Periodoruology 2000, Vol.
17, 1998, 151-175
Printed in Denmark . All rights reserved
Guided bone regeneration at
oral implant sites
CHRISTOPH H. F. HAMMERLE & THORKILD
Guided bone regeneration is an accepted method
successfully employed in dental practices to increase
the volume of the host bone at sites chosen for im-
plant placement. Orignally, the biological principIe
leading to the method of guided tissue regeneration
was discovered by Nyman and Karring (103,104,131,
133) in the early 1980s as a result of the desire to
regenerate lost periodontal tissues. As a conse-
quence, novel possibilities to regenerate periodontal
tissues with new root cementum, periodontal liga-
ment and alveolar bone became available (70, 71,
130, 134).
Soon, guided tissue regeneration found appli-
cations in other areas, including the regeneration of
bone tssue (129). As a result of animal experiments
(52, 54, 56, 167) and clinical applications in humans
(14, 34, 114, 116, 132, 184), guided tissue regenera-
tion has become a clinically accepted method for
augmenting bone in situations with an inadequate
volume for the placement of endosseous dental im-
plants. The formation of new bone in conjunction
with the placement of dental implants is also a clin-
ically well documented and successful procedure
(13, 51, 53, 100, 112, 116).
There is general agreement that guided bone re-
generation is difficult to perform and demandng re-
garding the skills and experience of the therapist.
Whereas enlargement of jaw bone in conjunction
with implant pIacement is the most frequent indi-
cation, it has also been used to increase the bone
volume in order to achieve better aesthetics (47).
This chapter discusses the scientific and clnical
aspects of guided bone regeneration based on avail-
able data.
Biological basis of guided bone
regeneration
In principIe, four methods have been descrbed to
increase the rate of bone forrnation and to augment
Copyright Munksgaard 1998
PERIODONTOLOGY 2000
ISSN 0906-6713
KARRING
the bone volume: osteoinduction by the use of ap-
propriate growth factors (148, 149, 181); osteocond-
uction, where a grafting material serves as a scaffold
for new bone growth (30, 149); distraction osteogen-
esis, by which a fracture is surgically induced and
the two fragments are then slowly pulled apart (91,
92); and finally, guided tissue regeneration, which
allows spaces maintained by barrier membranes to
be filled with new bone (50, 54, 56, 81, 109, 110, 135).
Since bochemical induction of bone formation
is still in an experimental phase, and since distrae-
ton osteogenesis cannot be applied in the healing
of local bone defects in the jaw bones, guided
bone regeneration and the use of bone grafting
materials are the only methods commonly applied
in clinical practice. Among the techniques de-
scribed, guided bone regeneration has shown the
best and most predictable results when employed
to fi11 peri-implant bone deficits with new bone
(13, 27, 34, 53, 75, 132).
Although bone regeneration using membrane bar-
riers is often successfully achieved in clinical prac-
tice, many problems remain and need to be resolved
to increase predictability. The problems most fre-
quently encountered with guided bone regeneration
include partial or total collapse of the barrier mem-
brane, exposure of membranes due to soft tissue
dehiscences resulting in local infection and incom-
pIete bone regeneration within the space provided
by the membrane. In order to overcome these diffi-
culties, often resulting in unsatisfactory clinicaI re-
sults, various attempts have been made to improve
the devices and the surgical techniques.
It soon became evident that improved knowledge
about the biological mechanisms and the temporal
dynamics of new bone formation under the con-
ditions of guided regeneration is critical. Scientists
and clinicians considered this knowledge a prerequi-
site to better understand the healing steps leading to
regenerated and fully mature bone in order to be
able to beneficially influence healing for further de-
151
Hdmmerle & Karring

152
Guided bane regeneratian at oral implant sites

153
 velopments in the mineral- ized bone, mature lamellar bone on on the size of the
the remnants of the
field and for since new bone is defect has previously
original tra- becular
increased predict- only formed at loca- scaffold. f. Remnants of been eluci- dated in an
ability of the clinical tions where the dark-staned, primary experimental rodent
outcomes. biomechanical stability trabecular scaffold are model. In cortical bone,
So far, the type of is guaranteed, that is, covered by new bone circular defects of less
bone being formed lamellae. g. By continuous
where pressure and than 200 11mhad the
by applying apposition of lamellar
ten sile forces are ex- bone, a primary osteon potential to heal with
the princple of guided cluded (177). (po) with a central blood concentric formation
tissue regeneration has Otherwise, an vessel is formed. h. As part of lamel- lar bone (97,
only been nvestigated intermediate tissue of normal bone turnover 155). In larger defects
in a few animals (79, osteoclasts were resorbing
with appropriate parts of the cortical bone of 200 to 500 11m, bone
110, 154) and so me mechanical properties healing was
followed by osteoblastic
human studies (81). will arise before bone appo- sition leading characterized by
Two of these animal ossification. to the formation of formation of a
studies were dealing The mechanism of secondary osteons (so).
trabecular network of
with surgically bone healing being woven bone bridging
prepared bone defects dependent the de- fect.
(79, 154). One study Subsequently, the
focused on tissue heal- spaces between the
ing in bone defects in Fig. 1. a. Newly formed trabecu- lae were filled
the mandible of dogs bone trabeculae (purple) with lamellar bone.
(154). The other closely follow the
pathway given by the However, in de- fects
experiment investigated of 500 11mand larger,
proliferating vessels
the temporal and (brown). b. The new bone bridging by direct
. spatial dynamics of (black) consists of forma- tion of bone
bone regeneration in irregularly shaped, delicate did not occur.
calvarial defects in trabeculae lined with
osteoid seams (os) and a Following 3 weeks of
rabbits (79). The third healing, such defects
layer of cuboidal
experiment ex- plored osteoblasts (arrows). exhibited a central are
the possibility of Collagen fibers (arrow a char- acterized by the
augmenting the heads) are progressively
presence of connective
naturally present bone embedded into the
mineralizing osteoid. C. tissue.
volume in the mandible The intermediate
A newly formed
of rats (10). trabeculae of woven bone connective tissue
In all these is embedded in a highly described in
experiments, a vascularized connec- tive the two above-
similar basic pattern tissue. The bright red mentioned experiments
of osteoid seam is covered
by a layer of osteoblasts (81, 154) pro- vided the
bone formation was
(arrows). Osteocytes are appropriate mechanical
observed. Initially,
encircled by the properties necess- ary
trabeculae of woven mineralizing bone to allow for unimpeded
bone proliferated into (arrowheads). d.
ingrowth of blood
the defecto In two Fluorochrome labeling
demonstrates the capil- laries during
studies, the space
sequential steps of the angiogenesis (Fg. la),
provided by the re- generation of which always precedes
membrane was filled mineralized bone. Bone bone formation (62).
with a newly formed stained in bright yellow
(tetracycline label) is
However, with in-
connective tissue
ofwoven nature (wb). creasing defect size the
matrix prior to the
Lamel- lar bone biomechanically stable
formation of deposition (arrows) is zone becomes
mineralized bone (79, labeled in red (alizarine successively limited to
81, label) and green (calceine
154). The investigators label). e. Osteoclasts the marginal area of the
concluded that the size (Oc) are resorbing the defect, whereas the
of the primarily formed woven central region is
defects did not allow bone (Wb). Osteo- blasts exposed to
(Ob) in their immediate
154
for direct formation of biomechanical forces
vicinity deposit layers of
presumably preventing detected. In the course
bone formation. Ths of bone apposition,
view is supported by surrounding
experimental and connective tissue fibers
clinical observations became embedded into
that showed that, in the osteoid and finally
large bone defects, integrated into the new
bone formation is bone. Within the
limited to the defect network of the
margins (ll, 50, 60, 80, trabecular scaffold,
123). numerous blood
In the experiment capillaries were
with the augmentation consistently found
of the mandibular connected with the
ramus in rats, in vessels of the opened
contrast, the new bone bone marrow cavity of
proliferated into the the adjacent bony
defect space without a defect borders. In
nonmn- eralized addition, a
connective tissue considerable
matrix occupying the
en- tire area for
regeneration (10).
Similar observations
regarding bone
formation
have been reported in
canine mandibular
and ro- dent calvarial
bone defects (79, 154).
The new bone
formation generally
originated from the
bony bor- ders of the
defecto This new bone
appeared as a scaf- fold
of delicate trabeculae
comprised of woven
bone, from which
several extensions were
directed towards the
center of the defects
(Fig. lb, c). The
surfaces o~ the
trabeculae were
commonly covered by
osteoid seams lined by a
dense layer of cuboidal
osteoblasts. The
trabeculae were
embedded in a well-
organized and
vascularized granulation
tissue. At various loca-
tions integration of
collagen fiber bundles
into the new bone
matrix could be 155
Hdmmerle & Karring

156
 Guided bone regeneration at oral implant sites
number of concluded that osseous borders facing the steps of guided bone
proliferating blood defect closure arising membranes cortical regeneration describe
capillaries ac- both from the margins bone was formed by bone healing in the
companied and even of the bone defect and continuous lamellar molar area in the
preceded the bone as slands may be a bone deposition. mandible (81). Hol- low
trabeculae growing faster healing process Finally, secondary titanium test cylinders
towards the mid-part of than marginal bone osteons were formed measuring 3.5 mm in
the defect (79, 154, formation alone. replacing the outer diameter, 2.5
162).As the mineralized Common to all these previously formed mm in inner diameter
bone grew, blood experiments was the cortical bone (Fig. Ih). and a height of 4 mm
vessels ly- ing in its finding that the bone The only available were placed into
immediate vicinity human data on the standardized holes in
volume increased with
sequential
became incorporated time and that the the retromolar area of
into the new bone primary hea!thy volunteers. The
matrix. intramembranous cyl- inders were placed
The remainder of the trabecular scaffold in such a way that 1.5
defect area, which was underwent intense to 2 mm of the test
not filled with bone remodeling: numerous devices was submerged
yet, contained loose osteo- clasts arose and below the level of the
connective tissue began to eliminate the surrounding bone, and
comprised of scarce primitive woven bone, 2 to 2.5 mm surpassed
collagen fibers without whereas a new the bone surface. The
a preferential orientation. generation of osteo- bone-facing ends of
Sparsely distributed blasts deposited mature the de- vices were left
cells, predominant!y lame llar bone layers on open. The soft tissue
fibroblasts and the woven bone facing ends were closed
macrophages as well as remnants (Fig. Id, e). by means of expanded
a moderate number of As a consequence of the polytetrafluoroethy- lene
wide blood capillaries continuous remodeling membranes (Gore-Tex
were seen. of the primary bony Periodontal Material",
In contrast to the network, most of the Flagstaff, AZ) before
findings in the other trabeculae contained the soft tissue flaps
studies, only a small, intensely were su- tured for
bone islands arose stained core of woven primary healing. After
within this fibrovascular bone sur- rounded by observation times
tissue in the calvaral thick bone layers of ranging from 2 to 36
defect model as regular lamellar tex- weeks, the cylinders
identified by means of ture and thus along with the
radiographs and serial comprised the regenerated tissue were
sections (79). Their secondary spongiosa harvested and
texture was consistent (Fig. lf). The analyzed.
with that of woven continuous growth of The tissue generated
bone, that is, ir- regular the bone tra- beculae at 2 and 7 weeks
bundles of collagen resulted in the exhibited a cylindrical
fibers and extremely narrowing of the shape, whereas the
nu- merous, large intertra- becular specimens harvested at
osteocytes, and they connective tissue and 12 weeks and at later
were without contact in the formation of time points, yielded the
with the marginal bone. primary osteons form of an hourglass.
The proliferation of containing vascular Specimens of 12
new bone in this pattern channels (Fg. weeks and less healing
has not been described 19). The presence of time almost entirely
pre- viously, unless a osteoid seams with contained soft tissue.
sutural growth area overlying osteoblasts Specimens with
was given ac- cess to indicated continuation generation times of 4
the defect area (11, of the osteogenic months and more
60). The investigators process. At the defect contained both 157
soft
 Hdmmerle & Karring
tissue and increasing alveolar
amounts of mineralized ridge
bone.
Up to a period of 6 To date, guided bone
months of healing, new regenera tia n can most
bone was primarily success- fully be used
fi11ingthe previously to regenerate localized
prepared defect within alveolar defects
the host bone.
Therefore, by reaching
the level of the
surrounding host bone,
true regeneration of
bone had occurred.
Interestingly, bone
formation did not come
to a halt at this point
but proceeded aboye
the borders of the
skeleton, thereby
altering the genetically
determined form of
the mandible. This
formation of new bone
beyond the skeletal bor-
ders by applying the
method of guided
tissue re- generation
was first demonstrated
on the calvaria of
rabbits (161).
Subsequently, these
findings were con-
firmed in other
experimental animals
such as rab- bits, rats,
and dogs (83, 99, 109,
110, 118, 122, 160). The
first guided bone
neogenesis in human s
was demonstrated by
applying the novel
model system used in
the present study.
Furthermore, neoforma-
tion of bone beyond the
skeletal borders can
also be achieved by the
combined use of bone
substitutes and
membranes (78, 159).

Treatment of
localized
158 of the
defects
 Guided bone regeneration at oral implant sites

Fig. 2. a. Insufficient bone volume to place an implant

under standard conditions in the right premolar region of
the mandibular arch in a 22-year-old caries-free patient.
b. Twosupporting screws of the Memfixsystem have been
placed in order to augment the local bone volume lat-
erally. c. The cortical bone has been perforated at multiple
locations to allow for bleeding from the bone marrow
spaces. d. An expanded polytetrafluoroethylene mem-
brane has been carefully adapted to the bony borders of
the defect being draped over the two supporting screws.
Stabilization of the membrane has been achieved by pla-
cing three Memfix fixation screws (Institut Straumann,
Waldenburg, Switzerland).

159
Hdmmerle & Karring
with new bone tissue either covered with
(Fig. 2-4). Although expanded
various attempts have polytetrafluoroethy-
been described aiming lene membranes,
at augmenting the bone covered with
over extended areas of membranes and
the jaw, no valid grafted with porous
technique or clinical hydroxyapatite or with
procedure has been a tissue growth matrix
presented so faro of porous
polytetrafluoroethylene,
grafted with these
Guided bone
same materials but not
regeneration
prior to covered wth
implant membranes, or finally,
placement neither grafted nor
cov- ered with
In situations with
membranes.
abone defect at a site,
Morphological and
where the primary
hstologi- cal analysis
stability of an implant
revealed that, in sites
cannot be achieved or
treated wth mem-
when implant
branes, with or without
placement is not
the addition of grafts,
possible in ideal
the entire space
location for subsequent
between the membrane
prosthetic therapy,
and the jaw bone was
guided bone
filled with bone. In the
regeneration prior to
absence of mern-
implantation represents
branes, bone formation
the method of choice.
was lacking.
Experimental
Later, in a similarly
research on ridge
designed study,
augmentation using
columns of cortical
guided bone
bone were used to
regeneration was
support membranes
presented in the early
in- tended for bone
1990s (167). In a dog
regeneration of
model, large defects of
previously prepared
the alveolar ridge were
alveolar ridge defects in
surgically prepared
dogs (174).Again, the
both in the mandible
me m- branes under
and in the maxilla.
this particular
The defects were
experimental situation
proved efficacious in
regenerating bone
within the space
created, whereas the
controls without mem-
branes failed to heal
with bone.

160
Hammerle & Karring

Fig. 3. 8. At membrane removal

surgery 9 months later, excellent
bone formation is observed. b. A
hollow-cylinder implant can be
placed in perfect location under
standard conditions.

156
Fig. 4. 8. After b. Radiographic
completion of prosthetic examination of the
treatment, the treatment resulto Close
mandibular arch is free adaptation of the
of edentulous spaces, marginal bone to the
thus in- creasing implant neck. Note that
chewing comfort and the perforations in the
aesthetics for the patient. cortical bone are still
The same clinical visible radiographically.
procedures were
performed in the area of
the second premolar at
the mandibular left
side. prepared in the
mandibular ramus of
rats (55). The sites of
The conclusions surgery were allowed to
drawn from these and heal during a period of
other ex- periments 12 weeks. Upon
were that the method surgical inspection it
of guided bone re- was found that
generation can indeed although, sorne bone
be successfully regeneration had taken
employed in the place at the defect
regeneration of alveolar borders, primarily soft
ridge defects 054, 167, connective tissue had
1 filled the defecto This
7 soft tissue was care-
4 fully removed and
) expanded
.
polytetrafluoroethylene
In the majority of
membranes were
the experimental
adapted buccally and
studies on guided bone
lingually to the bone
regeneration the effect
surrounding the
of this method was
defects. Histological
tested in situations in
analysis after 6 weeks
which the ridge
demonstrated complete
defects had been freshly
heal- ing of the
prepared. One might,
previous defects with
however, as- sume that
regenerated bone,
the reaction of the bone
whereas the control
when freshly in- jured
defects without
is different than the
membranes failed to
situation when a state
consistently heal with
of tissue equilibrium
bone. Hence, iso-
had been reached in
the defect area. In an
animal study,
transosseous defects
were

157
 Guided bone regeneration at oral implant sites

Fig. 5. a. The minimal width of the

ridge (arrows) in this patient with a
completely edentulous maxilla pre-
eludes standard implant therapy.
b. A titanium-reinforced expanded
polytetrafluoroethylene membrane
has been adapted to the surround-
ing bone in such a way that a space
is created between the membrane
and the knfe-lke ridge. The mem-
brane is secured in place by use of
titanium pins.

158
 Guided bone regeneration at oral implant sites
lation of the defect and mineralized bone to vertical bone height whether there is a
the adjacent bone from have formed up to a was measured, reaching biologically limited
the neighboring soft level 3 to up to a maximum of 7 maximum of bone
tissues seems to suffice 4 mm aboye the mm. gain, and if so, by what
for success- ful bone previous alveolar crest. In an attempt to parameters this
regeneration with Beyond this augment bone 2.7 mm maximum is
guided bone level, soft connective aboye the present crest influenced.
regeneration (Fig. 5, 6). tissue was found. Other at titanium implants On the one hand,
In a controlled invest- gators have in dogs, re- inforced according to the law
clinical study in seven reported more vertical expanded of Frost
patients with similar gain of bone (178). polytetrafluoroethylene (61), bone is resorbed
contralateral Six patients were mem- branes showed if it is not functionally
fenestration defects, treated with a 1.8 mm of gan, stimu- lated. On the
one side was treated similar method. In standard expanded other hand, if loading
with guided bone contrast to the above polytetrafluoroethylene surpasses a criti- cal
regeneration, whereas study, these thera- pists membranes revealed level, damage to the
the other one served grafted the area 1.9 mm and the bone implant-supporting
as control (51). The underneath the height increased by 0.5 bone my occur. In a
results demonstrated titanium-re- inforced mm in the controls recent dog study it was
that guided bone membranes with without membranes revealed that
regeneration treated autogenic bone grafts (99). No graft materials occlusalloading of
dehiscences were col- lected in a suction had been incorporated. newly regenerated bone
filter. Twelve months In both membrane may lead to partialloss
consistently filled with
following membrane groups, about 1 mm of of this bone (18). Of the
new bone. In the sites
placement, an average nonmineralized tissue 3-month gain in bone
where the defect had
gain of 5 mm of was present between height of 4.6 mm, the
only been covered by
the mineralized bone experimental sites
the mucoperiosteal
flap, denuded im- and the membrane at
plant surfaces devoid its highest point,
of bone coverage were corroborating the
ob- served at re-entry results of Simion et al.
surgery. (172). In accordance
On the one hand, with these data are
lateral ridge the results obtained
augmentation has with a perforated
been shown to be a dome-shaped ti- tanium
method with predictable space maintainer
success (15, 35-37, 51, (150). Although
128, 132). On the other vertical ridge
hand, the re- sults augmentation with
regarding vertical bone did occur, the
augmentation of the pres- ence of
alveolar ridge are nonmineralized
controversial. connective tissue
Implants protruding under- neath the top of
4 to 7 mm from the the dome was frequent.
bone crest were It appears that,
covered with depending on the
titanum-reinforced clinical treat- ment
ex- panded protocol, varying
polytetrafluoroethylene amounts of bone height
membranes in a re- may be gained. The
cent study in five factors critical for
patients (172). Biopsies success or failure have
taken 9 months not been worked out.
following membrane In addition, no data
placement revealed are available indicating 159
Hdmmerle & Karring

160
Fig. 6. Excellent bone regeneration is
observed 9 months latero An implant
with a diameter of 4.1 mm has been
placed into the regenerated bone.
Fig. 7. a. Histological section of a 3-month specimen comprising nonmineral-
ized connective tissue yielding the shape of an hourglass. Note the covering
expanded polytetrafluoroethylene membrane. The polished cylinder walls
prevented cellular attachment, thus allowing the tissue to be pulled away
from the walls. b. Histological section of a 9-month specimen. The height of
the mineralized tissue has reached 80% of the cylinder space. Note the un-
changed shape resembling an hourglass in comparison with the 3-month
specimen.

showed 1.8 mm of regenerated bone height still in-
tact at 6 months, whereas the control sites exhibited
4.3 mm of 4.8 mm initially still intacto Other investi-
gators have reported a loss in total bone volume fol-
lowing membrane removal but an increase in area
density of mineralized bone at titanium implants in
rabbit tibia over an observation period of 6 months
(47). The loss in volume observed in this study may
well be compensated by the documented increase in
area density of mineralized bone, thus providing the
peri-implant bone with a higher capacity to bear
loading forces.
In contrast, implants placed entirely into regener-
ated bone in another dog model were either restored
and subjected to loading forces or not restored (39).
AH implants were osseointegrated to a similar de-
gree, and no apparent differences were reported wth
respect to bone-remodeling activities. Control sites
that were augmented, but where no imp1ants had
been placed, demonstrated bone atrophy under-
neath the membranes. The investigators concluded
that placement of an imp1ant represents a stimu1us
sufficient to maintain regenerated bone and that the
regenerated bone was ab1e to withstand the loading
forces in this model system. The contrasting findings
between this study and the experiment discussed
aboye (18) may be based on the difference in healing
time allowed to the regenerated bone before loading.
In the former study, this time amounted to 9
months, whereas loading was initiated after 3
months in the latter.
Evidence emerging fram clinica1 studies also sug-
gests that the regenerated bone is capable of with-
standing the occlusa1loading forces exerted by func-
tional forces and is hence stable over time. A clinica1
follow-up study of 626 titanium imp1ants that had
either been placed into regenerated bone or adjacent
to which bone had been regenerated at their place-
ment revealed an overall cumulative success rate of
93.8% (62). The observation periods ranged fram 6
to 51 months. A prospective study involving 12 im-
plants over the observation period of 5 years demon-
strated stable peri-mplant marginal bone levels with
an average 0.3 mm of cumu1ative bone loss (38). This
bone loss is within the range of bone loss measured
for implants placed into pristine bone (187). These
preliminary data indicate that bone generated by
guided bone regeneration reacts to implant place-
ment and to functional loading like natural jaw
bone.

161
Guided bone regeneration at oral implant sites

159

Guided bone guided bone re-
regeneration in generation prior to was necessary in 41% of
conjunction implantation. The
with implant benefits of the
placement implants was 93.9%. In
simultaneous approach
are 1) reduced number the absence of compli-
Following tooth loss, the of surgical nterventons,
bone of the alveolar 2) shortened treatment
process has been shown time,
to be subjected to a 3) ideal placement of
continuous re- sorptive the implant into the deepest site initially to
process that is most alveolar housing of the
pronounced in the lost tooth and 4)
early phases after tooth reduction of treat- ment
removal (4, 6, 41). In costs.
order to reduce the
problems resulting Guided bone
from this loss of bone, regeneration at
dental implants have submerged implants. A
been placed into fresh recent multicenter
extraction sockets (14, study evaluated the
116, 132). When results of guided bone
implants are placed regeneration with
into extraction sockets, expanded polyte-
a partial incongru- ency trafluoroethylene
between the outer membranes for the
surface of the implant treatment of bone
and the bony walls of defects at implants
the socket often results placed into extraction
in abone deficit in the sockets (17), Forty-nine
peri-implant area. implants were placed
Instead of reducing the into extraction sockets
height of the alveolar immediately following
ridge in order to obtain removal of the teeth.
a sufficient width for The reasons for
implantation (179), extraction mainly
barrier mem- branes encom- passed advanced
have been demonstrated periodontal disease,
to be successfuIly root fractures and failed
applied in order to endodontic therapy.
allow the peri -implant Flap incisions prior to
area to be filled with extraction were
new bone in both performed with the
animal experiments aim of allowing for
(13, primary coverage of the
20, 184) and clinical membrane and the
studies (14, 19, 27, 53,
two-stage
63, 75,
implanto Primary
100, 101, 112).
stability was achieved
The one-stage
by preparing implant
method of combining
beds reaching into
implant placement with
pristine bone beyond
guided bone regeneration
the socket. Premature
has been applied much
removal of membranes
more frequently in
due to exposures,
clinical practice than the
inflammation of the
two-stage
160 method using
surrounding tissues or
Guided bone regeneration at oral implant sites
infections of the area 0.1 mm at re-entry.
However, in the 20
the sites. The l-year cases with premature
survival rate of the removal of the
rnembranes, a mean
re- sidual bone deficit
cations, the mean of 2.4 mm of an initial
bony defect fill was mean de- fect depth of
very good, changing 6.4 mm was present at
from 4.9 mm at the re-entry. The mean
amount of marginal
bone loss mesially and
distally of the implants,
which amounted to
0.72 mm over the 7.5
months of observation
time, compared
favorably to values for
implants placed into
pristine bone O, 146,
187). This study
illustrated that guided
bone regeneration is
very successful for
implants that are
immediately placed
into extraction sockets
in the absence of soft
tissue complications
during the healing
periodo
Exposures and
infections are common
findings as- sociated
with bone regeneration
at immediate im- plants
(8, 17, 157, 170, 184).
Conflicting results have
been reported
regarding the amount
of bone re- generation
in the presence of
exposures. Although
sorne investigators still
obtained very good
defect fill with new
bone in the presence
of membrane ex-
posures (53), it is
generally agreed that
membrane exposures
lead to compromised
results (17, 89, 170,
184, 190, 192) and that
proper flap desgn, a
careful
surgical technique and
 Guided bone regeneration at oral implant sites
a strict maintenance peri-implant de- fect
pro- gram minimize structure, the implant
postoperative wiIl be properly
complications (14). osseo- integrated
One matter of without the need for
initial discussion dealt guided bone re-
with the question of generation. In a
whether an implant that previous study in
is placed at the time of humans comparing
regenerative surgery bone fill in artificially
will actually be osseo- prepared defects
integrated by the between the test group
newly formed bone. using an expanded
Subsequent studies have polyte-
consistently documented trafluoroethylene
that this pro- cedure membrane and a
will lead to control group treated
osseointegration of the without membrane,
exposed titanium better results were ob-
implant surfaces 03,
21, 56, 66, 101, 172,
1
8
6
)
.
Depending on the
structure of the peri-
implant defect and the
presence or absence
of bony walls to
support the membrane,
different results
regarding bone fill have
been reported. In a
recent study (6), sites
with a bony wall
showed a mean
residual lack of bone of
0.3 mm at re-entry
surgery, whereas sites
with dehiscence defects
measured 0.6 mm on
aver- age. In situations
with extensive bone
defects follow- ing
tooth extractions, the
two-stage surgical ap-
proach is generally
preferred.
Extraction sockets
show an excellent
tendency for
spontaneous healing
with bone (3). One
might as- sume that, in
the presence of ideal
161
Hmrnerle & Karring
tained in the membrane group (138). These findings
are in agreement with results from other human and
animal studies in which the control groups consist-
ently failed to provide as good results as those ob-
tained in the test groups (51, 56). In contrast, other
investigators reported that undisturbed bone forma-
tion in fresh extraction sockets was quite good, so
that only few threads remained uncovered at the
time of abutment connection of submerged imrnedi-
ate implants (151).
Tissue healing and bone regeneration of extrae-
tion sockets are profoundly influenced by the inser-
tion of implants. The outcome of such a healing pro-
cess cannot be foreseen. Hence, conducting clinical
studies with negative controls is precluded for ethi-
cal reasons.
A disadvantage of combining guided bone re-
generation with implant placement is the fact that,
in case of a compromised treatment outcome re-
garding bone formation, only the more apical part
of the implant wiIl be properly osseointegrated. In
such situations, long-term prognosis is impaired
(58), and the rate of soft tissue complications is in-
creased (117). When the two-stage technique is ap-
plied, then the implant is placed in a second surgical
procedure, at membrane removal, and such a prob-
lem can adequately be dealt with at this momento
No data are available concerning the long- term
performance of implants placed under these clinical
conditions. Most of the data available represent new
developments with respect to the combination of
implant placement and the guided bone regenera-
tion procedure without the proper validation necess-
ary for general recommendation in patient treat-
ment. During the development period, the surgical
technique, the patient selection and the guidance of
the patient, as well as the proper membrane and, if
applicable, the optimal grafting material are being
tested and appropriately refined. FoIlowing this de-
velopment period, the successful treatment ap-
proaches should en ter an evaluation period, in
which the implants, placed under these specific pro-
tocols, can be evaluated on a long-term basis. Re-
sulting from this evaluation period, long-term sta-
bility of successfully applied treatment outcomes
can be determined.
Unfortunately, the application of nonresorbable
membranes necessitates a rather extensive second
surgical intervention for their removal. By using re-
sorbable membrane barriers this second surgery
may be limited to the minimum necessary for abut-
ment connection and prosthetic and aesthetic treat-
ment, or not be required at all in the case of trans-
162
mucosal implants (see the seetion on the benefit of
resorbable membranes in this chapter).
Guided bone regeneration at transmucosal im-
plants. In the studies diseussed aboye, surgery was
performed to submerge both the implant and the
membrane under the soft tissue flap, thus aiming at
healing by primary intention.
The teehnique of guided bone regeneration has
recently been used in eonjunction with the place-
ment of transmucosal implants into fresh extraetion
soekets (27, 45, 112, 180). Case reports using this
method were first presented in 1993 (45). The eritical
difference from the above-mentioned proeedures is
that the implant was deliberately left in a transmu-
cosal position during the entire phase of bone re-
generation. In a prospective study involving 16 con-
seeutively treated patients with 25 implants over an
observation period of 2.5 years, the details of this
method were deseribed (112). As opposed to the
above-described methods for immediate implan-
tation in conjunction with guided bone regenera-
ton, this teehnique does not aim at primary closure
of the flap completely covering both membrane and
implanto In contrast, the flap is adapted around the
neck of the implant, thus indeed covering the mem-
brane but leaving the implant in transmucosal posi-
tion.
The results of a study on 10 patients with surgical
re-entries 6 months following guided bone regenera-
tion therapy demonstrated successful bone gener-
ation into defects around transmucosal implants
(75). The mean fill of the defects with bone
amounted to 94%, which is in the upper range of the
defect fill reported in earlier investigations. Pre-
viously, mean bone fill was reported to amount to
75% (51), 90% (100), 94% (19) and 82% (53).
Comparison between the clinical results of im-
mediate transmueosal implants and implants placed
under standard conditions at 1 year following incor-
poration of fixed prostheses revealed favorable con-
ditions for the 20 patients in each of the two groups
(27). Low plaque and mucositis scores, similar
amounts of recession, probing pocket depth and
clinical attachment levels were registered.
It has previously been claimed that primary
wound closure following guided bone regeneration
surgery was a prerequisite for the formation of min-
eralized bone (34, 184). This statement was based on
the finding that bone formation was less favorable
when dehiscences occurred, compared with situ-
ations in which the soft tissues remained intact dur-
ing the entire regenerative period (17, 34, 89, 170,
Guided bone regeneration at oral implant sites

161
Hiimmerle & Karring
184, 192). As a implants. However, inflammation seen is cessive forces in very
consequence of these regeneration of the similar to that in unfavorable
results, it was concluded periodontal apparatus periodontal disease biomechanical situations
that a flap dehiscence is predictably achieved (113, 119, 127, 163, 164). were applied and lead
following primary around teeth in spite Peri- implant tissue to these findings.
wound closure of the fact that teeth are breakdown and actual Evidence in favor of
represents a located transmucosally loss of sorne implants bacterial causes of late
complication usually (102, 145). Numerous as a consequence of peri-im- plant tissue
leading to a articles have been occlusal overload have breakdown is most
compromised healing published documenting recently been reported overwhelming (115).
outcome. How- ever, on the intimate contact in an animal experiment Since the causes and
the one hand, implants between the pre- (93, pathogenesis of peri-
placed in a transmu- viously exposed root 94). It is important to implant and periodontal
cosal position do not surface and the newly note, however, that
lesions are similar, it is
truly ex-
impair the successful formed cementum with reasonable to anticipate
outcome of the bone inserting collagen that the treatment
regeneration process fibers. Based on these should be the same.
per se (27, 45, 75, results from periodontal Antimicrobial and
112). On the other regeneration studies, it regenerative therapies
hand, in accordance is reasonable to assume are estab- lished for the
with the re- sults of that previously exposed treatment of periodontal
studies evaluating implant surfaces can disease (69,
guided bone become osseointegrated 108, 145), and
regeneration at during bone regeneration antimicrobial treatment
submerged implants, in cases of transmucosal can be used
defect fill with new implant position. in the treatment of early
bone in the presence The method of peri-implantitis (59,
achieving 126).
of flap dehiscence,
regeneration around In two early studies
inflammation and
transmucosal implants on guided bone
infection was not as
can be particularly regeneration in the
successful as when a
beneficial when the treatment of peri-
flap dehis- cence did
combination of implant bone loss,
not occur (75). Hence,
implantation and re- ligature- induced tissue
infection control
sorbable membranes breakdown was
appears to be the key
may eliminate the need initiated around ti-
factor for an optimal
for a second surgical tanium implants in
treatment outcome
procedure. However, beagle dogs (72).After 5
rather than the mere
further studies testing rnonths, the ligatures
situation of sub-
resorbable membranes were removed and
merged or transmucosal
are necessary before regenerative therapy
implant position.
definite conducted. Membranes
Attempts to fill
defects around recommendations can of expanded
freshly placed sub- be made. polytetrafluo- roethylene
merged implants with were applied to isolate
bone have consistently the defects from the
been documented to Guided bone flap tissue and half of
regeneration in the implants were left
lead to osseointegration the treatment of
of the ex- posed in a transmucosal and
peri-implant
titanium implant defects half in a submerged
surfaces (13, 21, 56, 66, healing situ- ation.
Research suggests that Plaque control using
101,
peri-implant tissue antiseptics was per-
186). Osseointegration
destruc- tion may be formed for 1 week. At
has not been
caused by bacterial the transmucosal
documented following
infection and that the implant sites mechanical
bone regeneration
concomitant brushing was initiated
162
around transmucosal
 Guided bone regeneration at oral implant sites
after 1 week. Soft tissue during 12 weeks of
complications were undisturbed ligature
frequent and the induced plaque
mem- branes were accumulation. Guided
removed 4 weeks tissue regeneration
following placement. therapy was then
Histological analysis performed. Histologi-
revealed a complete cal analysis of the
failure of the attempt specimens retrieved
to regenerate the peri- after 2 months showed
implant bone (72, that new bone
165). formation occurred in
From these and other the space underneath
studies it may be the membrane and
concluded that, in fulfilled the histological
accordance with the criteria for
situation in peri- osseointegration (2).
odontics, regenerative More recent
therapies are not experimental data,
suitable for the however, have
treatment of infectious
diseases such as peri-
odontitis or peri-
implantitis. They can
successfully be applied,
however, in the
treatment of the
sequelae of such
disease processes: to
regenerate the de-
stroyed periodontal or
peri-implant tissues. It
is, therefore, of
paramount importance
to realize that the
infectious disease
process has to be
adequately treated,
prior to regenerative
surgery.
Successful re-
osseointegration of
bacterially con-
taminated implant
surfaces by the use
of guided tissue
regeneration was
reported in a recent
animal study (98). In
this experiment the
peri-implant bone
tissue had been
removed surgically.
Subsequently; the
implant surface was
allowed to be colonized
by pathogenic bacteria 163
Hiimmerle & Karring

164
 Guided bone regeneration at oral implant sites
questioned the following experimental regeneration of tissues obviously not be
possibility that implant bacterial breakdown after destruction due to demonstrated in any
surfaces once exposed are not impaired, but peri-implantitis are of these studies,
to plaque accumulation the applied treatment - limited to a few recent stability of the clinical
can be successfully debridement and case reports result over a period of
reosseointegrated (l40). cleaning with a documenting the use 1.5 years was
Following ligature- detergent - had not of guided bone documented
induced peri-implant rendered the implant regeneration in the radiographically in one
tissue breakdown, an surface biologically treatment of early and study (77). Successful
antibiotic regi- men acceptable for bone to late implant failures bone regeneration
was initiated. Three grow into contact with (77). Although the re- was ob- tained in spite
weeks later, flaps were it. estab- lishment of bone- of the fact that the
raised on the test sides, In a recent study to-implant contact on implants remained
the granulation tissue the effect of guded the surface previously transmucosal during
within the bone craters bone re- generation exposed to plaque the entire treatment
was curetted away and alone or in accumulation could periodo
the implants were combination with Before guided bone
carefully cleaned with a various bone substitutes regeneration treatment
detergent. After place- was evaluated in the for late peri-implant
ment of expanded treatment of peri- failures can be
polytetrafluoroethylene implant defects (87). recommended for
mem- branes and new Following lgature- routine use in practice,
cover screws, the flaps induced tissue sorne aspects of the
were sutured for primary breakdown, the defects clinical procedures still
healing. On the control were debrided and the have to be established.
side no local treatment exposed implant These as- pects include
was performed. surfaces cleaned with the appropriate
Histologcal analyss an air-pow- der abrasive antimicrobial therapy in
dem- onstrated no instrumento Histological terms of the choice of
resolution of the data revealed varying medication, the dosage,
defects and signs of amounts of bone the duration of this
inflammation on the regeneration depending treatment and the
control side. On the on the clinical optimal manipu- lations
test side tissue healing procedure. The best of the implant surface,
had taken place, results were ob- tained the ideal membrane
including bone re- with the combination material - resorbable or
generaton into the of guided bone re- nonresorbable - the
previous defect area. generation and bone defects most amenable
On the one hand, a substitutes. to treatment and the
connective tissue Furthermore, the proper time frame of
capsule 200-300 investigators reported the regeneration
11mthick was consistent contact periodo
consistently found in between regenerated
contact with the bone and the
implant surface previously exposed im-
previously exposed to plant surfaces. In
T
plaque accumulation. On contrast to previous h
the other hand, the investigations (140), the e
regenerating bone had treatment regimen for u
grown into contact with decontamination of the s
the newly placed implant chosen in this e
pristine cover screws. study had rendered the
These results surface biologically
o
demonstrate that the acceptable for new f
healing and regenerative bone to grow into b
capacity of the peri- contact with it. o
implant tissues Human studies of the n 165
 Hiimmerle & Karring
e genic bone is the most
g frequently used
material in this group.
r Xenogenic grafts
a encompass all materials
f of an origin other than
t the recipient's organism
s and may further be
a divided into materials
from the same species
n
but different
d individuals, materials
from other species and
s products of nonorganic
u origino De- mineralized
b freeze-dried bone
s represents an allograft
material, that is, from
t the same species, but
i not the same individual,
t which has widely
u been used in bone
t augmentation
e procedures.

m Biological behavior
a Introduction. A wide
t variety of graft
e materials have been
r employed in
i experimental studies or
in clnical practice. The
a range of materials
l used encompass
s autogenic cancellous
or cortical human
Classification of bone bone, xen- ogenic bone
graft materials transplants such as
Bone grafts have long demineralized freeze-
been used in dried human bone and
reconstructive surgery xenogenic bone sub-
with the aim of stitute materials such
increasing the bone as natural and
volume in the previous synthetic hy-
defect area. Bone droxyapatite,
grafts and bone deproteinized bovine
substitute materials bone mineral and
may be cIassified into calcium-phosphate
two main groups: compounds (73, 75, 78,
autogenic and 84,
xenogenic materials.
The term autogenic
graft refers to tissues
that are trans- planted
within one and the
166organismo Auto-
same

86, 105, 106, 136, 141-144, 159). The rationale for
using bone grafts in combination with guided bone
regeneration encompasses factors such as support-
ing the membrane in situations in which the defect
morphology will not adequately do so, to offer a
scaffold for ingrowth of capillaries and perivascular
tissue, in particular osteoprogenitor cells, and to
provide a carrier for factors enhancing bone forma-
tion. Although mechanical support can also be
achieved by the use of stiffer membranes, pins, mini-
screws or metal reinforcements of membranes (15,
34, 82, 99), the possible biological benefits of filler
materials cannot be achieved in other ways.
Bone substitutes should exhibit biocompatible
material properties. They should not elicit allergic or
immune reactions. They should be well tolerated
and integrated by the host tissues and ideally pro-
vide a scaffold for new bone to grow onto. It has
been postulated that they should gradually be re-
placed by newly formed bone. Their three-dimen-
sional structure should most closely resemble that of
natural bone with respect to macro- and micro-
porosities. Finally, they should compartmentalize
larger defects into smaller fragments comparable to
that of natural human bone (31).
Unfortunately, many of the products presently
available lack adequate scientific documentation to
recommend their general use in conjunction with
guided bone regeneration procedures. It is therefore
difficult, to critically appraise many of the obtainable
bone substitute materials.
Bone-inductive materials. The most intriguing
method of enhancing the local bone volume is by
inducing pluripotent mesenchymal cells to bone-
forming cells. Theoretically, this can be accom-
plished by supplying growth factors or suitable pro-
teins into the defect area. Demineralized freeze-
dried bone allograft is a substance that has been
widely used with the purpose of achieving osteoind-
uction. However, data from both animal experiments
and from human clinical studies are controversial
with respect to the bone- inducing effect of this ma-
terial. Although sorne earlier publications have pro-
vided encouraging data (141, 148, 149, 181), more
recent experiments have questioned the ability of
demineralized freeze-dried bone allograft to induce
new bone formation (5, 20-23, 142, 143). In this con-
text it appears that both the rank on the phylogen-
etic ladder as well as the source and the preparation
of the demineralized freeze-dried bone allograft pro-
foundly influence the final outcome. Animals rank-
ing high on the phylogenetic ladder are character-
Guided bane regeneratian at oral implant sites
ized by a low metabolic index and hence form bone
at a slower rate than lower-ranking animals (48). In
addition, they have been documented to exhibit
lower reactivity to osteoinductive stimuli (53). Both
factors may contribute to the confusion resulting
from contradictory results presented in different
studies. Whereas bone induction by demineralized
freeze-dried bone allograft has been shown in ro-
dents, this has not been conclusively demonstrated
in higher species such as dogs, monkeys or humans.
Moreover, sorne of the contrast in the results from
various studies possibly originates from the fact that
demineralized freeze-dried bone allograft prepara-
tions from different bone banks and from different
batches from the same bank may respond quite dif-
ferently (166). Therefore, it has been postulated that
assays should be developed to standardize the activ-
ity of demineralized freeze-dried bone allograft.
Another source of confusion may arise from the
fact that evidence that demineralized freeze-dried
bone allograft promotes bone formation has gener-
ally been provided at two different levels: the clinical
and the histologicallevel. There is general agreement
that the histological data are more reliable than clin-
ical measurements. Studies combining histological
and clinical data have recently reported a disparity
between the two methods of assessing the results of
0generation (21). Hence, conclusions drawn from
purely clinical evaluation of demineralized freeze-
dried bone allograft should be interpreted with cau-
tion.
Finally, there are contradictory results regarding
the resorbability of demineralized freeze-dried bone
allograft in the host tissues (20, 23, 142).
In conclusion, although demineralized freeze-
dried bone allograft holds sorne promise as an osteo-
inductive material for use in guided bone regenera-
tion procedures, it should be used with caution until
it can be provided in a well-standardized and con-
trolled form from the bone banks, and until its effi-
cacy in bone induction has been proven in nonhu-
man primates and in humans.
Transplantation of autogenic bone. It has long been
claimed that autogenic bone is the ideal material to
increase the bone volume of the jaw bone (31). Be-
fore the advent of guided bone regeneration, intra-
oral bone augmentation was commonly performed
by the use of autogenic bone transplants preferen-
tially taken from the iliac crest. Such a procedure is
very demanding regarding operator skills and logis-
tical support for the surgical intervention, is highly
stressful for the patient and causes considerable
163
Hdmmerle & Karring
 Guided bone regeneration at oral implant sites
post-operative pain, and shown. A group of 40 (96). One of the terials exhibiting large
the treatment is very patients consecutively reasons for these surface areas showed
costly. Ridge treated with this method differences may be better bone-graft
augmentation using demonstrated a very the three-dimensional contact than materials
bone grafts without low frequency of soft structures, including with a compara- tively
mem- branes is tissue complications the porosities of bone small surface area (86,
subjected to extensive and successful ridge grafts, which have been 105, 106).Deproteinized
resorption of the graft augmenta- tion in 66 documented to have bone mineral in its
(111, 175). Loss of graft sites. A mean gain in important ef- fects on unaltered form has
volume in the magni- crest width of 3.5 mm bone healing (49, 86, presumably ideal
tu de of 50% have been was measured allowing 105, 106, 183). Ma- architecture for use as
reported during healing implant placement in abone graft material.
over the period of 6 proper position in all However, due to
months. 66 sites. manipulations during
One of the possible These very good the purifi- cation
indications for guided results may be used as a process, different tissue
bone regeneration is the standard against which integration properties of
replacement of such new developments, the natural bone
procedures. A recent aiming at reduc- ing mineral may result.
study (95) has efforts necessary to Thus, bo- vine-derived
demonstrated that the obtain successful bone mineral exhibiting
results of guided bone treatment outcomes, natural crystal- linity
regeneration, when can be tested. (Bio-Oss, Geistlich,
cornbned with Wolhusen, Switzerland)
autogenic bone grafts, Xenogenic bone yielded increased
are superior to the substitutes. Xenogenic bone-to-graft contact
traditional method of bone sub- stitutes of compared with a
transplanting bone hydroxyapatite have product of the same
without adequate recently been de- origin but with larger
protection by barrier veloped. Experimental crystal size (Endobon,
membranes. In this dog studies have dealt with Merck Biomaterials,
study demineralized ma- terials Darm- stadt, Germany)
freeze-dried bone manufactured (96).
allograft and cortco- synthetically (68, 86, The results regarding
cancellous iliac 105, 144), derived from bone-to-graft contact
autografts with and corals or algae (73, 96, and hence the
without barrier 105, 106, 144) or osteoconductive
membranes of originated from natural properties attributed to
expanded bone mineral (25, 46, the materials tested
polytetrafluoroe- thylene 64, 76, vary considerably
were compared. The 78, 96, 107, 156, 159, between dif- ferent
best results were ob- 176, 188). These studies, rendering
tained with the materials are considered interpretation and
combination of the biocompatible and com- parison difficult
autogenic graft and the osteoconductive. (76, 78, 85, 86, 96).
membrane in terms of Nevertheless, Bone-to-graft contact
the graft volume in- considerable differences also depends, among
corporated as well as in their be- havior other factors, on the
the direct bone-to- based on material density of bone in the
mplant contacto properties have been vicinity of the graft. In
In a recent clinical re- ported. order to ameliorate
article (37),the Integration of interpretation of results,
successful com- bination natural bone mineral this factor should be
of autogenic cortico- has been shown to be taken into consideration
cancellous bone grafts superior to coral- or in the assessment of
and guided bone algae-derived hy- the osteoconductive
regeneration has been droxyapatite products
 Hdmmerle & Karring
properties of a bone mem-
substitute. Recently, brane made of
an "osteoconductvity polylactic acid, this
index" has been substitute im- proved
proposed, which was the amount of initial
calculated by using a soft tissue formation
model to detect phase and initially increased
association from the the rate of mineralized
direct bone-to-graft bone formation
contact and the area compared with blood-
density of bone in the filled controls.
vicinity of the graft It has been postulated
(76). It was postu- lated that formation of soft
that values aboye 1.0 tissue is a step of
indicate that the bone critical importance in
grows preferentially the sequence of
in contact with the
graft, whereas values
of less than 1.0
indicate that the bone-
to-graft contact is
taking place at a level
less than what could be
expected by randomly
occurring contact, and
therefore, the bone is
being hampered from
making graft contacto
Thus an index that
equals
1.0 indicates that bone-
to-implant contact is
occur-
ring at random. In that
study, this parameter
reached values of 2.9 at
the sites treated with
membrane and
deproteinized bovine
bone mineral and of 2.6
for the sites treated with
deproteinized bovine
bone mineral group,
indicating high
osteoconductivity of the
graft (76).
Recent studies have
evaluated a
deproteinized bo- vine
bone mineral as a filler
in a guided bone re-
generation procedure
model on the rabbit
skull (78,
159). In combination
with a
stiffbioresorbable
Guided bone regeneration at oral implant sites
Hdmmerle & Karring
events ultimately ultimately available for substitutes of natural
leading to mature bone to form (78, 81). bone mineral has re-
mineralized bone (78). The observed cently been described
In a recent acceleration of bone by Hammerle et al.
experiment, titanium formation in (7B). No qualitative
test tubes were conjunction with the differences were
implanted in the use of bone substitutes detectable in test and
retro molar area of in the rabbit skull control specimens,
healthy volunteers (81). model may be indicating that the
Regenerating tissue was attributed to the presence of the graft
cap- able of adhering to higher amount of material did not alter
the bony base from osteoblasts found in the basic pattern of
which it orig- inated the test specimens (78, bone formation (Fig. 8). Fig. 8. Bone regeneration
and to the expanded 159). With the increase These findings were around deproteinized
polytetrafluoroethylene in osteoblast numbers - similar to the bovine bone (DBB)from
membrane closing the description of the type a human specimen. Large
the only cells capable to
areas of the graft particles
flap facing opening of form bone - the rate of of bone formation
are in drect bone eontaet
the tube and thus bone formation rises. (new bone: nb). Sorne
separating the soft The application of the areas are in eontaet with
tissues from the space substitute material bone marrow tissue (brn).
Direet deposition of
inside the tube. The evidently created an
osteoid (os) produced by
surface of the inner environment that osteoblasts is oeeasionally
walls of the tube was allowed earlier visible. The newly
made up of polished immigration of formed bone is sub-
titanium, pre- venting osteoblasts into the jected to remodeling
activity as indicated by
cellular adherence (28, area intended for the presenee of
29, 42, 43). In the 2- guided bone osteoclasts. Similarly,
week specimens the regeneration. By de- osteocIasts (arrowheads)
tissue completely filled signing bone substitute are seen resorbing the
the in- side ofthe tube, materials with bone substitute.
whereas in the 7-week appropriate surface
and 12-week ones the characteristics, this
newly formed tissues biological mechanism found in previous
exhibited the shape of may be used with studies evaluating
an hourglass (Fig. 7a). greater benefit in bone sequential stages of
Apparently, during the regenera- tion guided bone
phase of fibroplasia, procedures. Several regeneration without
the regenerated soft studies have indicated the use of bone
tissues were pulled that the use of bone substitutes (79, 109,
away from the cylinder grafts of natural bone 154). The fact that the
walls rendering the mineral does not pattern of bone
shape observed. decrease bone-to- formation and the
Interestingly, even after implant contact when sequence of bone
obser- vation periods of used to treat peri- remodeling are not
up to 9 months, when implant defects in negatively influenced
the majority of the space guided bone regenera- by the use of this type
was occupied by new tion procedures as of bone substitute is
bone, this particu- lar compared with the use of particular im-
shape was unchanged of mem- branes alone portance for the
(Fig. 7b). The (25, 76, 188). application of this
investigators concluded The physiological method in oral
that the outer borders pattern of new bone implantology. Only
confined by the mature formation lamellar bone, owing
soft tissue, which arises with guided bone to its high
prior to mineraliza- regeneration in the biomechanical
tion, delimit the area presence of bone competence, optimally
 Guided bone regeneration at oral implant sites
fulfills the re-
quirements for taking
up loading forces
transferred by implants.
There is general
agreement that dense
synthetic
hydroxyapatite is
nonresorbable in vivo
(33, 68, 96, lOS, 184)
and that calcium
phosphate compounds
as well as coral- or
algae-derived materials
degrade over time (33,
73, 96). Conflicting
results, however, have
been published
regarding the long-term
per- formance of
natural bone mineral.
Although sorne
investigators have
reported rare signs of
biodegrada- tion or
complete lack of
breakdown (S7, 78,
156), others have
described definite graft
resorption (24,
76, 96, 107, 188) or
documented decrease
in area density of the
graft over time (2S).
In one of these studies,
active resorption of the
Bio-Oss particles by
osteoclasts was
demonstrated
unequivocally by
staining with
tartrate-resistant acid
phosphatase (76).
Although, the
resorption process by
osteoclasts has thus
been documented, no
data are available on
the rate of resorption
and on the behavior of
the re- sulting spaces.
One direction of
present research
involves the de-
Hdmmerle & Karring

166
Guided bone regeneration at oral implant sites

167
Hammerle & Karring
velopment of vesting procedure. Not ronal part of the implanto generation, the newly
h. Radiographic control of
resorbable grafting before this aspect has developed and
the implant and the
materials chemic- ally been included in the surrounding regenerated successful treatment
based on synthetic evaluation process bone prior to initiation of approaches should
polymers (185). These should a compre- prosthetic treatment. enter a validation
com- pounds offer a hensive benefit-risk period, in which the
number of advantages analysis of the various implants, for the
over presently used concepts for grafting in placement of which the
fillers. They can be guided bone incorporation of bone
custom made regarding regeneration be con- grafts and substi- tutes
re- sorption time, ducted. was indicated, should
stability and rigidity, Most of the data be evaluated on a
three-dimen- sional available with respect long- term basis with
structure and pore to the use respect to the stability
size, and finally they of bone grafts and bone of the suc- cessfully
can be used as carriers substitute materials obtained treatment
for compounds repre- sent presentations outcomes.
enhancing bone of new developments.
formation. In accord- ance with the
sequence of analysis T
described for im- plants h
Clinical applications placed in conjunction e
Human clinical studies with guided bone re-
on the use of bone b
grafts and of bone e
Fig. 9. a. Due to failed
substitutes are scarce.
endodontic treatment, n
Available data are tooth num- ber 34 has to e
mostly limited to case be extracted. Therapy
reports and reports of with an immediate implant
f
case series (16, 37, 57, and guided bone i
84, 128, 173), sorne of regeneration is favored t
over a conventional bridge
which report test and due to inappropriate o
control procedures (22, adjacent poten- tial f
65, 170, 192, 193). abutment teeth. b. Eight
r
Controlled long-term weeks following extraction
clinical studies are
of the root, the soft tissues e
lacking.
have healed over the s
extraction socket. c.
So far, autogenic Careful flap elevation has o
bone grafts in exposed the alveolar pro r
cess with the tooth
conjunction with guided
socket. d. A full-body
b
bone regeneration have plasma- sprayed implant a
yielded the best re- has been placed with b
sults with high primary stability into the
predictability (16, 37). a1veolus. e. Abone l
However, studies substitute of natural e
bone mineral is use to
involving harvesting of support a collagen
autogenic bone for membrane. f. The collagen m
transplantation should membrane has carefully e
not only present data been adapted to the bony
walls surrounding the m
on the success of the
treatment at the
defect and has been b
punched and slipped
regenerated site but over the shoulder of the
r
should also provide implanto g. At re-entry a
information about the surgery 6 months later, n
regenerated hard tissue is
morbidity and the
found in the previous e
discomfort caused to defect area around the co- s
168patient by the har-
the
 Guided bone regeneration at oral implant sites
lyglycolide and/or
Material developments polylactide or
and experimental copolymers thereof (90)
studies (Fig. 9a-h).
With the presentation Several design
of the first successful criteria have been
guided bone postulated for
regeneration membranes as being
procedures and the favorable for their
subsequent wide and use in guided bone
successful application regeneration. Thus, it
of expanded polyte- was postulated that the
trafluoroethylene membrane barrier
membranes, this should be permeable
material became for exchange of critical
standard for bone fluid substances with
regeneration. An putative nutritive or
obvious disad- vantage instructive function. It
of this material is that was later shown in an
it is nonresorbable animal experiment on
and, therefore, has to the rabbit skull that
be removed with a membrane
second sur- gical permeability is not a
procedure. Regarding prerequisite for guided
patient morbidity, risk bone regeneration, as
for tissue damage, and new bone had formed
from a cost-benefit in both the test and
point ofview, the control chambers
replacement of (160).
nonresorbable by The results of another
animal experiment
resorbable membranes
have
would be desirable.
shown that occlusive
Hence, recent ex-
bioresorbable
perimental research in
membranes made of
guided bone
polylactic or
regeneration has aimed
polyglycolic acid are
at developing
equally successful as
resorbable barrier
expanded
membranes for
polytetrafluoroethylene
application in the
membranes in
clinic.
regenerating bone in
Bioresorbable
transosseous defects in
materials that may be
used for the the rabbit mandibular
fabrication of ramus (152). How-
membranes all belong ever, bone formation in
to the groups of the defects separated
natural or synthetic by the resorbable
polymers. The best membranes was
known groups of associated with
polymers used for chondral
medical purposes are
collagen and aliphatic
polyesters. Currently
tested and used
membranes are made
of collagen or of po-
169
Hammerle & Karring

170

bone forrnation,
whereas the defects
treated with ex- panded
polytetrafluoroethylene
membranes were
associated with bone
formation along the
desmal pathway. Based
on an earlier study
(169), the investi- gators
concluded that since
the impermeable mem-
branes had prevented
oxygen from passing
from the soft tissues
into the area intended
for bone regenera- tion,
the low oxygen tension
in the defect area had
resulted in cartilage
formation as an
intermediary step prior
to bone formation
(152).
In accordance with
these findings are the
results of an experiment
evaluating the effect of
different "pore sizes"
of expanded
polytetrafluoroethylene
membranes in guided
bone regeneration on
the rat skull (191). It
was found that the
dome-shaped membranes
exhibiting internodal
distan ces of less than
8 um showed delayed
bone fill compared
with membranes, where
these distances ranged
from 20-
25 um or were in the
range of 100 um. In
additon, reported failures (12,
soft tissue integration
and peripheral sealing
associ- ated with the
small internodal
distance were re-
ported to be inferior.
Nevertheless, after 12
weeks, a similar degree
of bone fill was
observed with the
dfferent membrane (120, 121). Both
types.
From these studies
it may be
concluded that
membrane porosities
are indeed no
prerequisite for bone
formation, but optimal
pore sizes are advan-
tageous regarding
nutrient flow, wound
stabilization and
peripheral sealing to
prevent ingrowth of
soft tissue-forming
cells.
Unfortunately, most
of the available
resorbable membranes
are not capable of
maintaining space.
Therefore, they need to
be supported in one
way or another. The
most commonly used
method for membrane
support is to sustain it
with autogenic grafts or
with bone substitutes
(9, 139, 158, 192, 193),
whereas other methods
such as screws, pins
and re- inforcements
have also occasionally
been applied (67, 109).
Several animal
experiments have
demonstrated the
successful use of
bioresorbable
membranes in guided
bone regeneration (44,
78, 109, 120, 121, 123,
152, 158, 159, 168),
whereas only few have
32, 67, 157, 189). In
two recent experi-
ments, a polylactic acid
membrane was tested
in its ability to increase
the bone volume in
conjunction with an
autogenous bone graft
compared to controls
that were grafted only
Guided bone regeneration at oral implant sites
experiments showed A different approach
more bone formation was taken in
when the membranes experimental studies
were applied. These evaluating a form-stable
results demonstrate bioresorbable mem-
that soft polylactic brane made of
acid membranes are polylactic acid in
suitable for guided conjunction with a bone
bone regeneration substitute in a rabbit
procedures in skull model (78, 159).
conjunction with New bone was
autogenous grafts. demonstrated to form
underneath the
membrane beyond the
borders of the former
cal- varium. On the one
hand, this experiment
demon- strated that, in
principle, stiff,
bioresorbable mem-
branes are conducive to
bone regeneration and
bone neoformation. On
the other hand, after
the obser- vation period
of 2 rnonths, no overt
signs of break- down of
the membrane were
reported. In many clin-
ical situations a
resorption time
between 6 and 12
months is mandatory in
arder not to lose the
advan- tages of
resorbability.
R
e
s
u
lt
s
o
f
c
li
n
i
c
a
l
a
p
p
li
c
a
171
 Hammerle & Karring
ti re-entry operation 4 to
o 6 months following
n guided bone re-
s generaton surgery,
Beginning in the early 57% of the 39 defects
1990s and thereafter, treated with collagen
reports of cases or case and 57% of 14 defects
series were presented treated with ex- panded
describing the use of polytetrafluoroethylene
resorbable membranes membranes showed
for guided bone re- complete bone fill.
generation at exposed Incomplete bone
implant surfaces (IO, regeneration was found
88, 89, in 39% of the test sites
124, 125, 137, 139, and 29% of the control
193). Later, controlled sites. No gain of new
clinical studies were bone was found in 5%
published (171, 192). In of the test sites and
all of these re- ports a 15% of the control sites.
Iow rate of complications A high percentage of
involving inflam- mation exposure of membranes
of the flap covering the 09%) leading to early
site of regeneration and removal occurred in
exposures of membranes sites treated with ex-
were observed. In two panded
studies involving a polytetrafluoroethylene
larger number of membranes. Al- though,
the possibility for early
consecutively treated
resorption of colla- gen
patents, the results with
membranes is
respect to bone re-
mentioned in the article
generation were very
in cases
favorable. Bony defect
fill ranged from 83%
(193) to 92% (89).
Similar results were
reported in the
treatment of dehiscence
and fenestration defects
at threaded implants
with the use of
bioabsorbable
membranes made of
polyglyco- lide and
polylactide (125). Even
though no bone graft or
bone graft substitutes
were used, 14 out of 17
de- fects showed
complete bone fill at re-
entry.
In one of the
controlled clinical
studies, a collagen
membrane was tested
against an expanded
polyte- trafluoroethylene
172
membrane (192). At the
Guided bane regeneratian at oral implant sites

169
 2 8. Augthun M, Yildirim
of incomplete wound worked out, and the
- M, Spiekermann H,
closure, unfortunately, treatment approaches 4 Biesterfeld S.
no data are presented presented wiIl have to 4 Healing of bone
.
with respect to this be validated in larger, 5. Aspenberg P, Kalebo
defects in combination
with immediate
complication. well-controlled studies. P, Albrektsson T. implants using the
In the most recent Rapid bone healing membrane technique.
controlled clinical delayed by bone
Int J Oral Maxil- lofac
matrix implantation.
study, 18 im- plants Implants 1995: 10:
R Int J Oral Maxillo- fac 421-428.
with exposed threads Implants 1988: 3:
were divided into two
e 123-127.
9. Avera Sp, Stampley
WA, McAllister BS.
groups (171). In both f 6. Atwood DA. Histologic and clin-
Postextraction
groups the defects were e changes in the adult
ical observation of
resorbable and
filled with autogenous r mandible as illustrated nonresorbable barrier
bone. In the test group by microradiographs
a resorbable polylactic
e of midsagittal sections
membranes used in
maxillary sinus graft
or polyglycolic acid n and serial containment. Int J Oral
cephalometric
membrane was c roentgenograms. J
Maxillofac Implants
1997: 12: 88-94.
adapted, whereas in the e Prosthet Dent 10. Balshi TI. Hernandez
control group a standard 1 RE, Cutler RH, Hertzog CE
ex- panded
s 9 Treat-
6 ment of osseous
polytetrafluoroethylene 3
1. Adell R, Lekholm U, defects using Vicryl
membrane was Rockler B, Brnernark
: mesh (polyglactin
placed. Neither in the P-I, Lindhe J, Eriksson 1
910) and the
Brnernark implant: a
test nor in the control B, Sbordone L. 3
case report. Int J Oral
Marginal tissue :
group were any flap M
reactions at
dehiscences or osseointegrated 8 a
1 x
membrane exposures i
0
registered. Six to seven titanium fixtures. Int - l
months later, both J Oral Maxillofac Surg 8 l
1990: 15: 39-52. 2 o
groups re- vealed 4 f
2. Albrektsson T,
excellent bone Brnemark P-I, Hansson
. a
7. Aufdemorte T, Fox C, c
regeneration, with HA, Lndstrm J.
Boyce B, Triplett G,
values of Osseointegrated
Poser J, Moore G, I
89% and 98% defect titanium implants. m
Holt R. A novel
Requirements for en- p
filI. Although the test orthopaedic implant
suring a long-Iasting l
group yielded less direct bone anchorage
to repeatedly sample
a
bone fill and exhibited cancellous bone for n
in mano Acta Orthop
histomorphometric t
a higher vari- ability of Scand 1981: 52: 155-
analysis. In: Takahaski s
the results, no 170.
HE, ed. Bone
statistically significant 3. Amler MH. The time morphometry. 1
sequence of tissue Niigata: Nishi- mura,
differ- ence was found. regeneration in human
9
1990: 260-263. 9
In conclusion, these extraction 1
case reports and initial wounds. Oral Surg :
con- troIled clinical Oral Med Oral
Pathol Oral Radiol 6
studies demonstrate
Endod 1969: 27: 309- :
that resorbable 318.
membranes can be 4. Amler MH, Iohnson 8
used successfully for PL, Salman 1. 7
Histological and histo- -
bone re- generation at chemical investigation 9
implants with exposed of human alveolar 1
surface are as. However, socket healing in .
undisturbed extraction 11. Beck LS, Amento Ep,
before the methods
wounds. J Am Dent Xu Y, Deguzman L,
can be recommended Assoc 1960: Lee WP, Nguyen T,
for widespread clinical 6 Gillett NA. TGF-~1
1
practice, the fine :
induces bone closure
points of the treatment of skull de- fects:
temporal dynamics
protocols have to be
170 3 ofbone formation in
 defects ex- posed to rh 18. Becker W, Lekholm U, 143-154.
TGF-~1. J Bone Miner Dahlin C, Becker B, 22. Becker W, Urist M,
Res 1993: 8: 753-761. Donath K. The effect of Becker BE, Jackson W, Parry
12. Becker J, Meissner T, clinical loading on DA, Bar-
Reichart PA. Gesteuerte bone regenerated by
Knochen- GTAM barriers: a study
regeneration mit in dogs. Int J Oral
Membranen aus Maxillofac Implants
Polyesterurethan. Im- 1
plantologie 1995: 2: 9
151-161. 9
13. Becker W, Becker B, 4
:
Handelsman M,
Ochsenbein C, AI-
brektsson T. Guided 9
tissue regeneration :
for implants placed
into extraction sockets: 3
0
a study in dogs. J
5
Peri- odontol1991: -
62: 703-709. 3
14. Becker W, Becker BE. 1
Guided tissue 3
regeneration for im- .
plants placed into 19. Becker W, Lekholm U,
extraction sockets and Dahlin C, Becker B,
for implant dehiscences: Higuchi K, van
surgical techniques Steenberghe D.
and case reports. Int J Immediate placement
Periodontics Restorative of titanium im- plants
Dent 1990: 10: 377-391. into fresh extraction
15. Becker W, Becker BE, sockets protected by
McGuire MK. Localized e-PTFE membrane
ridge aug- mentation barriers. A clinical
using multicenter study. Int J
absorbable pins and Oral Maxillofac
ePTFE barrier Implants 1994: 9: 31-
membranes: a new 40.
surgical approach. Int 20. Becker W, Lynch SE,
J Periodontics Lekholm U, Becker
Restorative Dent 1994: BE, Caffesse R, Donath
14: 48-61. K, Sanchez R. A
16. Becker W, Becker BE, comparison of ePTFE
Polizzi G, Bergstrom mem- branes alone or
C. Autogenous bone in combination with
grafting of bone defects platelet-derived growth
adjacent to implants factors and insulin-like
placed into immediate growth factor-I or
extraction sockets in demin- eralized freeze-
patients: a prospec- tive dried bone in
study. Int J Oral promoting bone
Maxillofac Implants formation around
1994: 9: 389-396. immediate extraction
17. Becker W, Dahlin C, socket implants. J
Becker BE, Lekholm U, van Peri- odontol 1992: 63:
Steen- 929-940.
berghe D, Higuchi K, 21. Becker W, Schenk R,
Kultje S. The use of e- Higuchi K, Lekholm U,
PTFE barrier membranes Becker BE.
for bone Variations in bone
promotion around regeneration adjacent
titanium im- plants to implants aug- mented
placed into extraction with barrier
sockets: a prospective membranes alone, or
multi- center study. Int with demin- eralized
J Oral Maxillofac freeze-dried bone or
Implants 1994: 9: 31- autologous grafts: a
4 study in dogs. Int J
0 Oral Maxillofac
. Implants 1995: 10:
171
Hdmmerle & Karring

172
Hdmmerle & Karring
told M, Vincenzzi G, cells. Int J Oral Regeneration and 38. Buser D, Dula K, Lang
DeGeorges D, Maxillofac Implants enlargement of jaw Np, Nyman S. Long-
Niederwanger M. 1988: 3: 231-246. bone using guided term stability of
Clin- ical and 29. Brunette DM, tissue regenera- tion. osseointegrated
histologic observations Chehroudi B, Gould Clin Oral Implants implants in bone
of sites implanted TRL. Electron micro- Res 1990: 1: 22-32. regenerated with the
with intraoral scopic observations 35. Buser D, Dula K, membrane technique.
autologous bone on the effects of Belser U, Hin Hp, Berthold Clin Oral Implants
grafts or allografts. 15 surface topography on H. Localized Res 1996: 7:
human case reports. J the behavior of cells ridge augmentation 1
Periodontol 1996: 67: attached to using guided bone 7
1025-1033. percutaneous and regeneration. 1. 5
Surgical procedures in -
23. Becker W, Urist MR, subcutaneous
1
Tucker LM, Becker implants. In: Laney the maxilla. Int J
8
BE, Ochsenbein e. WR, Tolman DE, ed. Periodontics Re- 3
Human demineralized Proceedings of the storative Dent 1993: .
freeze-dried bone: Second International 13: 13-29. 39. Buser D, Ruskin J.
inadequate induced Congress on Tissue 36. Buser D, Dula K, Higginbottom F,
Belser UC, Hirt H-P, Hardwick R, Dahlin C,
bone formation in Integration in Oral,
Berthold H. Local-
athymic mice. A Orthopedic, and Schenk RK.
ized ridge augmentation
preliminary reporto J Maxillofacial Osseointegration of
using guided bone
Periodontol 1995: 66: Reconstruction. regeneration. titanium implants in
822-828. 11. Surgical procedure bone regenerated in
24. Bereiter H, Melcher Carol Stream. IL: in the mandible. Int J membrane-protected
GA, Gautier E, Huggler Periodontics defects: a his- tologic
Quintessence Pub-
AH. Erfah- Restorative Dent study in the canine
lishing CO., 1990: 21-
rungen mit Bio-Oss, 1995: 15: 11-29. mandible. Int J Oral
31.
einem bovinen Apatit, 37. Buser D, Dula K, Hirt Maxillofac Implants
30. Buch F, Albrektsson
bei verschied- enen Hp, Schenk RK. Lateral 1995: 10: 666-681.
T, Herbst E. The
klinischen ridge aug- mentation 40. Buser D, Weber Hp,
bone growth chamber
Indikationsbereichen. using autografts and Donath K, Fiorellini JP,
for quantification of
Hefte Unfallheilkd barrier membranes. Paquette DW; Williams
electrically induced
1991: 216: 118-126. A clinical study in 40 Re. Soft tissue
osteo- genesis. J
25. Berglundh T, Lindhe J. partially edentulous reactions to non-
Orthop Res 1986: 4:
Healing around patients. Int J Oral submerged un- loaded
194-203.
implants placed in Maxillofac Surg 1996: titanium implants in
31. Burchardt H. The
bone defects treated biology ofbone graft 54: 420-432. beagle dogs. J
with Bo-Oss". An repair. Clin Orthop Periodontol
experimental study in 1983: 174: 28-42. 1
the dogo Clin Oral 32. Busch O, Solheim E, 9
Implants Res 1997: 8: Bang B, Tornes K. 9
117-124. Guided tissue re- 2
26. Boyne PI. Cole MD, :
generation and local
Stringer D, Shafqat delivery of insulinlike 6
JP. A technique for growth factor 1 by 3
osseous restoration of bioerodible :
deficient edentulous polyorthoester
maxillary ridges. J Oral 2
membranes in rat
Maxillofac Surg 1985: 2
calvarial defects. Int J 5
43: 87-91. Oral Maxillofac -
27. Bragger U, Harnmerle Implants 1996: 11: 2
CHF, Lang NP. 498-505. 3
Immediate transmu- 33. Buser D, Bernard JP, 5
cosal implants using Hofmann B, Lussi A, .
the principIe of Mettler D, 41. Carlsson GE,
guided tissue re- Schenk RK. Evaluation Thilander H,
generation. II. A cross- of bone filling Hedegrd B.
sectional study materials in mem- Histologic changes in
comparing the clin- brane-protected the upper alveolar
ical outcome 1 year defects of the process after
after immediate to mandible. A extractions with or
standard implant histomorpho- metric without insertion of
placement. Clin Oral study in miniature an immediate full
Implants Res 1996: 7: pigs. Clin Oral denture. Acta Odontol
268-276. Implants Res (in Scand 1967: 25: 21-43.
28. Brunette DM. The press). 42. Chehroudi B, Gould
effects of implant surface 34. Buser D, Bragger U, TRL, Brunette DM. Effects
topography of a
Lang Np, Nyman S.
on the behavior of grooved 173
titanium
 Hdmmerle & Karring
coated implant surface Clin Oral Implants Res membrane tech- nique:
on epithelial celI 1 an experimental study
behavior in vitro and 9 in monkeys. Scand J
in vivo. J Biomed 9 Plast Reconstr Hand
Mater Res 1989: 3 Surg 1990: 24: 13-19.
2 :
53. Dahlin C, Lekholm U,
3
Becker W, Becker B,
: 4 Higuchi K, Cal- lens A,
:
van Steenberghe D.
1 Treatment of
0 2
6 fenestration and
0 dehiscence bone
7 3
- - defects around oral
1 2 implants using the
0 0 guided tissue
8 9 regeneration
5 . technique: a
.
48. Coulson RA. prospective multicenter
43. Chehroudi B, Gould Relationship between study. Int J Oral
TRL, Brunette DM. fluid flow and O2 de- Maxillofac Implants
Titanium-coated mand in tissues in 1995: 10:
micromachined vivo and in vitro. 3
Perspect Biol Med 1
grooves of different 1 2
dimensions affect 9 -
8 3
epithelial and 1
connective-tissue cells 3
8
:
differently in vivo. J .
Biomed Mater Res
1990: 24: 1203-1219. 2
7
44. Chung Cp, Kim DK, Park :
YJ, Nam KH, Lee SJ.
Biological
effects of drug-Ioadable 1
biodegradable 2
1
membranes for guided
-
bone regeneration. J 1
Periodont Res 1997: 32: 2
172- 6
1 .
7 49. Daculsi G, Passuti N.
5 Effect of the
.
macroporosity for OS5-
45. Cochran DL, Douglas
eous substitution of
HE. Augmentation of
calcium phosphate
osseous tissue around ceramics. Bio- materials
non-submerged 1990: 11: 86-87.
endosseous dental 50. Dahlin C, Alberius P,
implants. Int Linde A.
r Periodontics Osteopromotion for
Restorative cranio- plasty. An
Dent 1993: 13: experimental study in
506-519. rats using a membrane
46. Cohen RE, Mullarky technique. J Neurosurg
RH, Noble B, Comeau 1991: 74: 487-491.
RL, Neiders ME. 51. Dahlin C, Andersson
Phenotypic L, Linde A. Bone
characterization of augmentation at
mononuclear cells fenestrated implants
following anorganic by an osteopromotive
bovine bone implantation membrane technique.
in rats. J Periodontol1994: A controlled clinical
65: 1008-1015. study. Clin Oral
47. Cortellini P, Bartolucci Implants Res 1991: 2:
E, Clauser C, Pini Prato 159-165.
GP. Local- ized ridge 52. Dahlin C, Gottlow J.
augmentation using Linde A, Nyman S. Healing
guided tissue of maxil-
regeneration in humans. lary and mandibular
174A report of nine cases. bone defects by a

54. Dahlin C, Linde A, Gottlow J, Nyman S. Healing of bone
defects by guided tissue regeneration. Plast Reconstr Surg
1988: 81: 672-677.
55. Dahlin C, Sandberg E, Alberius P, Linde A. Restoration of
mandibular nonunion bone defecto Int J Oral Maxillofac
Surg 1994: 23: 237-242.
56. Dahlin C, Sennerby L, Lekholm U, Linde A, Nyman S.
Generation of new bone around titanium implants using
a membrane technique: an experimental study in rabbits.
Int J Oral Maxillofac Implants 1989: 4: 19-25.
57. Dies E Etienne D, Bou Abboud N, Ouhayoun J-P. Bone
regeneration in extraction sites after immediate place-
ment of an e-PTFE membrane with or without a bo-
material. A report of 12 consecutive cases. Clin Oral Im-
plants Res 1996: 7: 277-285.
58. Dietrich U, Lippold R, Dirmeier T, Behneke W, Wagner W
Statistische Ergebnisse zur Implantatprognose am Beispi-
el von 2017 IMZ- Implantaten unterschiedlicher Indikat-
ionen der letzten 13 Iahre. Z Zahnarztl Implantol 1993: 9:
9-18.
59. Ericsson 1, Persson LG, Berglundh T, Edlund T, Lindhe J.
The effect of antimicrobial therapy on periimplantitis
lesions. An experimental study in the dogo Clin Oral Im-
plants Res 1996: 7: 320-328.
60. Frame JW. A convenient animal model for testing bone
substitute materials. J Oral Surg 1980: 38: 176-180.
61. Frost HM. Bone remodeling dynamics. Springfield, IL: CC
Thomas, 1963.
62. Fugazzotto PA. Success and failure rates of osseointe-
grated implants in function in regenerated bone for 6 to
51 months: a preliminary reporto Int J Oral Maxillofac Im-
plants 1997: 12: 17-24.
63. Fugazzotto PA, Shanaman R, Manos T, Shectman R. Ges-
teuerte Knochenregeneration um Titanimplantate: Be-
rieht ber die Behandlung von 1503 Stellen mit klinsch-
em Reentry. Int J Oral Maxillofac Implants 1997: 17: 277-
283.
64. Fukuta K, Har-Sha M\T, Collares MV, Lichten JB, Jackson
IT. Comparison of inorganic bovine bone mineral par-
ticles with porous hydroxyapatite granules and cranial
bone dust in the reconstruction of full thickness skull de-
fect. J Craniofac Surg 1992: 3: 25-29.
65. Gher ME, Quintero G, Assad D, Monaco E, Richardson AC.
Bone grafting and guided bone regeneration for mmedi-
ate dental implants in humans. J Periodontol 1994: 65:
881-991.
66. Gotfredsen K, Nimb L, Buser D, Hjertng-Hansen E.
Evaluation of guided bone regeneration around implants
placed into fresh extraction sockets. An experimental
study in dogs. J Oral Maxillofac Surg 1993: 51: 879-884.
67. Gotfredsen K, Nimb L, Hjerting-Hansen E. Immediate im-
plant placement using a biodegradable barrier, poly-
hydroxybutyrate-hydroxyvalerate reinforced with poly-
glactin 910. Clin Oral Implants Res 1994: 5: 83-91.
68. Gotfredsen K, Warrer K, Hjertng-Hansen E, Karring T. Ef-
fect of membranes and porous hydroxyapatite on healing
in bone defects around titanium dental implants. An ex-
perimental study in monkeys. Clin Oral Implants Res
1991: 2: 172-178.
69. Gottlow J. Periodontal regeneration - a review. In: Lang
Np, Karring T, ed. First European Workshop on Periodon-
tology. Carol Stream, IL: Quintessence Publishing CO.,
1994: 172-192.
Guided bone regeneration at oral implant sites
70. Gottlow J, Nyman S, Karring T, Lindhe J. New attachment
formation as the result of controlled tissue regeneration.
J Clin Periodontol1984: 11: 494-503.
71. Gottlow J, Nyman S, Lindhe J, Karring T, Wennstr6m J.
New attachment formation in the human periodontium
by guided tissue regeneration. Case reports. J Clin Peri-
odontol 1986: 13: 604-616.
72. Grunder U, Hrzeler MB, Schpbach P, Strub JR. Treat-
ment of lgature-nduced peri-implantitis using guided
tissue regeneration: a clinical and histologic study in the
beagle dogo Int J Oral Maxillofac Implants 1993: 8: 282-
293.
73. Guillemin G, Patat J.-L, Fournie J, Chetail M. The use of
coral as abone graft substitute. J Biomed Mater Res 1987:
21: 557-567.
74. Hammerle CHE Bragger U, Brgin W, Lang NP. The effect
of the subcrestal placement of the polished surface of ITI
implants on the marginal soft and hard tissues. Clin Oral
Implants Res 1996: 7: 111-119.
75. Hamrnerle CHE Bragger U, Schmid B, Lang NP. Successful
bone formation at immediate transmucosal implants. Int
J Oral Maxillofac Implants (in press).
76. Harnmerle CHE Chiantella GC, Karring T, Lang NP. The
effect of a deproteinized bovine bone mineral on bone
regeneration around titanium dental implants. Clin Oral
Implants Res (in press).
77. Hammerle CHE Fourmousis 1, Winkler JR, Weigel C, Brag-
ger U, Lang NP. Successful bone fill in late peri-irnplant
defects using guided tissue regeneration. A short com-
munication. J Periodontol 1995: 66: 303-308.
78. Hammerle CHE Olah AJ, Schmid J, Flckiger L, Winkler
JR, Gogolowski S, Lang NP. The biological effect of depro-
teinized bovine bone on bone neoformation on the rabbit
skull. Clin Oral Implants Res 1997: 8: 198-207.
79. Hammerle CHE Schmid J, Lang Np, Olah AJ. Temporal
dynamics of healing in rabbit cranial defects using guided
bone regeneration. J Oral Maxillofac Surg 1995: 53: 167-
174.
80. Harnmerle CHE Schmid J, Olah AJ, Lang NP. Osseous
healing of experimentally created defects in the calvaria
of rabbits using guided bone regeneration. Clin Oral Im-
plants Res 1992: 3: 144-147.
81. Hammerle CHE Schmid J, Olah AJ, Lang NP. A novel
model system for the study of experimental bone forma-
tion in humans. Clin Oral Implants Res 1996: 7: 38-47.
82. Hardwick R, Scantlebury TI, Sanchez R, Whitley N,
Ambruster J. Membrane design criteria for guided bone
regeneration of the alveolar ridge. In: Buser D, Dahlin C,
Schenk RK, ed. Guided bone regeneration in implant den-
tistry. Carol Stream, IL: Quintessence, 1994: 101-136.
83. Hjertng-Hansen E, Helbo M, Aaboe M, Gotfredsen K,
Pinholt EM. Osseointegration of subperiosteal implant via
guided tissue regeneration. A pilot study. Clin Oral Im-
plants Res 1995: 6: 149-154.
84. Hjorting-Hansen E, Worsaae N, Lemons JE. Histologic re-
sponse after implantation of porous hydroxylapatite cer-
amic in humans. Int J Oral Maxillofac Implants 1990: 5:
255-263.
85. Holmes RE, Bucholz RW, Mooney V. Porous hydroxyapa-
tite as a bone-graft substitute in metaphyseal defects. A
histometric study. J Bone Ioint Surg 1986: 66A: 904-911.
86. Holmes RE, Bucholz RW, Mooney V. Porous hydroxyapa-
tite as abone graft substitute in diaphyseal defects: a his-
tometric study. J Orthop Res 1987: 5: 114-121.
175
Hammerle & Karring

172
Hammerle & Karring
87. Hrzeler MB, 91. I1izarov GA. The De- fektgrosse. Helv biological concept of
Quiones CR, tension-stress effect Chir Acta 1972: 39: guided tissue
Schpbach P, Morrison on the genesis and 409-411. regeneration - animal
EC, Caffesse RG. growth of tissues. l. 98. Jovanovic SA, Kenney and human studies.
The influence of EB, Carranza FA, Periodontol 2000
Treatment of per-
stability of fixation and Donath K. The re- 1993: 1: 26-
implantitis using
generative potential of 3
guided bone soft tissue
plaque-induced 5
regeneration and bone preservation. Clin .
periimplant bone
grafts, alone or in Orthop 1989: 238: 103. Karring T, Nyman S,
defects treated by a
cornb- nation, in 249- Lindhe J. Healing following
submerged membrane
beagle dogs. 2. 2 implan-
technique: an
Histologic findings. 8
1 experimental study.
Int J Oral Maxillofac Int J Oral Maxillofac
.
Implants 1997: 12: Implants 1993:
92. Ilizarov GA. The
168-175. 8
tension-stress effect
88. Hrzeler MB, Strub :
on the genesis and
JR. Guided bone
regeneration around growth of tissues. Il. 1
exposed implants: a The influence of the 3
new bioresorbable rate and fre- quency -
of distraction. Clin 1
device and biore- 8
sorbable membrane Orthop 1989: 239:
.
pins. Pract Periodontics 263-285.
99. Jovanovic SA, Schenk
Aesthet Dent 93. Isidor E Loss of
osseointegration caused RK, Orsini M, Kenney
1 EB. Supracres- tal bone
9 by occlusalload
of oral implants. A formation around
9
5 clinical and dental implants: an
: radiographic study in experi- mental dog
monkeys. Clin Oral study. Int J Oral
7 Maxillofac Implants
: Implants Res 1996: 7:
143-152. 1995: 10:
3 94. Isidor F. Histological 2
7 evaluation of peri-implant 3
- bone at -
4 3
implants subjected
7 1
to occlusal overload .
.
or plaque ac- 100. Jovanovic SA,
89. Hrzeler MB, Weng
cumulation. Clin Oral Spiekermann H. Bone
D, Hutmacher D.
Knochenregener- ation Implants Res 1997: 8: regeneration around
um Implantate - eine 1-9. titanium dental
klinische Studie mit 95. Iensen OT, Greer RO, implants in dehisced
Iohnson L, Kassebaum defect sites: a clin-
einer neuen D. Vertical
resorbierbaren ical study. Int J Oral
guided bone-graft
Membran. Dtsch Maxillofac Implants
augmentation in a
Zahnrztl Z 1996: 1992: 7: 233-245.
new canine man-
5 101. Iovanovc SA,
dibular model. Int J Spiekermann H, Richter
1
: Oral Maxillofac EL Koseoglu M.
Implants 1995: 10: Guided tissue
3 regeneration around
2
3 titanium dental im-
-
5 plants. In: Laney WR,
7
-
. Tolman DE, ed. Tissue
3
90. Hutmacher D, 4 integration of oral,
Hrzeler MB, 4 orthopedic and
Schliephake H. A . maxillofacial
review of material 96. Iensen SS, Aaboe M, reconstruction. Carol
properties of Pinholt EM, Hjertng- Stream, IL:
biodegradable and Hansen E, Melsen E Quintessence
bioresorbable polymers Ruyter IE. Tissue Publishing Company,
and devices for GTR reaction and material 1992: 208-
charac- teristics of four 2
and GBR applications.
Int bone substitutes. Int J 1
Oral Maxillofac Im- 5
J Oral .
Maxillofac plants 1996: 11: 55-66.
102. Karring T, Nyman S,
Implants 97. Johner R. Zur
1996: ll: Knochenheilung in Gottlow J. Laurell L.
667-678. Development of the
Abhangikeit van der 173
 Hammerle & Karring
tation of periodontitis tuberosities by guided cross-sectional
affected roots into bone tissue regeneration. An retrospective study.
tissue. J ex- perimental study Int J Oral Maxillofac
Clin Periodontoll980: in the rato Clin Oral Surg 1986: 15:
7: 96-105. 53-61.
Implants Res 1994:
104. Karring T, Nyman S, 5: 245-253. 118. Linde A, Thorn C,
Lindhe L Sirirat M.
111. Krekeler G, ten Dahln C, Sandberg E.
Potential for root
Bruggenkate CM, Creation of new bone
resorption during
Oosterbeek HS. by an osteopromotive
periodontal healing. J
Verbes- serung des membrane technique.
Clin Periodontol
1984: 11: 41-52. Implantatbettes durch An ex- perimental
Augmentation mit au- study in rats. J Oral
105. Kasperk C, Ewers R.
tologem Knochen. Z Maxillofac Surg 1993:
Tierexperimentelle
Zahnarztl Implantol 51:
Untersuchungen zur
1993: 9: 231- 892-897.
Einheilungstendenz
236. 119. Lindhe J, Berglundh T,
synthetischer,
112. Lang Np, Bragger U, Ericsson I, Liljenberg
koralliner und aus
Hamrnerle CHE B, Marinello C.
Algen gewonnener
Immediate transmu- Experimental
(phykogener)
cosal implants using breakdown of per-
Hydroxylapatitmateriali-
the principle of implant and peri-
en. Z Zahnarztl
Implantol 1986: 2: 242- guided tissue re- odontal tissues. A
248. generation (GTR). 1. study in the beagle
106. Kasperk C, Ewers R, Rationale, clinical dogo Clin Oral Im-
Simons B, Kasperk R. procedures, and 2 l/2- plants Res 1992: 3: 9-
Algae-derived year results. Clin Oral 16.
(phycogene) Implants Res 1994: 5:
hydroxylapatite. Int J 154-163.
Oral Maxillofac Im- 113. Lang Np, Bragger U,
plants 1988: 17: 319- Walther D, Beamer B,
324. Kornman KS.
107. Klinge B, Alberius P, Ligature-induced peri-
Isaksson S, Ionsson mplant infection in
AJ. Osseous re- sponse cynomolgus monkeys.
to implanted natural 1. Clinical and
bone mineral and radiographie findings.
synthetic hydroxylapatite Clin Oral Implants Res
1993: 4: 2-11.
ceramic in the repair 114. Lang Np, Harnmerle
of experimental skull CHE Bragger U,
bone defects. J Oral Lehmann B, Nyman
Maxillofac Surg 1992: SR. Guided tissue
50: 241- regeneration in
249. jawbone defects prior
108. Kornman KS. The role to implant placement.
of antimicrobials in Clin Oral Implants Res
prevention and 1994: 5: 92-
treatment of 97.
periodontal disease. 115. Lang Np, Mombelli A,
In: American Academy Tonetti MS, Bragger
of Periodontology, ed. U, Hammerle CHE
Perspectives on oral Clnical trials on
antimicrobial therapies for peri-
therapeutics. Littleton: implant infec- tions.
PSG Publishing Ann Periodontol
Company, 1987: 1997: 2: 343-356.
37-46. 116. Lazzara RM.
109. Kostopoulos L, Immediate implant
placement into extrae-
Karring T.
tion sites: surgical and
Augmentation of the
restorative advantages.
rat rnan- dible using
Int J Peri- odontics
guided tissue
Restorative Dent
regeneration. Cln Oral
1989: 9: 333-343.
Implants Res 1994: 5:
117. Lekholm U, Adell R,
75-82. Lindhe J. Marginal tissue
110. Kostopoulos L, Karring reactions
T, Uraguchi R. at osseointegrated
174Formation of jaw- bone titanium fixtures. II. A
Guided bone regeneration at oral implant sites

175
120. Lundgren AK, for guided bone re- in the monkey. J Clin defects with and
Lundgren D, Sennerby generation in Periodontol1982: 9: without expanded
L, Taylor A, Gottlow J, connection with 257-265. polytetrafluoroethylene
Nyrnan S. implant installation. 131. Nyrnan S, Karring T, mem-
Augmentation of skull CJin Oral Implants Res Lindhe J, Planten S.
1994: 5: 177-184. Healing following
bone using a biore-
125. Mayfield L, Nobrus implantation of
sorbable barrier
periodontitis affected
supported by N, Attstrorn R, Linde
roots into gingival
autologous bone A. Guided bone
connective tissue. J
grafts. C\in Oral regeneration in dental
Clin Periodontol 1980:
Implants Res 1997: 8: implant treatment
7: 394-401.
90-95. using a bioab- sorbable 132. Nyman S, Lang Nl]
121. Lundgren AK, Sennerby membrane. CJin Oral Buser D, Bragger U.
L, Lundgren D, Taylor A, Implants Res 1997: 8: Bone regeneration
Gottlow 10- adjacent to titanium
J, Nyman s. Bone 1 dental implants using
augmentation at 7 guided tissue
titanium implants .
regeneration. A report
using autologous bone 126. Mombell A, Lang NP.
of 2 cases. Int J Oral
grafts and a Antimicrobial
Maxillofac Im- plants
bioresorbable barrier. treatment of peri-im-
1990: 5: 9-14.
CJi plant infections. Clin
133. Nyrnan S, Lindhe J,
n Oral Implants Res Karring T. Reattachment -
Or 1992: 3: 162-168.
al new attach-
127. Mombell A, Van mento In: Lindhe J,
Im
pla Oosten MAC, Schrch ed. Textbook of
nts E, Lang NP. The clinical periodonto-
Re microbiota associated logy. 2nd edn.
s with successful or Copenhagen:
19 failing osseo- integrated
97: Munksgaard, 1989:
titanium implants. 450-473.
8:
82- Oral Microbiol 134. Nyrnan S, Lindhe J,
89. Immunol Karring T, Rylander
122. Lundgren D, Lundgren 1 H. New attach- ment
AK, Sennerby L, 9 following surgical
8
Nyrnan S. Aug- treatment of human
7
mentation of : periodontal disease. J
intramembranous CJin Periodontol
bone beyond the 2 1982: 9: 290-296.
skeletal envelope using : 135. Nyrnan SR, Lang NP.
an occlusive titanium Guided tissue regeneration
and den-
barrier. An experi- 1 tal implants.
mental study in the 4 Periodontol20
rabbit. CJin Oral 5 00 1994:
Implants Res 1995: - 4: 109-118.
6 1
136. Nystrom E, Legrell
: 5
1 PE, Forssell A,
. Kahnberg K-E. Com-
6
7 128. Nevins M, Mellonig JT. bined use of bone
- The advantages of grafts and implants in
7 localized ridge the severely re- sorbed
2 augmentation prior to maxilla. Int J Oral
. Maxillofac Surg 1995:
implant placement. A
123. Lundgren D, Nyman S, staged event. Int J 24: 20-25.
Mathiesen T, Isaksson S, 137. Pajarola GE Sailer HE
Periodontics
Kling B.
Restorative Dent 1994: Studer S. Steuerung
Guided bone
14: 97-111. der Knochen-
regeneration of cranial regeneration um
129. Nyrnan S. Bone
defects, using biode- Implantatpfeiler durch
regeneration using the
gradable barriers: an eine resorbierba- re
principie of guided
experimental pilot Folie. Z Zahnrztl
tissue regeneration. J
study in the rab- bit. J Implantol 1993: 9:
Clin Periodontol1991:
Craniomaxillofac Surg 18: 494-498. 181-183.
1992: 20: 257-260. 130. Nyrnan S, Gottlow J, 138. Palmer RM, F10yd PO,
124. Lundgren D, Sennerby Karring T, Lindhe J. Palmer PJ, Smith BJ,
L, Falk H, Friberg B, Nyrnan The regenerative Iohansson CB,
S. The
potential of the Albrektsson T. Healing
use of a new
periodontal ligament. of implant dehiscence
176bioresorbable barrier An experimental study
 branes: a controlled HR, Oonath K, Bang borders at ti- tanium
clinical and G. Titanium implant implants. A kinetic 1
histological study. Clin insertion into dog study in the rabbit 9
O alveolar ridges tibia. Clin Oral Implants 7
r :
augmented by allogenic Res 1997: 8: 103-116.
a
l material. Clin Oral 148. Reddi AH. Cell
Implants Res 1994: 5: biology and 3
213- biochemistry of 0
I 1
m 2 endochondral bone
-
p 1 development. Coll 3
l 9 Rel Res 1981: 1: 209- 1
a . 226. 1
n 143. Pinholt EM, Haanaes 149. Reddi AH, Weintroub .
t HR, Roervik M, Oonath K.
S, Muthukumaran N. 154. Schenk RK, Buser O,
s Bang G.
Biologic prin- cipIes of Hardwick WR, Oahlin
Alveolar ridge
bone induction. Orthop C. Healing pat- tern of
R augmentation by
osteoinductive CJin North Am 1987: bone regeneraton in
e
materials in goats. 18: membrane-protected
s
Scand J Oent Res de- fects: a histologic
2
1990: 100: 361-365. 0 study in the canine
1
144. Pinholt EM, Ruyter 7 mandible. Int J Oral
9
IE, Haanaes HR, Bang - Maxillofac Implants
9
G. Chernical, physical, 2 1994: 9: 13-29.
4
1 155. Schenk RK.
: and histologic studies
2
on four commercial . Willenegger HR. Zur
5 apa- tites used for 150. Renvert S, Claffey N, Histologie der
: alveolar ridge primaren
Orafi H, Albrektsson
augmentation. J Oral T. Supracrestal bone Knochenheilung.
9 Maxillo- fac Surg 1992: growth around
8 50: 859-867. Modifikationen und
partially inserted
- 145. Quiones CR, Caffesse Grenzen der Spal-
1 titanium implants in
RG. Current status of dogs. A pilot study. theilung in
0
guided peri- odontal Clin Oral Implants Res Abhanggket von der
4
. tissue regeneration. 1996: 7: 360- Defektgrosse.
139. Parodi R, Santarelli G, Periodontol2000 3 Unfallheil- kunde 1977:
Carusi G. Application 1995: 9: 55- 6 80: 155-160.
of slow-re- sorbing 6 5 156. Schlickewei W, Riede
collagen membrane to 8 . UN, Yu J, Ziechmann W,
periodontal and peri- . 151. Rosenquist B, Grenthe Kuner EH,
im- plant guided tissue 146. Quirynen M, Naert 1, B. Immediate
regeneration. Int J van Steenberghe O. placement of im-
Periodontics Re- Fixture design and plants into extracton
storative Oent 1996: overload influence sockets: implant
16: 174-185. marginal bone loss survival. Int J Oral
140. Persson LG, Ericsson and fixture success in Maxillofac Implants
1, Berglundh T, the Brnernark system. 1996: 11: 205-209.
Lindhe J. Guided bone Clin Oral Implants Res 152. Sandberg E, Oahlin C,
1 Linde A. Bone
regeneration in the
9
treatment of regeneration by the
9
periimplantitis. Clin 2 osteopromotion
Oral Implants Res :
1996: 7: 366-372. technique using
141. Pinholt EM, Bang G, 3 bioabsorbable mem-
Haanaes HR. Alveolar :
branes. An
ridge augmen- tation by experimental study in
1
osteoinduction in rats. rats. J Oral Maxillofac
0
Scand J Oent Res 4 Surg 1993: 51: 1106-
1990: - 1114.
9 1 153. Sato K, Urst MR.
8 1 lnduced regeneration
: 1
of calvara by bone
.
morphogenetic protein
4 147. Rasmusson L,
Sennerby L, Lundgren O, (BMP) in dogs. Clin
3
Nyman S. Orthop
4
- Morphological and 1
4 dimensional changes 9
1 8
after barrier re- moval 5
.
in bone formed :
142. Pinholt EM, Haanaes beyond the skeletal 177
Hammerle & Karring
Hammerle & Karring
Seubert B. Influence 162. Schmid J, Wallkamm im- plants utilizing a using resorbable and
of humate on calcium B, Hammerle CHF, resorbable collagen nonresorbable
hydroxyapa- tite Gogolewski S, Lang membrane: clinical membranes associ-
implants. Arch Orthop NP. The significance of and histologic results. ated with bone
Trauma Surg 1993: angiogenesis in guided Int J Periodontics autografts: a
112: 275- bone regeneration. Clin Restorative Dent comparative clinical
279. Oral Implants Res 1993: 13: 71-83. study. Int J Oral
157. Schliephake H, 1997: 8: 244-248. 169. Shaw JK, Basset CAL. Maxillofac Implants
Kracht D. Vertical 163. Schou S, Holmstrup The effect of varying 1997: 12: 159-167.
ridge augmentation P, Hjorting-Hansen E, oxygen con- centrations 172. Simio n M, Trisi P,
using polylactic Lang N. on osteogenesis and Piattelli A. Vertical ridge
membranes in Plaque-induced embryonic cartilage augmentation
conjunction with marginal tissue in vitro. J Bone Ioint using a membrane
immedi- ate implants reactions of osseointe- Surg Am 1967: 49: 73- technique associated
in periodontally grated oral implants: 80. with osseointe- grated
compromised a review of the ! 170. Simio n M, Baldoni implants. Int J
extraction sites: an iterature. C!in Oral M, Rossi P, Zaffe D. A Periodontics
Implants Res 1992: 3: comparative Restorative Dent 1994:
experimental study in
149-161. study of the 1
dogs. Int J Oral
164. Schou S, Holmstrup effectiveness of e- 4
Maxillofac Implants
PTFE membranes with :
1997: 12: 325-334. P, Keiding N, Fiehn
N-E. Micro- biology and without early
158. Schliephake H,
of ligature- exposure during the 4
Neukam FW, 9
induced marginal healing periodo Int J
Hutmacher D, Becker 7
inflammation around Periodontics
J. En- hancement of -
osseointegrated Restorative Dent 1994:
bone ingrowth into a 5
implants and 14: 167-180. 1
porous hydroxylapa-
171. Simion M, Misitano U, 1
tite-matrix using a ankylosed teeth in
cynomolgus monkeys Gionso L, Salvato A. .
resorbable polylactic
Treatment of 173. Skoglund A, Hising P,
membrane. An (Macacafascicularts.
Clin Oral Im- plants dehiscences and Young C. A clinical
experimental pilot fenestrations around
Res 1996: 7: 190-200. and histologic
study. J Oral Maxillofac dental implants
165. Schpbach P, Hrzeler examination in
Surg 1994: 52:
M, Grunder U. Implant- humans of the
57-63. tissue in- osseous response to
159. Schmid J, Hammerle terfaces following im- planted natural
CHF, Flckiger L, treatment of peri-
174 bone mineral. Int J
Gogolewski S, Winkler implantitis using Oral Maxillofac Im-
JR, Rahn B, Lang NP. guided tissue plants 1997: 12: 194-
Blood filled spaces regeneration. Clin 199.
with and without filler Oral lmplants Res 174. Smukler H, Porto
materials in guided 1994: Barboza E, Burliss C. A new
bone regeneration. A 5: 55-65. approach
comparative 166. Schwartz Z, Mellonig to regeneration of
experimental study in surgically reduced
IT, Carnes DR, De La
the rabbit using biore- alveolar ridges in
Fontaine J, Cochran
sorbable membranes. dogs: a clinical and
DL, Dean DD, Boyan
C!in Oral Implants Res histologic study. Int J
BD. Ability of
1997: 8: 75- Oral Maxillofac
commercial
81. Implants 1995: 10:
demineralized freeze-
160. Schmid J, Hammerle 537-551.
dried bone allograft
CHF, Olah AJ, Lang 175. ten Bruggenkate CM,
to induce new bone
NP. Membrane Kraaijenhagen HA,
formation. J
permeability is van der Kwast WAM,
Periodontol 1996: 67:
unnecessary for Krekeler G, Oosterbeek
918-926.
guided generation of HS. Autogenous
167. Seibert J, Nyman S.
new bone. Clin Oral Localized ridge maxillary bone grafts
Implants Res 1994: 5: augmentation in dogs: in conjunction with
125-130. a pilot study using placement of ITI
161. Schmid J, Hammerle membranes and endos- seous implants:
CHF, Stich H, Lang NP. hydroxyapatite. J Peri- a preliminary report.
Suprapl-
odontol 1990: 3: 157- Int J Oral Maxillofac
anr", a novel implant 165. Surg 1992: 21: 81-84.
system based on the 168. Sevor Il. Meffert RM, 176. Thaller SR, Hoyt J,
principie of guided Cassingham RJ. Borjeson K, Dart A,
bone generation. Clin Regeneration of de-
Tesluk H. Recon-
Oral Implants Res hisced alveolar bone
struction of calvarial
1991: 2: adjacent to
defects with anorganic
199-202. endosseous dental
bovine bone mineral
 Hammerle & Karring
(Bio-Oss) in a rabbit 8 Implants Res 1991: 2:
model. J Craniofac 9 1
Surg 9 6
. 6
1
182. van Drie HJY, Beertsen -
9
W, Grevers A. Hea!ing 1
9
7
3 of the gin- giva
1
: following installment .
of Biotes" implants in 187. Weber H, Buser D,
4
: beagle dogs. In: de Fiorellini J, Williams R.
Putter C, de Lange Radiographic
7 GL, de Groot K, Lee
9 AJC, ed. Advances
- in biomaterials.
8
Amsterdam: EIsevier
4
. Science Publishers,
177. Tillmann T. 1988: 485-490.
Skelettsystem. In: 183. van Eeden SP,
Leonhardt H, Tillmann Ripamonti U. Bone
B, Tondury G, Zilles differentiation in po-
K, ed. Anatomie des rous hydroxyapatite
Menschen. Stuttgart: in baboons is
Thieme, 1987: 51-90. regulated by the ge-
178. Tinti C, Parma- ometry of the
Benfenati S, Polizzi substratum: imp!
G. Vertical ridge aug- ications for
mentation: what is reconstructive
the limit? Int J craniofacial surgery.
Periodontics Restora- Plast Reconstr Surg
tive Dent 1996: 16: 1994: 93: 959-
220-229. 9
6
179. Tolman DE, Keller EE.
6
Endosseous implant .
placement im- 184. Wachtel HC, Langford
mediately following A, Bernimou!in JP, Reichart
dental extraction and P.
alveoloplasty: Guided bone
preliminary report regeneration next to
with 6-year follow-up. osseointegrated im-
Int J Oral Maxil- lofac plants in humans. Int
Implants 1991: 6: 24- J Oral Maxillofac
28. Implants 1991: 6:
180. Tritten CB, Bragger U, 1
Fourmousis 1, Hammerle 2
CHF. 7
Transmukosale -
1
Direktimplantate:
3
Einzelzahnsofortverso 5
r- gung. Schweiz .
Monatsschr 185. Wallkamm B, Schmid
Zahnmed 1994: 2: J, Hammerle CHF,
122-126. Gogolewski S, Lang
181. Urist MR. Bone: NP. Effect of a
formation by autoinduction. bioresorbable foam
Science (Polyfoam'") on
1 experimental bone
9
neoformation. J Dent
6
5 Res (in press: IADR
: abstract).
186. Warrer K, Gotfredsen
K, Hjorting-Hansen E,
1
Karring T.
5
0 Guided tissue
: regeneration ensures
osseointegration of
8 dental implants placed
9 into extraction sockets.
3 An experi- mental study
- in monkeys. C!in Oral
 Guided bane regeneratian at oral implant sites

evaluation of crestal bone levels adjacent to nonsub- ous implant surfaces: a pilot study. Int J Oral MaxiJlofac
merged titanium implants. Clin Oral Irnplants Res 1992: Implants 1991: 6: 294-303.
3: 181-188. 191. Zellin G, Linde A. Effects of different osteopromotive

175
188. Wetzel AC, Stich H, membrane porosities
Caffesse RG. Bone on experimental bone
appositon onto neogenesis
oral irnplants in the in rats. Biomaterials
sinus area fiJled wth 1996: 17: 695-702.
different graft- ing 192. Zitzmann N, Naef R,
materials. A Scharer P. Gesteuerte
histologica! study in Knochenregen- eration
beagle dogs. Clin Oral und Augmentation in
Implants Res 1995: 6: der Implantatchirurgie
155-163. mit Bio-Oss und
189. Wildfang J, Merten Membrantechniken.
AH, Schafer F. Vergleichende Dtsch Zahnarztl Z
Untersu- 1996:
chung zur GTR mr 51: 366--369.
resorbierbaren und 193. Zitzmann NU, Naef
nicht resorbier- baren R, Schpbach P,
Folien. Z Zahnarztl Scharer P. Sofort-
Implantol1994: 10: oder verzogertes
137-143. Sofortimplantat
190. Zablotsky M, Meffert versus Spatimplantat
R, CaudiJI R, Evans G. bei Anwendung der
Histological
Prinzipien der
and clinica! gesteuerten Knochen-
comparisons of guided regeneration. Acta
tissue regeneration on Med Dent Helv 1996:
dehisced 1: 221-227.
hydroxylapatite-coated
and titanium endosse-

176