RESEARCH AND EDUCATION

SECTION EDITOR
LOUIS J. BOUC:HER

Osseointegration and its experimental background

Per-Ingvar Brinemark, M.D., Ph.D.*
University 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
down to a thickness of only 10 to 20 pm. Circulation
was maintained in this thin layer of bone and with very
of hard and soft tissues. Its objective is a predictable few signs of microvascular damage, which is the
tissue response to the placement of tooth root ana- earliest and most sensitive indication of tissue injury.
logues. Such a response must be a highly differentiated These intravascular studies of bone marrow circulation
one, and one that becomes organized according to also revealed the intimate circulatory connection
functional dema:nds. Since 1952, we have studied the among marrow, bone, and joint tissue compartments.
concept of tissue4ntegrated prostheses at the Laborato- Subsequent studies of the regeneration of bone and
ry of Vital Microscopy at the University of Lund, and marrow emphasized the close functional connection
subsequently at the Laboratory for Experimental Biol- between marrow and bone in the repair of bone
ogy at the University of GGteborg. Our collaborators in defects.
this research have included representatives from medi- We, therefore, performed a series of in vivo studies
cal and dental faculties, various research institutes, and on bone, marrow, and joint tissue with particular
departments of technology. The basic aim has been to emphasis on tissue reaction to various kinds of injury:
define limits for clinical implantation procedures that mechanical, thermal, chemical, and rheologic. We were
will allow bone and marrow tissues to heal fully and also concerned with the various therapeutic possibili-
remain as such, rather than heal as a low differentiated ties to minimize the effect of such trauma. Aiming at a
scar tissue with unpredictable sequelae. The studies restitution ad integrum, we further sought to identify
involved analyses of tissue injury and repair in diverse additional traumatic factors such as wound disinfec-
sites in different animals, with particular reference to tants and to explore the development of procedures that
microvascular structure and function. Special emphasis promote predictable healing of differentiated tissues.
was placed on analyzing the disturbances caused in the We also performed long-term in vivo microscopic
intravascular rhelology of blood by means of a series of studies of bone and marrow response to implanted
different methodological approaches. The objective of titanium chambers of a screw-shaped design. These
this article is a brief review of the various investiga- studies in the early 1960s strongly suggested the
tions that have led to the clinical application of osseo- possibility of osseointegration since the optical cham-
integration. bers could not be removed from the adjacent bone once
they had healed in. We observed that the titanium
CONCEPT DEVELOPMENT chambers were inseparably incorporated within the
The initial concept of osseointegration stemmed bone tissue, which actually grew into very thin spaces
from vital microscopic studies of the bone marrow of in the titanium. Interdisciplinary clinical cooperation
the rabbit fibula., which was uncovered for visual with plastic surgeons and otolaryngologists enabled us
inspection in a modified intravital microscope at high to study the repair of mandibular defects and replace-
resolution in accordance with a very gentle surgical ment of ossicles by means of autologous bone grafts.
preparation technique. With special instrumentation, Desired anatomic shapes of bone grafts were pre-
the marrow could be studied in transillumination in formed in rabbits and dogs and subsequently applied
vivo, and in situ, after the covering bone was ground 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,
Presented at the Toronto Conference on Osseointegration in Clinical
Dentistry, Toronto, Ont., Canada, and the Academy of Denture
with the most successful being the one based on the
Prosthetics, San Diego, Calif. prior integration of titanium fixtures on both sides of
*Professor and Head, Laboratory of Experimental Biology, Depart- the defect to be created later. When the fixtures had
ment of Anatomy. 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 felt that both osseointegration and autologous bone
edges was maintained by titanium splints, and the grafts would be useful in these clinical defect situa-
tissue defect was compensated for by an autologous tions.
graft of trabecular bone and marrow (Figs. 1 and 2). Teeth were extracted in dogs and replaced by
Separate studies were performed on the healing and osseointegrated screw-shaped titanium implants (Fig.
anchorage stability of titanium tooth root implants or 4). Fixed prostheses were connected after an initial
fixtures of various sizes and designs. We found that healing time of 3 to 4 months without loading (Fig. 5).
when such an implant was introduced into the marrow In this manner, the fixtures were allowed to heal under
cavity, and following an adequate immobilized healing a mucoperiosteal flap, which was then pierced for
period, a shell of compact cortical bone was formed abutment connection and subsequent prosthetic treat-
around the implant without any apparent soft tissue ment.
intervention between normal bone and the surface of The anterior teeth, including the canines, were
the implant (Fig. 3). usually retained and the premolars and first molars
We observed a direct correlation among microtopo- removed. Different types of prosthetic designs were
graphy of the titanium surface, the absence of contam- used; we started with a design similar to the one used
ination, the preparatory handling of the bone site, and for complete dentures and ended up with a gold
the histologic pattern elicited in the adjacent bone. In a porcelain fixed prosthesis (Fig. 6). Radiologic and
separate study, fixtures were installed in the tail histologic analyses of the anchoring tissues showed that
vertebrae of dogs with successful integration even when integration could be maintained for 10 years in dogs
abutments were allowed to pierce through the skin. with maintained healthy bone tissue and without
On the basis of the findings in these experimental progressive inflammatory reactions.
studies, we decided to perform a series of experiments At the time the animals were killed, the titanium
that would enable us to develop clinical reconstructive fixtures could not be removed from the host bone unless
procedures for the treatment of major mandibular cut away. The anchorage capacity of the separate
defects, including advanced edentulous states. It was implants was determined as 100 kg in the lower jaw

400 SEPTEMBER 1983 VOLUME 50 NUMBER 3

 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 based on preformation of the graft at the donor site to
implants led to fractures in the jaw bone per se, not at the desired anatomy. At the same time, we integrated
the actual interface. Microradiographic analyses fixtures in the graft-to-be. The bone graft was made
revealed load-related remodeling of the jaw bone to adapt to the required anatomy within a titanium
around the implant, even in those cases where the mold. Donor sites were tibiae and ribs of rabbits and
implants were in very close proximity to the nasal and dogs.
sinus mucoperiosteum at installation. These long-term experimental studies suggested the
In order to reconstruct severely resorbed edentulous possibility of achieving and maintaining bone anchor-
jaws, we developed a special grafting procedure. It was age 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 A procedure of preformation was applied with the
penetration of titanium abutments could be used with- proximal metaphysis of the tibia used as the donor site.
out untoward reactions in edentulous jaws, and also for The combination of preformed grafts with integrated
the attachment of‘titanium chambers for vital micros- fixtures provided good long-term clinical results.
copy in rabbit and dog tibiae. Immediate autologous bone and marrow grafts are now
We carried out vital microscopic studies on human being tried; and our longitudinal experiences indicate
microcirculation and intravascular behavior of blood that with an extremely careful prosthodontic proce-
cells at high resolution by means of an implanted dure, immediate bone grafts can also provide good
optical titanium chamber in a twin-pedicled skin tube long-term results. They have the advantage of requir-
on the inside of the left upper arm of healthy volun- ing only one major surgical procedure as compared to
teers. The tissue reaction as revealed by intravascular two for the preformed graft, but the disadvantage of
rheologic phenomena was studied in long-term experi- less predictable survival of the grafted bone.
ments in these chambers without indications of inflam- In those patients in whom the loss of jaw bone is not
matory processes. It, therefore, seemed reasonable to limited to the alveolus but also includes a discontinuity
assume that bone anchorage according to the principle of the jaw bone, a preformed autologous bone graft
of osseointegration might also work in humans, and we from the iliac bone has been used and has provided
treated our first edentulous patients in 1965. good, predictable, long-term results. In accordance
In those edentulous jaws where the remaining bone with the same basic principle as for preformed alveolar
was inadequate for fixture anchorage, a composite bone grafts, the desired graft is prepared in the iliac
reconstruction procedure was developed. bone with a few connections left to the compact bone

402 SEPTEMBER 1983 VOLUME 50 NUMBER 3

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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 ups indicate that such procedures do not provide
surrounded by a. titanium mold and a titanium foil. predictable and good long-term function. Attempts at
Fixtures are installed in two directions to produce anchoring an implant by means of a regenerated
anchorage for a splint connecting the graft to the fibrous tissue layer forming a simulated periodontal
remaining part of the mandible and to provide anchor- ligament have also been unsuccessful. It has been stated
age for a fixed partial denture. Clinical long-term in bone reconstruction literature that direct anchorage
follow-up has shown that the grafted bone remains in to living bone of load-bearing implants does not work
its prepared shape even in the articular region. in the long run. Contrary to this concept, we now
suggest that the edentulous jaw can be provided with
OSSEOINTEGRATION IN jaw bone-anchored prostheses according to the princi-
CLINICAL DENTISTRY ple of osseointegration with good and predictable
The edentulous jaw is a typical example of a tissue long-term prognosis.
defect that causes different degrees of functional distur- Orthopedic reconstructions that use nonbiologic
bances. A well-fitting denture appears to be an accept- prosthetic materials frequently rely on implant anchor-
able alternative to natural teeth as long as the anatomy age by a space filler of so-called bone cement: methyl
of the residual hard and soft tissues provides good methacrylate. The induced surgical and chemical trau-
retention for the prosthesis. Progressive loss of alveolar ma results in death of osteocytes at the anchorage
bone tends to undermine the relative stability of the interface. After an initial period of adequate implant
denture and can create severe problems of both a retention, the damaged bone becomes resorbed and the
functional and psychosocial nature (Fig. 7). implant is subsequently kept in place only by low
Different procedures have been advocated to anchor differentiated soft tissue, a kind of scar tissue.
dental prostheses in the soft or hard tissues of the The implant is then separated from healthy bone by
edentulous mouth. However, long-term clinical follow- 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 morphol-
ogy corresponding to jaw bone topography represented in C and E, respectively.

tion as well as shielding of the surrounding bone from

the load stimulus required for adequate bony remodel-
ing 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
Fig. 8. Schematic representation of anchorage unit membrane. On the other hand, the osseointegrated
based on principle of screw-connected compo- implant is directly connected to living remodeling bone
nents: fixture, abutment, and center screw for
prosthesis attachment. Apical part of titanium fix- without any intermediate soft tissue component; there-
ture is designed to cut and thread bottom of fix- fore, it provides directly transferred loads to the
ture site. 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 1 6 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 = Contact between fixture and bone (immobilization);
q 2 = hematoma in closed cavity,
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.

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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
Fig. 11. A, Successfully integrated lower jaw fixtures appears to be maintained. During the remodeling
after 6 years of function. B, Fixture on left is not phase, some marginal bone is lost as a consequence of
osseointegrated, although it is indirectly immobilized
by prosthesis that is stabilized by remaining inte- the installation surgical trauma and adaptation to the
grated fixtures. masticatory load (Fig. 9).
Even with extreme care at the surgical preparation
stage of the fixture site (Fig. lo), the bone at the
and marrow tissues to heal as such and not as low interface is injured (A) and the required alignment at
differentiated scar tissue. the 400 A level cannot be produced mechanically. It is
In order to create osseointegration, the preparation provided by newly formed bone tissue (B), a biologic
of the bone must be done so that minimal tissue injury process that requires approximately 3 to 6 months.
is produced. In the handling of the edentulous jaw, it is When a controlled load is applied to the bone through
important to recognize a few principles that are valid the implant, the bone remodels to an architecture
for all implant procedures. A minimal amount of related to the direction and magnitude of the load (C) .
remaining bone should be removed, and the basic If the surgical trauma is too intense or if the load is
topography of the region should not be changed. The applied too early or without proper control, osseointe-
retention of the original or transitional denture should gration is not achieved (D), with a connective tissue
be maintained during the healing period. If osseointe- anchorage resulting. Sometimes such a soft tissue layer
gration is not obtained and the implant is removed or if is extremely thin: only a few microns wide. It may then
for some other reason the patient wants to return to provide a variable short-term anchorage, but in the
conventional denture wear, this should then function in long run the attachment’s prognosis becomes dubious.
the same way as before installation of the implants. The soft tissue layer tends to increase in width;
Only one shape and dimension of implant should be therefore, such a fixture should be removed and
required, and after 20 years of experimental and eventually replaced (Fig. 11).
clinical development we have selected a screw-shaped When osseointegration has been obtained and the
implant made of pure titanium. Its dimensions of an fixtures are subjected to load-bearing under controlled
outer diameter of 3.7 mm and a length of 10 mm allow conditions, the placement of the fixtures can be limited
its use in almost every edentulous jaw, regardless of the to the area between the mental foramina in the lower
volume and topography of the remaining bone tissue jaw and between the anterior sinus recesses in the
(Fig. 8). upper jaw. Cantilevered extensions can be used so that
Both prostheses and abutments are connected to the an adequate replacement dentition can be provided.
fixtures by screws so that the prostheses can be Fixtures can be positioned even distal to the sinus and
removed from the abutments and the abutment from mental foramen; but, because this is not required for
the fixture for technical adjustments. The abutment the edentulous reconstruction per se and can actually
can also be removed and the mucoperiosteum closed cause clinical problems, it seems rational to restrict
over the fixture for shorter periods of time or perma- anchorage to these sites.
nently. The existence of a titanium fixture in the jaw A minimum of four fixtures appears to be adequate
bone does not seem to cause adverse effects, and bone for support of a full arch prosthesis in the edentulous
resorption arising from disuse atrophy appears to be jaw (Fig. 12, A and B). However, if morphologically
reduced. If osseointegration is lost, the fixtures can be feasible, six fixtures are installed to provide a certain

406 SEPTEMBER 1983 VOLUME 50 NUMBER 3

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Fig. 12. A and B, Diagrammatic and orthopantomographic representation of four

osseointegrated fixtures supporting upper and lower full arch prostheses. Orthopanto-
mogram 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 trans-

epithelial 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 APPLICATIONS

.O
B Extraoral application of titanium fixtures has been
used since 1976. A specially designed fixture has been
Fig. 13. Diagrammatic representation of jaw bone used to anchor hearing aids for bone-conducting
anatomy in a frontal sagittal section illustrates biome-
chanical situation for implants in relation to various devices. It is placed behind the ear in patients with
degrees of resorption of alveolar process. A, Normal certain audiologic impairments. Similar fixtures have
anatomy as compared with extreme bone resorption also been used as anchorage for auricular epitheses
prevailing in most of treated patients. B, In extreme (maxillofacial prostheses). A special procedure for
resorption a very unfavorable leverage situation handling the skin and subcutaneous tissue relationship
develops. This is due to distance between jaw bone
and occlusal plane and to direction of implants that to the abutment enabled us to handle soft tissue
support prosthesis (see Fig. 12, E). problems, and all installed fixtures became and have
remained integrated. Fifteen patients were supplied
reserve should a fixture not become integrated or lose with this kind of bone-conducting hearing aid between
its integration over the years (Fig. 12, C and D). 1977 and 1982. Eighteen patients were provided with
While extremely careful surgical handling of the 20 auricular epitheses attached to 78 fixtures between
hard and soft tissues is required to achieve osseointe- 1979 and 1982. Using the same basic anchorage
gration of the implants, the maintenance of the osseoin- principle, we are now developing methods, for exam-
tegration relies on equally careful prosthodontic thera- ple, for tissue integration of epitheses that replace the
py. Careful and frequent control and adjustment of orbital sections of the maxilla.
occlusion are essential. The artificial teeth are made of Osseointegration has also been applied to long bones
acrylic resin, which tends to compensate for the resil- in the reconstruction of damaged or diseased joints. So
ience of the periodontium. Most of the edentulous far, osseointegrated fixtures have been used as anchor-
patients treated by osseointegration present an extreme age for joint prostheses in the metacarpophalangeal
degree of alveolar bone resorption. The vertical dimen- joints. There seems to be two advantages with the
sions of the tissue defect to be covered by the prosthesis osseointegrated joint prosthesis: (1) direct anchorage to
demand particular skill and consideration in its design living remodeling bone provides important mechanical
to ensure load bearing without mechanical failures and stability for the function of the joint and the hand and
at the same time to make sure that phonetic and (2) the mechanical components constituting the joint
cosmetic requirements are met (Fig. 13). itself are facultatively removable from the fixtures.
Clinical evidence for the lasting integration of pros- Therefore, a replacement joint mechanism can easily
thesis-loaded fixtures has been obtained from osseoin- be installed in the future as a result of wear of
tegrated fixtures that were removed along with sur- components, or if a better design or material becomes
rounding bone because of mechanical rather than available.
biologic failures. Fig. 14 shows a typical example of a Work is now in progress to explore the possible
well-functioning integrated upper jaw fixture removed value of osseointegrated joint prostheses in the distal
by trephine with surrounding bone after 6 years of radioulnar joint and in the elbow joint as well as in
clinical function. The bone could not be removed from joint replacement in the lower extremity, particularly
the (integrated) fixtures without destroying the inter- the knee and the hip joints.
face. Under the light microscope, the anatomic congru- Finally, preliminary studies have been performed on
ence of the anchoring bone to the geometry of the the attachment of prosthetic substitutes for lost fingers,
(scrutinized) fixture is illustrated; and, in scanning hands, and arms and lower legs to osseointegrated
electron microscopy, processes of osteoblasts seem to fixtures by means of skin-penetrating abutments as the
grow on the titanium surface. method of connection.

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OSSEOINTEGRATION

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, High-
resolution 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 over- REFERENCES

view of the conceptual development and the experi- A reference list enumerating the relevant research
mental and clinical application of osseointegration. Its referred to in this overview is available from the author
long-term clinical dental application has already been under the following headings:
demonstrated and documented in Sweden. I hope that 1. Blood as a mobile tissue and studies on intravas-
my material will provoke and catalyze similar experi- cular rheology of blood
mental work and clinical application elsewhere. 2. Vital microscopy techniques

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3. Microvascular structure and function in normal The invaluable assistance of the late Viktor Kuikka is acknowl-
edged. He helped design and develop the mechanical components
and diseased conditions used for anchorage as well as the surgical instruments.
4. Tissue injury and repair
5. Tissue-integrated prostheses in oral and craniofa-
cial reconstruction Reprint requests to:
DR. GEORGEA. ZARB
6. Immediate and preformed autologous grafts UNIVERXR OF TORONTO
7. Bone, marrow, joint, and tendon anatomy, physi- FACULTYOF DENTISTRY
ology, and pathophysiology 124 EDWARDST.
TORONTO, ONT. M5G lG6
CANADA
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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