J Oral Maxillofac Surg 31: 469e484, 2002
Schroder F, Schwenzer N: The results of surgery of large mandibular cysts with
simultaneous bone transplantation. Osterr Z Stomatol 67: 140e146, 1970
Schulte W: Die Eigenblutfllung: Eine neue Methode zur Versorgung
grerer Knochendefekte nach intraoralen Eingriffen. Dtsch Zahnarztl Z 15:
910e914, 1960
Schulte W: Die Knochenregeneration nach der Ausschlung groer Kieferzysten und
ihre Konsequenzen fr die Operationstechnik. Dtsch Zahn-Mund-Kieferheilk 45:
177e206, 1965
Spengos MN: Irradiated allogenic bone grafts in the treatment of odontogenic cysts.
J Oral Surg 32: 674e678, 1974
Srouji S, Rachmiel A, Blumenfeld I, Livne E: Mandibular defect repair by TGF-beta
and IGF-1 released from a biodegradable osteoconductive hydrogel. J Craniomaxillofac Surg 33: 79e84, 2005
Thieme V, Muller EI, Magdefessel U, Raabe G, Berger G: Filling cystic bone defects
with surface-modied alpha-tricalcium phosphate. A clinical, radiographical
and histological study. Dtsch Z Mund Kiefer Gesichtschir 12: 18e24, 1988
Thorwarth M, Schultze-Mosgau S, Kessler P, Wiltfang J, Schlegel KA: Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite.
J Oral Maxillofac Surg 63: 1626e1633, 2005
van Doorn ME: Enucleation and primary closure of jaw cysts. Int J Oral Surg 1: 17e25,
1972
Velich N, Nemeth Z, Hrabak K, Suba Z, Szabo G: Repair of bony defect with
combination biomaterials. J Craniofac Surg 15: 11e15, 2004
Weiss P: Experiences with the Kiel bone graft in the surgical treatment of maxillary
cysts. Langenbecks Arch Klin Chir Ver Dtsch Z Chir 306: 86e91, 1964
Wolfe SA: Autogenous bone grafts versus alloplastic material in maxillofacial
surgery. Clin Plast Surg 9: 539e540, 1982
Wolff KD, Swaid S, Nolte D, Bckmann RA, Hlzle F, Mller-Mai C: Degradable
injectable bone cement in maxillofacial surgery: indications and clinical
experience in 27 patients. J Craniomaxillofac Surg 32: 71e79, 2004
Wu W, Chen X, Mao T, Chen F, Feng X: Bone marrow-derived osteoblasts seeded
into porous beta-tricalcium phosphate to repair segmental defect in canines
mandibula. Ulus Travma Acil Cerrahi Derg 12: 268e276, 2006
Xin R, Leng Y, Chen J, Zhang Q: A comparative study of calcium phosphate formation
on bioceramics in vitro and in vivo. Biomaterials 26: 6477e6486, 2005
Yim JH, Lee JH: Spontaneous bone regeneration after enucleation of bone cyst:
a radiographic analysis. Free papers e poster presentation 2009
Younger EM, Chapman MW: Morbidity at bone graft donor sites. J Orthop Trauma 3:
192e195, 1989
Yuan J, Cui L, Zhang WJ, Liu W, Cao Y: Repair of canine mandibular bone defects
with bone marrow stromal cells and porous beta-tricalcium phosphate.
Biomaterials 28: 1005e1013, 2007
Zerbo IR, Bronckers AL, de Lange GL, van Beek GJ, Burger EH: Histology of human
alveolar bone regeneration with a porous tricalcium phosphate. A report of two
cases. Clin Oral Implants Res 12: 379e384, 2001