Osseointegration

INTRODUCTION : Since tooth loss from disease and trauma has always been a feature of mankind’s existence, it is not surprising that the history of tooth replacement is a long one. Evidence from ancient civilizations shows that attempts were made to replace missing teeth by banding artificial tooth replacements to remaining teeth with metal many centuries ago. For the mechanism of attachment, clinicians have long sought an analog for periodontal ligament. Experiments were made to develop a fibrous attachment that could serve the same purpose as the periodontal ligament but all in vain. The periodontal ligament in a specialized structure which serves not only as an efficient attachment mechanism but also as a shock absorber and sensory organ, so it was impossible to reproduce.

HISTORY OF OSSEOINTEGRATION : Implants may indeed be anchored in bone by means of surrounding sheath of connective tissue, but in general this has not shown the degree of organization and specialization that would allow it to pass as a substitute for the periodontal ligament. In most cases, loading leads to gradual widening of fibrous tissue layer and loosening of implant, with consequent implant failure. In contrast to periodontal ligament, a fibrous tissue sheath is a poorly differentiated layer of scar tissue.

Dr. Per Ingvar Branemark, an anatomist is credited as the person who has coined the term “osseointegration�. Branemark along with his team was working in the laboratory of the vital microscopy (1952), laboratory of experimental Biology, University of Goteberg Sweden, (1960), Institute of Applied biotechnology, Goteberg (1978). The main study of his group was to understand the mechanism of bone healing and bone response to the thermal, mechanical, chemical injuries by using vital microscopy.

Vital microscopy, is a type of the miniature microscope, which is introduced in to the living organisms. E.g. Rabbit in their study the titanium

(Ti) chambers were used for placing the vital microscope into the rabbit’s fibula. After the studying of the bone biomechanics in one animal, the team used to recover the vital microscope and place it into the other animal model. While recovering Branemark observed that the Ti chambers were firmly adherent to the bone. By this observation they concluded that the titanium was firmly integrated to the bone and later they used Ti screws and Ti bars for reconstruction of the long bones and mandibles of the dogs.

After ensuring the favourable bone response to the Ti, the team tried to replace the teeth for the dogs. The Ti implants also showed good response for the mucosa and skin penetrating implants. The implants, which used for replacement of the teeth in the dogs showed good integration upto 10 years and the implants could bear the load of upto 100 Kgs without failure at the bone-implant interface. By observing this property the integration between the bone and Ti screws was termed as “osseointegration”.

The Ti vital microscopic chambers were used to analyze microcirculation in the healthy and diabetic human volunteers without any signs of inflammation around the Ti chamber. In 1965, first human edentulous patient was treated by using the Ti screws (implants) by reconstruction of resorbed edentulous arches using autologus tibial bone grafts.

The salient features of Branemark and his team’s work  About more than 50 designs of Ti screws (Implants) were tested and used.  The surgical protocol followed was : two stage surgery, which was proved beneficial.  Minimal trauma during the surgery results in bone regeneration rather than bone repair at the implant site.  Non-contaminated implants (sterile and clean implants) proved good integration.

 Prosthesis and abutments were screw attached for more technical flexibility.  There were more mechanical failures at the interface rather than biological failures.

Mr. Victor Kuikka helped in designing the hardware parts in this study. In the longitudinal study of the Ti implants from 1965 to 1974 showed a success rate of 99% in mandibles and 89% in maxilla.

In the mean time Schroeder et al. (1970), the members of the international team for development of oral implants (I.T.I) studied the Ti plasma sprayed Cp Ti cylindrical implants in Monkey models and achieved the firm integration between the implant and the tissues. In their study the bone was joined to implant by fine bridges of fibrous tissue. They termed this union as functional ankylosis.

DEFINITION AND OTHER TERMINOLOGIES : Osseointegration : Branemark defined it “as a direct contact between the bone and metallic implants, without interposed soft tissues layers” (1969).

Later it is modified “as a direct structural and functional connection between ordered, living bone and the surface of a load carrying implant” (1977). [Structurally oriented definition] American Academy of Implant Dentistry (1986) : Contact established without interposition of non-bone tissue between normal remodeled bone and an implant entailing a sustained transfer and distribution of load from implant to and within the bone tissue.

Meffert et al. (1987) Subdivided into Adaptive Osseointegration : Osseous tissue approximating the surface of the implant without apparent soft tissue interface at light microscopic level.

Biointegration : Is a direct biochemical bone surface attachment confirmed at electron microscopic level.

Zarb and T. Albrektsson (1991) : It is a process whereby clinically asymptomatic rigid fixation of alloplastic materials is achieved and maintained, in bone during functional loading.

Schroeder et al (1970’s) : Coined the term “Functional Ankylosis”.

[The Swiss Academy] Other Terminologies : Osteopreservation (Stallard R.E.) : It is a made of tissue integration around healed functioning endosteal dental implant in which the prime load bearing tissue at the interface is a peri-implant ligament composed of osteostimulatory collage. It limits the further bone resorption.

Used in case of plate/blade form endosseous implants and endodontic stabilizers.

Periosteal integration : It is a made of tissue integration around a healed, functioning, subperiosteal implant in which the load bearing tissue is the sheath of dense collagenous tissue constituting the outer layer of periosteum.

MECHANISM OF OSSEOINTEGRATION : After the surgical placement of implants into endosteal location, the traumatized bone around these implants begins the process of wound healing. As mentioned previously, it can be separated into the inflammatory phase, the proliferative phase, and the maturation phase. This is summarized in Table along with some of the specific aspects of bone healing during these stages.

Phase one inflammatory phase : The placement of implants into bone involves the creation of an osseous defects with the subsequent filling of this defect with an implant device. Even with the most careful surgical manipulation of osseous tissues,

the generation of a thin layer of necrotic bone in the peri-implant region is inevitable.

In addition, exact microscopic fit between the implant and the surgical defect is not possible, leaving local areas of dead space where the implant does not directly contact osseous tissue. When the implant is exposed to the surgical site, it comes to contact with extracellular fluid and cells. This initial exposure of the implant to the local tissue environment results in rapid adsorption of local plasma proteins to the implant surface.

Shortly thereafter, these proteins are enzymatically degraded and undergo conformational changes, degradation, and replacement by other proteins.

Platelet contact with synthetic surfaces causes their activation and liberation of their intracellular granules resulting in release of serotonin and histamine, leading to further platelet aggregation and local thrombosis. Blood contact with proteins and foreign materials leads to the initiation of the clotting cascade via the intrinsic and extrinsic pathways, causing blood coagulation in the aforementioned peri-implant dead spaces and within the damaged local microvascular circulation. Activation of the clotting cascade also leads to the formation of bradykinin, which is a strong mediator of vasodilation and endothelial permeability.

During this initial implant host interaction, numerous cytokines are release from the local cellular elements. These cytokines have numerous functions, including regulating adhesion molecule production, altering cellular proliferation, increasing vascularization rate, enhancing collagen synthesis, regulating bone metabolism and altering migration of cells into a given area. Table 4.2 lists some of the cystokines believed to be important in tissue implant integration. These initial events in healing of implants are largely chemical in nature and correspond to the beginning of a generalized inflammatory response that occurs with any surgical insult.

The next events noted to occur during this phase of wound healing consist of a cellular inflammatory response. Initially, it is nonspecific in nature and consists mainly of neutrophil emigration into the area of damaged tissue. Its duration is variable but generally peaks during the first 3 to 4 days following surgery. The role of this cell is primarily phagocytosis and digestion of debris and damaged tissue. Neutrophils are accompanied by smaller numbers of eosinophils. Eosinophils have a similar phagocytic function and they can also digest antigen antibody complexes. These cells are attracted to the local area by chemotactic stimuli and then migrate from the intravascular space to the interstitial space by diapedesis. End products of this phagocytic process are carried away from the local area by the lymphatic circulation. Neutrophils and eosinophils are end state cells and thus further division is not possible. They act as a type of first stage cellular defence and their duties are later augmented by the lymphocyte and the monocyte.

Toward the end of the first week, the generalized inflammatory response becomes more specific in nature. Increasing numbers of thymus dependent lymphocytes (T cells) bursa equivalent lymphocytes (B cells), killer (K) cells, natural killer (NK) cells and macrophages are found in the wound at this time. These cells respond to foreign antigens such as bacteria and plaque debris that have been introduced into the area during the surgical procedure. These antigens are processed and presented to the B and T cell populations by macrophages. Four functionally distinct T cell populations respond and perform regulatory, inflammatory, cytotoxic and augumentary functions resulting in a variety of effector modalities. Cellular intercommunication is essential for effective immunoregulatory function and this is accomplished with the release of soluble signal molecules called lymphokines. Lymphokines are specific cytokines released from local cellular elements that effect immunologic function.

Macrophages are the predominant phagocytic cell found in the wound by the fifth to sixth postoperative day. These cells are derived from circulating monocytes, which originate from the bone marrow via monoblast differentiation. Macrophages have the ability to ingest immunologic and non-immunologic particles by phagocytosis and attempt to digest these particles with lysosomal enzymes. They have cell surface receptors that are instrumental in the killing of bacteria, fungi, and tumor cells. As mentioned previously, macrophages also process and present foreign antigens to lymphocytes as part of the cellular immune response. In contrast to the neutrophil, this cell is not an end state cell and thus has the ability to undergo mitosis. Macrophages cal also fuse to form multinuclear foreign body giant cells to ingest larger particles. The mechanism by which they recognize and ingest non-immunologic materials, however, is not well understood, but it has been shown that hydrophobic materials, such as polytetrafluoroethylene and roughened plastics, are more easily taken up by macrophages than are hydrophilic materials. In addition, it seems that adsorbed proteins on the surface of the foreign bodies, particle size, particle shape, surface texture and related free surface energy play some role in the ingestion of these particles by macrophages.

The reaction of macrophages on exposure to foreign materials depends on the physical and chemical nature of the material. In an in vitro experiment examining the effects of particles of commonly implantable metals on mouse peritoneal macrophage rate demonstrated that particles of titanium, chromium and molybdenum were phagocytized and produced no abnormal morphologic abnormalities or release of lactate dehydrogenase (LDH). In contrast, particles of cobalt, nickel and cobalt-chromium alloy cause marked changes in cellular morphology and release of LDH. Some materials act directly on the macrophage, whereas other materials act through the immunologic involvement of lymphocytes. The mechanism by

which they induce an inflammatory response is thought to be through the release and activation of certain mediators of inflammation, including lysosomal

enzymes,

prostaglandins,

complement

and lymphokines.

Ultimately the reaction of macrophages to an implant governs the global tissue reaction to the material. A few macrophages not associated with an overt inflammatory response are normally located on intact implant cells long after implantation, however, is generally problematic in nature and suggests the presence of a chronic inflammatory reaction and probable implant failure.

Phase Two Proliferative Phase : Shortly after the implant is inserted into bone, the proliferative phase of implant healing is initiated. During this phase, vascular ingrowth occurs from the surrounding vital tissues, a process called neovascularization. In addition, cellular differentiation, proliferation and activation occur during this phase, resulting in the production of an immature connective tissue matrix that is eventually remodeled. As noted previously, this phase of bone repair begins while the inflammatory phase is still active.

During the placement of implants into their endosseous locations, interruption of the local microcirculation occurs in the surgical areas.

Regeneration of this circulation must eventually occur if wound healing is to begin as early as the third postoperative day. Metabolism of the local inflammatory cells, fibroblasts, progenitor cells and other local cells creates an area of relative hypoxia in the wound area. This results in the development of an oxygen gradient with the lowest oxygen tension near the wound edges. This hypoxic state combined with certain cytokines, such as basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) is responsible for simulating this angiogenesis. bFGF seems to activate hydrolytic enzymes, such as collagenase and plasminogen, which help to dissolve the basement membranes of local blood vessels. This

initiates the process of endothelial budding, which progresses along the established chemotactic gradient. Once the anastomoses of the capillary buds are developed and a local microcirculation is reestablished, the improved tissue oxygen tension results in a curtailment of the secretion of these angiogenic growth factors. In addition, the new circulation provides the delivery of nutrients and oxygen necessary for connective tissue regeneration.

Local mesenchymal cells begin to differentiate into fibroblasts, osteoblasts and chondroblasts in response to local hypoxia and cytokines released from platelets, macrophages, and other cellular elements. These cells begin to lay down an extracellular matrix composed of collagen, glycosaminoglycans, glycoproteins and glycolipids. The initial fibrous tissue and ground substance that are laid down eventually form into a fibrocartilaginous callus and this callus is eventually transformed into a bone callus with a process similar to endochondral ossification. Ossification centers begin within secretory vesicles that are liberated from the local osteoblasts. These vesicles called matrix vesicles, are rich in phosphate and calcium ions and also contain the enzymes alkaline phosphatase and phospholipase A2. This callus transformation is aided by improved oxygen tension and enhanced nutrient delivery that occurs with improvement of local circulation. The initial bone laid down is randomly arranged (Woven type) bone that is eventually remodeled.

In vivo studies using an optical chamber (vital chamber) implanted in along bones of animal models have been instrumental to the understanding of the healing process that occurs in the peri-implant space. They have revealed that vascular ingrowth precedes ossification. Capillary ingrowth appears initially and it matures to be a more developed vascular network during the first three weeks after implant insertion. Ossification is initially visualized during the first week, peaks during the third to fourth week and

arrives at a relatively steady state by the sixth to eight week. Long term follow up (> 1 year) of these unloaded implants reveals little change from the picture seen at the 6 to 8 week period with only some condensation of bone and some reorientation of the vascular pattern.

Phase Three Maturation Phase : The necrotic bone in the peri-implant space that resulted from operative trauma must eventually be replaced with intact living bone for complete healing to occur. Appositional woven bone is laid down on the scaffold of dead bone trabeculae by differentiated mesenchymal cells in the advancing granulation tissue mass. This process occurs concurrently with the ossification of the fibrocartilaginous callus noted previously.

Simultaneous resorption of these “composite� trabeculae and the newly formed bone, coupled with the deposition of mature concentric lamellae eventually results in complete bone remodeling, leaving a zone of living a zone of living lamellar bone that is continuous with the surrounding basal bone.

Traditional placement of endosseous implants involves a two stage surgical procedure in which the implant is placed during the first stage and then allowed a healing period of several months before the transmucosal portion is placed. When the superstructure is fabricated, loading of the implants can be initiated. Bone remodeling occurs around an implant in response to a load transmitted through the implant to the surrounding bone. In a histopathologic comparison of loaded and unloaded implants, Donath et al. showed that unloaded implants contacted small bone lamellae that were interrupted by many areas of bone marrow and parts of the haversian canal system. Loaded implants were surrounded by a more compact type of bone with only small bone free areas near the haversian canals. The lamellae around the implant area remodeled according to the exposed load, which with passage of time, shows a characteristic pattern of well organized concentric lamellae with formation of osteons in the traditional manner. The load dependent remodeling of bone follows the same principles that govern fracture healing.

Under normal circumstances, healing of implants is usually associated with a reduction in the height of alveolar marginal bone. Approximately 0.5 to 1.5 mm of vertical bone loss occurs during the first year after implant insertion. After this point, a steady state is reached and normal bone loss occurs at a rate of approximately 0.1 mm per year. The rapid initial bone loss can be attributed to the generalized healing response resulting from the inevitable surgical trauma, such as periosteal elevation, removal of marginal bone and bone damage caused by drilling. The later steady state bone loss probably reflects normal physiologic bone resorption. Factors such as excessive surgical trauma, excessive loading or the presence of peri-implant inflammation may accelerate this normal resorptive process. In a prospective review of hydroxylapatite (HA) coated implants Block and Kent found that the presence of keratinized gingiva in the peri-implant region strongly correlated to bone maintenance in the posterior mandibular region.

Thus, if excessive losses of marginal bone are noted, one must consider the possibility of inappropriate loading of the implant or the presence of peri-implant inflammation and step should be taken to rectify the problem before excessive implant support is lost.

MUCOPERIOSTEAL HEALING :

Implants are placed into their endosteal position through incisions in the mucoperiosteum. They can be placed using a one stage technique, in which the endosteal and transmucosal portions of he implant are allowed to heal as a single unit, or a two staged technique, in which the endosteal component is placed initially followed some time later by the placement of the transmucosal portion after a period of healing. Healing of the mucoperiosteal complex around implants is of paramount importance for the longevity of prosthetic reconstructions. An understanding of the biologic processes involved in generalized wound repair and how soft tissue wounds heal around implant fixtures is vital information for appropriate management of implant patients. As in the previous section on bone healing, there are also three phases of wound healing in soft tissue wounds : inflammatory, proliferative and maturation phases. In addition, there is also significant overlap between these phases as they pertain to mucoperiosteal wound healing.

Phase one inflammatory phase : The inflammatory phase of wound healing for the mucoperiosteal complex is essentially the same as that mentioned in the previous section on bone healing. It involves an initial vascular response followed by platelet aggregation and activation, the clotting cascade and then an initial non-specific cellular inflammatory response consisting of infiltrates of predominantly neutrophils. This is followed shortly thereafter by a more specific cellular inflammatory response consisting of infiltrates of predominantly neutrophils. This is followed shortly thereafter by a more specific cellular inflammatory response marked by increased number of lymphocytes and macrophages. Cytokines also play an important role in the healing of soft tissue wounds.

Phase two proliferative phase :

The proliferative phase of wound healing begins within hours of the injury and is characterized by the establishment of an active population of epithelial and connective tissue cells and the beginning of he reestablishment of wound integrity. Migration and proliferation of epithelial cells is seen within the first 24 to 48 hours of wound healing. The stimulus for growth and migration of thee cell results from loss of contact inhibition and from a temporary decrease in the local level of tissue specific growth inhibitors called chalones. A watertight seal is usually established within the first 24 hours after primary wound closure, but little structural strength is provided by the seal.

The main connective tissue cell involved in the proliferative phase of soft tissue wound healing is the fibroblast. Differentiation of mesenchymal cells and proliferation and migration of the preexisting population of local fibroblasts occur as a result of hypoxia and the release of cytokines from local

cellular

elements,

including

platelets

and

macrophages.

Neovascularization provides the foundation for fibroblastic proliferation by supplying the local area with the nutritional support required to maintain this enhanced metabolic state. Fibroblasts produce ground substance, collagen and elastic fibers. The major components of ground substance are proteoglycans

and

glycoproteins.

Glycoproteins

are

adhesive

macromolecules. They interact with cells and constituents of the extracellular matrix that interact with cells to promote adhesion, migration and proliferation and alter gene expression. Proteoglycans are large molecules composed of protein cores to which are attached side chains of glycosaminoglycans, which are polysaccharide chains formed from repeating disaccharide units. Proteoglycans are classified according to their dominant disaccharide unit and include hyaluronate, chondroitin, dermatan, keratin and heparin. These molecules retain water and form bulky gels that fill most of the extracellular space. The major proteoglycan in connective

tissues early in inflammation is hyaluronic acid. Its concentrations decrease after the fifth day simultaneously with an increase in concentrations of other proteoglycans, dermatan sulfate and chondroitin-4 sulfate, the collective function of all of the elements of the ground substance, among other things includes the binding of connective tissue elements, stabilization and facilitation of collagen maturation and facilitation of cellular function.

Collagen and elastic fibers, the major protein structures in connective tissues are also produced by the fibroblast. Collagen formation is microscopically detected between the fourth and sixth days, but biochemical evidence of collagen formation is noted between the second and fourth days.

During the formation of collagen, three polypeptide chains are produced and hydroxylated which occurs under the influence of propyl hydroxylase, which is an enzyme that requires vitamin C, molecular oxygen, ferrous iron and Îą - ketoglutarate as cofactors for proper function. These molecules and the combined to form a triple helix called procollagen. After glycosylation, procollagen is secreted from a triple helix called procollagen. After glycosylation, procollagen is secreted from the cell and the terminal telopeptides are then cleaved by an enzyme, procollagen peptidase, which is also secreted by the fibroblast. The resultant molecule, tropocollagen combines with other tropocollagen molecules to form collagen fibrils and the collagen fibrils are then combined to form collagen fibers. These structures are stabilized by intermolecular and intramolecular cross linkages.

Elastic fibers are also produced in a similar fashion. Tropoelastin molecules and secreted from the fibroblast and the resultant elastin molecules are combined with microfibrillar proteins to form elastic fibers. Elastin is a hydrophobic protein that provide resiliency to tissues that allows them to stretch and return to their original form.

The proliferative phase of wound healing is marked by cellular proliferation and synthetic activity. Collagen degradation by collagenases

secreted from fibroblasts, epithelial cells, neutrophils and macrophages, occurs simultaneously with collagen synthesis, but the net effect during the proliferative phase of wound healing is in favour of collagen deposition.

Termination of this phase of wound healing marked by an increase in local collagen content and a decrease in the number of local fibroblasts. Collagen content of the wound rises rapidly between the 6 th and the 17th day but increases only slightly between the 17th day and the 42nd day. At the beginning of this phase, the tensile strength of the wound is provided by epithelialization, blood vessel growth and aggregation of proteins. Collagen deposition increases the tensile strength significantly during this phase and the magnitude is proportional to the collagen content of the tissues.

Phase three maturation phase : During the final phase of wound healing, maturation of the deposited collagen occurs. There is no sharp demarcation between the end of the proliferative phase and the beginning of the maturation phase because collagen maturation occurs continuously shortly after initial deposition.

Collagen deposited during earlier phases of wound healing shows a non purposeful arrangement. Even though the collagen content of wound may be near maximal levels after 3 weeks of wound healing, the bursting strength of the wound in on about 15% of the normal skin level at this time. As time proceeds however, the unorganized fibrils are replaced larger, thicker and better organized fibers, with the final result being one of ‘lacing” the wound edges together with a three dimensional weave. This is made possible by the continuous turnover of collagen by fibroblasts with balanced synthesis and degradation. Improvement in strength of the wound is thus possible without an increase in total collagen content. The bursting strength of the wound is noted to improve dramatically from 3 to 9 weeks, reaching a level of 70% of normal skin by the end of this period. By 6 months, the bursting strength of the wound is approximately 90% of the level of normal skin. It must be noted, however, that the bursting strength of a wound plateaus after this period and does not usually reach that of the original tissue.

IMPLANT TISSUE INTERFACE :  It consists of implant and bone interface.  Implant and connective tissue interface.

ďƒ˜ Implant and epithelium interface.

Implant and bone interface : On observing the implant and bone interface at the light microscopic level (100X) it shows that close adaptation of the regularly organized bone next to the Ti implants.

Scanning electron microscopic study of the interface shows that parallel alignment of the lamellae of haversian system of the bone next to the Ti implants. No connective tissue or dead space was observed at the interface. Ultra microscopic study of the interface (500 to 1000X) shows that presence of amorphous coat of glycoproteins on the implants to which the collagen fibers are arranged at right angles and are partly embedded into the glycoprotein layer.

Mechanism of attachment : As a general rule cells do not bind directly to the foreign materials. The cells binds to each other or any other foreign materials by a layer of extracellular macro molecules (glycoproteins).

The glycoprotein layer in between the cells or in between the tissues will be at a thickness of 10 to 20 nm (100 to 200 A0).

At the interface the glycoprotein layer of normal thickness (10-20 nm) is adsorbed on the implant surface within the help of adhesive macromolecules like Fibronectin, Laminin, Epibiolin, Epinectin, Vitronectin (serum spreading factor), Osteopontin, thrombospodin and others. At the molecular level the macromolecules contains Tri-peptides made up of Arginin-glycin-Aspertic acid (RGD). The cells like fibroblasts and other connective tissue cells contain binding elements called as “integrins�. The integrins recognizes the RGDs and bind to them.

The macromolecules are adherent more firmly to the metallic oxide layer on the Ti implants. The mode of attachment between the oxide layer and the macromolecules may be of covalent bonds, ionic bonds or van-der-walls bonding.

Implant connective tissue interface : The connective tissue above the bone attaches to the implant surface in the similar manner as that of the implant bone interface. The supra crestal connective tissue fibers will be arranged parallel to the surface of the implant. Because of this type of the attachment the interface between the connective tissue and implant is not as strong as that of the connective tissue and tooth interface. But the implant connective tissue interface is strong enough to withstand the occlusal forces and microbial invasions.

Implant epithelial interface : The implant epithelial interface is considered as Biologic seal by many authors. At this interface the glycoprotein layer is adherent to the implant surface to which hemidesomosomes are attached. The hemidesmosomes connect the interface to the plasma membrane of the epithelial cells. Because of this attachment the implant epithelial interface is almost similar to the junctional epithelium. For the endosseous implants the sulcus depth varies from 3 to 4mm.

Factors of importance to ensure a reliable bone anchorage of an implanted device :

In most cases whenever an implant is inserted in bone, healing will dependent on the conditions like adequate cells, nutrition to these cells and adequate stimuli for repair. However, bone tissue is different from soft tissue in some aspects. In the first place bone will at least under ideal conditions, heal without any scar formation due to ongoing creeping substitution that will gradually replace the bone with newly formed hard tissue. Secondly, even if the repair process is disturbed so that no (or very little) healing ensures, the dead bone may (like a dead branch of a tree) still be capable of carrying some loads and thereby contribute to function. This may in clinical practice be the case in many hip and knee arthroplasties. Such replacements may tolerate the load put upon them by an elderly patient, but not the more heavy stress likely in young individuals where the results are much less good than with senior citizens. The delicate balance between bone formation and bone resorption may be exemplified through the known coupled function between bone cellular elements of opposing function such as osteoblasts and osteoclasts. Many authors claim that the one cell will need the other to be in an active state. This is further exemplified in the creeping substitution process.

Even if osseointegrated implants have been documented to result in excellent long-term results, this does not necessarily imply that every implant system claimed to be dependent on osseointegration will result in an acceptable clinical outcome. On the contrary, there are several reasons for primary as well as secondary failure of osseointegration.

These failures may be attributed to an inadequate control of the six different factors known to be important for the establishment of a reliable, long-term osseous anchorage of an implanted device. These factors are : 1. Implant biocompatibility

2. Design characteristics 3. Surface characteristics 4. The state of the host bed 5. The surgical technique and 6. The loading conditions There is a need to control these factors more or less simultaneously to achieve the desirable goal of a direct bone anchorage.

IMPLANT BIOCOMPATIBILITY :

With respect to metals, commercially pure (c.p) titanium, niobium and possibly tantalum are known to be most well accepted in bone tissue. In the case of c.p. titanium, there is likewise a documented positive long term function. The reason for the good acceptance of these metals does probably relate to the fact that they are covered with a very adherent, self-repairing oxide layer which has an excellent resistance to corrosion.

Whereas the load bearing capacity of c.p. titanium is sufficiently documented in the case of oral implants, there is less known about niobium in this aspect. Other metals such as different cobalt-chromoemolybdenum alloys and stainless steels have demonstrated less good take in the bone bed, but it is uncertain if this is valid for every possible such alloy and if it is biocompatibility effect alone that is responsible for their less satisfactory incorporation into bone, compared with c.p. titanium. A significantly impaired interfacial bone formation compared to c.p. titanium has been found with titanium-6 aluminium-4 vanadium alloy, probably dependent on a less good biocompatibility of the alloy.

One concern with metal alloys is that one alloy component may leak out in concentrations high enough to cause local or systemic side effects.

Ceramics such as the calcium phosphate hydroxyapatite (HA) and various types of aluminium oxides are proved to be biocompatible and due to insufficient documentation and very less clinical trials, they are less commonly used. With respect to HA, the available literature points to at least a short term (<10 weeks) enhanced interfacial bone formation in comparison to various reference metals. This represents a potential clinical benefit of HA, whereas the risk or coat loosening with subsequent problems represents a potential risk.

IMPLANT DESIGN (MACRO STRUCTURE) :

There is at present, sufficient long-term documentation only on threaded types of oral implants that have been demonstrated to function for decades without clinical problems. However, unthreaded implants may function too, even if there is a total lack of positive documentation with respect to bone saucerisation, a problem that caused failure of many early types of oral implants. With currently used cylindrical implants, many authors reported more severe bone resorption than would have been expected with certain screw designs. It must be observed that there are other unthreaded implant designs that may give an excellent long term clinical result.

The threaded implants provide more functional area for stress distribution than the cylindrical implants. The design of the threads may also influence the long term osseointegration. For e.g. V-shaped thread transfer the vertical forces in a angulated path, may not be efficient in stress distribution as that of the square shaped threads.

IMPLANT SURFACE (MICRO STRUCTURE, SURFACE TOPOGRAPHY) : With respect to the surface topography there is clear documentation that most smooth surfaces do not result in an acceptable bone cell adhesion.

Such implants do therefore end up as being anchored in soft tissue despite the material used. Clinical failure would be prone to occur.

Some microirregularities seem to be necessary for a proper cellular adhesion even if the optimal surface topography remains to be described. With a gradual increase of the surface topographical irregularities, problems due to an increased ionic leakage are prone to occur. With plasma sprayed titanium surfaces for instance, more than 1600 ppm titanium has been reported in implant adjacent haversian systems, probable resulting in an impairment of osteogenesis.

Another surface parameter is the energy state where a high surface energy has been regarded as positive for implant take due to an alleged, improved cellular attachment. One practical way of increasing the surface energy is the use of glow discharge (plasma cleaning). However, published reports have not been able to confirm the superiority of so artificially enhanced implant energy levels. One reason for this lack of confirmation of the surface energy hypothesis could be that the increased surface energy would disappear immediately when the implant makes in contact with the host tissues.

Many researchers recommended various procedures for improving the surface energy or surface characteristics of the implants to improve the osseointegration. Stefini C.M. et al. (2000) recommended to apply platelet derived growth factor and insulin like growth factors on the implant surface before placing into the cervical bed. According to their results this method showed better wound healing and rapid integration.

Musthafa K. et al (2000) reported to sand blast the titanium implants with titanium oxide particles (45-90Âľ) to achieve higher rate of cell attachment.

Other authors like Lima Y.J. et al. (2001) and Orsini Z. et al. (2000) reported to perform acid etching of the titanium implants by hydrofluoric acid, aqueous nitric acid and sodium hydroxide to reduce the contact angle less than 100 for better cell attachment and utilization of 1% hydrofluoric acid + 30% nitric acid to clean the implant surface and to remove the alumina particles after sand blasting which improves the osseointegration.

Nishiguchi S. et al (2001) reported to provide alkali + heat treatment to improve the amount of bone bonding, i.e. 5 mol/lt NaOH at 60 0C for 24 hours and 6000C for 1 hour (Dog study).

Rich and Harris presented some of the salient features of fibroblasts during healing i.e. Rugophalia: attracted towards rough surfaces, Haptotaxis: the directional cell movement that depends upon adhesive gradients on the substratum, Contact guidance : the tendency of the cells to be guided in their direction of locomotion by the shape of substratum.

These properties denotes that the implant fixture with rough surface topography and more surface energy promotes faster and complete osseointegration.

STATE OF THE HOST BED : If available, the ideal host bed is healthy and with an adequate bone stock. However, in the clinical reality, the host bed may suffer from previous irradiation, ridge height resorption and osteoporosis, to mention some undesirable states for implantation. Previous irradiation need not be an absolute contraindication for the insertion of oral implants. However, it is preferable that some delay is allowed before an implant is inserted into a previously irradiated bed. Furthermore, some 10-15% poorer clinical results must be anticipated after a therapeutical dose of irradiation. The explanation for less satisfactory clinical outcome found in irradiated beds could be vascular damage, at least in part. One attempt to increase the healing conditions in a previously irradiated bed is by using hyperbaric oxygen, as a low oxygen tension definitely has negative effects on tissue repair. This is further verified by the finding that heavy smoking, causing among other things a local oral vasoconstriction, is one factor that will lower the expected outcome of an implantation procedure.

Other common clinical host bed problems involve osteoporosis and resorbed alveolar ridge. Such clinical states may constitute an indication for ridge augmentation with bone grafts. However, present clinical technique for bone grafting are under debate and it appears that 6-year success of oral implants in the 75% range is a realistic outcome after most such procedures. This figure is slightly alarming seen against the fact that, at least in the maxilla, 10-20% of an average edentulous population may be in need of a bone graft to improve the host bed and allow for the insertion of implants. On the contrary, if the bone quality and quantity in the maxilla is controlled, the expected outcome of an oral implantation procedure is similar to that of the mandible.

As stated by Branemark et al. and Misch, the bones with D1 and D2 bone densities shows good initial stability and better osseointegration.

The bone densities D3 and D4 shows poor prognosis. Many authors have recommended to select suitable implants depending upon the quality and quantity of the available bone, i.e., HA coated or Ti plasma coated implants are better for D3 and D4 and conventional threaded implants for D1 and D2 bone qualities.

SURGICAL CONSIDERATIONS :

The main aim of the careful surgical preparation of the implant bed is to promote regenerative type of the bone healing rather than reparative type of the bone healing. If too violent a surgical technique is used, frictional heat will cause a temperature rise in the bone and the cells that should be responsible for bone repair will be destroyed. Bone tissue is more sensitive to heat than previously believed. In the past the critical temperature was regarded to be in the 56 0C range, as this temperature will cause denaturation of one of the bone enzymes, alkaline phosphatase. However, the critical time / temperature relationship for bone tissue necrosis is around 470C applied for one minute. At a temperature of 500C applied for more than one minute we are coming close to a critical level where bone repair becomes severely and permanently disturbed. This critical temperature should be seen against observed frictional heat at surgical interventions. In the orthopaedic field, despite adequate cooling, temperatures of 90 0C have been measured. High drilling temperatures in the dental field are to be expected when drilling, particularly in the dense mandible.

Erickson R.A. recommended the importance of using well sharpened drills, slow drill speeds, a graded series of drills (avoid making, for instance, a 4mm hole in one step) and adequate cooling by profuse irrigation. By using such a controlled technique it has been demonstrated in clinical studies that overheating may be totally avoided. The mechanical injury will of course remain and is quite sufficient to trigger a proper healing response. Erickson also recommended bone cutting speed of less than 2000 rpm and tapping at a speed of 15 rpm with irrigation.

Hence, the surgical preparation sequences as well as the instruments depend upon the quality of the bone as shown in the diagram.

Another surgical parameter of relevance is the power used at implant insertion. Too strong a hand will use in bone tension and a resorption response will be stimulated. This means that the holding power of the implant will fall to dangerous levels after a strong insertion torque. A moderate power at the screwing home of an implant is therefore recommended. With other implant designs there may be a need for implantation of the implant at insertion and other rules may apply.

Surgical fit of the fixture : The accurate fit consists of more surface contact, less dead space and thus better healing.

LOADING CONDITIONS :

From histological investigations of animal as well as human implants we know that, irrespective of control of surgical trauma and other relevant parameters, the implant will, in the early remodeling phase, be surrounded by soft tissue. This means that some weeks after implant insertion it will be particularly sensitive to loading that results in movements, as movement will stimulate more soft tissue formation, leading eventually to a permanent soft tissue anchorage. In essence, the situation is similar to that of a fracture. Loading of an unstabilized fracture will result in soft tissue healing and poor function, whereas stabilization with plates or plaster of Paris will ensure a satisfying rigidity leading to bone healing of the fracture. The case of an implant is, in principle, very similar. Premature loading will lead to soft tissue anchorage and poor long-term function, whereas postponing the loading by using a two stage surgery will result in bone healing and positive long term function. The length of time loading should be avoided is dependent on the implantation site as well as on the bone bed quality. Furthermore, there may be cases where an almost immediate loading would not disturb the bone healing response, but in general loading must be controlled if osseointegration is to occur.

Branemark with his controlled implant system advocated the use of a 3 month loading delay in the mandible and a 4-6 month delay in the healthy maxilla where the bone is, as a rule, more cancellous in character. However, these precise unloaded times are empirically based and to the knowledge of the author there are no published studies comparing different unloaded periods and relating this to implant success. Furthermore, from a bone biologic point of view a more suitable design would be to have the implant unloaded and then gradually increase the load in the manner of the Sarmiento technique for functional braces in fracture healing. In the similar way Misch et al.

recommended progressive loading criteria or staged loading and implant protective occlusion for better maturation of the bone surrounding the implants. The problem in the case of oral implants is how properly to define to the patient how a gradual increase of load should be controlled ; a complicated task not the least since the appropriate loading pattern also depends on individual patients factors.

Recently, many authors are reporting the results of immediate loading of the endosseous implants. According to them the physiological loading of the healing implants promotes better osseointegration.

Sagara et al (1993) also showed evidence of osseointegration when titanium screw implants were immediately loaded with a unilateral prosthesis. Their findings showed that osseointegration did occur, although the immediately loaded implants exhibited less direct bone contact than with the delayed loading which were used as controls.

Salama et al (1995) reported on two patients in whom titanium root form implants were immediately loaded and successfully utilized to support provisional fixed restoration in the maxilla and mandible. Both the patients were followed from 37 to 40 months after implant placement and immediate loading. All implants osseointegrated and were restored with a fixed prosthesis.

Babbush and co-workers (1986) showed implant success rate of 88% to 97% over 5 to 13 years with immediate loading implants.

Lederman

and

colleagues

(1998)

histologically

confirmed

osseointegration with 70% to 80% bone to implant contact in a mandibular symphysis necropsy specimen after 12 years of implant and prosthesis function in a 95 year old patient.

Peitelli and colleagues (1997) found significantly greater bone-toimplant contact in 24 immediately loaded mandibular implants compared with 24 unloaded.

THE SUCCESS CRITERIA (ALBERKTSSON ET AL) : 1)

The individual unattached implant should be immobile when tested clinically.

2)

The radiographic evaluation should not show any evidence of radiolucency.

3)

The vertical bone loss around the fixtures should be less than 0.2 mm per year after first year of implant loading.

4)

The implant should not show any signs of pain, infection, neuropathies, parasthesia, violation of mandible canals and sinus drainage.

5)

The success rate of 85% at the end of 5 year and 80% at the end of 10 service.

METHODS OF EVALUATION OF OSSEOINTEGRATION : Invasive methods : 1) Histological sections (10 microns sections).

2) Histomorphometric â&#x20AC;&#x201C; to know the percentage of bone contact.

3) Transmission electron microscopy 4) By using torque gauges 5) Pull out tests.

The invasive methods are usually used in the animal experiments.

Non-invasive methods : 1) Tapping with a metallic instruments : The fixture produces ringing sound, it osseointegrated, produces dull sound if fibrous integration.

2) The radiographs 3) Perio test : Checks mobility and damping system.

Normal values : -5 to + 5 PTV 4) Dental fine tester : evaluates the mobility, should be less than 5Âľ.

5) Reverse torque test with 20 N cm.

6) Resonance frequency analysis : this method gives the idea of amount, rate of osseointegration. This method can be utilized for healing or failing implants.

SCOPE OF THE OSSEOINTEGRATION : The osseointegrated endosseous implants are utilized for providing the prosthesis or stabilizing the various structure of the body. A schematic representation of the scope of the osseointegration is depicted in the diagram.

CONCLUSION : The â&#x20AC;&#x153;osseointegrationâ&#x20AC;? is a multifactorial entity. Achieving the osseointegration of the endosteal dental implants needs understanding of the many clinical parameters.

BIBLIOGRAPHY : 1)

Osseointegration in clinical dentistry – Branemark, Zarb, Albrektsson

2)

Osseointegration and occlusal rehabilitation – Sumiya Hobo

3)

Contemporary Implant Dentistry – Carl. Misch

4)

Endosseous implants for Maxillofacial reconstruction – Block and Kent

5)

Implants in Dentistry –Block and Kent

6)

Dental and Maxillofacial Implantology – John. A. Hobkrik, Roger Watson

7)

Endosseous Implant : Scientific and Clinical Aspects – George Watzak

8)

Optimal Implant Positioning and Soft Tissue management – Patrik Pallaci

9)

Osseointegration in craniofacial reconstruction. T. Albrektssson.

10)

Osseointegration in dentistry : an introduction : Philip Worthington, Brein. R. Lang, W.E. Lavelle.

11)

Effect of implant surface topography on behaviour of cells –D.M. Brunette IJOMI 1988 ; 3 : 231-246

12)

Implant stability assessment – Neil M. IJP, 1998 ; 5 : 491-500.

13)

Osseointegration and its experimental background. P.I. Branemark.

JPD, 1983, 50 : 399-410.

14)

D.C.N.A., 1986 ; 10-34, 151-160

15)

D.C.N.A., 1992 ; 36, 1-17

16)

Structural aspects of the interface between tissue and Titanium implants. K.A. Hanson, T. Albrektsson. JPD, 1983 ; 50 : 108-113.

17)

Biocompatibility of Titanium Implants. B. Kasemo. JPD, 1983; 50:832-37.

18)

Direct Bone Anchorage. T. Albrektsson et al. IJP, 1990 ; 3 : 30-41.

19)

Mechanism of Osseointegration. J.E. Davis. IJP, 1998 ; 11 :391-401.

20)

The attachment mechanism of epithelial cells. T.R.L. Gould. J. Perio.

Rest 1981 ; 16 : 611-616.

21)

The effects of early occlusal loading on one stage titanium alloy implants in beagle dogs : A pilot study : Sagara. M, Ahagawa Y, Nikai.

H, Tsuru. H, JPD 1993 ; 69 : 281-288.

22)

Immediate loading of bilaterally splinted titanium root form implants in fixed prosthodontics : Salama.K, Rose EF, Salama.M, Betts. N.J ; Int J. Periodont Rest Dent 1995 ; 15 : 345-361.

23)

Titanium plasma sprayed screw implants for reconstruction of the edentulous mandible : Bubbush C.A, Kent J.N, Wislik DJ ; J Oral Maxillofac Surg. 1986 ; 144 : 274-282.

24)

Long-lasting osseointegration of immediate located, bar-connected TPS screws after 12 years of function : A histologic case report of a 95year old patient : Ledermann PD ; Int J Periodont Restorative Dent 1998 ; 18 : 553-563.

25)

Immediate loading of titanium plasma sprayed screw-shaped implants in man : A clinical and histological report of two cases: Peattelli A, Corigliano M, Scrano A ; J Periodontal 1997 ; 68 : 591-597.

CONTENTS  INTRODUCTION  HISTORY OF OSSEOINTEGRATION  DEFINITIONS AND OTHER TERMINOLOGIES  MECHANISM OF OSSEOINTEGRATION • INFLAMMATORY PHASE • PROLIFERATIVE PHASE • MATURATIVE PHASE  FACTORS RESPONSIBLE FOR OSSEOINTEGRATION • MATERIAL BIOCOMPATIBILITY • IMPLANT DESIGN : MACRO STRUCTURE • IMPLANT SURFACE : MICRO STRUCTURE • STATE OF HOST BED • SURGICAL CONSIDERATIONS • LOADING CONDITIONS  CLINICAL EVALUATION OF OSSEOINTEGRATION  SCOPE OF OSSEOINTEGRATION  CONCLUSION  REFERENCES