A prerequisite for a successful implant treatment is that the implant is placed with primary stability and successfully integrates into the jaw bone in a prosthodontically driven, predetermined position. For osseointegration of the implant to take place, it is essential that the living bone be treated carefully during the procedure to place the implant. Clinicians therefore need to understand the composition and nature of living bone before undertaking dental implant procedures.

The requirement for implants to be placed in the correct prosthodontically determined position often means that there is a lack of bone volume to completely embed the implant. Implants that are not completely covered in bone may be at risk of a variety of complications including soft tissue recession, inflammation and infection due to colonization of the exposed implant surface with bacterial biofilms, and even loss of the implant due to insufficient bone support. Grafting procedures to augment the volume of bone are often necessary to ensure that implants are fully covered in bone. This module will describe the composition and nature of living bone, grafting materials used in dental implantology, as well as the different healing modes of the different grafts.

In the first part of the module, the basic aspects of bone biology will be described. This will be divided into three parts: the anatomy of bone, which can be divided into macroscopic and microscopic anatomy, bone modeling and remodeling, and the components of bone, both cellular and non-cellular.

The skeleton changes over the lifetime of an individual due to growth, modeling, and remodeling. During childhood, these changes are characterized by bone formation and growth, which results in the development of skeletal structures characteristic of adult shape and form.

Nowhere is this process more dramatic than in the growth and development of the cranium from the embryonic stage through postnatal growth into adulthood. During this time, the maxilla and mandible also develop and grow together with the eruption of teeth. The process by which bones acquire their shape and size is called bone modeling. In bone modeling, appositional growth of bone tissue occurs on the outer and inner surfaces of the bones and generally enhances the total amount of bone mass.

Macroscopically, bone is categorized as cortical (or compact) bone and cancellous (or trabecular) bone. In this image of the head of the femur bone, the outer aspect or surface of the bone is cortical or compact bone. The inner or central aspect is cancellous or trabecular bone, as can be seen in this cross section through the femur. The bone marrow is located within the cancellous compartment of bone.

Cortical bone consists mainly of osteons, which are also known as Haversian systems. Each osteon contains blood vessels and nerves in a central canal, surrounded by layers of compact bone. In cross section under a microscope, the osteons often appear as concentric circles.

Cancellous bone consists of a framework of bone organized into a three-dimensional lattice called trabeculae. The spaces are filled with marrow and blood vessels. The bone marrow is a specialized connective tissue which produces red blood cells and many white blood cells, platelets, and bone-forming cells. It also contains fat cells and other connective tissue elements.

Under higher magnification, bone can be further categorized as woven or lamellar. Woven bone is immature bone that forms rapidly during fetal growth or after an injury to mature bone - for example, after a fracture or when a tooth has been extracted. Woven bone forms to quickly fill a defect in the bone, and its collagen fibrils have a random orientation. Woven bone is mechanically weak and is soon replaced by lamellar bone. Lamellar bone is mature bone that has a regular, parallel orientation of the collagen fibrils, which form distinct layers. Lamellar bone is mechanically strong.

Bone remodeling is the process in which bone is renewed. Bone remodeling is essential to regulate the mineral balance in bone in order to maintain bone strength. The stress and strain on bone during normal function results in microdamage. The remodeling process removes the damaged bone and replaces it with new bone. This process allows the body to repair microdamage in bone matrix and to prevent accumulation of microdamage in old bone, which could lead to reduced bone strength and stiffness and reduced resistance to fracture. Remodeling allows bone to adapt to the changing mechanical needs during the lifetime of an individual. If there is an imbalance in the remodeling process, a gradual decrease in bone density can occur over time, causing osteoporosis.

Bone remodeling is a lifetime process of bone renewal and is also referred to as bone turnover. Annual turnover rates are between 30% and 100% in growing children, in contrast to adults, in whom rates of 5% to 15% are expected. There are four stages of bone remodeling. During resorption, specialized cells called osteoclasts are activated and dissolve or resorb old bone. In the reversal phase, bone forming cells or osteoblasts begin to appear on the surface of the resorbed bone. During formation, the osteoblasts lay down new bone or osteoid to completely replace the resorbed bone. The final stage is mineralization, when hydroxyapatite is incorporated into the osteoid. These specialized cells will be described in more detail later in this module. In remodeling, bone resorption and formation are closely coupled. Under normal healthy conditions in adults, bone resorption and apposition during remodeling are balanced in time, space, and amount so that the bone mass of the body remains more or less constant.

Next, the components of bone will be considered. Bone consists of approximately 10% cells and 90% extracellular matrix. The bone cells are the osteoblasts, the bone lining cells, the osteocytes, and the osteoclasts. The extracellular matrix consists of about 35% organic and 65% inorganic material. Each of these components will now be described in more detail.

The cells of the bone will now be described. The osteoblasts are bone cells that form new bone. They are large cells and contain one nucleus. They work in groups to lay down a collagen matrix called osteoid. Osteoblasts also produce growth factors such as the bone morphogenetic proteins, which may stimulate bone healing.

Osteocytes are osteoblasts that become entrapped inside the calcified bone matrix. Approximately 10% of osteoblasts become osteocytes. Osteocytes reside inside small cavities in the bone, the osteocytic lacunae. Osteocytes are interconnected with each other and with the osteoblasts and lining cells on the bone surface. The exact function of the osteocytes is not understood. They are, however, thought to have a role in the regulation of osteoblasts and osteoclasts.

The remaining osteoblasts that do not become osteocytes turn into bone lining cells or undergo cell death. The lining cells occupy the surface of mineralized bone with the primary function of providing nutritional transfer from the surface of the bone to osteocytes within the calcified matrix.

The osteoclasts are the bone resorbing cells and can be seen in this histological section as multinucleated cells lining the surface of the bone where resorption occurs. Resorption is the process by which bone mineral is removed, which is part of the normal bone remodeling process. Multinucleation is thought to improve the efficiency of the cell in resorbing bone.

Next, the extracellular bone matrix will be described. The extracellular bone matrix consists of about 35% organic and 65% inorganic material. About 90% of the organic phase is collagen type I fibers, while the remaining 10% consists of various non-collagenous proteins. The bone matrix also contains growth factors such as the bone morphogenetic proteins important for bone healing. The inorganic phase of bone matrix consists of low-crystallinity carbonated hydroxyapatite.

Basic Aspects of Bone Biology, Key Learning Points: Macroscopically, bone has a cortical and a cancellous compartment. Microscopically, bone is characterized as woven or immature bone, and lamellar or mature bone. Bone is basically composed of 10% cells and 90% extracellular matrix. The main bone cells are osteoblasts, osteocytes, lining cells, and osteoclasts. The extracellular bone matrix is composed of 35% organic and 65% inorganic material. Modeling refers to the formation and growth of bones. Remodeling refers to the continuous, normal turnover of bone.

In the next section, bone grafts and bone substitutes will be described. Bone grafts and bone substitutes may be classified according to their source of origin in relation to the intended recipient. Autogenous bone grafts are obtained from the same individual. They are also referred to as autologous bone grafts. Allogeneic bone grafts are obtained from a genetically distinct individual of the same species, and are also referred to as allografts. In contrast, xenogeneic bone grafts or xenografts are obtained from a different species than the intended recipient. Alloplastic bone substitutes are synthetically produced materials.

Autogenous bone graft or autograft refers to bone originating from the same patient, and it can be harvested from intraoral or extraoral sites. Intraoral bone is commonly harvested from the bone tissue neighboring the defect site, which is a good source of autogenous bone when relatively small volumes of grafting material are required. In cases where larger amounts are needed, bone can be harvested from the anterior mandibular ramus or the mandibular symphysis, as shown in this clinical image. When even larger amounts of bone are needed, extraoral harvesting may be required from donor sites such as the iliac bone, the tibia, and the calvarium. Bone blocks are large pieces of autogenous bone. Autogenous bone that has been harvested by bone scrapers and chisels is in the form of small chips and is referred to as a particulated graft. Particulated grafts can also be made from block grafts by using special milling machines to break down the block.

Allogeneic bone graft or allograft refers to bone originating from another human, either a living donor or a postmortem source. Usually the allogeneic bone is harvested from the iliac bone or tibia and can be fresh-frozen, freeze-dried, or demineralized freeze-dried bone.

Finally, alloplastic bone substitutes or alloplasts are substitutes that are synthetically produced in the laboratory, like hydroxyapatite, beta-tricalcium phosphate, polymers, bioglasses, titanium, or combinations thereof. This is an example of an alloplastic bone substitute that is a biphasic calcium phosphate construct consisting of 60% hydroxyapatite and 40% beta-tricalcium phosphate.

Classification of Bone Grafts and Substitutes, Key Learning Points: Bone grafts and substitutes can be classified depending on their source in relation to the intended recipient. Bone grafts and substitutes may be classified as autogenous bone, allogeneic bone, xenogeneic bone, or alloplastic bone substitute.

Regardless of the type of bone augmentation required, the type of bone graft or bone substitute used should be able to integrate with host bone and/or the implant itself. Different graft types have different mechanisms of action, and the properties of the materials can have an influence on the bone healing outcomes.

There are three recognized mechanisms of action through which bone grafts can integrate with the surrounding host bone: Osteogenesis is the mechanism whereby new bone is formed by osteoblasts that are present in the graft. In autogenous bone grafts, the osteoblasts must survive the transplantation procedure to remain viable and retain the capacity to form new bone. Osteogenesis may also occur via osteoblast cell constructs that are added to bone grafts and bone substitutes. Osteoconduction is the mechanism whereby bone formation is enhanced by providing a scaffold for osteogenic cells that are present in the local environment of the host. These cells migrate and colonize the scaffold and then produce new bone. Lastly, osteoinduction is the mechanism whereby the graft induces bone formation by stimulating undifferentiated mesenchymal cells to turn into osteoblastic phenotypes that produce bone.

Autogenous bone is considered the "gold standard" in most grafting procedures. Depending on the indication for grafting and the amount of graft needed, autogenous bone can be used in a particulated form, as a block graft, or as combination of both. Irrespective the form, autogenous bone graft healing involves a sequence of specific yet overlapping phases. Placement of the graft during surgery results in the formation of a hematoma in the surgical site and around the graft. The surgical procedure also evokes an acute inflammatory reaction consistent with every type of tissue trauma. Apart from inflammatory cells, osteoblast and osteoclast precursors migrate into the wound. Within a day, granulation tissue begins to form through proliferation of vascular elements from the surrounding host bone. Next, osteoclastic resorption of the graft commences, resulting in release of bone morphogenetic proteins from the bone matrix. The release of bone morphogenetic proteins signals the start of osteoinductive activity. In parallel with osteoclastic activity, osteoblasts from the host bed start to migrate into the wound and onto the graft and begin to produce new bone, consistent with osteoconduction. The graft gradually takes part in the normal remodeling process including bone resorption and new bone formation, which eventually leads to incorporation and replacement of the graft.

Incorporation of a bone graft substitute resembles that of autogenous bone. Integration starts with hematoma formation and inflammation, followed by granulation tissue formation. In contrast to autogenous bone, however, bone graft substitute integration proceeds with osteoconduction in the vast majority of bone substitute materials. Bone substitutes do not remodel in the same way that autogenous bone grafts do, but they can undergo resorption to varying degrees, either cell-mediated or by dissolution or both. A large number of bone substitute materials, however, barely resorb at all.

Autogenous bone is the only type of graft that contributes to bone regeneration via all three mechanisms. The osteoblasts in the autograft that survive the harvesting and transplantation procedure are responsible for osteogenesis; the graft itself provides a scaffold for osteoblasts from the host site to migrate into, facilitating osteoconduction; lastly, the growth factors included within the graft matrix and released during graft resorption facilitate osteoinduction. In this context, should it be noted that only a limited number of cells can be expected to survive the grafting procedure. Allogeneic bone grafts may be divided into two categories: mineralized and demineralized. Mineralized allografts - for example, fresh frozen bone allograft and freeze dried bone allograft - contribute to bone regeneration primarily through osteoconduction, but they may also possess some potential for osteoinduction. On the other hand, demineralized freeze dried bone allograft is thought to contribute to bone regeneration primarily through osteoinduction, and only secondarily by osteoconduction. Variation in processing of allogeneic material from tissue banks results in great variation in the osteoconductive potential of demineralized freeze dried bone. Finally, xenogeneic and alloplastic bone substitutes promote bone formation primarily through osteoconduction.

The extent of graft incorporation and replacement, its dimensional stability, and the duration of the healing process all depend on a variety of factors. Among these factors are the type and form of the graft, its corticocancellous composition, the size of the graft, and the size and morphology of the defect. Also, the quality of the surgical procedure itself and aspects related to the systemic health of the host both play a role in the above processes.

Particulated autogenous bone has the advantage of relatively fast incorporation in comparison with autogenous bone blocks. However, it lacks structural stability during the early stages of healing and, depending on the local defect or site anatomy, it often must be contained - for example, by means of a guided bone regeneration membrane or a mesh. Particulated autogenous bone also undergoes extensive and rather unpredictable resorption. In contrast to particulated autogenous bone, bone blocks provide good structural stability from the early phases of healing and show better dimensional stability; however, these require more time to incorporate, and resorption up to 50% of the bone block volume is often observed. The bone blocks require fixation during the healing period.

There is large variation in the physicochemical characteristics of the various bone substitutes available in the market, including their composition, particle size and form, and surface properties. This can also be the case within the same type of bone substitute material. Differences in physicochemical characteristics among bone substitutes may influence the outcome of healing in terms of the amount of new bone formation as well as residual biomaterial in a site grafted with a given bone substitute. Differences in the amount of new bone formation can be due to true differences in the osteoconductive potential of the biomaterial, but may also partly be explained by differences in resorption capacity among the various bone substitutes, which in turn determines the space available for new bone tissue formation within the defect site. For example, beta-tricalcium phosphate is replaced rather quickly, while sintered bovine bone is resistant to resorption and will be present in the augmented site for decades.

Bone Graft Healing, Key Learning Points: There are three mechanisms of action by which bone grafts and substitutes promote bone regeneration: osteogenesis, osteoconduction, and osteoinduction. Only autogenous bone grafts promote bone regeneration by all three mechanisms. Allogeneic grafts promote bone regeneration by osteoconduction and osteoinduction. Xenogeneic and alloplastic materials promote bone regeneration by osteoconduction.

Autogenous bone and bone substitute grafts heal in phases. Different characteristics among bone substitutes, and even within the same type of substitute, dictate performance in terms of bone formation. Autogenous particulated bone incorporates faster compared to a bone block but has less dimensional stability. Bone formation in a bone substitute-grafted defect depends on the osteoconductive potential of the material and its capacity to resorb.

Biological Principles of Bone Grafting, Module Summary: Bone is comprised of several types of cells and a mineralized matrix. Bone grafts can be classified as autogenous, allogeneic, xenogeneic, or alloplastic. There are three mechanisms of action by which bone grafts promote bone regeneration: osteogenesis, osteoconduction, and osteoinduction. Only autogenous bone grafts promote bone regeneration by all three mechanisms; xenografts and allografts may promote bone regeneration by osteoconduction. Autogenous particulated bone incorporates faster compared to an autogenous bone block but has less dimensional stability. Bone formation in a bone substitute-grafted defect depends on the osteoconductive potential of the material and also on its capacity to resorb.