Osseointegration: Experimental Background & Clinical Dentistry

RESEARCH AND EDUCATION
SECTION
EDITOR
LOUIS J. BOUC:HER
Osseointegration and its experimental background
Per-Ingvar
University
Brinemark,
M.D., Ph.D.*
of G6teborg and Institute for Applied Biotechnology, Gateborg, Sweden
0
sseointegration in clinical dentistry depends on an
understanding o:f the healing and reparative capacities
of hard and soft tissues. Its objective is a predictable
tissue response to the placement of tooth root analogues. Such a response must be a highly differentiated
one, and one that becomes organized according to
functional dema:nds. Since 1952, we have studied the
concept of tissue4ntegrated prostheses at the Laboratory of Vital Microscopy at the University of Lund, and
subsequently at the Laboratory for Experimental Biology at the University of GGteborg. Our collaborators in
this research have included representatives from medical and dental faculties, various research institutes, and
departments of technology. The basic aim has been to
define limits for clinical implantation procedures that
will allow bone and marrow tissues to heal fully and
remain as such, rather than heal as a low differentiated
scar tissue with unpredictable sequelae. The studies
involved analyses of tissue injury and repair in diverse
sites in different animals, with particular reference to
microvascular structure and function. Special emphasis
was placed on analyzing the disturbances caused in the
intravascular rhelology of blood by means of a series of
different methodological approaches. The objective of
this article is a brief review of the various investigations that have led to the clinical application of osseointegration.
CONCEPT
DEVELOPMENT
The initial concept of osseointegration stemmed
from vital microscopic studies of the bone marrow of
the rabbit fibula., which was uncovered for visual
inspection in a modified intravital microscope at high
resolution in accordance with a very gentle surgical
preparation technique. With special instrumentation,
the marrow could be studied in transillumination in
vivo, and in situ, after the covering bone was ground
Presented at the Toronto Conference on Osseointegration in Clinical
Dentistry, Toronto, Ont., Canada, and the Academy of Denture
Prosthetics, San Diego, Calif.
*Professor and Head, Laboratory of Experimental Biology, Department of Anatomy.
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down to a thickness of only 10 to 20 pm. Circulation
was maintained in this thin layer of bone and with very
few signs of microvascular damage, which is the
earliest and most sensitive indication of tissue injury.
These intravascular studies of bone marrow circulation
also revealed the intimate circulatory connection
among marrow, bone, and joint tissue compartments.
Subsequent studies of the regeneration of bone and
marrow emphasized the close functional connection
between marrow and bone in the repair of bone
defects.
We, therefore, performed a series of in vivo studies
on bone, marrow, and joint tissue with particular
emphasis on tissue reaction to various kinds of injury:
mechanical, thermal, chemical, and rheologic. We were
also concerned with the various therapeutic possibilities to minimize the effect of such trauma. Aiming at a
restitution ad integrum, we further sought to identify
additional traumatic factors such as wound disinfectants and to explore the development of procedures that
promote predictable healing of differentiated tissues.
We also performed long-term in vivo microscopic
studies of bone and marrow response to implanted
titanium chambers of a screw-shaped design. These
studies in the early 1960s strongly suggested the
possibility of osseointegration since the optical chambers could not be removed from the adjacent bone once
they had healed in. We observed that the titanium
chambers were inseparably incorporated within the
bone tissue, which actually grew into very thin spaces
in the titanium. Interdisciplinary clinical cooperation
with plastic surgeons and otolaryngologists enabled us
to study the repair of mandibular defects and replacement of ossicles by means of autologous bone grafts.
Desired anatomic shapes of bone grafts were preformed in rabbits and dogs and subsequently applied
clinically with long-term follow-up. In an extensive
series, the repair of major mandibular and tibia1 defects
in dogs was studied. Various procedures were used,
with the most successful being the one based on the
prior integration of titanium fixtures on both sides of
the defect to be created later. When the fixtures had
become safely incorporated within the bone, a defect
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Fig. 1. A, Schematic representation of experimental defects in mandible and tibia in
dog that were reconstructed by means of autologous marrow and spongious bone grafts
stabilized by titanium splints secured to osseointegrated fixtures in both sides of defect.
B, Topography of lower leg in dog at time of resection of tibia. Two lateral tibia1
stabilizers were used. Periosteum was completely removed in area of defect. C,
Reconstructed tibia 3 years later with stabilizers removed. D, Radiograph illustrates
anatomy of stabilizing-fixtures and splints.
was created, the topographical relation between the cut
edges was maintained by titanium splints, and the
tissue defect was compensated for by an autologous
graft of trabecular bone and marrow (Figs. 1 and 2).
Separate studies were performed on the healing and
anchorage stability of titanium tooth root implants or
fixtures of various sizes and designs. We found that
when such an implant was introduced into the marrow
cavity, and following an adequate immobilized healing
period, a shell of compact cortical bone was formed
around the implant without any apparent soft tissue
intervention between normal bone and the surface of
the implant (Fig. 3).
We observed a direct correlation among microtopography of the titanium surface, the absence of contamination, the preparatory handling of the bone site, and
the histologic pattern elicited in the adjacent bone. In a
separate study, fixtures were installed in the tail
vertebrae of dogs with successful integration even when
abutments were allowed to pierce through the skin.
On the basis of the findings in these experimental
studies, we decided to perform a series of experiments
that would enable us to develop clinical reconstructive
procedures for the treatment of major mandibular
defects, including advanced edentulous states. It was
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felt that both osseointegration and autologous bone
grafts would be useful in these clinical defect situations.
Teeth were extracted in dogs and replaced by
osseointegrated screw-shaped titanium implants (Fig.
4). Fixed prostheses were connected after an initial
healing time of 3 to 4 months without loading (Fig. 5).
In this manner, the fixtures were allowed to heal under
a mucoperiosteal flap, which was then pierced for
abutment connection and subsequent prosthetic treatment.
The anterior teeth, including the canines, were
usually retained and the premolars and first molars
removed. Different types of prosthetic designs were
used; we started with a design similar to the one used
for complete dentures and ended up with a gold
porcelain fixed prosthesis (Fig. 6). Radiologic and
histologic analyses of the anchoring tissues showed that
integration could be maintained for 10 years in dogs
with maintained healthy bone tissue and without
progressive inflammatory reactions.
At the time the animals were killed, the titanium
fixtures could not be removed from the host bone unless
cut away. The anchorage capacity of the separate
implants was determined as 100 kg in the lower jaw
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Fig. 2. A, Experimental defect in dog’s mandible reconstructed with stabilizing buccal
antcllingual titanium splints and autologous marrow and spongious bone graft anchored
to integrated fixtures. B, Reconstructed area 6 months later.
Fig. 3. A to C, Experimental titanium fixture incorporated in dog’s tibia illustrating
new bone formation around fixture in medullary cavity.
and 30 to 50 kg in the upper jaw. Efforts to extract the
implants led to fractures in the jaw bone per se, not at
the actual interface. Microradiographic
analyses
revealed load-related remodeling of the jaw bone
around the implant, even in those cases where the
implants were in very close proximity to the nasal and
sinus mucoperiosteum at installation.
In order to reconstruct severely resorbed edentulous
jaws, we developed a special grafting procedure. It was
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based on preformation of the graft at the donor site to
the desired anatomy. At the same time, we integrated
fixtures in the graft-to-be. The bone graft was made
to adapt to the required anatomy within a titanium
mold. Donor sites were tibiae and ribs of rabbits and
dogs.
These long-term experimental studies suggested the
possibility of achieving and maintaining bone anchorage under unlimited loading of dental prostheses in the
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Fig. 4. A, In first experimental studies, a combination of subperiosteal and transosseous
titanium implants was used. This was found to provide anchorage but also uncontrolled
soft tissue reactions. Therefore, separate screw-shaped titanium fixtures were developed,
B, which were finally designed after experimental evaluation of about 50 different types
of implants.
Fig. 5. Diagrammatic representation of main steps and procedures for anchorage of a
prosthesis to osseointegrated jaw bone fixtures. A, Preoperative situation. B, Fixture
installed and covered by mucoperiosteal tissues. C, Abutment connected to fixture after a
healing period. D and E, Prosthesis attached to abutment.
dog attached to osseointegrated fixtures. Soft tissue
penetration of titanium abutments could be used without untoward reactions in edentulous jaws, and also for
the attachment of‘titanium chambers for vital microscopy in rabbit and dog tibiae.
We carried out vital microscopic studies on human
microcirculation and intravascular behavior of blood
cells at high resolution by means of an implanted
optical titanium chamber in a twin-pedicled skin tube
on the inside of the left upper arm of healthy volunteers. The tissue reaction as revealed by intravascular
rheologic phenomena was studied in long-term experiments in these chambers without indications of inflammatory processes. It, therefore, seemed reasonable to
assume that bone anchorage according to the principle
of osseointegration might also work in humans, and we
treated our first edentulous patients in 1965.
In those edentulous jaws where the remaining bone
was inadequate for fixture anchorage, a composite
reconstruction procedure was developed.
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A procedure of preformation was applied with the
proximal metaphysis of the tibia used as the donor site.
The combination of preformed grafts with integrated
fixtures provided good long-term clinical results.
Immediate autologous bone and marrow grafts are now
being tried; and our longitudinal experiences indicate
that with an extremely careful prosthodontic procedure, immediate bone grafts can also provide good
long-term results. They have the advantage of requiring only one major surgical procedure as compared to
two for the preformed graft, but the disadvantage of
less predictable survival of the grafted bone.
In those patients in whom the loss of jaw bone is not
limited to the alveolus but also includes a discontinuity
of the jaw bone, a preformed autologous bone graft
from the iliac bone has been used and has provided
good, predictable, long-term results. In accordance
with the same basic principle as for preformed alveolar
bone grafts, the desired graft is prepared in the iliac
bone with a few connections left to the compact bone
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Fig. 6. A, Edentulous upper and lower jaw in a dog with three fixtures integrated in
each jaw. B, An acrylic resin prosthesis. C, A chrome-cobalt superstructure. D, Two
fix,tures support a prosthesis made of porcelain baked to metal with molar tooth as a
cantilevered abutment.
and the marrow tissue. The graft-to-be is partly
surrounded by a. titanium mold and a titanium foil.
Fixtures are installed in two directions to produce
anchorage for a splint connecting the graft to the
remaining part of the mandible and to provide anchorage for a fixed partial denture. Clinical long-term
follow-up has shown that the grafted bone remains in
its prepared shape even in the articular region.
OSSEOINTEGRATION IN
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The edentulous jaw is a typical example of a tissue
defect that causes different degrees of functional disturbances. A well-fitting denture appears to be an acceptable alternative to natural teeth as long as the anatomy
of the residual hard and soft tissues provides good
retention for the prosthesis. Progressive loss of alveolar
bone tends to undermine the relative stability of the
denture and can create severe problems of both a
functional and psychosocial nature (Fig. 7).
Different procedures have been advocated to anchor
dental prostheses in the soft or hard tissues of the
edentulous mouth. However, long-term clinical follow-
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ups indicate that such procedures do not provide
predictable and good long-term function. Attempts at
anchoring an implant by means of a regenerated
fibrous tissue layer forming a simulated periodontal
ligament have also been unsuccessful. It has been stated
in bone reconstruction literature that direct anchorage
to living bone of load-bearing implants does not work
in the long run. Contrary to this concept, we now
suggest that the edentulous jaw can be provided with
jaw bone-anchored prostheses according to the principle of osseointegration with good and predictable
long-term prognosis.
Orthopedic reconstructions that use nonbiologic
prosthetic materials frequently rely on implant anchorage by a space filler of so-called bone cement: methyl
methacrylate. The induced surgical and chemical trauma results in death of osteocytes at the anchorage
interface. After an initial period of adequate implant
retention, the damaged bone becomes resorbed and the
implant is subsequently kept in place only by low
differentiated soft tissue, a kind of scar tissue.
The implant is then separated from healthy bone by
a soft tissue layer, which provides inadequate reten-
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Fig. 7. Radiographs of main types of resorption anatomy in patients comprising our
clinical material. A, Orthopantomogram showing advanced resorption. B, Profile
radiogram showing extreme resorption. C, D, and E, Typical progressive bone loss in
edentulous jaw at 5-year interval. F, Diagrammatic representation of lower jaw morphology corresponding to jaw bone topography represented in C and E, respectively.
Fig. 8. Schematic representation of anchorage unit
based on principle of screw-connected components: fixture, abutment, and center screw for
prosthesis attachment. Apical part of titanium fixture is designed to cut and thread bottom of fixture site.
tion as well as shielding of the surrounding bone from
the load stimulus required for adequate bony remodeling and maintenance. This will also occur even if the
preparation of the implant site provides adequate
anatomic congruence between the geometry of the
implant and the bone site since both surgical and
immediate loading trauma will lead to the formation of
a thin layer of connective tissue at the bone-implant
interface. In a long-term context, such an interface
constitutes a locus minoris resistentiae that allows
small relative movements between implant and bone.
This suggests a risk of inflammatory reactions and a
propagation of bacteria and their products from the
oral cavity to the anchorage region if the implant is
connected to an abutment that pierces skin or mucous
membrane. On the other hand, the osseointegrated
implant is directly connected to living remodeling bone
without any intermediate soft tissue component; therefore, it provides directly transferred loads to the
anchoring bone. The decisive problem is to allow bone
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Fig. 9. A, Radiograph of a lower jaw fixture that, together with three other fixtures, has
supported a full arch prosthesis for 17 years. B, Densitometric
profile measured along
dashed line (Kontron
IBAS image analysis system, Munich, West Germany). An
important feature is “condensation”
of bone toward interface zone.
C
2
6
1
7
a
Fig. 10. Diagrammatic representation
of biology of osseointegration.
A, Threaded bone
site cannot be made perfectly congruent to implant. Object of making threaded socket in
bo’ne is to provide immobilization
immediately
after installation
and during initial
healing period. Diagram is based on relative dimensions of fixture and fixture site.
2 = hematoma in closed cavity,
2 = Contact between fixture and bone (immobilization);
bordered by fixture and bone; 3 = bone that was damaged by unavoidable thermal and
mechanical trauma; 4 = original undamaged bone; and 5 = fixture. B, During unloaded
healing period, hematoma becomes transformed into new bone through callus formation
(6). 7 = Damaged bone, which also heals, undergoes revascularization,
and de- and
remineralization.
C, After healing period, vital bone tissue is in close contact with fixture
surface, without any other intermediate
tissue. Border zone bone (8) remodels in
response to masticatory load applied. D, In unsuccessful implants, nonmineralized
connective tissue (9), constituting
a kind of pseudoarthrosis,
forms in border zone at
implant. This development
can be initiated by excessive preparation trauma, infection,
loa.ding too early in the healing period before adequate mineralization
and organization
of .hard tissue has taken place, or supraliminal
loading at any time, even many years after
integration has been established. Osseointegration
cannot be reconstituted. Connective
tissue can become organized to a certain degree, but in our opinion it is not a proper
anchoring tissue because of its inadequate mechanical and biologic capacities, which
result in creation of a locus minoris resistentiae.
q
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Fig. 11. A, Successfully integrated lower jaw fixtures
after 6 years of function. B, Fixture on left is not
osseointegrated, although it is indirectly immobilized
by prosthesis that is stabilized by remaining integrated fixtures.
and marrow tissues to heal as such and not as low
differentiated scar tissue.
In order to create osseointegration, the preparation
of the bone must be done so that minimal tissue injury
is produced. In the handling of the edentulous jaw, it is
important to recognize a few principles that are valid
for all implant procedures. A minimal amount of
remaining bone should be removed, and the basic
topography of the region should not be changed. The
retention of the original or transitional denture should
be maintained during the healing period. If osseointegration is not obtained and the implant is removed or if
for some other reason the patient wants to return to
conventional denture wear, this should then function in
the same way as before installation of the implants.
Only one shape and dimension of implant should be
required, and after 20 years of experimental and
clinical development we have selected a screw-shaped
implant made of pure titanium. Its dimensions of an
outer diameter of 3.7 mm and a length of 10 mm allow
its use in almost every edentulous jaw, regardless of the
volume and topography of the remaining bone tissue
(Fig. 8).
Both prostheses and abutments are connected to the
fixtures by screws so that the prostheses can be
removed from the abutments and the abutment from
the fixture for technical adjustments. The abutment
can also be removed and the mucoperiosteum closed
over the fixture for shorter periods of time or permanently. The existence of a titanium fixture in the jaw
bone does not seem to cause adverse effects, and bone
resorption arising from disuse atrophy appears to be
reduced. If osseointegration is lost, the fixtures can be
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removed, with new bone formation observed in the
implant site and preservation of the original jaw bone
anatomy. In this way even if osseointegration is not
achieved or maintained, the jaw bone is not destroyed
or left with major defects.
Healing time for bone tissue requires that fixtures
implanted in carefully prepared sites in the jaw bone be
left in situ without load bearing for a period of 3 to 6
months. This period depends on the varying repair
potential of the edentulous jaw bone. When abutments
have been connected by the prosthesis, the jaw bone
around the implant remodels over a period of 1 or more
years until a “steady state” is reached. This state is
characterized by negligible’ bone resorption and
appears to be maintained. During the remodeling
phase, some marginal bone is lost as a consequence of
the installation surgical trauma and adaptation to the
masticatory load (Fig. 9).
Even with extreme care at the surgical preparation
stage of the fixture site (Fig. lo), the bone at the
interface is injured (A) and the required alignment at
the 400 A level cannot be produced mechanically. It is
provided by newly formed bone tissue (B), a biologic
process that requires approximately 3 to 6 months.
When a controlled load is applied to the bone through
the implant, the bone remodels to an architecture
related to the direction and magnitude of the load (C) .
If the surgical trauma is too intense or if the load is
applied too early or without proper control, osseointegration is not achieved (D), with a connective tissue
anchorage resulting. Sometimes such a soft tissue layer
is extremely thin: only a few microns wide. It may then
provide a variable short-term anchorage, but in the
long run the attachment’s prognosis becomes dubious.
The soft tissue layer tends to increase in width;
therefore, such a fixture should be removed and
eventually replaced (Fig. 11).
When osseointegration has been obtained and the
fixtures are subjected to load-bearing under controlled
conditions, the placement of the fixtures can be limited
to the area between the mental foramina in the lower
jaw and between the anterior sinus recesses in the
upper jaw. Cantilevered extensions can be used so that
an adequate replacement dentition can be provided.
Fixtures can be positioned even distal to the sinus and
mental foramen; but, because this is not required for
the edentulous reconstruction per se and can actually
cause clinical problems, it seems rational to restrict
anchorage to these sites.
A minimum of four fixtures appears to be adequate
for support of a full arch prosthesis in the edentulous
jaw (Fig. 12, A and B). However, if morphologically
feasible, six fixtures are installed to provide a certain
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Fig. 12. A and B, Diagrammatic
and orthopantomographic
representation
of four
osseointegrated fixtures supporting upper and lower full arch prostheses. Orthopantomogram shows topography of reconstruction after 6 years. C and D, If adequate space is
available between maxillary sinuses or mandibular foramina, six fixtures are installed as
support. E, This profile radiogram illustrates how prosthesis can be extended to provide
an. adequate dentition even in molar region.
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Biopsies from the mucoperiosteum around the transepithelial abutment show a similar appearance of the
soft tissue cells providing a seal toward the oral cavity.
Biophysical and biochemical analyses of long-term
experimental and clinical material indicate that there is
in fact an active interchange between the implanted
titanium fixture and the soft and hard tissues, which
eventually results in improved anchorage over the
years.
OTHER
B
.O
Fig. 13. Diagrammatic representation of jaw bone
anatomy in a frontal sagittal section illustrates biomechanical situation for implants in relation to various
degrees of resorption of alveolar process. A, Normal
anatomy as compared with extreme bone resorption
prevailing in most of treated patients. B, In extreme
resorption a very unfavorable leverage situation
develops. This is due to distance between jaw bone
and occlusal plane and to direction of implants that
support prosthesis (see Fig. 12, E).
reserve should a fixture not become integrated or lose
its integration over the years (Fig. 12, C and D).
While extremely careful surgical handling of the
hard and soft tissues is required to achieve osseointegration of the implants, the maintenance of the osseointegration relies on equally careful prosthodontic therapy. Careful and frequent control and adjustment of
occlusion are essential. The artificial teeth are made of
acrylic resin, which tends to compensate for the resilience of the periodontium. Most of the edentulous
patients treated by osseointegration present an extreme
degree of alveolar bone resorption. The vertical dimensions of the tissue defect to be covered by the prosthesis
demand particular skill and consideration in its design
to ensure load bearing without mechanical failures and
at the same time to make sure that phonetic and
cosmetic requirements are met (Fig. 13).
Clinical evidence for the lasting integration of prosthesis-loaded fixtures has been obtained from osseointegrated fixtures that were removed along with surrounding bone because of mechanical rather than
biologic failures. Fig. 14 shows a typical example of a
well-functioning integrated upper jaw fixture removed
by trephine with surrounding bone after 6 years of
clinical function. The bone could not be removed from
the (integrated) fixtures without destroying the interface. Under the light microscope, the anatomic congruence of the anchoring bone to the geometry of the
(scrutinized) fixture is illustrated; and, in scanning
electron microscopy, processes of osteoblasts seem to
grow on the titanium surface.
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APPLICATIONS
Extraoral application of titanium fixtures has been
used since 1976. A specially designed fixture has been
used to anchor hearing aids for bone-conducting
devices. It is placed behind the ear in patients with
certain audiologic impairments. Similar fixtures have
also been used as anchorage for auricular epitheses
(maxillofacial prostheses). A special procedure for
handling the skin and subcutaneous tissue relationship
to the abutment enabled us to handle soft tissue
problems, and all installed fixtures became and have
remained integrated. Fifteen patients were supplied
with this kind of bone-conducting hearing aid between
1977 and 1982. Eighteen patients were provided with
20 auricular epitheses attached to 78 fixtures between
1979 and 1982. Using the same basic anchorage
principle, we are now developing methods, for example, for tissue integration of epitheses that replace the
orbital sections of the maxilla.
Osseointegration has also been applied to long bones
in the reconstruction of damaged or diseased joints. So
far, osseointegrated fixtures have been used as anchorage for joint prostheses in the metacarpophalangeal
joints. There seems to be two advantages with the
osseointegrated joint prosthesis: (1) direct anchorage to
living remodeling bone provides important mechanical
stability for the function of the joint and the hand and
(2) the mechanical components constituting the joint
itself are facultatively removable from the fixtures.
Therefore, a replacement joint mechanism can easily
be installed in the future as a result of wear of
components, or if a better design or material becomes
available.
Work is now in progress to explore the possible
value of osseointegrated joint prostheses in the distal
radioulnar joint and in the elbow joint as well as in
joint replacement in the lower extremity, particularly
the knee and the hip joints.
Finally, preliminary studies have been performed on
the attachment of prosthetic substitutes for lost fingers,
hands, and arms and lower legs to osseointegrated
fixtures by means of skin-penetrating abutments as the
method of connection.
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Fig. 14. A, Upper jaw fixtures with surrounding bone removed because of failure of
mechanical components after 6 years of function with persisting integration. Specimen
was removed by a trephine and cut longitudinally into two halves with a diamond disk.
B, In light microscopy, bone threads of fixture site are clearly defined. C, Highresolution scanning electron micrograph of an osteoblast with its cellular processes
adapted to surface of fixture shown in A.
In conclusion!, I have attempted to present an overview of the conceptual development and the experimental and clinical application of osseointegration. Its
long-term clinical dental application has already been
demonstrated and documented in Sweden. I hope that
my material will provoke and catalyze similar experimental work and clinical application elsewhere.
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REFERENCES
A reference list enumerating the relevant research
referred to in this overview is available from the author
under the following headings:
1. Blood as a mobile tissue and studies on intravascular rheology of blood
2. Vital microscopy techniques
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3. Microvascular structure and function in normal
and diseased conditions
4. Tissue injury and repair
5. Tissue-integrated prostheses in oral and craniofacial reconstruction
6. Immediate and preformed autologous grafts
7. Bone, marrow, joint, and tendon anatomy, physiology, and pathophysiology
For the list of references, write:
Prof. P-I. Brinemark
Institute for Applied Biotechnology
Box 33053
S-400 33 Gijteborg
Sweden
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The invaluable assistance of the late Viktor Kuikka is acknowledged. He helped design and develop the mechanical components
used for anchorage as well as the surgical instruments.
Reprint requests to:
DR. GEORGEA. ZARB
UNIVERXR OF TORONTO
FACULTYOF DENTISTRY
124 EDWARDST.
TORONTO, ONT. M5G lG6
CANADA
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