вход по аккаунту



код для вставкиСкачать
THE ANATOMICAL RECORD 245:410-425 (1996)
Soft and Hard Tissue Response to Endosseous Dental Implants
University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania
The last two decades have seen a remarkable growth in the
development of dental implants and their incorporation into the practice of
dentistry. This turn of events was made possible by an improved understanding of the biological response of living tissues to implants as well as
clinical trials that validated the long-term success of these implants. Despite major structural differences between teeth and implants, such as the
absence of a periodontal ligament around implants, the latter appear to
provide a reliable functional replacement for their natural counterparts.
This review briefly summarizes the major structural differences of the interfacial region of teeth and dental implants and their supporting tissues. It
focuses on our current understanding of the soft and hard tissue responses
to submerged and nonsubmerged root-form dental implants. The influence
of a number of factors that affect the tissue response is reviewed, including
biomaterials, implant design, surgical technique, and the local microbiota.
Our recently acquired ability to modulate wound healing with guided tissue regeneration and growth factors will undoubtedly play an important
role in the future utilization and success rates of dental implants.
0 1996 Wiley-Liss, Inc.
Key words: Soft tissue, Hard tissue, Dental implants, Junctional epithelium, Tissue interface
It is only in the last two decades that dental implants
have become predictably successful for the replacement
of teeth lost to trauma or disease. This success is due in
a large measure to the abandonment of the trial and
error approach to implant development and its replacement by a strategy based on sound biology, an understanding of materials science, and well-conceived clinical trials. As a result, data were generated that
demonstrated the reliability of artificial tooth root substitutes implanted directly into bone, (i.e., endosseous
implants). The geometric growth in the utilization of
implants worldwide is testimony to the impact this
treatment modality is having on modern dentistry.
The main reason for the success of contemporary
dental implants is the biocompatibility of modern implant materials with the tissues into which they are
inserted. In addition, the tissues have the ability to
adapt to the implants in such a way that masticatory
function can be maintained, albeit with an attachment
apparatus that differs structurally from that of natural
teeth. When failures occur, they are generally the result of errors in clinical judgment rather than problems
intrinsic to the biology of the implant-tissue interface.
A brief summary of the major differences between
the biological structure and function of the supporting
tissues of teeth and implants will be presented. The
major focus of this review will be on our current understanding of the interactions in the interfacial zone
between root-form dental implants and the surrounding (or periimplant) tissues.
In natural teeth the structural continuity of tooth
and periodontal tissues in the recently erupted,
healthy dental unit is the product of a well-integrated
series of developmental events. These begin with interactions between ectodermal and endodermal components that lead to the formation of the tooth per se (i.e.,
dentin, enamel, and pulp). The tooth follicle that surrounds the developing tooth gives rise to the periodontal structures (i.e., the periodontal ligament, alveolar
bone proper, and cementum). The developmental process leads to the intimate apposition on dentin of a
cementum layer in which are embedded collagenous
fibers that are continuous with the principal fibers of
the periodontal ligament. The alveolar bone proper,
which anchors the other end of the periodontal fibers,
forms the inner lining of the dental alveolus which
houses the root of the functioning tooth (for additional
details, see reviews by Schroeder 1986, 1991).
The supraalveolar portion of the fully erupted, functional tooth is surrounded by the soft tissues of the
gingiva that are attached t o the tooth by epithelial and
connective tissue elements, namely the junctional epithelium and dentogingival fibers (Fig. 1A). The outer
Address reprint requests to Max A. Listgarten, University of Pennsylvania, School of Dental Medicine, 4001 Spruce Street. Philadelphia, PA 19104.
Fig. 1 . A Diagrammatic illustration of the interfacial region between a tooth and the periodontal tissues. The dentin surface is
marked by thick arrows. The gingiva is attached to the enamel (ES,
enamel space) by junctional epithelium (JE)and dento-gingivalfibers
(DGF) which extend from the gingival connective tissue (CT) into the
cementum layer (C) that covers the root. The primary anchorage is
through the periodontal ligament (PL), the fibers of which are embedded in cementum (C) and the bone of the alveolar process (AP).
AM, alveolar mucosa; GS, gingival sulcus; OE, oral epithelium. B
Corresponding view of an implant, the surface of which is marked by
arrowheads. The relationship of the gingiva to the implant is similar
to that in A, except that dento-gingival fibers are absent. Anchorage
is provided by direct contact (or osseointegration)of the implant surface with the bone of the alveolar process (AP).
epithelial lining of the gingiva (oral gingival epithelium) is continuous with the sulcular epithelium that
lines the shallow sulcus between the marginal gingiva
and the tooth. Both of these stratified, squamous epithelial linings demonstrate varying degrees of keratinization in the absence of inflammation. They are continuous with the nonkeratinizing junctional epithelium
which forms the most coronal junction of the gingiva to
the tooth (Listgarten, 1972a; Schroeder and Listgarten,
1977;Schroeder, 1986). The dentogingival fibers, which
are anchored in the cementum covering the cervical
portion of the root, provide a firm connection between
the gingiva and the tooth (Hassell, 1993).
The maintenance of the structural integrity of the
periodontal tissues throughout life is dependent not
only on their proper development, as summarized
above, but on the ability of the body to deal effectively
with the wear and tear to which these structures are
exposed on a daily basis. The maintenance of the attachment apparatus requires effective defenses against
physical and chemical injuries and the ability to deal
with infections from the ever-present oral microbiota.
The intact gingival epithelial lining and junctional
epithelium serve as the primary lines of defense against
physical injury and bacterial invasion. Salivary secretions, with their lubricating and antimicrobial properties, increase the effectiveness of the epithelial barrier
in preventing damage to the deeper structures. Should
the epithelium be breached, an effective inflammatory
response is generally able to localize injuries to the
superficial portion of the periodontium and clear the
tissues of invading bacteria. The inflammatory reaction
not only limits the extent of tissue damage but also
assists in the mobilization of various cells needed to
regenerate lost or injured tissues or at least repair structures that cannot be regenerated.
For this process to work, a comprehensive inventory
of cells must be available that can differentiate into the
various cell types that normally inhabit this region
(McCulloch, 1993). In addition, a complex communications network must be in place that allows cells to perform their various functions in an integrated and effective manner. The chemical mediators of these
communications within and among cells are currently
the subject of intensive investigations. They include
not only traditional endocrine secretions but a host of
mediators of the inflammatory process and growth factors (Kiritsy and Lynch, 1993) now generally included
under the broad category of cytokines.
The product of various cells, cytokines act by binding
to specific receptors on cell surfaces, thereby triggering
assorted biological responses that modulate the structure and function of the regional tissues (O’Neal et al.,
1992; Hefti, 1993). An ever-expanding array of matrix
metalloproteinases (Birkedal-Hansen et al., 1993) and
their inhibitors, secreted in response to cytokine activity, serve as cellular tools that alter the structure and
composition of the intercellular matrix.
In contrast to natural teeth which develop with and
within the tissues that will eventually provide them
with their periodontal support, endosseous implants are
introduced as artificial structures into a site which is
surgically created within mature tissues. Consequently, the periimplant tissue support that permits the
implant to function in a masticatory capacity is the
result of a wound healing process rather than a developmental one. The soft and hard tissues around the
implant will react to the surgical injury in a manner
that will depend on a number of factors, including the
nature of the cells a t the implant site, the physical and
chemical nature of the implants, and the magnitude of
occlusal forces applied to the implants at various stages
of the healing process and later during masticatory
In the absence of good oral hygiene, the oral microbiota may give rise to a chronic inflammation of the
periimplant tissues, or periimplantitis, analogous to
periodontitis around teeth. Like periodontitis, periimplantitis can lead to implant loss. Therefore, good oral
hygiene is as important for the long-term retention of
dental implants, as it is for the preservation of the
natural dentition.
The major distinguishing features between the toothl
periodontium and the implant/periimplant tissue interfaces is the absence around most implants of a true
periodontal ligament and the cementum layer that anchors the principal fibers of the gingiva and periodontal ligament to the implant (Fig. 1) (Listgarten et al.,
1991; Donley and Gillette, 1991). The periodontal ligament contains the cellular elements that make it possible for teeth to move within their bony envelope.
Cells in the ligament are responsible for the coordinated cycles of bone resorption and bone deposition
that result in tooth movement when physiologic forces
are applied to teeth, either by the surrounding soft tissues or the orthodontist. Because implants lack this
ligament, forces may be applied to them without noticeable effect on their position within the jaw. For this
reason, implants can be successfully used as anchorage
for orthodontic tooth movement (Roberts et al., 1989;
Wehrbein and Diedrich, 1993). How the periimplant
tissues react to the surgical placement of an endosseous
implant t o form a more or less stable interface with this
artificial object will be covered in greater detail in the
following sections.
Submerged (Two-Stage) Implants
Because it is impossible to totally sterilize the oral
cavity, some bacterial contamination of the surgical
site is unavoidable. In general, microorganisms derived from the resident microbiota that contaminate a
surgical site after surgical flap closure are readily
This review will limit itself to a discussion of the
tissue response to root-form endosseous dental implants, since they are the most commonly used. They
can be divided into two major types, submerged (or
two-stage) and nonsubmerged (or one-stage) implants
(Fig. 2). Both types require a surgical entry and preparation of the recipient site prior to placement of the
implant fixture. In the case of submerged or two-stage
implants, the implant fixture is surgically inserted into
bone as part of a first-stage surgical operation and completely covered with the mucosal lining postoperatively, thereby allowing the tissues to heal around the
implant in a protected, bacteria-free environment (Fig.
2A). Following a suitable healing period, a secondstage surgical procedure is required to connect the submerged fixture to the oral environment by means of a
transmucosal abutment (Fig. 2B). The fixture and the
abutment are connected to one another, usually with a
screw. Nonsubmerged or one-stage implants are inserted in a single-stage surgical procedure so that the
most coronal portion of the implant immediately protrudes through the mucosal lining, making a secondstage intervention unnecessary (Fig. 2C,D). The positioning of the implant, with its occlusal surface
approximately flush with the mucosal surface, prevents premature masticatory function from interfering
with the healing process. However, careful hygiene to
control potential postoperative infections of dental
plaque origin is required (Bauman et al., 1992; Schou
et al., 1992). Available data indicate that the success
rates of one- and two-stage implants are comparable
(Babbush and Shimura, 1993; Buser et al., 1991b;
Adell et al., 1981).
Fig. 2. Diagrammatic illustrations of submerged (two-stage) and
nonsubmerged (one-stage) implants in a mesio-distal plane. A: Submerged implant with cover screw (CS) during healing phase. A microgap (MG) is located near the crest of the alveolar process (AP), between the cover screw and the implant fixture (IF). CT, gingival
connective tissue; JE, junctional epithelium; OE, oral epithelium. B:
Submerged implant after connection to the restoration (R) which, in
this case, also acts as the transmucosal connector. The junctional
epithelium (JE) extends to the micro-gap located near the alveolar
crest. C: Nonsubmerged implant during healing phase. The cover
screw (CS)is exposed and the micro-gap (MG) between the cover
screw and the implant fixture (IF) is located at or near the tissue
surface, well clear of the alveolar process (AP). D Nonsubmerged
implant after placement of the restoration (R).The micro-gap (MG)
remains close to the tissue surface. Apical migration of the junctional
epithelium (JE) is minimal, with a substantial connective tissue collar (CT) between the junctional epithelium and the crest of the alveolar process (AP).
cleared by the normal host defenses. However, the oc- case with the dentogingival junction, is mediated by
clusal portion of the implant fixture that will be con- junctional epithelium coronally and connective tissue
nected later with the transmucosal abutment may trap apically. Comparative histometric studies of noninbacteria during the insertion process (Quirynen and flamed implants and teeth, in dogs (Berglundh et al.,
van Steenberghe, 1993; Quirynen et al., 1994). Despite 1991, 1992) and monkeys (Lang et al., 19931, indicate
the presence of a cover screw, which protects the screw few differences in the distribution of the surrounding
hole from being penetrated by tissue components (Fig. soft tissue layers. The similarity in the soft tissue mea2A), bacteria under the cover screw may proliferate surements around teeth and implants is maintained
and cause a chronic inflammatory reaction during the even in the presence of early gingivitis (Berglundh et
initial healing phase. To minimize this potential com- al., 1992).
plication, special attention must be paid to flushing out
The unavoidable presence of microorganisms in the
any trapped bacteria a t the time of surgery. Applica- sulcus region of teeth or implants usually results in a
tion of an antibiotic ointment to the screw hole has also mild round cell inflammatory infiltrate that is localbeen recommended to minimize postoperative infec- ized to the lamina propria adjacent to the sulcus and
tions (Babbush et al., 1987). Contamination through junctional epithelium. The presence of such an infilthe surgical incision is unlikely, since access is gener- trate does not necessarily lead to loss of attachment. It
ally gained through some type of envelope flap, which probably reflects a normal host response to the presis designed so that the incision is located away from the ence of the resident microbiota. Should excessive bacimplant.
terial deposits accumulate in the sulcus region-for exLittle published information is available on the his- ample, as a result of neglected oral hygiene-loss of
tological characteristics of the healing mucosa over attachment due to chronic inflammation could occur.
submerged implants. Presumably, in the absence of Such loss of attachment could also result from changes
significant infection originating from beneath the in the composition of the microbiota, including an incover screw, the initial clot is resorbed, and a dense creased number of virulent species.
collagenous lamina propria is formed over the implant
If a gingivitis is experimentally induced in dogs and
which lies more or less flush with the level of the al- allowed to progress for 90 days, the inflammatory inveolar crest. In the case of protruding implants or in- filtrate tends to extend further apically around imadequate circulation to the overlying mucosal flap, plants than around teeth with gingivitis (Ericsson et
premature exposure of the occlusal portion of the im- al., 1992). The difference in the volume and apical explant is possible, as a result of localized tissue necrosis. tension of the inflammatory infiltrate is even more
In such a case, a junctional epithelium presumably de- marked in ligature-induced periodontitis and periimvelops from undifferentiated basal cells of the adjacent plantitis (Lindhe et al., 1992).
epithelium. We know that oral epithelium can give rise
Ligature-induced periodontitis and periimplantitis
to junctional epithelium from studies of wound healing have been used as models to study the destruction of
following gingivectomy around natural teeth (Listgar- periodontal and periimplant tissues under controlled
ten, 197213). Premature exposure of a stable, sub- conditions. The lesions result primarily from an
merged implant does not seem to affect the long-term increased bacterial load, due to the plaque-retentive
prognosis of the implant, which essentially becomes ligature, and possibly qualitative changes in the microbiota. In the presence of ligature-induced inflammaconverted to a nonsubmerged implant.
If the implant heals without becoming exposed, it tion in the dog model, the cellular infiltrate around
must be surgically uncovered to install the transmu- implants was greater, progressed more apically, and
cosal abutment, which connects the tissue-integrated caused more bone destruction than around teeth
implant fixture to the intraoral environment. Many (Lindhe et al., 1992). The greater extent of breakdown
clinicians prefer a flap procedure to gain access to the around implants as compared to teeth was attributed
implant rather than cutting a round window through primarily to the lack of dentogingival fiber insertions
the mucosa directly over the implant. A flap provides in implants (compare Fig. lA,B). However, the influbetter access and flexibility, should it become neces- ence of a long junctional epithelium extending to the
sary to recontour or reposition the tissues adjacent to subgingival abutment junction cannot be excluded, at
the implants, and tends to preserve more of the exist- least for two-stage implants (compare Fig. 2B,D).
Unlike the above results in dogs, clinical measureing masticatory mucosa (Hertel et al., 1994).
The connection of the transmucosal abutment will ments around teeth and one-stage implants in monresult in a narrow gap between the fixture and the keys were comparable before as well as after ligatureabutment, the size of which will vary according to the induced inflammation (Lang et al., 1993).The different
precision with which the parts were designed and man- results between the dog and monkey models could be
ufactured. This gap is usually located near the bone due to species variation. However, this is not likely,
surface (Fig. 2B). Theoretically, the gap could serve as since such differences have not been reported in past
a potential source of infection by bacteria that may studies of ligature-induced periodontal disease in these
become trapped in it during the second-stage surgical animals. A more likely reason is the presence of a subprocedure or during the immediate postoperative pe- gingival gap in the two-stage implants used in the dog
riod. However, as will be seen later, there is no evi- studies, whereas one-stage implants, consisting of a
dence that bacterial contamination of the gap region in single element, were used in the monkeys.
In the dogs, two-stage implants tended to show a
two-stage implants has any effect on probing measurements, as compared to one-stage implants that have no greater thickness of supracrestal connective tissue
than teeth (1.7 mm vs. 1.1 mm) and parallel orientagap.
The junction of the gingiva with an implant, as is the tion of the gingival connective tissue fibers to the im-
plant surface instead of the more or less perpendicular
insertion of dentogingival fibers typical of teeth (Ericsson and Lindhe, 1993). Probing depths tended to be
greater around implants than teeth (2.0 mm vs. 0.7
mm), an observation that the authors attribute to the
architecture of the supracrestal connective tissue
around the implants. They consider this tissue to be
less resistant to the passage of a probe than the inserted dentogingival fibers around teeth.
Since the implants were separated from the soft tissue specimens for histological processing, the actual
tissue-implant interface was no longer intact. Therefore, it is questionable how reliably the authors could
locate the position of the probe tip or the soft tissue
landmarks in relation to the implant surface. It is
likely, for example, that the apical extent of the junctional epithelium was underestimated, due to epithelial tears a t the tissue-implant interface, with portions
of the junctional epithelium remaining attached to the
discarded fixture.
Schou et al. (19931, who worked with a monkey
model, came to the conclusion that the lack of a periodontal ligament could also be a factor in the relative
susceptibility of periimplant tissues to ligature-induced breakdown. Their conclusion, however, is open to
challenge. First, they experimentally created ankylosed teeth that lack a periodontal ligament by extracting and reimplanting teeth after drying the roots. They
then induced chronic inflammation with ligatures
around normal teeth, ankylosed teeth, and titaniumcoated polycarbonate implants. After 7 weeks, significant bone loss was observed around implants and ankylosed teeth but not around nonankylosed teeth.
However, the bone loss was considerably greater
around the implants than around the ankylosed teeth.
No convincing explanation was given to explain these
findings. It is possible that reimplantation of the teeth
to achieve ankylosis did not result in the restoration of
a dentogingival connective tissue junction with the
same quality as the original, particularly with respect
to the density of dentogingival fiber insertions. Therefore, while the reimplanted teeth may have been more
resistant to breakdown than implants, they failed to
match the resistance of the undisturbed teeth. Thus,
the differences among the three experimental groups is
more likely attributable to differences in the structure
of the dentogingival junction than the mere presence or
absence of a periodontal ligament.
Adell et al. (1986) reported that in relatively inflammation-free implants placed in humans, some decrease
in probing depth takes place after 6 months postinsertion, from an initial depth of 3.8 mm to an average
probing depths ranging from 2.4-2.9 mm. The original
probing depth likely represents mean measurements
taken close to the alveolar crest, whereas the shallower
measurements reflect decreased probe penetration,
probably due to increased connective tissue density and
decreased inflammation. Lekholm et al. (1986) reported an average probing depth of 3.8 mm for 125
fixtures placed in 20 patients, with the greater measurements associated with inflammatory changes. The
depth of the measurements suggests that they were
taken with the probe tip close to the alveolar crest.
Unlike the situation in most animal experiments,
two-stage implant abutments in humans are changed
a t least once, namely when the healing abutments are
replaced by the abutment incorporated in the restoration (Fig. 2B). Changing abutments probably favors
the development of a long junctional epithelium extending close to the gap between fixture and abutment,
a situation which differs from that in the dog model,
where the original abutment is left in place (Ericsson
and Lindhe, 1993; Berglundh et al., 1991). A long junctional epithelium in conjunction with an adjacent inflammatory infiltrate would favor more apical probing
Apse et al. (1989) measured probing depths around
teeth and two-stage implants in partially edentulous
patients with similar plaque and gingival indices. Implants routinely gave mean probing depths greater
than those of natural teeth by a magnitude of around
0.8 mm (3.29 vs. 2.47). The discrepancy between the
two is likely due to a longer junctional epithelium
around the implants, extending close to the gap, and
possibly a more apical extension of the inflammatory
infiltrate not detectable on visual inspection.
When wound healing is completed, following second
stage surgery, the mucosa should be tightly adapted to
the abutment. Many clinicians prefer the periimplant
gingiva to consist of fixed masticatory rather than
moveable lining mucosa (Adell et al., 1981; Buser,
1987; ten Bruggenkate et al., 1990; Artzi et al., 1993).
However, Wennstrom et al. (1994) reported no correlation between the periodontal status of implants, in
function for a t least 5 years, and the width of the surrounding masticatory mucosa.
Nonsubmerged (One-Stage) lmpiants
The healing of the soft tissues following the insertion
of one-stage implants resembles that which takes place
around transmucosal abutments after second stage
surgery (Figs. 2,3). The major differences between the
two types of implants is the absence in one-stage implants of the gap between the implant fixture and the
transmucosal abutment, which is typical of two-stage
systems, and the transmucosal location of the onestage implant immediately after insertion. While the
trapping of bacterial contaminants in the supracrestal
region is much less likely with nonsubmerged systems
that lack the subgingival gap, much greater postoperative care is required t o prevent gingival infection during initial healing, since these implants are immediately exposed to the oral environment (Gotfredsen et
al., 1991).
Following insertion of the fixture and readaptation
of the soft tissues to the implant, a clot fills the residual
voids between the soft tissues and the fixture. Organization of the clot is accomplished by ingrowth of granulation tissue from the surgical flap and the adjacent
bone. In the case of periodontal surgery, granulation
tissue also originates from the periodontal ligament.
This source of granulation tissue is obviously missing
around conventional implants where the recipient site
is drilled directly into edentulous bone. It is the absence of granulation tissue of periodontal ligament origin that accounts for the major structural difference in
the anchorage between teeth and implants to the adjacent bone.
Under experimental conditions, it is possible to generate a tooth-like attachment apparatus around im-
Fig. 3.A Histologic section through nonsubmerged (one-stage)implant replica made from titanium-coated epoxy resin, 3 months after
insertion in a dog mandible. B = bone of alveolar process; G = gingiva; I = implant. Bar = 1mm. B: Magnified view of alveolar crest
(AC) region of A. Note minimal sulcus formation and minimal apical
migration of junctional epithelium (single arrow). With the exception
of a shallow groove in the crestal region, the alveolar process is in
direct contact with the titanium layer coating the implant replica
(double arrow). Bar = 0.2 mm. C Magnified view of the gingival
region in A. The arrow indicates the junction of the smooth collar
region (above arrow) with the rough-surfaced apical region. The connective tissue fibers run predominantly in a plane parallel to the
titanium-coated implant surface. Bar = 50 pm. D Magnified view of
A. Bone (B) surrounding the implant replica is in direct contact with
the titanium coating (arrows). Bar = 0.2 mm. (Figs 3A and 3B Reproduced from Listgarten et al., 1992, with permission of the publisher.)
plants, with a cementum layer adherent to the implant
surface, anchoring the connective tissue fibers of a
periodontal-like ligament. To achieve this unusual
healing pattern, implants were purposefully inserted
into recipient sites adjacent to residual root tips still
surrounded by their periodontal ligament. Progenitor
cells in the granulation tissue derived from the periodontal ligament migrated to the implant surface and
were able to reconstitute a tooth-like attachment apparatus around the implant, with a cementum layer
adherent to the implant surface and ligament fibers
embedded in it (Buser et al., 1990a,b; Warrer et al.,
1993). These highly specialized cells are not found in
the granulation tissue that participates in the normal
healing process after implant placement. Therefore,
this healing pattern represents a very atypical one for
implants. Nevertheless, the observation is of great biologic interest, as it highlights the unique cellular contribution of the periodontal ligament t o wound healing.
On the basis of periodontal wound healing studies
(Listgarten et al., 19821, we know that following the
repositioning of surgical flaps, epithelium begins to
proliferate from the cut gingival margin along the inner surface of the flap. It migrates as a thin sheet of
cells between the newly organized clot lining the flap
and nonorganized remnants of the clot and other debris
located on the root surface. When the epithelial cells
reach the granulation tissue that binds the basal portion of the flap to the tooth, they stop their apical migration, become attached to the tooth, and begin to
migrate coronally. In the process they clear the wound
of accumulated debris and reestablish a n organic connection between the gingiva and the root surface by
means of a long junctional epithelium.
Presumably, a similar process occurs following the
surgical placement of one-stage implants. Precisely
drilled receptor sites will insure a tight fit at the crest
of the preparation, thereby allowing the granulation
tissue to rapidly bridge the small space left between
the bone and the implant. The proliferating epithelium
will thus be prevented from growing in between the
implant and the bone. It is to be expected that in the
first 3 weeks after one-stage implant placement, or in
the case of two-stage implants after abutment connection, a long junctional epithelium will become established, which will extend from the base of the gingival
sulcus to a level close to the alveolar crest. It bears
emphasizing that the formation of the junctional epithelium proceeds in an apico-coronal direction, from
epithelium that initially migrated from the gingival
margin toward the base of the flap.
In vitro data indicate that epithelial cells migrate
more readily on smooth- than rough-surfaced titanium
(Cochran et al., 1994). The epithelial cells adjacent to
the implant surface form typical hemidesmosomes and
a basal lamina which mediate their attachment to the
surface (James and Schultz, 1974; Listgarten and Lai,
1975; Bauman et al., 1993) yet allow the cells to move
coronally. The extent to which supracrestal connective
tissue eventually replaces the apical portion of the
junctional epithelium (Listgarten et al., 1982) will depend in part on the degree to which inflammation in
the supracrestal region can be controlled.
The granulation tissue in the supracrestal region
eventually becomes remodeled into a dense collagenous
connective tissue with the majority of fibers running in
a direction more or less parallel to the implant surface
(Figs. lB, 2D, 3C) (Buser et al., 1992; Listgarten et al.,
1991, 1992). In a histologic study in dogs, Buser et al.
(1992) reported limited apical extension of the junctional epithelium. Immediately apical to the epithelium, next to the implant, they reported a 50-100 p,m
wide supracrestal connective tissue collar composed of
dense, scar-like, relatively avascular connective tissue.
The presence of connective tissue fibers running parallel to the implant surface is the usual finding around
most types of implants. A few reports indicate the possibility of perpendicular fiber insertions in the case of
rough-surfaced, porous implants (Schroeder et al.,
1981; Deporter et al., 1988; Buser et al., 1989; Pilliar,
1991). It is evident, however, that perpendicular fiber
insertions are rare and are not a common finding following the placement of most implant types, even when
they have relatively rough but nonporous surfaces
(Buser et al., 1991a; Listgarten et al., 1992).
Because of the gap between abutment and fixture in
two-stage implants, inflammation following abutment
connection is theoretically more likely to persist
around two-stage than one-stage implants. The absence of this potential bacterial trap around one-stage
implants should facilitate the undisturbed organization of the postsurgical clot and the formation of a
wider collar of supracrestal connective tissue than
would be the case with two-stage implants. Therefore,
one might expect deeper probing depths to persist
around two-stage than one-stage implants.
Yet this is by no means obvious from published clinical measurements. Buser et al. (199Oc, 1991b) reported average probing depths around one-stage implants of 2.69-2.81 mm between 1 and 2 years after
implantation. This is shallower than the 3.8 mm reported by Lekholm et al. (1986) for two-stage implants
but is similar to average probing depths of 2.89 mm
reported by Apse et al. (1989) and the mean measurements of 2.4-2.9 mm observed by Adell et al. (1986)
after tissue healing was complete. Therefore, there is
no detectable difference between one- and two-stage
implants with respect to clinical probing depth measurements after they have been in function for several
months or longer. Definitive histological evidence,
based on block sections of intact tissue-implant interfaces, is still lacking to show what differences, if any,
exist in the comparative healing of periimplant tissues
to one- and two-stage implants.
Although implants were separated from their surrounding tissues prior to processing, Abrahamsson et
al., (1996)have recently demonstrated similar tissue to
implant relationships in 1-stage and 2-stage implants,
6 months following abutment installation.
Control of Epithelial Migration
Junctional epithelial proliferation is a characteristic
feature of periodontal sites that are inflamed (Listgarten, 1986; Page and Schroeder, 1982). In health, the
junctional epithelium has a relatively smooth external
basal lamina and occupies a relatively stable position
on the tooth surface. In the presence of inflammation,
it develops numerous papillary extensions which in-
vade the adjacent inflamed connective tissue. The junctional epithelium also tends to proliferate in an apical
direction as dentogingival fibers are destroyed. The absence of dentogingival fibers around implants has been
blamed for the more rapid apical extension of the inflammatory process around implants as compared to
teeth (Lindhe et al., 1992), a process which may also
promote apical proliferation of the junctional epithelium. Inflammation may also affect the expression of
various cytokeratins in the gingival epithelia (Bosch et
al., 1989) and generate a variety of cytokines that can
influence the behavior of adjacent epithelial cells
(MacKenzie, 1988).
Mackenzie et al. (1991) have reported that different
portions of the gingival connective tissue may differentially affect the expression of cytokeratins in human
gingival epithelia. In an earlier review of mesenchymavepithelial interactions, MacKenzie and Hill (1984)
stated that connective tissues play a key role in controlling epithelial morphogenesis and cytodifferentiation. Given the importance of connective tissue controls
on epithelium, it is likely that gingival connective tissues play an important role in determining the degree
of apical proliferation of the junctional epithelium.
One factor which may explain the limited downgrowth of mature junctional epithelium around teeth
and implants may be related to differences in the interactions between epithelial cells and various constituents of the gingival connective tissue, namely the
lamina propria and what has been described by Mackenzie and Hill (1984) and Mackenzie and Fusenig
(1983) as “deep” connective tissues. Deep connective
tissue beds appear to lack the physical structure andlor
the diffusible substances required to stimulate epithelial cell migration and differentiation. Whereas the
lamina propria of the gingiva will stimulate the overlying epithelium to proliferate and maintain a multilayered, keratinizing phenotype, deep connective tissues may inhibit both the proliferation as well as the
differentiation of gingival epithelium. If the deeper
portions of the gingival connective tissues share the
same properties as the deep connective tissues in
Mackenzie’sexperiments, epithelial migration could be
inhibited when the advancing edge reaches this region.
Thus, in addition to other factors discussed previously,
the apical extent of the junctional epithelium may be
determined by the presence in gingiva of deep connective tissues that inhibit epithelial migration. Presumably, similar controlling mechanisms are operational
around both implants and teeth.
the long term, osseointegration is considered to be
more predictably successful than a fibrous union.
Brhnemark et al. (1977)described osseointegration as
a relationship where “bone tissue is in direct contact
with the implant, without any intermediate connective
tissue.” Later, Brinemark et al. (1985) stated that osseointegration represents “a direct structural and functional connection between ordered, living bone and the
surface of a load-carrying implant.” This latter definition fails to include healing of bone to implants that are
not in function yet have all the morphologic characteristics of being osseointegrated by the first definitionfor example, implants in situ-prior to abutment
connection. The definition has been repeatedly reinterpreted. Perhaps one of the more extreme reinterpretations states that since “there is no acceptable histologic
correlate to the term ‘osseointegration,’ ” implants that
healed with a histologically distinct fibrous union but
were clinically stable also should be considered as osseointegrated (Nystrom et al. 1993).
In order to minimize further confusion, the term osseointegration, as used in this review, describes a direct
contact between living bone and the implant surface,
based on histological evidence of the type available
around the time the definition was coined (Schroeder et
al., 1976; Brinemark et al. 1977). While clinical signs,
particularly with dynamic percussion devices (Teerlink
et al., 19911, may suggest that osseointegration has
taken place, the interpretation of these signs as evidence of osseointegration can only be presumptive,
since, with current technology, only histological sections can provide definite proof of the absence of fibrous
tissue between the bone and the implant.
The nature of the implant to bone interface depends
on numerous factors, including the type of implant
(Smith, 19931,the surgical technique and quality of the
surrounding bone structure, the timing and magnitude
of implant loading, and the degree of postsurgical oral
Type of Implant
Today most root-form implants are composed of materials that will allow healing by osseointegration,
with titanium being the most common. Others generally known to heal by osseointegration include hydroxyapatite and aluminium oxide ceramics (Stef lik et
al., 1992a,b) and zirconium (Albrektsson et al., 1985;
Akagawa et al., 1993).It has been amply demonstrated
that a strong bond can become established between
bone and implants made of commercially pure grade
titanium (Brinemark et al., 1977; Schroeder et al.,
1981, 1991; Albrektsson et al., 1983). However, titaDENTAL IMPLANTS
nium does not have the ability to induce osteogenesis
The healing of bone tissue around endosseous im- from potential osteogenic precursor cells in marrow
plants has been the subject of a large number of pub- (Rahal et al., 19931,nor does it possess osteoconductive
lications (for recent reviews see Listgarten et al., 1991; properties (i.e., the ability to induce bone to grow along
Bidez and Misch, 1992; Roberts et al., 1992; Kohn, its surface). Given the heterogeneity in bone structure
1992; Albrektsson and Zarb, 1993; De Lange and De at the various sites receiving titanium implants, a
Putter, 1993; Steflik et al., 1993a). Unlike teeth, which great deal of variation in bone contact can be expected
are anchored to the alveolar bone by a periodontal lig- (Ettinger et al., 1993).
By contrast, hydroxyapatite ceramic implants and
ament, implants placed in bony sites heal either by
forming a direct and intimate contact to bone, com- hydroxyapatite coatings exhibit osteoconductive propmonly referred t o as osseointegration (Brinemark et erties (De Lange and de Putter, 1993; Weinlaender et
al., 1977,1985), or a looser union mediated by a fibrous al., 1992; Gottlander et al., 1992; Teranobu et al.,
capsule, or “fibrosteal integration” (Weiss, 1986). For 1989). As a result, new bone tends to spread along the
implant surface, thereby forming a thin layer of compact bone, even in areas where the implant is adjacent
to marrow spaces. While hydroxyapatite coatings may
contribute to more rapid osseointegration in the early
stages of healing, they do not seem to confer any advantages over the long term. The slow resorption of
hydroxyapatite coatings has been interpreted by some
as placing such implants a t greater risk than plain
titanium implants. However, there are no convincing
data to support this belief (Zablotsky, 1992).
Assorted stainless steel and chrome cobalt alloys
that constitute the mainstay of orthopedic implants
(Albrektsson and Hansson, 1986; Linder, 1989; Linder
et al., 1989) and certain titanium alloys (Johansson et
al., 1989) were thought to be incapable of healing by
osseointegration. However, more recent investigations
have identified some of these and other materials as
having a similar ability to bind to bone, including vitallium (Niki et al., 1991; Johansson et al., 1991; Albrektsson and Johansson, 1991), niobium and various
steel alloys (Albrektsson and Johansson, 1991; Johansson and Albrektsson, 1991), hydroxyapatite ceramic
(Gottlander and Albrektsson, 1991; Lemons and Bidez,
1991; Smith et al., 1992; De Lange and De Putter,
1993), and bioglass (Lemons and Bidez, 1991). However, Barth et al., (1990) were unable to confirm the
osseointegration of a glass ceramic they tested in parallel with titanium implants.
To favor retention and distribute functional forces
more evenly (Skalak, 1983; Brunski, 1991), some implant designs incorporate a screw thread in addition to
the basic cylindrical form that characterizes most of
the current implant models. However, the long-term
success rate appears to be similar for screw-shaped and
non-screw-shaped root-form implants (Buser et al.,
1991b). Some designs increase the surface area available for tissue integration by using rough surfaces such
as plasma-sprayed surfaces or by roughening the surface by acid-etching or sandblasting techniques. While
short-term differences have been reported between percentage of bone contact (Buser et al., 1991a) and shear
strength (Wilke et al., 1990; Carlsson et al., 1988) for
various surface textures, there is no clear evidence of
long-term superiority of one surface texture over another.
It should be stated in passing that the poor track
record of blade implants is not so much the result of
their unique shape as of some other critical factors that
were ignored in the early days of their use. These include their fabrication with materials that were not
readily able to achieve osseointegration, inadequate
surgical technique, and premature loading, to name a
few of the main causes of failure. While long-term data
are not available at this time, there is some indication
that blade implants fabricated with modern materials,
inserted with good surgical technique and without
overheating bone, and not prematurely loaded can become osseointegrated and provide satisfactory prosthetic support (Lum et al., 1991).
Surgical Technique and Bone Structure
Most systems provide instrumentation that allows
the surgeon to create an intrabony recipient site for the
implant that will provide a tight fit for the implant
fixture, thereby preventing fibrous tissue ingrowth and
interference with osseointegration. The instrumentation is designed to create a suitable site with minimal
trauma to the bone, thereby maintaining the vitality of
most of the remaining bone cells. Preparation of the
recipient site in an edentulous ridge requires special
care with respect t o asepsis, avoidance of excessive
trauma to the soft and hard tissues, achieving primary
stability of the implant in situ, and good postoperative
In the case of one-stage implants, additional care
must be given to avoid plaque accumulation during
the critical wound healing phase that immediately
follows the placement of the implants. Since one-stage
implants are placed in direct communication with the
oral cavity, good coaptation of the flap edges and the
regular use of disinfecting mouth rinses promote rapid
healing of the soft tissues around the implant, thereby
forming a seal that prevents bacterial ingress. Assuming that all the critical steps in the placement of an
implant are followed, the wound healing process
should lead to osseointegration. Continuous remodelling will preserve the intimate contact with the bone
and the reparative potential needed to offset functional wear and tear (Listgarten et al., 1991; Roberts,
Disinfection of the oral cavity and the use of sterile
operating conditions have been considered essential for
many years (Branemark et al., 1985). Recently, a comparative study of a strict operating room protocol compared to a more relaxed aseptic technique failed to reveal a statistically significant difference in the success
rate of implants placed under either protocol (Sharf
and Tarnow, 1993). However, the results should be interpreted with caution, since the failure rate is low
with either technique and the clinical trial had relatively little statistical power to discriminate between
two relatively successful techniques.
Avoidance of tissue trauma is inherent to any surgical intervention, since it minimizes the risk of infection
and optimizes the repair process. Bone is uniquely sensitive to environmental trauma. For example, it has
been reported that heating bone to 47°C for 1 min is
capable of killing osteogenic cells, thereby compromising the chances of achieving ideal healing. Therefore,
particular emphasis must be placed on avoiding excessive heating of the bone by using serial drills, relatively low drilling speeds, abundant irrigation, light
hand pressure, and sharp instruments (Ericsson and
Albrektsson, 1983).
Whether one- or two-stage implants are used, much
attention must be given to achieving good primary stability at the time of implant placement and avoiding
premature loading of the implant (Brunski, 1991).
Both of these factors could result in sufficient micromovement to interfere with healing by osseointegration. The quality and quantity of bone at the recipient
site are also key elements in achieving primary stability (Brhemark et al., 1985). There should be enough
bone volume to totally surround the intrabony portion
of the implant and a sufficient amount of compact bone
to supply the rigid immobilization required for osseointegration.
Following the insertion of the implant into the precisely cut recipient site, the fibrinous clot a t the interface should occupy a minimum volume, a situation that
will facilitate the organization and replacement of the
clot by bone. A precise fit in the region of the crest is
critical. Because of the close proximity of the gingival
tissues to the recipient site, any space between the
crestal bone and the implant is likely to become invaded by gingival rather than bone cells, with the result that fibrous tissue rather than bone will fill that
space. A precise fit will also insure primary stability, a
prerequisite for osseointegration.
Despite good surgical technique, it is likely that a
thin seam of bone adjacent to the prepared site will
become nonvital along the entire recipient site. This is
not critical as long as the damage is limited. First, the
rate of bone resorption is relatively slow and does not
progress a t an even rate over all the damaged surfaces.
Therefore, it is unlikely that remodelling of the damaged bone will interfere with primary stability of the
implant and osseointegration. Evidence of active remodelling close to the implant surface has been provided by bone markers administered a t specific time
intervals following implant placement (Roberts et al.,
1984, 1986).
Considerable bone formation near the implant can be
detected as early as 3 days after implant placement.
However, several weeks are needed for replacement of
the intervening tissue with bone at the implant surface
(Roberts et al., 1984). Early bone formation is characterized by a callus-like woven bone which originates
from the cut bone surface (Clokie and Warshawsky,
1995). Later in the repair process, between 6 and 16
weeks, the woven bone is remodelled into lamellar
bone (Roberts et al., 1984; Clokie and Warshawsky,
1995), either as trabecular bone or osteon-containing
(Haversian) bone, depending on the local bone structure (Sennerby et al., 1992).
Autoradiographic and ultrastructural studies of
early wound healing of experimental titanium implants in rat tibias have indicated various patterns of
bone growth in relation to the implants. In addition to
confirming the conversion of the trabecular bone, laid
down in the early stages of healing, into more compact
bone, the results indicate that bone can grow toward
the implant from more distant sites as well as away
from it after having started to form on the implant
surface (Nanci et al., 1994).
After the implant is in function, further remodelling
will depend on the magnitude an direction of the applied forces. It has been shown that after implants are
placed in function, remodelling results in increased
bone volume and density in the cervical region, as compared to unloaded control implants (Piatelli et al.,
1993a). Interestingly, in this particular study the percentage bone contact did not differ between loaded and
unloaded implants.
It is clear that cancellous bone with large marrow
spaces does not provide the same physical support for a
freshly inserted implant as that provided by compact
bone, Therefore, it is desirable to prepare the recipient
site so as to include at least part of it within compact
bone, thereby insuring that primary stability will be
achieved and that functional forces will be more
readily withstood. In general, remodeling after implant
insertion will follow the pattern of the preexisting bone
(Parr et al., 1993). Where compact bone was present, it
will be replaced with compact bone. Where sparse tra-
becula contacted the bone, sparse bony contacts will be
reestablished (Listgarten et al., 1992).
An implant located in very cancellous bone will generally have only a small portion of its surface in contact
with a few bone spicules, the rest of the surface being in
contact with the nonmineralized contents of the marrow spaces. By contrast, an implant in compact bone
may approach 100% bone contact, since cellular and
marrow elements are sparse. However, the stability of
an implant is not solely dependent on the percentage of
bone contact. Greater stability can be achieved when
an implant is located in compact bone as compared to
one with a comparable bone contact ratio but located in
cancellous bone (Sennerby et al., 1992). Interestingly,
the failure rate of implants does not seem to be affected
by osteoporosis (Dao et al., 1993).
Histological studies of successfully osseointegrated
implants have generally shown a direct contact of the
surrounding bone with the implant. However, studies
at the ultrastructural level have revealed much more
variation a t the implant to bone interface than is evident from light microscopic studies. These reports indicate that the degree of proximity of bone to the implant surface falls within a range that extends from
intimate contact between the bone and the implant
(Fig. 4) Brunette et al., 1991; Listgarten et al., 1992)to
the presence of nonmineralized and mineralized intervening layers of varying width and electron density
(Linder et al., 1983; Albrektsson et al., 1983,1985; Albrektsson and Hansson, 1986; Ericson et al., 1991; Sennerby et al., 1991; Steflik et al., 1992a,b, 1993a,b; De
Lange and De Putter, 1993; Piatelli et al., 1993b;Nanci
et al., 1994). It is not clear to what extent these differences are due to true structural variations or to different methodologies employed by the investigators to examine the interfacial region.
Should excessive devitalization of bone occur as a
result of thermal injury, osseointegration will be compromised, and a fibrous capsule is likely to form between the implant surface and the bone. A similar reaction is likely if the implant does not achieve primary
stability or is loaded prematurely, before the bone has
become sufficiently remodelled around it to prevent micromotion during functional movements (Brunski,
1991).Fibrous capsules may also form around implants
made of materials that do not readily osseointegrate,
such as vitreous carbon. The presence of fibrous capsules after healing is not considered acceptable for dental implants, since implants that heal in this manner
appear t o have a less predictable and less successful
track record than osseointegrated implants (Albrektsson and Sennerby, 1990).
Such fibrous layers should not be confused with the
thin, acellular layers reported in the interfacial region
of bone and implants. These layers, resembling a lamina limitans, are composed of glycoconjugates such as
osteopontin (Nanci et al., 1994) and do not affect the
long-term survival of implants, as fibrous capsules
might. They are fully compatible with the structural
descriptions of osseointegrated implants and their reported long-term success rates. These layers appear
similar in structure and composition to the cement
lines seen at bone interfaces as a result of cyclic deposition and remodelling (McKee and Nanci, 1993).
Placing implants directly into bone grafts remains a
Fig. 4. Transmission electron micrograph of the interface between
osseointegrated, titanium-coated epoxy resin replica (T,titanium
coating) and the adjacent bone (B). The section was made after demineralization of the tissue block which reveals the individual collagen fibers (arrowheads)of the bone matrix. Note the intimate contact
between the titanium surface and the individual collagen fibers of the
bone matrix. Bar = 0.25 pm.
questionable procedure, even with an ideal grafting
material such as the iliac crest autograft, since the
implants appear to heal by fibrous encapsulation (Nystrom et al., 1993). This result may be due to the relatively great distance which exists between the implant
and the closest source of well-vascularized bone. A similar problem may exist with implants placed in recipient sites generated by sinus elevation procedures. Histologic studies of bone cores obtained from such sites
indicate retention of allografted elements with very
sparse ingrowth of host bone, even 6 months postoperatively, although the results with autogenous bone
grafts seem more promising (Nishibori et al., 1994).
In order to promote the ingrowth of desirable progenitor cells into a wound and keep out undesirable cell
types, a variety of physical cell barriers have been devised. These devices, usually in the form of membranes, help to create or maintain tissue compartments
and promote granulation of the space with desirable
cells (O’Neal et al. 1994). Originally devised to regen-
erate lost attachment around periodontally diseased
teeth (Karring et al., 19931, guided tissue regeneration
(GTR) has found numerous applications, including the
augmentation of alveolar ridge dimensions prior to or
in conjunction with implant placement (Seibert and
Nyman, 1990; Dahlin et al., 1991; Lang et al., 1994b;
Schenk et al., 1994) and the placement of implants into
recent extraction sockets (Warrer et al., 1991; Gotfredsen et al., 1993; Lekholm et al., 1993; Becker et al.,
1994; Gher et al., 1994a,b; Lang et al., 1994a). GTR has
also been reported to be successful in achieving osseointegration to surgically as well as pathologically
denuded implant surfaces and to titanium as well as
hydroxyapatite-coated fixtures (Zablotsky et al., 1991;
Jovanovic et al., 1993; Caudill, 1993; Lundgren et al.,
1994). To facilitate the maintenance of a compartment
for tissue ingrowth, titanium-reinforced membranes
have been developed which appear to be particularly
helpful in ridge augmentation procedures (Jovanovic et
al., 1995). However, therapeutic outcomes with GTR
are not consistent or predictable, and premature exposure of the barrier, a relatively common occurrence, as
well as infection around the membranes can severely
compromise the degree of tissue regeneration (Warrer
et al., 1991; Gotfredsen et al., 1993; Becker et al., 1994;
Lang et al., 1994b; Rominger and Triplett, 1994).
Schenk et al. (1994) have provided some excellent
histological data on the regeneration of large ridge defects. The importance of maintaining the integrity of
the tissue compartment in which regeneration is expected is well demonstrated. The results also clearly
show how the new bone is derived from the osseous
surfaces adjacent to the defect and undergoes a maturation process leading to a denser trabecular network.
The structural reorganization of the lamellar bone is
reminiscent of that of normal membrane bone development and maturation. Similar observations were reported by Hammerle et al. (1995) in healing calvarial
defects produced in a rabbit model.
In one animal experiment, in which different types of
dental implants were intentionally stripped of bone
and contaminated with dental plaque, results have
shown that regeneration of lost bone is possible. Osseointegration could be demonstrated in discrete portions of the surface following cleansing of the implant
surfaces with a powder abrasive and citric acid, followed by guided tissue regeneration. The authors reported greater bone contact to hydroxyapatite-coated
than titanium implants (Jovanovic et al., 1993). On the
other hand, healing with fibrous tissue was the predominant healing pattern in a similar study, but without the use of citric acid. In another study, little difference in the healing pattern was detected between
implants treated with guided tissue regeneration and
those treated by conventional debridement (Schupbach
et al., 1994). Even in noncontaminated dehiscences, intentionally produced at the time of implant insertion,
guided tissue regeneration resulted in covering the defects with a bone-like tissue which, however, was not in
intimate contact with the implant surface (Palmer et
al., 1994). While clinical studies in human subjects
suggest a beneficial effect of GTR on the repair of periimplant defects, the studies often lack adequate controls (Jovanovic et al., 1992; Shanaman, 1994) and reproducibility by other investigators.
crepant findings may be due in part to differences in
the growth factors tested, their dosages and mode of
In order to optimize the ingrowth of desirable cells administration, and differences in the experimental deinto tissue compartments created by GTR, attempts signs and animal models.
The application of growth factors to improve wound
have been made to combine the procedure with topical
applications of growth factors (Lynch et al., 1991; healing around implants is still in an embryonic stage,
Becker et al., 1992; Amar and Chung, 1994; Graves and much more experimental work is needed to deterand Cochran, 1994;Wang et al., 1994).Platelet-derived mine dosage, mode of application, sequence of delivery,
growth factor (PDGF) and insulin-like growth factor-I and optimal combinations that will achieve the desired
(IGF-I) are found in bone and have the ability not only aims. Until now, some of this work has been hampered
to stimulate osteoblastic activity but also to act as by the cost and lack of availability of these agents.
chemoattractant in order to recruit important cells to However, modern production techniques should allevithe wounded area (Kiritsy and Lynch, 1993; Lynch, ate both the cost and shortage of these biologically pow1994). When applied topically to fenestration defects in erful agents. Eventually, the benefit of growth factors
dogs, PDGF stimulated periodontal ligament fibroblast on wound healing around implants will have to be asproliferation, regardless of the presence of a barrier sessed in well-controlled clinical trials.
membrane (Wang et al., 1994). In combination, PDGF
and IGF-I appear to promote the formation of a denser
trabecular network around recently inserted implants Abrahamsson, I., T. Berglundh, J. Wennstrom, and J. Lindhe. 1996
The periimplant hard and soft tissues at different implant systhan comparable controls, with a greater percentage of
tems. A comparative study in the dog. Clin. Oral Implants Res.,
bone contacts on the implants (Lynch et al., 1991;
in press.
Becker et al., 1992). PDGF, a dimeric protein consist- Adell,
R., U. Lekholm, B. Rockler, and P.-I. Brlnemark 1981 A 15ing of two distinct polypeptides, exists in three isoyear study of osseointegrated implants in the treatment of the
edentulous jaw. Int. J . Oral Surg., 10:387-416.
forms, two of which are also capable of inducing prostaglandin-mediated bone resorption (Cochran et al., Adell, R., U. Lekholm, B. Rockler, P.-I. Brlnemark, J . Lindhe, B.
Eriksson, and L. Sbordone 1986 Marginal tissue reactions at os1993).
seointegrated titanium fixtures. I. A 3-year longitudinal prospecIn a series of reviews on regeneration (Linde et al.,
tive study. Int. J. Oral Maxillofac. Surg., 15:39-52.
1993; Amar and Chung, 1994; Graves and Cochran, Akagawa, Y., Y. Ichikawa, H. Nikai, and H. Tsuru 1993 Interface
histology of unloaded and early loaded partially stabilized zirco1994; O”ea1 et al., 19941, the authors suggested that
nia endosseous implant in initial bone healing. J . F’rosthet. Dent.,
the osteopromoting activity of GTR could probably be
enhanced with a variety of growth factors, including Albrektsson,T., P.-I. Brlnemark, H.-A. Hansson, B. Kasemo, K. Larsson, I. Lunstrom, D.H. McQueen, and R. Skalak 1983 The interbone morphogenetic proteins (BMP). Sailer and Kolb
face zone of inorganic implants in vivo: Titanium implants in
(1994) reported three cases in which BMP combined
bone. Ann. Biomed. Eng., 11:l-27.
with iliac bone grafts resulted in excellent healing Albrektsson,
T., and H.-A. Hansson 1986 An ultrastructural characaround compromised implants. However, the absence
terization of the interface between bone and sputtered titanium
or stainless steel surfaces. Biomaterials, 7:201-205.
of suitable controls and the low number of treated cases
precludes any reliable generalization. By incorporating Albrektsson, T., H.-A. Hansson, and B. Ivarsson 1985 Interface analysis of titanium and zirconium bone implants. Biomaterials,
bovine BMP fractions in an insoluble collagenous bone
matrix, that served both as a vehicle and as a spacer for Albrektsson, T., and C. Johansson 1991 Quantified bone tissue reactions to various metallic materials with reference to the so-called
GTR, Ripamonti et al. (1994)reported improved regenosseointegration concept. In: The Bone-Biomaterial Interface.
eration of furcation defects in baboon molars over deJ.E. Davies, ed. University of Toronto Press, Toronto, pp. 357fects treated with the matrix alone. They concluded
that recombinant human BMPs are potentially valu- Albrektsson, T., and L. Sennerby 1990 Direkte Verankerung von
Oralen Implantaten: Klinische und experimentelle Betrachtunable adjuncts to the regeneration of periodontal tissues.
gen des Konzepts der Osseointegration. Parodontologie, 1:307By means of recombinant human transforming
growth factor (31 (rhTGF-Pl) applied locally to skull Albrektsson,
T., and G.A. Zarb 1993 Current interpretations of the
defects in rabbits, Beck et al. (1993) were able to demosseointegrated response: Clinical significance. Int. J. Prosthodont., 6:95-105.
onstrate the ability of rhTGF-(31 to stimulate the reS., and K.M. Chung 1994 Clinical implications of cellular bicruitment and proliferation of local osteoblasts, al- Amar,
ologic advances in periodontal regeneration. Curr. Opin. Perithough remodelling rates were not altered. Similar
odontol., 128-140.
findings were obtained by Aufdemorte et al. (1993) by Awe. P., R.P. Ellen. C.M. Overall. and G.A. Zarb 1989 Microbiota and
crevicular fluid collagenase activity in the osseointegrated dental
means of experimental implants, the central compartimplant sulcus: A comparison of sites in edentulous and partially
ment of which could be loaded with TGF-(3 or control
edentulous patients. J. Periodont. Res., 24:96-105.
vehicle. Despite increased osteoblastic activity and, to Artzi,
Z., H. Tal, 0. Moses, and A. Kozlovsky 1993 Mucosal considera lesser extent, osteoclastic activity, the volume of traations for osseointegrated implants. J . Prosth. Dent., 70:427-432.
becular bone formed after 22 days of implantation in Aufdemorte, T.B., W.C. Fox,G.R. Holt, H.S. McGuff, A.J. Ammann,
and L.S. Beck 1993 An intraosseous device for studies of bonebaboon tibias was comparable to that in control imhealing. The effect of transforming growth factor beta. J . Bone
plants. TGF-P1 also is a promoter of osteoclastic activJoint Surg. [Am.] 74:1153-1161.
ity (Cochran et al., 1993). On the other hand, Selvig et Babbush, C.A., A. Kirsch, P.J. Mentag, and B. Hill 1987 Intramobile
al. (1994) failed to demonstrate any beneficial effect on
cylinder (IMZ) two-stage osteointegrated implant system with
the intramobile element (IME): Part I. Its rationale and procebone regeneration, as compared to control sites, when
dure for use. Int. J. Oral Maxillofac. Implants, 2:203-216.
experimentally created bone defects in dog mandibles
C.A., and C.A. Shimura 1993 Five-year statistical and clinwere treated with a topical application of a mixture of Babbush,
ical observationswith the IMZ two-stage osteointegrated implant
IGF-11, basic fibroblast growth factor (FGF), and transsystem. Int. J . Oral Maxillofac. Implants, 8:245-253.
forming growth factor (TGF-(31).These apparently dis- Barth, E., C. Johansson, and T. Albrektsson 1990 Histologic comparGROWTH FACTORS AND GTR
ison of ceramic and titanium implants in cats. Int. J . Maxillofac.
Implants, 5~227-231.
Bauman. G.R.. M. Mills, J.W. RaDlev. and W.W. Hallmom 1992
Plaoue-inducedi n f l a k a t i o n aioind imulants. Int. J . Oral Maxil1of;lc. Implants, 7:330-337.
Bauman, G.R., J.W. Rapley, W.W. Hallmon, and M. Mills 1993 The
peri-implant sulcus. Int. J. Oral Maxillofac.Implants, 8:273-280.
Beck. L.S.. E.P. Amento. Y. Xu. L. Dewman. W.P. Lee. T. Nrmven.
and N.A. Gillett 1993 TGF-beta <induces bone closure 07 skull
defects: Temporal dynamics of bone formation in defects exposed
to rhTGF-beta. J . Bone Miner. Res., 8:753-761.
Becker, W., C. Dahlin, B.E. Becker, U. Lekholm, D. van Steenberghe,
K. Higuchi, and C. Kultje 1994 The use of e-PTFE barrier membranes for bone promotion around titanium implants placed into
extraction sockets: A prospective multicenter study. Int. J. Oral
Maxillofac. Implants, 9:31-40.
Becker, W., S.E. Lynch, U. Lekholm, B.E. Becker, R. Caffesse, K.
Donath, and R. Sanchez 1992 A comparison of e-PTFE membranes alone or in combination with platelet-derived growth factors and insulin-like growth factor-I or demineralized freezedried bone in promoting bone formation around immediate
extraction socket implants. J. Periodontol., 63:929-940.
Berglundh, T., J. Lindhe, I. Ericsson, C.P. Marinello, B. Liljenberg,
and P. Thomsen 1991 The soft tissue barrier a t implants and
teeth. Clin. Oral Implants Res., 2331-90.
Berglundh, T., J. Lindhe, C. Marinello, I. Ericsson, and B. Liljenberg
1992 Soft tissue reaction to de novo plaque formation on implants
and teeth. An experimental study in the dog. Clin. Oral Implants
Res., 3:l-8.
Bidez, M.W., and C.E. Misch 1992 Issues in bone mechanics related to
oral implants. Implant Dent., 1:289-294.
Birkedal-Hansen, H., W.G.I. Moore, M.K. Bodden, L.J. Windsor, B.
Birkedal-Hansen, A. DeCarlo, and J.A. Engler 1993 Matrix metalloproteinases: A review. Crit. Rev. Oral Biol. Med., 4:197-250.
Bosch, F.X., J.P. Ouhayoun, B.L. Bader, C. Collin, C. Grund, I. Lee,
and W.W. Franke 1989 Extensive changes in cytokeratin expression patterns in pathologically affected human gingiva. Virchows
Arch. B. Cell. Pathol., 58:59-77.
Brimemark, P.-I., B.O. Hansson, R. Adell, U. Breine, J. Lindstrom, 0.
Hallen, and A. ohman 1977 Osseointegrated implants in the
treatment of the edentulous jaw. Experience from a 10-year period. Scand. J. Plast. Reconstr. Surg., 2(Suppl.):16.
Brhemark, P.-I., G.A. Zarb, and T. Albrektsson 1985 Tissue Integrated Prostheses. Osseointegration in Clinical Dentistry. Quintessence, Chicago.
Brunette, D.M., J. Ratkay, and B. Chehroudi 1991 Behaviour of osteoblasts on micromachined surfaces. In: The Bone-Biomaterial
Interface. J.E. Davies, ed. University of Toronto Press, Toronto,
pp. 170-179.
Brunski, J.B. 1991 Influence of biomechanical factors a t the bonebiomaterial interface. In: The Bone-Biomaterial Interface. J.E.
Davies, ed. University of Toronto Press, Toronto, pp. 391-404.
Buser, D. 1987 Die Vestibulumplastik mit freien Schleimhauttransplantaten bei Implantaten im zahnlosen Unterkiefer. Schweiz.
Monatschr. Zahnmed., 97:766-772.
Buser, D., B.K. Schenk, S. Steinemann, J.P. Fiorellini, C.H. Fox, and
H. Stich 1991a Influence of surface characteristics on bone integration of titanium implants. J . Biomed. Mater. Res., 25:889902.
Buser, D., H. Stich, G. Krekeler, and A. Schroeder 1989 Faserstrukturen der periimplantaren Mukosa bei Titanimplantaten. Eine
tierexperimentelle Studie am Beagel-Hund. Z. Zahnartzl. Implantol., 5: 15-23.
Buser, D., K. Warrer, and T. Karring 1990a Formation of a periodontal ligament around titanium implants. J. Periodontol., 61 :597601.
Buser, D., K. Warrer, T. Karring, and H. Stich 1990b Titanium implants with a true periodontal ligament: An alternative to osseointegrated implants? Int. J. Oral Maxillofac. Implants, 5:113116.
Buser, D., H.P. Weber, U. Bragger, and C. Balsiger 1991b Tissue
integration of one-stage IT1 implants: 3-year results of a longitudinal study with hollow-cylinder and hollow-screwimplants. Int.
J. Oral Maxillofac. Implants, 6~405-412.
Buser, D., H.P. Weber, and N.P. Lang 199Oc Tissue integration of
non-submerged implants. 1-year results of a prospective study
with 100 IT1 hollow-screw and hollow-cylinder implants. Clin.
Oral Implants Res., 1:33-40.
Buser, D., H.P. Weber, K. Donath, J.P. Fiorellini, D.W. Paquette, and
R.C. Williams 1992 Soft tissue reactions to non-submerged un-
loaded titanium implants in Beagle dogs. J. Periodontol.,63:226236.
Carlsson, L., T. Riistlund, B. Albrektsson, and T. Albrektsson 1988
Removal torques for polished and rough titanium implants. Int.
J . Oral Maxillofac. Implants, 3:21-24.
Caudill, R. 1993 Histologic analysis of the osseointegration of endosseous implants in simulated extraction sockets with and without
e-PTFE barriers. Part 11: Histomorphometric findings. J . Oral
Implantol., 19:209-215.
Clokie, C.M.L., and H. Warshawsky 1995 Morphologic and radioautographic studies of bone formation in relation to titanium implants using the rat tibia as a model. Int. J. Oral Maxillofac.
Implants, 10:155-165.
Cochran, D.L., C.A. Rouse, S.E. Lynch, and D.T. Graves 1993 Effects
of platelet-derived growth factor isoforms on calcium release from
neonatal mouse calvaria. Bone, 14:53-58.
Cochran, D.L., J . Simpson, H.-P. Weber, and D. Buser 1994 Attachment and growth of periodontal cells on smooth and rough titanium. Int. J. Oral Maxillofac. Implants, 9:289-297.
Dahlin, C., U. Lekholm, and A. Linde 1991 Membrane induced bone
augmentation of titanium implants. Int. J. Periodont. Rest.
Dent., 11:273-282.
Dao, T.T.T., J.D. Anderson, and G.A. Zarb 1993 Is osteoporosis a risk
factor for osseointegration of dental implants? Int. J. Oral Maxillofac. Implants, 8:137-144.
De Lange, G., and C. De Putter 1993 Structure of the bone interface
to dental implants in vivo. J. Oral Implantol., 19:123-135.
Deporter, D.A., P.A. Watson, R.M. Pilliar, T.P. Howley, and J. Winslow 1988 A histological evaluation of a functional endosseous,
porous-surfaced, titanium alloy dental implant system in the dog.
J. Dent. Res., 67:1190-1195.
Donley, T.G., and W.B. Gillette 1991 Titanium endosseous implantsoft tissue interface: A literature review. J. Periodontol., 62:153160.
Ericson, L.E., B.R. Johansson, A. Rosengren, L. Sennerby, and P.
Thomsen 1991 Ultrastructural investigation and analysis of the
interface of retrieved metal implants. In: The Bone-Biomaterial
Interface. J.E. Davies, ed. University of Toronto Press,Toronto,
pp. 425-436.
Ericsson, A.R., and T. Albrektsson 1983 Temperature threshold levels
for heat-induced bone tissue injury: A vital-microscopic study in
the rabbit. J. Prosthet. Dent., 5O:lOl-107.
Ericsson, I., T. Berglundh, C. Marinello, B. Liljenberg, and J. Lindhe
1992 Long-standing plaque and gingivitis at implants and teeth
in the dog. Clin. Oral Implants Res., 3:99-103.
Ericsson, I., and J. Lindhe 1993 Probing depth a t implants and teeth.
An experimental study in the dog. J. Clin. Periodontol., 20:623627.
Ettinger, R.L., J.D. Spivey, D.-H. Han, and G.F. Koorbusch 1993 Measurement of the interface between bone and immediate endosseous implants: A pilot study in dogs. Int. J. Oral Maxillofac.
Implants, 8:420-427.
Gher, M.E., G. Quintero, D. Assad, E. Monaco, and A.C. Richardson
1994a Bone grafting and guided bone regeneration for immediate
dental implants in humans. J . Periodontol., 65:881-891.
Gher, M.E., G. Quintero, J.B. Sandifer, M. Tabacco, and A.C. Richardson 1994b Combined dental implant and guided tissue regeneration therapy in humans. Int. J. Periodont. Rest. Dent., 14:
Gotfredsen, K., L. Nimb, D. Buser, and E. Hjorting-Hansen 1993
Evaluation of guided bone regeneration around implants placed
into fresh extraction sockets: An experimental study in dogs. J.
Oral Maxillofac. Surg., 71:879-884.
Gotfredsen, K., E. Rostrup, E. Hjorting-Hansen, K. Stoltze, and E.
BudtzJorgensen 1991 Histological and histomorphometrical
evaluation of tissue reactions adjacent to endosteal implants in
monkeys. Clin. Oral Implants Res., 2:30-37.
Gottlander, M., and T. Albrektsson 1991 Histomorphometric studies
of hydroxyapatite-coated and uncoated CP titanium threaded implants in bone. Int. J. Oral Maxillofac. Implants, 6:399-404.
Gottlander, M., T. Albrektsson, and L.V. Carlsson 1992 A histomorphometric study of unthreaded hydroxyapatite-coated and titanium-coated implants in rabbit bone. Int. J. Oral Maxillofac. Implants, 7:485-490.
Graves, D.T., and D.L. Cochran 1994 Periodontal regeneration with
polypeptide growth factors. Curr. Opin. Periodontol., 178-186.
Hammerle, C.H., J. Schmid, N.P. Lang, and A.J. Olah 1995 Temporal
dynamics of healing in rabbit cranial defects using guided bone
regeneration. J. Oral Maxillofac. Surg., 53:167-174.
Hassell, T.M. 1993 Tissues and cells of the periodontiurn. In: Peri-
odontal TissuesCtructure and Function. Periodontology 2000,
Vol. 3. T.M. Hassell, ed. pp. 9-38. Munksgaard, Copenhagen.
HeRi, A.F. 1993 Aspects of cell biology of the normal periodontium.
In: Periodontal Tissues-Structure and Function. Periodontology
2000, Vol. 3. T.M. Hassell, ed. pp. 64-75. Munksgaard, Copenhagen.
Hertel, R.C., P.A. Blijdorp, W. Kalk, and D.L. Baker 1994 Stage 2
surgical techniques in endosseousimplantation. Int. J. Oral Maxillofac. Implants, 9:273-278.
James, R.A., and R.L. Schultz 1974 Hemidesmosomesand the adhesion of junctional epithelial cells to metal implants-a preliminary report. Oral Implantol., 4:294-302.
Johansson, C., J. Lausmaa, M. Ask, H.A. Hansson, and T. Albrektsson
1989 Ultrastructural differences of the interface zone between
bone and Ti6A14V or commercially pure titanium. J. Biomed.
Eng., lr3-8.
Johansson, C.B., and T. Albrektsson 1991 A removal torque and histomorphometric study of commercially pure niobium and titanium implants in rabbit bone. Clin. Oral Implants Res., 2:24-29.
Johansson, C.B., L. Sennerby, and T. Albrektsson 1991 A removal
torque and histomorphometric study of bone tissue reactions to
commerciallypure titanium and vitallium implants. Int. J. Oral
Maxillofac. Implants, 6:437-441.
Jovanovic, S.A., E.B. Kenney, F.A. Carranza, Jr., and K. Donath 1993
The regenerative potential of plaque-induced peri-implant bone
defects treated by a submerged membrane technique: An experimental study. Int. J . Oral Maxillofac. Implants, 8:13-18.
Jovanovic, S.A., R.K. Schenk, M. Orsini, and E.B. Kenney 1995 Supracrestal bone formation around dental implants: an experimental dog study. Int. J. Oral Maxillofac. Implants, 10:23-31.
Jovanovic, S.A., H. Spiekermann, and E.J. Richter 1992 Bone regeneration around titanium dental implants in dehisced defect sites:
A clinical study. J . Oral Maxillofac. Implants, 7~233-245.
Karring, T., S. Nyman, J. Gottlow, and L. Laurel1 1993 Development
of the biologic concept of guided tissue regeneration-animal and
human studies. In: Periodontal Regeneration. Periodontology
2000, Vol. 1. J.G. Caton, ed. pp. 26-35.
Kiritsy, C.P., and S.E. Lynch 1993 Role of growth factors in cutaneous
wound healing: A review. Crit. Rev. Oral Biol. Med., 4:726-760.
Kohn, D.H. 1992 Overview of factors important in implant design. J.
Oral Implantol., 18~204-219.
Lang, N.P., U. Bragger, C.H. Hammerle, and F. Sutter 1994a Immediate transmucosal implants using the principle of guided tissue
regeneration. I. Rationale, clinical procedures and 30-month results. Clin. Oral Implants Res., 5~154-163.
Lang, N.P., U. Bragger, D. Walther, N. Beamer, and K.S. Kornman
1993 Ligature-induced pen-implant infection in cynomolgus
monkeys. I. Clinical and radiographic findings. Clin. Oral Implants bs., 4:2-11.
Lang, N.P., C.H. Hammerle, U. Bragger, B. Lehmann, and S.R. Nyman 1994b Guided tissue regeneration in jawbone defects prior to
implant placement. Clin. Oral Implants Res., 5:92-97.
Lekholm, U., R. Adell, J. Lindhe, P.-I. Brinemark, B. Eriksson, B.
Rockler, A.-M. Lindvall, and T. Yoneyama 1986 Marginal tissue
reactions at osseointegratedtitanium fixtures. 11. Cross-sectional
retrospective study. Int. J. Oral Maxillofac. Surg., 15:53-61.
Lekholm, U., W. Becker, C. Dahlin, B. Becker, K. Donath, and E.
Morrison 1993 The role of early versus late removal of GTAM
membranes on bone formation a t oral implants placed into immediate extraction sockets. Clin. Oral Implants Res., 4:121-129.
Lemons, J.E., and M.W. Bidez 1991 Endosteal implant biomaterials
and biomechanics. In: Endosteal Dental Implants. R. V. McKinney, Jr., ed. Mosby, St. Louis, pp. 27-36.
Linde, A., P. Alberius, C. Dahlin, K. Bjurstam, and Y. Sundin 1993
Osteopromotion:A soft-tissue exclusion principle using a membrane for bone healing and bone neogenesis. J. Periodontol., 64:
Linder, L. 1989 Osseointegration of metallic implants. I. Light microscopy in the rabbit. Acta Orthop. Scand., 60:129-134.
Linder, L., T. Albrektsson, P.4. Brinemark, H.-A. Hansson, B. Ivarsson, U. Jonsson, and I. LundstrGm 1983 Electron microscopic analysis of the bone-titanium interface. Acta Orthop. Scand., 54:4552.
Linder, L., K. Obrant, and G. Boivin 1989 Osseointegration of metallic implants. 11. Transmission electron microscopy in the rabbit.
Acta Orthop. Scand., 60:135-139.
Lindhe, J., T. Berglundh, I. Ericsson, B. Liljenberg, and C. Marinello
1992 Experimental breakdown of peri-implant and periodontal
tissues. A study in the beagle dog. Clin. Oral Implants Res., 3:916.
Listgarten, M.A. 1972a Normal development structure, physiology
and repair of gingival epithelium. Oral Sci. Rev., 1:3-68.
Listgarten, M.A. 1972b Ultrastructure of the dento-gingivaljunction
after gingivectomy. J. Periodont. Res., 7:151-160.
Listgarten, M.A. 1986 Pathogenesis of periodontitis. J. Clin. Periodontol., 13:418-425.
Listgarten, M.A., D. Buser, S.G. Steinemann, K. Donath, N.P. Lang,
and H.P. Weber 1992 Light and transmission electron microscopy
of the intact interfaces between non-submerged titanium-coated
epoxy resin implants and bone or gingiva. J. Dent. Res., 71:364371.
Listgarten, M.A., and C.-H. Lai 1975 Ultrastructure of the intact
interface between an endosseous epoxy resin dental implant and
the host tissue. J. Biol. Buccale, 3:13-28.
Listgarten, M.A., N.P. Lang, H.E. Schroeder, and A. Schroeder 1991
Periodontal tissues and their counterparts around endosseousimplants. Clin. Oral Implants Res., 2:l-19.
Listgarten, M.A., S. Rosenberg, and S. Lerner 1982 Progressive replacement of epithelial attachment by a connective tissue junction after experimental periodontal surgery in rats. J. Periodontol., 53:659-670.
Lum, L.B., O.R. Beirne, and D.A. Curtis 1991 Histologicevaluation of
hydroxyapatite-coated versus uncoated titanium blade implants
in delayed and immediately loaded applications. Int. J. Oral Maxillofac. Implants, 6:456-462.
Lundgren, D., L. Sennerby, H. Falk, B. Friberg, and S. Nyman 1994
The use of a new bioresorbable barrier for guided bone regeneration in connection with implant installation. Case reports. Clin.
Oral Implants Res., 5:177-184.
Lynch, S. 1994 The role of growth factors in periodontal repair and
regeneration. In: Periodontal Regeneration. Current Status and
Directions. A.M. Polson, ed. Quintessence,Chicago, pp. 179-198.
Lynch, S., D. Buser, R.A. Hernandez, H.P. Weber, H. Stich, C.H. Fox,
and R.C. Williams 1991 Effects of the platelet-derived growth
factor/insulin-like growth factor-I combination on bone regeneration around titanium dental implants. Results of a pilot study in
beagle dogs. J . Periodontol., 62:710-717.
Mackenzie, I.C. 1988 Factors influencing the stability of the gingival
sulcus. In: Periodontology Today. B. Guggenheim, ed. S. Karger,
Basel, pp. 41-49.
Mackenzie, I.C., and N.E. Fusenig 1983 Regeneration of organized
epithelial structure. J . Invest. Dermatol.. 81:1899-194s.
Mackknzie, I.C., and M.W. Hill 1984 Connectbe tissue influences on
patterns of epithelial architecture and keratinization in skin and
oral mucosa of the adult mouse. Cell Tissue Res., 235~551-559.
Mackenzie, I.C., G. Rittman, Z. Gao, I. Leigh, and E.B. Lane 1991
Patterns of cytokeratin expression in human gingival epithelium. J. Periodont. Res., 26:468-478.
McCulloch, C.A.G. 1993 Basic considerations in periodontal wound
healing to achieve regeneration. In: Periodontal Regeneration.
Periodontology 2000, Vol. 1. J.G. Caton, ed. pp. 16-25. Munksgaard, Copenhagen.
McKee, M.D., and A. Nanci 1993 Ultrastructural, cytochemical and
immunocytochemicalstudies on bone and its interfaces. Cells and
Materials, 3:219-243.
Nanci, A., G.F. McCarthy, S. Zalzal, C.M.L. Clokie, H. Warshawsky,
and M.D. McKee 1994 Tissue response to titanium implants in
the rat tibia: Ultrastructural, immunocytochemical and lectincytochemical characterization of the bone-titanium interface.
Cells and Materials, 4:l-30.
Niki, M., G. Ito, T. Matsuda, and M. Ogino 1991 Comparative pushout data of bioactive and non-bioadive materials 6f similar rugosity. In: The Bone-Biomaterial Interface. J.E. Davies, ed. University of Toronto Press, Toronto, pp. 350-356.
Nishibori, M., N.J.Betts, H. Salama, and M.A. Listgarten 1994 Shortterm healing of autogenous and allogeneic bone grafts after sinus
lifting: A report of two cases. J. Periodontol., 65:958-966.
Nystrom, E., K.-E. Kahnberg, and T. Albrektsson 1993 Treatment of
the severely resorbed maxillae with bone graft and titanium implants: Histologic review of autopsy specimens. Int. J. Oral Maxillofac. Implants, 8:167-172.
O’Neal, R.B., J.J. Sauk, and M.J. Somerman 1992 Biological requirements for material integration. J. Oral Implantol., 18:243-255.
ONeal, R., H.-L. Wang, R.L. MacNeil, and M.J. Somerman 1994 Cells
and materials involved in guided tissue regeneration. Curr. Opin.
Periodontol., 141-156.
Page, R.C., and H.E. Schroeder 1982 Periodontitis in Man and Other
Animals: A Comparative Review. S. Karger, Basel.
Palmer, R.M., P.D. Floyd, P.J . Palmer, B.J. Smith, C.B. Johansson,
and T. Albrektsson 1994 Healing of implant dehiscence defects
with and without expanded polytetrafluoroethylene membranes:
A controlled clinical and histological study. Clin. Oral Implants
Res., 5:98-104.
Parr, G.R., D.E. Steflik, and A.L. Sisk 1993 Histomorphometric and
histologic observations of bone healing around immediate implants in dogs. Int. J. Oral Maxillofac. Implants, 8:534-540.
Piatelli, A,, A. Ruggeri, M. Franchi, N. Romasco, and P. Risi 1993a An
histologic and histomorphometric study of bone reactions to unloaded and loaded non-submerged single implants in monkeys: A
pilot study. J . Oral Implantol., 19:314-319.
Piatelli, A,, P. Trisi, N. Romasco, and M. Emanuelli 199313 Histologic
analysis of a screw implant retrieved from man: Influence of
early loading and primary stability. J. Oral Implantol., 19:303306.
Pilliar, R.M. 1991 Quantitative evaluation of the effect of movement
at a porous coated implant-bone interface. In: The Bone-Biomaterial Interface. J.E. Davies, ed. University of Toronto Press, Toronto, pp. 380-386.
Quirynen, M., C.M.L. Bollen, H. Eyssen, and D. van Steenberghe
1994 Microbial penetration along the implant components of the
Brlnemark system@.An in vitro study. Clin. Oral Implants Res.,
Quirynen, M., and D. van Steenberghe 1993 Bacterial colonization of
the internal part of two-stage implants. An in vivo study. Clin.
Oral Implants Res., 5:239-244.
Rahal, M.D., P.-I. Brhnemark, and D.G. Osmond 1993 Response of
bone marrow to titanium implants: Osseointegration and the establishment of a bone-marrow-titanium interface in mice. Int. J .
Oral Maxillofac. Implants, 8~573-579.
Ripamonti, U., M. Heliotis, B. van den Heever, and A.H. Reddi 1994
Bone morphogenetic proteins induce periodontal regeneration in
the baboon (Pupio ursinus). J . Periodont. Res., 29:439-445.
Roberts, W.E. 1993 Fundamental principles of bone physiology, metabolism and loading. In: Osseointegration in Oral Rehabilitation. I. Naert, D. van Steenberghe, P. Worthington, eds. Quintessence, London, pp. 157-170.
Roberts, W.E., K.J. Marshall, and P.G. Mozsary 1989 Rigid endosseous implant utilized as anchorage to protract molars and close
an atrophic extraction site. Angle Orthod., 60:135-152.
Roberts, E.W., L.C. Poon, and R.K. Smith 1986 Interface histology of
rigid endosseous implants. Oral Implantol., 12:406-416.
Roberts, W.E., K.E. Simmons, L.P. Garetto, and R.A. DeCastro 1992
Bone physiology and metabolism in dental implantology: risk factors for osteoporosis and other metabolic bone diseases. Implant.
Dent., 1:11-21.
Roberts, W.E., R.K. Smith, Y. Zilberman, P.G. Mozsary, and R.S.
Smith 1984 Osseous adaptation to continuous loading of rigid
endosseous implants. Am. J . Orthod., 86:95-111.
Rominger J.W., and R.G. Triplett 1994 The use of guided tissue regeneration to improve implant osseointegration. J . Oral Maxillofac. Surg., 52:106-112.
Sailer, H.F., and E. Kolb 1994 Application of purified bone morphogenetic protein (BMP) on cranio-maxillo-facial surgery. BMP in
compromised surgical reconstructions using titanium implants.
J. Craniomaxillofac. Surg., 22:2-11.
Schenk, R.K., D. Buser, W.R. Hardwick, and C. Dahlin 1994 Healing
pattern of bone regeneration in membrane-protected defects: A
histological study in the canine mandible. Int. J . Oral Maxillofac.
Implants, 9:13-29.
Schou, S., P. Holmstrup, E. Hjorting-Hansen, and N.P. Lang 1992
Plaque-induced marginal tissue reactions of osseointegrated oral
implants: A review of the literature. Clin. Oral Implants Res.,
Schou, S., P. Holmstrup, K. Stoltze, E. Hjorting-Hansen, and K.S.
Kornman 1993 Ligature-induced marginal inflammation around
osseointegrated implants and ankylosed teeth. Clin. Oral Implants Res., 4:12-22.
Schroeder, A,, 0. Pohler, and F. Sutter 1976 Gewebereaktion auf ein
Titan-Hohlzvlinderimplantatmit Titan-Spritzschichtoberflache.
Schweiz. M6natszeitsihr. Zahnheilk., 86:?13-727.
Schroeder, A., F. Sutter, and G. Krekeler 1991 Oral Implantology.
Georg Thieme Verlag, Stuttgart.
Schroeder, A., E. van der Zypen, H. Stich, and F. Sutter 1981 The
reaction of bone, connective tissue and epithelium to endosteal
implants with sprayed titanium surfaces. J. Maxillo. Fac. Surg.,
9: 15-25.
Schroeder, H.E. 1986 The periodontium. In: Handbook of Microscopic
Anatomy, Vol 5. Springer-Verlag, Berlin.
Schroeder, H.E. 1991 Oral Structural Biology. George Thieme Verlag,
Schroeder, H.E., and M.A. Listgarten 1977 Fine structure of the developing epithelial attachment of human teeth. In: Monographs
in Developmental Biology, 2nd ed. A. Wolsky, ed. S. Karger,
Schiipbach, P., M. Hiirzeler, and U. Grunder 1994 Implant-tissue interfaces following treatment of periimplantitis using guided tissue regeneration. A light and electron microscopic study. Clin.
Oral Implants Res., 5:55-65.
Seibert, J., and S. Nyman 1990 Localized ridge augmentation in dogs:
A pilot study using membranes and hydroxyapatite. J . Periodontol., 61:157-165.
Selvig, K.A., U.M. Wikesjo, G.C. Bogle, and R.D. Finkelman 1994
Imuaired early bone formation in Deriodontal fenestration defects
in dogs following application of ihsulin-like factor (11). Basic fibroblast growth factor and transforming growth factor beta 1.J.
Clin. Periodontol., 21:380-385.
Sennerby, L., L.E. Ericson, P. Thomsen, U.Lekholm, and P. Astrand
1991 Structure of the bone-titanium interface in retrieved clinical oral implants. Clin. Oral Implants Res., 2~103-111.
Sennerby, L., P. Thomsen, and L.E. Ericson 1992 A morphometric and
biomechanic comparison of titanium implants inserted in rabbit
cortical and cancellous bone. Int. J. Oral Maxillofac. Implants,
Shanaman, R.H. 1994 A retrospective study of 237 sites treated consecutively with guided tissue regeneration. Int. J. Periodont.
Rest. Dent., 14:293-302.
Sharf, D.R., and D.P. Tarnow 1993 Success rates of osseointegration
for implants placed under sterile versus clean conditions. J . Periodontol., 64:954-956.
Skalak, R. 1983 Biomechanical considerations in osseointegrated
prostheses. J. Prosthet. Dent., 49:843-848.
Smith, D.C. 1993 Dental implants: Materials and design considerations. Int. J. Prosthodont., 6:106-117.
Smith, K.G., C.D. Franklin, R. van Noort, and D.J. Lamb 1992 Tissue
response to the implantation of two new machinable calcium
phosphate ceramics. Int. J . Oral Maxillofac. Implants, 7:395400.
Steflik, D.E., P.J. Hanes, A.L. Sisk, G.R. Parr, M.J. Song, F.T. Lake,
and R.V. McKinney 1992a Transmission electron microscopic and
high voltage electron microscopic observations of the bone and
osteocyte activity adjacent to unloaded dental implants placed in
dogs. J. Periodontol., 63:443-452.
Steflik, D.E., G.R. Parr, A.L. Sisk, P.J. Hanes, and F.T. Lake 199213
Electron microscopy of bone response to titanium cylindrical
screw-type endosseous dental implants. Int. J. Oral Maxillofac.
Implants, 7:497-507.
Steflik. D.E.. A.L. Sisk, G.R. Parr. L.K. Gardner. P.J. Hanes, F.T.
Lake, D.J. Berkery, and P. Brewer 1993a Osteogenesis at the
dental implant interface: high-voltage electron microscopic and
conventional transmission electron microscopic observations. J.
Biomed. Mater. Res., 27:791-800.
Steflik, D.E., A.L. Sisk, G.A. Parr, F.T. Lake, and P.J. Hanes 1993b
Experimental studies of the implant-tissue interface. J. Oral Implantol., 19:90-94.
Teerlinck, J., M. Quirynen, P. Darius, and D. van Steenberghe 1991
Periotest: An objective clinical diagnosis of bone apposition toward implants. Int. J. Oral Maxillofac. Implants, 6:55-61.
ten Bruggenkate, C.M., G. Krekeler, W.A.M. van der Kwast, and H.S.
Oosterbeek 1990 Palatal mucosal grafts for oral implant devices.
In: Clinical and Radiological Aspects of Oral Implants, With Special Emphasis on the I.T.I. Hollow Cylinder Implant. C.M. ten
Bruggengate, ed. Thesis, Free University of Amsterdam. Pasmans, Gravenhage, pp. 49-58.
Teranobu, O., I. Naito, N. Takahashi, M. Fujiwara, K. Iwata, M.
Umeda, K. Shimada, K. Kurioka, H. Kawamoto, K. Shimada, and
T. Kawai 1989 The influence of sintering condition and surface
shape of hydroxyapatite ceramics for the osteoconductivity. In:
Oral Implantology and Biomaterials, Progress in Biomedical Engineering, Vol. 7. H. Kawhara, ed. Elsevier, New York, pp. 233238.
Wang, H.L., T.D. Pappert, W.A. Castelli, D.J. Chiego, Jr., Y. Shyr,
and B.A. Smith 1994 The effect of platelet-derived growth factor
on the cellular response of the periodontium: An autoradiographic study on dogs. J. Periodontol., 65:429-436.
Warrer, K., K. Gotfredsen, E. Hjorting-Hansen, and T. Karring 1991
Guided tissue regeneration ensures osseointegration of dental
implants placed into extraction sockets. An experimental study
in monkeys. Clin. Oral Implants Res., 2:166-171.
Warrer, K., T. Karring, and K. Gotfredsen 1993 Periodontal ligament
formation around different types of dental titanium implants. I.
The self-tapping screw type implant system. J . Periodontol., 64:
Wehrbein, H., and P. Diedrich 1993 Endosseous titanium implants
during and after orthodontic load-an experimental study in the
dog. Clin. Oral Implants Res., 4:76-82.
Weinlaender, M., E.B. Kenney, V. Lekovik, J. Beumer, P.K. Moy, and
S. Lewis 1992Histomorphometry of bone apposition around three
types of endosseous dental implants. Int. J . Oral Maxillofac. Implants, 7:491-496.
Weiss, C.M. 1986 Tissue integration of dental endosseous implants:
Description and comparative analysis of the fibrosseous integration and osseous integration systems. J . Oral Implantol., 12:169214.
Wennstrom, J.L., F.Bengazi, and U. Lekholm 1994 The influence of
the masticatory mucosa on the peri-implant so& tissue condition.
Clin. Oral Implants Res., 5:l-8.
Wilke, H.J., L. Claes, and S. Steinemann 1990 The influence of various titanium surfaces on the interface shear strength between
implants and bone. In: Clinical Implant Materials, Advances in
Biomaterials, Vol. 9.Elsevier, New York, pp. 309-314.
Zablotsky, M., R.Meffert, R. Caudill, and G. Evans 1991 Histological
and clinical comparisons of guided tissue regeneration on dehisced hydroxylapatite-coated and titanium endosseous implant
surfaces: A pilot study. Int. J. Oral Maxillofac. Implants, 6.294303.
Zablotsky, M.H. 1992 Hydroxyapatite coatings in implant dentistry.
Implant Dent., 1.253-257.
Без категории
Размер файла
2 214 Кб
Пожаловаться на содержимое документа