Osseointegration notes
- 1. Osseointegration It is just as true in dentistry as in other disciplines that the more useful a technology, the more rapidly are its limits challenged by the user and that, in turn, user demand drives the necessity for refinements and improvements in the technology. An obvious example would be the rapid evolution of computers over the last few decades that has led to our almost indispensable reliance on the ubiquitous microchip. Similarly, in dentistry, over the last few decades there has been an increasing use of endosseous (in-bone) implants as a means of providing a foundation for intra-oral prosthetic devices, from full arch dentures to single crowns, or other devices for orthodontic anchorage or distraction osteogenesis. While there is no question that the popularity of endosseous implants for these treatment modalities is based on increasingly convincing data of long-term clinical success rates, it is this very success that has prompted the use of implants in more challenging clinical situations than were previously envisioned. Thus, single root implants previously employed in only anterior mandibular and maxillary sites are now commonly inserted into posterior regions where there is less cortical bone to provide initial mechanical stabilization. Indeed, the clinical success of implant therapy has led to the emergence of new operative procedures, such as sinus lifts, to increase local bone stock to accommodate implant placement. Similarly, implants that would previously only be placed into occlusal function after an extended initial healing period of several months are now loaded increasingly earlier in a matter of weeks, days, or even hours!. These radical changes in the practice of implant dentistry have been made possible through the evolution of a more profound understanding of the essential requirements of individual case treatment planning, improvements in surgical procedures, and the evolution of the design of the implants themselves such that almost a million dental implant procedures are now conducted, annually, worldwide. Therefore, the unequivocal success of endosseous dental implants is driving the need for continuing refinements in implant design and optimization of the biological healing response following implant placement. The story of osseointegration began with an accidental discovery forty years ago. A young Swedish scientist, Per-Ingvar Branemark, was studying the function of blood and marrow, and wanted to be able to see inside the fibula bone in a rabbit's leg. He made a viewing chamber by screwing a cylinder of titanium into the fibula. Titanium is a lightweight metal that is resistant to corrosion even in hostile environments such as the body of a rabbit, and Branemark was able to watch the marrow making blood cells. On completing his study, however, he was irritated to discover that bone had grown into the threads of the titanium cylinder so that he was unable to remove the expensive equipment. A few years later, Branemark was studying the effects of eating, drinking and smoking on blood cells, and developed a tiny titanium viewing chamber which he inserted into a fold of soft tissue in the upper arm of medical student volunteers. The chambers were left in place for months as the study proceeded and caused no adverse reaction. Only then did it occur to Branemark that a metal which could form such a strong bond with bone, without triggering a reaction from the body's immune system, could be extremely useful in surgery.
- 2. He was soon able to act on this finding. In 1965, Branemark's team operated on a man born with deformed chin and jaw, who could neither eat nor speak normally. They inserted titanium screws and posts into his mouth and attached a set of dentures. Almost three decades later, the teeth were still in action. Branemark, now professor of applied biotechnology at the University of Gothenburg, and his group have since installed a million titanium fixtures in 300 000 patients, some with deformities, others with severe dental problems. Ninety-five per cent of prostheses in the upper jaw have been successful, and 99 per cent of those in the lower jaw. The biocompatibility of titanium, or the body's lack of reaction to it, is due to the stable and unreactive layer of oxide that forms on its surface. If the metal is scratched with a sharp instrument, the oxide layer 'self-repairs' in nanoseconds, even when surrounded with saline or bodily fluids, according to Tomas Albrektsson, professor of biomaterials at the University of Gothenburg. With most implants, the body's immune system reacts to the material after surgery, stimulating fibrous repair. Titanium, with its oxide layer, does not provoke a reaction from the immune system, allowing normal bone repair to take place so that there is a secure bond between implant and bone. Per-Ingvar Branemark OSSEOINTEGRATION is defined as a direct structural and functional connection between ordered, living bone and the surface of a load-carrying implant. Zarb & Albrektsson (1991) OSSEOINTEGRATION is a process whereby clinically asymptomatic rigid fixation of alloplastic materials is achieved, and maintained, in bone during functional load. Implant materials used Ceramic : Aluminium Oxide, Zirconium Oxide, Carbon, Carbon-Silica compounds Metallic : Titanium, Titanium alloy Titanium Metal with low weight, high strength/weight ratio, low modulus of elasticity, excellent corrosion resistance, excellent biocompatibility and easy shaping and finishing Grade 1 CP Ti Grade 2 CP Ti Grade 3 CP Ti Grade 4 CP Ti Ti alloy Tensile strength (MPA) 240 345 450 550 930
- 3. Titanium alloys are far superior to pure titanium in terms of mechanical properties. Fatigue strength of Ti Alloy is 4 times greater than Grade 1 Ti and almost 2 times greater than Grade 4 Ti. Hence long term fracture of implant bodies is greatly reduced when Ti Alloys are used instead of pure Ti. Titanium and its alloys represent the closest approximation to the stiffness of bone of any surgical grade metal used as an artificial replacement of skeletal structures. Ti Alloy represents the best compromised solution between biomechanical strength, biocompatibility and the potential for relative motion at the bone-implant interface. Interesting aspect of titanium implants (cpTi or Ti6Al4V) is that it immediately after exposure to air forms an oxide layer over the surface (2 to 5nm in thickness) THE OXIDE LAYER Most pure metals are covered by an oxide layer. It will be the surface of the metal that comes into contact with the host tissue. Different surfaces have very different absorption properties which affect biocompatibility. This oxide is highly protective and prevents direct contact between the environment and the metal itself. It means, in the context of implants, that a contact is never established between the implant metal and the host tissue, but rather between the tissue and the surface oxide of the implant. Because the latter has completely different chemical properties than the metal itself, it is the biocompatibility of the oxide that is the relevant parameter from a chemical point of view. Therefore, one should choose a metal that forms a very stable surface oxide such as TiO2 , ZrO2 , AL2 O3 , Ta2 O5 . The surface is a dynamic interface, with increase in thickness of the oxide layer when the implant is positioned in bone than is left in air. Corrosion is caused by dissolution of the protecting oxide layer, which may be a severe problem with some implant materials. Albrektsson et al 1981: 6 factors for reliable osseointegration 1. Implant biocompatibility 2. Implant design 3. Implant surface 4. State of host bed 5. Surgical technique 6. Loading conditions
- 4. 1. Biocompatibility C.p. Titanium, Niobium and Calcium Phosphates such as HA are well tolerated Titanium alloys, aluminum oxides, cobalt-chrome-molybdenum and stainless steels are less well tolerated 2. Implant Design Categorized as cylinder type, screw type, press fit or a combination Cylinder or press fit : Has friction fit insertion, less risk of pressure necrosis from too tight an insertion pressure, no need of bone tap even in dense bone, and cover screw in place already since no rotational force reqd to insert implant. Popular in 1980s. Reports of crestal bone loss aft 5 yrs of loading due to fatigue overload, shear loads, less BIC. More than 90 implant body designs available in market. 3 types of forces to counter by the implant design : compression, tension and shear Bone strongest when loaded in compression, 30% weaker in tension and 65% in shear Thread designs ‘V’shaped, Square or power threads, Reverse buttress and Buttress Screw type Cylinder type
- 6. 3. Implant surface Turned surfaces Sandblasted surfaces Plasma sprayed surfaces Titanium plasma spray Acid etched surface Anodized surfaces Hydroxyapatite TiUnite surface : Nobel biocare (pore size : 1-10μm) Turned surface Sandblast acid etched surface 4. State of the Host bed A good and healthy bone bed is preferrable Low ridge height, osteoporosis and previous irradiation are not contraindications for implant placement in contrast to ongoing bone infection 5. Surgical technique Surviving cells and good, fitting preparation of the surgical site
- 7. 6. Loading conditions Implant incorporation may be compared to healing of fractures Immediate occlusal-loading – Temporary or definitive restoration and loading within 2 weeks of implant insertion Early occlusalloading – Between 2 weeks and 3 months Delayedor stagedocclusalloading – After more than 3 months The safe procedure remains two stage surgery with unloaded periods 3-6 months. With a controlled two stage technique, very good clinical results with steady state bone have been reported (Friberg et al 2005).
- 8. Bone healing is certainly a fascinating biological accomplishment of the skeletal tissues and one of the rare examples in which regenerative processes fully restore the original structure and function. This is achieved by a sequence of cellular activities that closely resemble the development and growth of bone during embryonic and postnatal life. In intramembranous (or direct) ossification, bone is formed directly in the mesenchyme. The majority of bones in the trunk and the extremities, however, are preformed as cartilaginous models and substituted later on by bone in the process of endochondral (or indirect) ossification. Bone regeneration follows similar pathways: in direct (or primary) healing, a scaffold of woven bone, closely associated with an expanding vascular net, invades the granulation tissue that organizes the initially formed blood clot. In indirect (or secondary) healing, connective tissue and/ or fibrocartilage differentiates within the fracture gaps and is replaced by bone as in endochondral ossification. Osseointegration clearly belongs to the category of direct or primary healing. Originally, it was defined as direct bone deposition on the implant surfaces (9), a fact also called “functional ankylosis” (48). In a more comprehensive way, osseointegration is characterized as “a direct structural and functional connection between ordered, living bone and the surface of a load-bearing implant” (39). Osseointegration can be compared with direct fracture healing, in which the fragment ends become united by bone, without intermediate fibrous tissue or fibrocartilage formation. A fundamental difference, however, exists: osseointegration unites bone not to bone, but to an implant surface: a foreign material. Thus the material plays a decisive role for the achievement of union. Prerequisites for osseointegration Materialand surface properties Osseointegration shares many prerequisites with primary fracture healing, such as precise fitting (anatomical reduction), primary stability (stable fixation) and adequate loading during
- 9. the healing period. In addition, osseointegration requires a bioinert or bioactive material and surface configurations that are attractive for bone deposition (osteophilic). Bioinert materials do not release any harmful substances and therefore do not elicit adverse tissue reactions. Titanium, either commercially pure or in certain alloys, is generally recognized as being bioinert and used extensively in both dental and orthopedic surgery. A bioactive material is thought to cause a favorable tissue reaction, either by establishing chemical bonds with tissue components (hydroxyapatite) or by promoting cellular activities involved in bone matrix formation. Bioactivity is currently restricted to compounds of poor mechanical quality and can only be applied as a coating (hydroxyapatite, carriers for inductors and growth factors). The notion that surface properties of implants might influence the elaboration of a bone-implant contact is relatively new. It could be anticipated that rough surfaces will improve adhesive strength compared with smooth ones. This assumption is now confirmed by numerous animal experiments that measured the push- and pull-out strength or removal torque values. The observation that a rough surface favors bone deposition and thus gradually increases the extent of the bone implant interface was somewhat surprising. It is now supported by numerous experimental studies. Roughness can be further characterized by the shape and dimension of the surface irregularities. The degree of mechanical interlock increases with the roughness of the substrate. At the same time, the structure and function of the bone implant contact changes. A smooth surface only transmits compressive forces, with little resistance against shear, and apparently none against traction. A mild roughness <10µm) augments the resistance against shear. Adhesion, however, requires either a chemical bond or a microporosity (micro protrusions and micro undercuts of 20-50 µm) that leads to a micro indentation between bone and metal. Macroporosity (pore size 100-500 µm) favors bony in-growth and is widely used as porous coatings (beads, sintered wire mesh, multilayered lattices) in orthopaedic implants. Finally, the macro-design or shape of an implant has an important bearing on the bone response: ongrowing bone concentrates preferentially on protruding elements of the implant surface, such as ridges, crests, teeth, ribs or the edge of threads, that apparently act as stress risers when load is transferred. Primary stability and adequate load The tissue response to a freshly installed implant greatly depends on the mechanical situation. As in direct fracture healing, it requires perfect stability if bone is expected to be formed. In a fracture, a stable fixation is obtained by exact adaptation and compression of the fragments. The primary stability of implants depends on their appropriate design and precise press fitting at surgery. Primary stability must counteract all forces that could create micromotion between the implant and the surrounding tissues. Or, in other words, it should build up enough preload to compensate for functional load. It thus determines not only the size but also the direction of the forces that are considered to remain adequate. All these parameters must be specified, and this makes it understandable why immediate functional loading may be adequate for such systems as bar- connected screws, whereas others require a prolonged, unloaded healing period before a supraconstruction can be installed.
- 10. Biology of osseointegration Events comparable to an extraction socket healing (Amler 1969) The healing of a wound includes four phases: 1. Blood clotting 2. Wound cleansing 3. Tissue formation 4. Tissue modeling and remodeling. These phases occur in an orderly sequence but, in a given site, may overlap in such a way that in some areas of the wound, tissue formation may be in progress while in other areas tissue modeling is the dominating event. Important events in bone formation 1. Blood clotting: Immediately after tooth extraction, blood from the severed blood vessels will fill the cavity. Proteins derived from vessels and damaged cells initiate a series of events that lead to the formation of a fibrin network. Platelets form aggregates (platelet thrombi) and interact with the fibrin network to produce a blood clot (a coagulum) that effectively plugs the severed vessels and stops the bleeding. The blood clot acts as a physical matrix that directs cellular movements and contains substances that are of importance for the continuation of the healing process. Thus, the clot contains substances that (1) influence mesenchymal cells (i.e. growth factors), and (2) affect inflammatory cells. These substances will induce and amplify the migration of various types of cells, as well as their proliferation, differentiation and synthetic activity within the coagulum. Although the blood clot is crucial in the initial phase of wound healing, its removal is mandatory to enable the formation of new tissue. Thus, within a few days after the tooth extraction, the blood clot will start to break down, i.e. "fibrinolysis" starts. 2. Wound cleansing: Neutrophils and macrophages migrate into the wound, engulf bacteria and damaged tissue and clean the site before tissue formation starts. The neutrophils enter the wound early while macrophages come into the scene somewhat later. The macrophages are not only involved in the cleaning of the wound but they also release several growth factors and cytokines that further promote the migration, proliferation and differentiation of mesenchymal cells. Once the debris has been removed and the wound has become "sterilized", the neutrophils undergo a programmed cell death (i.e. apoptosis) and are removed from the site through the action of macrophages. The macrophages subsequently withdraw from the wound. In the extraction socket, a portion of the traumatized bone facing the wound will undergo necrosis and will be removed by osteoclastic activity. Thus, osteoclasts also may participate in the wound cleansing phase of the bone healing. 3. Tissue formation: Mesenchymal, fibroblast-like cells which migrate into the wound from, for example, the bone marrow, start to proliferate and deposit matrix components in an extracellular location. In this manner a new tissue, i.e. granulation tissue, will gradually replace the blood clot. From a didactic point of view the granulation tissue may be divided into two portions: (1) early granulation tissue, and (2) late granulation tissue. A large number
- 11. of macrophages, a few mesenchymal cells, small amounts of collagen fibers and sprouts of vessels make up the early granulation tissue. The late granulation tissue contains few macrophages, but a large number of fibroblast-like cells and newly formed blood vessels present in a connective matrix. The fibroblast-like cells continue (1) to release growth factors, (2) to proliferate, and (3) to deposit a new extracellular matrix that guides the ingrowth of new cells and the further differentiation of the tissue. The newly formed vessels provide the oxygen and nutrients that are needed for the increasing number of cells in the new tissue. The intense synthesis of matrix components exhibited by these mesenchymal cells is called fibroplasia while the formation of new vessels is called angiogenesis. Through the combined fibroplasia and angiogenesis a provisional connective tissue is established. The transition of the provisional connective tissue into bone tissue occurs along the vascular structures. Thus, osteoprogenitor cells (e.g. pericytes) migrate and gather in the vicinity of the vessel. They differentiate into osteoblasts that produce a matrix of collagen fibers which takes on a woven pattern. The osteoid is hereby formed and the process of mineralization is initiated in its central portions. The osteoblasts continue to lay down osteoid and occasionally cells are trapped in the matrix and become osteocytes. The newly formed bone is called woven bone. The woven bone is the first type of bone to be formed and is characterized by (1) its rapid deposition along the route of vessels, (2) the poorly organized collagen matrix, (3) the large number of osteoblasts that are trapped in its mineralized matrix, and (4) its low load-bearing capacity. The woven bone forms as finger-like projections along the newly formed vessels. Trabeculae of woven bone are shaped and encircle the vessel. The trabeculae become thicker through the deposition of further woven bone, cells (osteocyts) are entrapped and the first set of osteons, the primary osteons are organized. The woven bone is occasionally reinforced by the deposition of so called parallel-fibered bone that has its collagen fibers organized not in a woven but in a concentric pattern. 4. Tissue modeling and remodeling: The initial bone formation is a fast process. Within a few weeks, the entire extraction socket will be occupied with woven bone or as this tissue is also called, primary bone spongiosa. The woven bone offers (1) a stable scaffold, (2) a solid surface, (3) a source of osteoprogenitor cells, and (4) ample blood supply for cell function and matrix mineralization. The woven bone with its primary osteons is gradually replaced by lamellar bone and bone marrow through the processes of modeling and remodeling as described earlier. In the remodeling process the primary osteons are replaced with secondary osteons. The woven bone is first through osteoclastic activity resorbed to a certain level. This level of the resorption front will establish the so-called reversal line, which is also the starting point for the new bone formation building up a secondary osteon. Although the modeling and remodelling may start early it will take several months until all woven bone in the extraction socket is replaced by bone marrow and lamellar bone. Incorporation by woven bone formation The first bone tissue formed is woven bone. It is often considered as a primitive type of bone tissue and characterized by a random, felt-like orientation of its collagen fibrils, numerous, irregularly shaped osteocytes and, at the beginning, a relatively low mineral density. But it has an outstanding capacity: it grows by forming a scaffold of rods and plates and thus is able
- 12. to spread out into the surrounding tissue at a relatively rapid rate. The formation of the primary scaffold is coupled with the elaboration of the vascular net and results in the formation of a primary spongiosa that can bridge gaps of less than 1 mm within a couple of days. Woven bone is the ideal filling material for open spaces and for the construction of the first bony bridges between the bony walls and the implant surface. Woven bone usually starts growing from the surrounding bone towards the implant, except in narrow gaps, where it is simultaneously deposited upon the implant surface. Woven bone formation clearly dominates the scene within the first 4 to 6 weeks after surgery. Adaptation of bone mass to load (deposition of parallel-fibered and lamellar bone) Starting in the second month, the microscopic structure of newly formed bone changes, either towards the well-known lamellar bone, or towards an equally important but less known modification called parallel-fibered bone. Lamellar bone is certainly the most elaborate type of bone tissue. Packing of the collagen fibrils into parallel layers with alternating course (comparable to plywood) gives it the highest ultimate strength. Parallel-fibered bone is an intermediate between woven and lamellar bone: the collagen fibrils run parallel to the surface but without a preferential orientation in that plane. This is clearly seen in polarized light: lamellar bone is strongly birefringent (anisotropic), and parallel-fibered bone is not (isotropic). Another important difference is found in the linear apposition rate: for human lamellar bone, this amounts to only 1-1.5 μm/day; for parallel-fibered bone it is 3-5 times larger. As far as the growth pattern is concerned, both types cannot form a scaffold like woven bone, but merely grow by apposition on a preformed solid base. Considering this last condition, three surfaces are qualified as a solid base for deposition of parallel fibered and lamellar bone: woven bone formed in the first period of osseointegration, pre-existing or pristine bone surface and the implant surface. Woven bone formed in the first period of osseointegration Deposition of more mature bone on the initially formed scaffold results in reinforcement and often concentrates on the areas where major forces are transferred from the implant to the surrounding original bone. Pre-existing or pristine bone surface This becomes obvious in sites where implants are surrounded by cancellous bone. Quite frequently, the trabeculae become necrotic due to the temporary interruption of the blood supply at surgery. Reinforcement by a coating with new, viable bone compensates for the loss in bone quality (fatigue), and again may reflect the preferential strain pattern resulting from functional load. The implant surface Bone deposition in this site increases the bone-impIant interface and thus enlarges the load- transmitting surface. Extension of the bone-implant interface and reinforcement of pre- existing and initially formed bone compartments are considered to represent an adaptation of the bone mass to load. Dental implants are less suitable for the demonstration of this inter- relationship than prostheses such as artificial hips, which are preferentially surrounded by cancellous bone that responds almost predictably and rapidly to changes in magnitude and
- 13. direction of load. This justifies the inclusion of some samples taken from our studies dedicated to orthopedic implants in this chapter that otherwise deals with the dental aspects of osseointegration. Adaptation of bone structure to load (bone remodeling and modeling) Bone remodeling characterizes the last stage of 0sseointegration. It starts around the third month and, after several weeks of increasingly high activity, slows down again, but continues for the rest of life. In cortical, as well as in cancellous bone, remodeling occurs in discrete units, often called a bone multicellular unit, as proposed by Frost. Remodeling starts with osteoclastic resorption, followed by lamellar bone deposition. Resorption and formation are coupled in space and time. In cortical bone, a bone multicellular unit consists of a squad of osteoclasts (cutting cone) that form a sort of drill-head and produce a cylindrical resorption canal with a diameter equal to an osteon, that is, 150-200 μm. The cutting cone advances with a speed of about 50 pm per day, and is followed by a vascular loop, accompanied by perivascular osteoprogenitor cells. About 100 μm behind the osteoclasts, the first osteoblasts line up upon the wall of the resorption canal and begin to deposit concentric layers of lamellar bone. After 2-4 months, the new osteon is completed. In the healthy skeleton, resorption and formation are not only coupled, but also balanced, thus maintaining the skeletal mass over a longer time period. If formation does not match resorption, a local deficit in bone mass occurs that accumulates with time and may cause osteoporosis. Histological section illustrating a bone multicellular unit (BMU). Note the presence of a resorption front with osteoclast (OC) and a deposition front that contains osteoblasts (OB), and osteoid (OS). Vascular structures (V) occupy the central area of the BMU. RL = reserval line; LB = lamellar bone.
- 14. Osborn and Newesley 1980 Drawings to show the initiation of distance osteogenesis (A) and contact osteogenesis (B) where differentiating osteogenic cells line either the old bone or implant surface respectively. The insets show the consequences of these two distinctly different patterns of bone formation. In the former the secretorily active osteoblasts, anchored into their extracellular matrix by their cell processes, become trapped between the bone they are forming and the surface of the implant. The only possible outcome is the death of these cells. On the contrary, in contact osteogenesis, de novo bone is formed directly on the implant surface, with the cement line in contact with the implant (insert) and is equivalent to the osteonal interface. Contact osteogenesis Cells participating in contact osteogenesis
- 15. Platelets : 1st cells to migrate towards implant surface (property of microtopography of the rough implant surface) Further activation of platelets at a distant site leading to release of cytokines and growth factors like PDGF and TGF-β
- 16. Activation of osteogenic cells and migration of these cells through the 3 dimensional fibrin matrix towards implant surface Attachment/adhesion of osteogenic cells over implant surface
- 17. Change in cell polarity and secretion of collagen poor calcified osteoid matrix : 1st formed matrix (cement line) Osteoblasts get entrapped to form osteocytes as the new collagen rich osteoid matrix begins to form over the implant surface