Extract_Bone, Biomaterials & Beyond

Contents

Surgical Approaches........................................................37 Factors Influencing the Clinical Outcome ......................38 Anatomy of the Lesion.................................................38 Patient-Related Factors................................................45 Clinical suggestions ....................................................45 Conclusions.....................................................................45 Recommended Reading...................................................46

CHAPTER 1

An Introduction to Guided Bone Regeneration...........................1 Ugo Covani, Massimiliano Ricci, Simone Marconcini

Bone Biology......................................................................1 General Aspects.............................................................1 Cortical (Compact) Bone..............................................1 Cancellous (Spongy or Trabecular) Bone.......................2 Cellular Components....................................................3 Bone Matrix..................................................................4 Marrow.........................................................................4 Blood Flow in Bone.......................................................5 Tissue Engineering............................................................5 Basic Principles.............................................................5 Design and Production of Scaffolds................................5 Bone Healing: A Cellular Mechanism...........................7 Guided Bone Regeneration................................................8 Introduction..................................................................8 Bone Surface...............................................................10 Bone Defect Features...................................................10 Membranes .....................................................................11 Biomaterials.....................................................................11 Classification..............................................................12 Conclusion......................................................................13 Recommended Reading...................................................17

CHAPTER 4

Fresh Extraction Socket Management........47 Antonio Barone, Adriano Piattelli, JosĂŠ Luis Calvo-Guirado, Fortunato Alfonsi, Bruno Negri, Giovanna Iezzi

Background......................................................................47 Indications and Contraindications for Ridge Preservation......................................................59 Indications and Contraindications for Immediate Implantation.............................................59 Surgical Technique..........................................................59 Fresh Extraction Socket Management..........................62 Ridge Preservation.......................................................62 Immediate Implant......................................................66 Conclusion......................................................................69 Recommended Reading...................................................69 CHAPTER 5

Maxillary Sinus Augmentation.......................71

CHAPTER 2

Bone Tissue Reactions to Bone Substitutes.............................................. 19

Paolo Martegani, Ferdinando D’Avenia, Maurizio Silvestri, Sanjiv Kanagaraja

Lars Sennerby, Ulf Nannmark

Background......................................................................71 Indications and Contraindications based on Anatomy and Physiopathology of the Maxillary Sinus.....................71 The Transcrestal Approach in Maxillary Sinus Augmentation.....................................73 Grafting Biomaterials for Sinus Lift Procedures..............74 Sinus Lift via the Lateral Approach Technique................75 Osteotomy Window Technique (Window Wall In Situ)................................................76 Osteoplasty Window Technique (Window Wall Removed).............................................76 Membrane Separation.................................................76 Membrane Elevation...................................................77 Sinus Grafting Procedures...........................................78 Sinus Grafting Procedures combined with Crestal Reconstruction............................................................78 Conclusion......................................................................91 Recommended Reading...................................................91

Introduction..................................................................... 19 Mechanisms of Bone Healing.......................................... 19 Healing of Autogenous Bone Grafts.................................21 Incorporation of Various Bone Substitutes.......................21 Tissue Reactions to Porcine Bone Substitutes.................24 Conclusion .....................................................................27 Recommended Reading...................................................29 CHAPTER 3

Periodontal Regeneration.................................31 Roberto Rossi, Maria Gabriella Grusovin, Tobias Thalmair, Hannes Wachtel

Background......................................................................31 Treatment Options for Infrabony Defects........................32 Materials for Regeneration..............................................35 XI

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Contents

Techniques for Soft Tissue Correction around Teeth.....137 Coverage of Gingival Recessions with Autografts........137 Coverage of Gingival Recessions with Xenografts........137 Techniques for Soft Tissue Management around Implants.............................................................142 Soft Tissue Management in the Aesthetic Zone...........142 Soft Tissue Augmentation at the Time of Extraction or Implant Placement...............................142 Socket Preservation Combined with Soft Tissue Augmentation............................................................142 Immediate Implants...................................................145 Delayed Implant Approach........................................145 Soft Tissue Augmentation following Implant Placement.........................................148 Soft Tissue Augmentation in the Functional Zone.........151 Soft Tissue Management with Xenografts......................154 Conclusion....................................................................156 Recommended Reading.................................................156

CHAPTER 6

The Bone Lamina Technique: A Novel Approach To Bone Augmentation.........................................................93 Hannes Wachtel, Christian Helf, Tobias Thalmair

Background......................................................................93 Biocompatibility..........................................................93 Tissue Integration........................................................93 Cell Occlusivity..........................................................94 Space-making Properties..............................................94 Clinical Applications........................................................94 Technique........................................................................96 Conclusion....................................................................102 Recommended Reading.................................................106 CHAPTER 7

Reconstruction of Horizontal Ridge Defects......................................................................107

CHAPTER 10

Arndt Happe, Christer Slotte

Surgical Treatment of Peri-Implant Bone Lesions.........................157

Background....................................................................107 Treatment Options in the Reconstruction of Horizontal Ridge Defects.......................................107 Autogenous Bone Grafts................................................107 Xenogenic Bone Grafts..................................................109 The Bone Lamina Technique.....................................109 Clinical Application..................................................110 The Dual-Block Technique........................................110 Treatment Concept....................................................115 Conclusion ...................................................................118 Recommended Reading.................................................118

Christer Slotte

Background....................................................................157 Case Presentations........................................................158 Case 1.......................................................................158 Case 2.......................................................................158 Case 3.......................................................................160 Case 4.......................................................................160 Case 5.......................................................................160 Discussion.....................................................................165 Conclusion....................................................................165 Recommended Reading.................................................166

CHAPTER 8

The Inlay Technique in the Treatment of Posterior Mandibular Atrophy................119

CHAPTER 11

Treatment of Extreme Cases..........................167

Pietro Felice, Roberto Pistilli, Carlo Barausse

Patrick Palacci

Background....................................................................119 Indications and Contraindications.................................122 Surgical Technique........................................................122 Conclusions...................................................................133 Recommended Reading.................................................133

Background....................................................................167 Case Presentations........................................................167 Case 1.......................................................................167 Case 2.......................................................................171 Case 3.......................................................................175 Case 4....................................................................... 175 Recommended Reading................................................. 175

CHAPTER 9

Soft Tissue Augmentation..............................135 Stefan Fickl

Background....................................................................135 Indications for Soft Tissue Augmentation......................136 Scientific Significance of Soft Tissue Augmentation around Teeth.............................................................136 Scientific Significance of Soft Tissue Augmentation around Dental Implants............................................136 Use of Biomaterials in Soft Tissue Augmentation........136

Conclusions............................................................. 183 Antonio Barone, Ulf Nannmark

Index.............................................................................. 185

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An Introduction to Guided Bone Regeneration* Ugo Covani, Massimiliano Ricci, Simone Marconcini

Bone Biology General Aspects Bone tissue can be broadly defined as connective tissue specialised in the supporting function. It originates from the mesenchymal tissue and is made up of cells and an intercellular substance which contains a large number of collagen fibres. The main feature of such an intercellular substance is that it is rich in minerals–this is what is responsible for its strength, hardness and resistance to pressure, traction and torsion. From a macroscopic point of view, two varieties of bone exist: cortical and cancellous/trabecular bone.

Cortical (Compact) Bone Cortical or compact bone (Figure 1.1) is made up of a structure of Haversian systems, or osteons. Each osteon is a cylinder running parallel to the long axis of the diaphysis. In the centre of each osteon is the so-called Haversian canal which is lined with endosteum containing blood vessels, nerves and loose connective tissue. Surrounding each canal are 4-20 concentric lamellae of collagen fibres. The Haversian canals are round or oval in cross section. They generally run in a longitudinal direction. Each osteon communicates with the marrow cavity, the periosteum, and with each other through transverse or oblique canals–the Volkmann’s

Fig. 1.1 Compact cortical bone with small marrow spaces can be observed (Acid fuchsin-toluidine blue 40×).

(*) The histological images have been kindly supplied by Prof. Adriano Piattelli (University of Chieti-Pescara, Italy) and his team.

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canals. The osteocytes are arranged circumferentially around the central canal in parallel with the lamellae and are interconnected by fine processes of osteocyte cytoplasm–the filopodia.

The osteocytes are housed in lacunae interconnected by canaliculi containing these fine cytoplasmic processes. Irregular areas of lamellar bone are present between the Haversian systems, or interstitial lamellae. These are remnants of previous Haversian systems which have been remodelled. Each osteon is separated from its neighbour and from interstitial lamellae by a cement line which stains darkly with haematoxylin. The outermost and innermost layers of cortical bone contain no Haversian canals, and the lamellae are arranged parallel to the periosteal and endosteal surfaces to form the so-called circumferential lamellae (outer and inner circumferential lamellae).

Cancellous (Spongy or Trabecular) Bone Cancellous or spongy bone consists of a series of interconnecting plates of bone–the trabeculae. Each bone trabecula contains collagen fibres arranged in parallel lamellae. The surface of the trabecula is covered by an attenuated layer of flattened cells–the resting osteoblasts.

Such a structure, in addition to providing a large surface area for metabolic activities of bone, gives mechanical strength without the disadvantages of undue weight (Figure 1.2).

The thickest and strongest trabeculae are arranged in the direction subjected to the greatest stress (according to Wolff ’s Law).

From a histological point of view, cancellous bone consists of two main types: ●● Primary bone tissue (non-lamellar bone). This bone is also known as “coarse-fibred”, “woven” or immature bone. It is characterised by the presence of randomly orientated coarse collagen fibres clearly visible under polarisation microscopy (Figures 1.3-1.4). Non-lamellar (woven) bone is seen in the bones of foetuses and young children. It is the osseous tissue first deposited on the calcified cartilage matrix in endochondral ossification; moreover, it is the first tissue to appear in the repair of bone (fracture healing). ●● Secondary bone tissue (lamellar bone). This bone is also known as mature bone. It is characterised by the presence of collagen fibres arranged in parallel layers or sheets (lamellae) readily apparent when viewed under polarisation microscopy. Lamellar bone is present in both structured types of adult bone, cortical (compact) bone and cancellous (spongy or trabecular) bone.

a

b

Fig. 1.2 a) Haversian systems in the cortical compact bone are present (Acid fuchsin-toluidine blue 100×); b) Haversian systems are present in the cortical compact bone. Presence of collagen fibres with a parallel orientation, as occurs in lamellar bone, can be observed (Polarised light 100×).

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Fig. 1.3 Immature bone and lamellar bone are present. In some areas, the newly formed bone appears to be undergoing a remodeling process (Acid fuchsin-toluidine blue 40×).

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Fig. 1.4 Immature bone and lamellar bone are observed. Presence of collagen fibers with a parallel orientation, as occurs in lamellar bone, can be observed (Polarised light 100×).

Cellular Components Bone is a highly specialised type of connective tissue consisting of cells and an intercellular matrix. There are three cell types: ●● Osteoblasts. The bone-forming cells, located on the surfaces of bone lying side by side like a simple cuboidal epithelium (Figure 1.5). These cells are responsible for the synthesis of organic components of the bone-matrix (Figure 1.6). When active, they show high alkaline phosphatase activity. ●● Osteocytes. The cells occupying the lacunae in the bone matrix (Figure 1.7). They possess long thin cytoplasmic processes, the filopodia, located in thin cylindrical spaces or canals in the bone matrix. Nutrients and oxygen pass between the blood vessels and distant osteocytes by the arrangement of the canaliculi. Osteocytes also break down the bone matrix by osteocytic osteolysis to release calcium for calcium homeostasis. ●● Osteoclasts. Large, multi-nucleated cells formed by the fusion of monocytes. They lie in shallow depressions on the bone surface called the Howship’s lacunae.

Fig. 1.5 Woven bone and rim of osteoblastic cells near a blood vessels can be detected (Acid fuchsin-toluidine blue 100×).

Fig. 1.6 Woven bone and rim of osteoblastic cells that actively produce osteoid matrix (Acid fuchsin-toluidine blue 200×).

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a

b

Fig. 1.7 a-b) Woven bone with wide osteocyte lacunae and osteoid matrix can be seen (Acid fuchsin-toluidine blue 200×).

Bone Matrix The bone matrix is composed of: ●● Organic matter. Consisting of type I collagen fibres embedded in a ground substance containing proteoglycans and glycoproteins. The collagen fibres are made up of bundles of fibrils which resist the pulling forces. ●● Inorganic matter. Inorganic matter consists of stiffening substances designed to resist bending and compression. The bone mineral is an analogue of crystals of calcium phosphatecalcium hydroxyapatite (Ca10(PO4)6(OH)2), a substance that can only be seen under electron microscopy. It is this association of hydroxyapatite with collagen fibres which is responsible for the hardness of bone.

Marrow This tissue fills the cylindrical cavities of long bones and occupies the spaces of cancellous bones. In long bones, marrow is yellow in colour consisting mainly of fat cells and some marrow cells (Figure 1.8). In contrast, the marrow in flat and short bones is red in colour and contains connective tissue, blood vessels and numerous “marrow cells”–myelocytes, erythroblasts, giant cells and some fat cells (Figure 1.8). The marrow bone is the organ of haematopoiesis. This process occurs in all bones at birth. With maturation, haematopoiesis is confined to the vertebral column, the bones of the pelvic girdle, the ribs, skull and the proximal end of long bones.

Fig. 1.8 Fig 8 Trabecular bone with wide marrow spaces is present (Acid fuchsin-toluidine blue 40×).

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Blood Flow in Bone The basic components of the vascular system, the principal nutrient artery and the metaphyseal arteries, carry blood from the circulation almost exclusively into the medulla. The intravascular pressure in the medulla is higher than in the periosteal area. This pressure gradient is the chief factor maintaining the blood flow in bone centrifugally. The periosteal arterioles convey blood to the diaphyseal cortex only along the heavy fascial attachments.

Their terminal branches anastomose in the cortex with the terminal branches of the medullary arterial system. The medullary arterial supply provides circulation to the inner two-thirds of the cortex, leaving the periosteal arterial supply to provide circulation to the remaining outer third of the cortex.

Tissue Engineering Basic Principles The goal of tissue engineering and regenerative medicine is the implementation of techniques to create a product, which, in this case, is bone tissue. The most important aspect of this subject is the investigation of the interactions between cells with the matrix and environmental factors. In response to this interaction, cells may proliferate and produce matrix molecules.

Biomaterials are used in tissue engineering and regenerative medicine as a scaffold. Regardless of their composition, biomaterials should be chosen bearing a number of factors in mind: 1. The scaffold must have a microstructure able to accommodate cells and their functions– a porous structure is generally necessary. The adequate porosity and the required pore diameter and pore orientation can vary with tissue type.

2. The scaffold has to be adsorbable. The degradation rate of the material may be determined based on the rate of new tissue formation and the normal period for remodelling of the tissue at the implantation site.

3. The mechanical proprieties of the biomaterial employed as a scaffold are important for providing temporary support of applied loads and for resisting the contractile forces that may be exerted by the seeded cells prior to implantation. The stiffness of the scaffold is also important because it affects the strain in the ingrown and surrounding tissues.

It should be considered that the scaffold plays a different role during the regeneration process: it serves as a framework to support cellular migration into the defect from surrounding tissues. Before it is adsorbed, a scaffold can serve as a matrix for cell adhesion and can facilitate and regulate certain cellular processes, such as mitosis synthesis and migration. This may be mediated by ligands for cell receptors. Moreover, the scaffold may serve as a delivery vehicle for exogenous cells, growth factors and genes. The scaffold reinforces the defect to maintain the shape of the defect and prevents distortion to the surrounding tissue. Finally, a scaffold can serve as a barrier to prevent the infiltration of other tissues.

Design and Production of Scaffolds Many methods have been used to produce porous materials suitable for use as scaffolds: ●● Manipulation of fibres into non-woven and woven structures. ●● Incorporation of sacrificial pore-forming agents including ice and soluble particles. ●● Use of self-assembling molecules. ●● Use of solid free form fabrication.

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The natural tissue regeneration requires three components that must be present and work together: cells, signal and matrix (or scaffold) (Figure 1.9). This concept of a triangular set of elements means that an absence or dysfunction of any one element will halt tissue regeneration.

Cells Cells are thought to be pluripotent stem cells or cells that have only partially differentiated along their lineage. In bone regeneration, the cells range from CD34 marrow cells or colony forming unit cells, at their earliest stages, all the way to the preosteoblasts cells and even the endosteal or periosteal osteoblasts.

Signals The signals are the growth and differentiation factors including the PDGFs, several forms of transforming growth factors, among which numerous BMPs are included. These growth factors act on the external cell membrane receptors to stimulate an expression of a normal gene.

Matrix (or scaffold) The matrix is a scaffold or latticework on which tissue is grown and over which cells migrate.

Considering allogenic or xenogenic bone as a scaffold is not exactly correct. The actual biologic scaffold is exposed collagen and the cell adhesion molecules, fibrin and fibronectin form plasma and vitronectin secreted by platelets. The value of any biomaterial is its ability to adhere these molecules on its surface. This also remains true for dental implants. The bone contact is not directly on the titanium surface but is mediated by these molecules that are first deposited. Osteoblasts secrete a cementing line of sialoprotein and osteopontin into which actual bone becomes stabilised.

Matrix

Signal

Cells

Fig. 1.9 This drawing shows the three components involved in bone regeneration: matrix, cells and signal.

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Bone Healing: A Cellular Mechanism When a drill penetrates into bone marrow, stem cells and endosteal osteoblasts are exposed.

In addition, the cavity, which has just been formed, is progressively filled by blood containing a large number of platelets. If we insert a biomaterial in this cavity, its surface is surrounded by a blood clot in the microspace between bone and the implant surface. In the first phase, platelet degranulation releases PDGF-AA/AB/BB and TGF beta 1 and beta 2, vascular endothelial growth factor, epidermal growth factor and vitronectin. Moreover, the clotted plasma fraction of the blood deposits fibrin and fibronectin on the biomaterial surface and forms a connection bridge between the bony wall and the same biomaterial surface. The released growth factors act on the exposed marrow cells, endothelial cells and endosteal osteoblasts to generate an angiogenic and mitogenic effect in addition to migrations and cellular differentiation (Figure 1.10). As cells divide, they push daughter cells forward in a “creeping substitution� and as the parent osteoblast matures, it secretes an osteoid and becomes an osteocyte. Continued cellular division and the creeping substitution process, bridges the space between the drill site wall and the biomaterial.

This biomaterial represents the matrix on which the cell adhesion molecules (from blood and platelet) can adhere, connecting the graft particles more tightly together and to the bone walls. The signals come from the growth factors when the platelets degranulate into the blood clot, while the cells come from open marrow spaces (Figure 1.11).

Fig. 1.10 When a biomaterial is inserted in a cavity, its surface is surrounded by a blood clot. Moreover, the clotted plasma fraction of the blood deposits fibrin and fibronectin on the biomaterial surface and forms a connection bridge between the bony wall and the same biomaterial surface.

Fig. 1.11 The released growth factors act on the exposed marrow cells, endothelial cells and endosteal osteoblast to generate an angiogenic and mitogenic effect in addition to migrations and cellular differentiation.

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Guided Bone Regeneration Introduction Guided Bone Regeneration (GBR) was invented as a therapy in order to achieve bone regeneration via the use of barrier membranes. The concept, behind this technique, seeks to create a secluded anatomic site to promote healing. It was first introduced 50 years ago, when cellulose acetate filters were experimentally used for the regeneration of nerves and tendons.

Other authors reported new bone formation beneath plastic cages adapted over decorticated femoral defects in the dog. Later animal studies reported enhanced osseous healing of rib, radial and femoral bone defects via the application of cellulose acetate and Millipore filters.

In the maxillofacial area, successful results have also been reported following the placement of mechanical barriers over jawbone defects in rabbits and over cranial defects in rats. These experimental studies provided significant evidence that bone regeneration is significantly enhanced when the invasion of soft tissue into osseous defects is mechanically impeded.

However, in these early studies, most authors attributed the success of the barriers to the preservation and protection of the blood clot rather than to the colonisation of the secluded space created by the osteogenic cell population.

Several years ago the Guided Tissue Regeneration (GTR) principle was introduced, according to which, regeneration of a certain type of tissue is achieved when cells with the capacity to regenerate the particular type of lost tissue are allowed to populate the defect during healing.

The GBR treatment concept originates from the GTR principle. As a result, the GBR rationale advocated the mechanical exclusion of undesirable soft tissues from growing into the osseous defect, thereby allowing only osteogenic cell populations derived from the parent bone.

The GBR technique involves the surgical placement of a cell occlusive membrane facing the bone surface, in order to physically seal off the skeletal site requiring regeneration. Furthermore, the membrane creates and maintains a secluded space thus providing an environment for the osteoprogenitor cells. GBR allows new bone formation in areas where vertical and/or horizontal defects are present. The basic principle of this technique is to create an area close to vital bone which may contain a protected blood clot without forces which could dislocate it.

Considering the above, three components are necessary: ●● a membrane which is able to prevent blood clots from instability due to muscular action; ●● a biomaterial which can improve stability of the clot and sustain the overlying membrane from collapsing into the defect; ●● and adjacent vital bone which can offer vascular support.

GBR follows a series of events similar to other processes of osteogenesis. In order to explain such phases we can easily divide this process into three different parts: Phase 1: Spongy Bone Formation (4-6 weeks) It includes clot formation and migration of blood vessels from the neighbouring bone in the area of regeneration. This allows osteoid tissue to be obtained which is made up of woven bone around new blood vessels. It should be noticed that in the case of four-wall defects, this process starts from the periphery to the centre; whereas, in two-wall defects the process, which is more difficult for the absence of surrounding bone, starts from the centre towards the periphery (centripetal) (Figures 1.12). In this phase, the central part has still not regenerated and it includes connectival fibres without any orientation, fibroblast and disorganised new vessels.

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a

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b

Fig. 1.12 a-b) Phase 1 includes formation of blood vessels from the neighbouring bone in the area of regeneration. This allows one to obtain osteoid tissue from the centre to the periphery.

Phase 2: Spongy Bone Maturation and Cortical Bone Formation (2-3 months) The osteoid tissue is progressively mineralized, and in the peripheral areas new cortical bone is present which is made up lamellar bone. Lamellar bone is slower to appear as it needs the formation of parallel collagen fibres (Figure 1.13).

Phase 3: Maturation of Cortical Bone and Remodelling (after 4 months) A large number of osteoclasts eliminate fibrous tissue and new osteoblasts deposit lamellar bone with a reduction of connective tissue. In the peripheral area we can see cortical bone deposition, while in the centre new spongy bone (much more similar to native bone) is formed (Figure 1.14).

All these phases can be modified depending on the characteristics of the defect that the oral surgeon has to treat.

Fig. 1.13 Augmented bone. Formation of bone trabeculae, composed by not yet mineralised matrix and woven bone, is noticeable; large osteocyte lacunae can also be observed (Acid fuchsin-toluidine blue 40Ă—).

Fig. 1.14 Preexisting cortical compact mature bone and woven bone can be distinguished by the different affinity for the staining. Specifically, the mature bone appears lightly stained, whilst the immature bone is shows a strong affinity for the staining (Acid fuchsin-toluidine blue100Ă—).

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Bone Surface It is crucially important that the area to regenerate has a sufficient amount of medullary bone under the cortical part. This is fundamental because by perforating the cortical layer some advantages can be obtained. First of all, an increase of growth factors concentration can be gained. In addition, a large number of osteoblast cells can migrate into the medullary areas more easily. Finally, new blood vessel formation can be promoted.

Considering the above, the presence of a large cortical layer represents an important disadvantage because of the insufficient angiogenesis which may jeopardise bone regeneration.

It should be finally kept in mind that, although perforation of the cortical layer is universally considered as the optimal choice, there is no scientific evidence that this behaviour is really useful. Experiments in rabbit calvaria have shown that no advantages in healing were offered by perforating cortical bone.

Bone Defect Features The features of bone defects as well as dimensions can influence the result of bone regeneration. Considering their capacity to maintain the biological space unaided, we can divide bone defects into those that self-maintain space and those are not self-maintaining. For instance, a postextractive alveolus – if intact – can be considered easy to regenerate since its walls can contain and protect blood clots. On the other hand, flat defects including the edentulous area or area with fenestration prove difficult to regenerate.

On the basis of these considerations the bone defects that require a GBR procedures can be identified as vertical or horizontal; even though the blood clot stability seems to be more difficult in the case of vertical bone defects.

Intrabony Defects This is a four-wall defect where cortical areas are preserved. This is the most favourable defect since the blood clot remains stable.

Horizontal Defects According to the classification of L. Vanden Bogaerde, we can observe two types: ●● Closed defects: where the walls close to the implant are well maintained. ●● Open defects: where one or more walls surrounding the implant are missing.

Vertical Defects These are most common in the posterior parts of maxilla and mandible. They require increased bone volume in order to place an implant (Case Report 1).

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Membranes The function of a membrane is to protect a clot and avoid muscular traction without angiogenesis. A membrane has to satisfy the following requirements: ●● It should be biocompatible so as to avoid dangerous reactions. ●● It should be selectively permeable so as to allow molecular exchange. ●● It should have adequate mechanical features so as to maintain a stable clot. ●● It should be easy to apply and modify.

We can divide membranes into two main types: non-resorbable and resorbable membranes.

Non-resorbable Membranes Non-resorbable membranes have been the most commonly studied. They are made up of expanded polytetraflurethylene, which allows molecular diffusion and acts as a barrier for cells. In addition, it has an ideal rigidity for manipulation. This membrane has two parts: the internal layers which are able to protect the biomaterial, and the external layer which is much more porous allowing the growth of soft tissue. Some types of these membranes have an internal structure in titanium which increases their capacity to maintain volume.

The main disadvantage in their use is the need for a second intervention in order to remove them; moreover, the possibility of infection is quite probable in case of exposure. This fact can induce the necessity of a rapid removal. Titanium membranes represent a second type of non-resorbable membrane. Their use is ideal when combined with autologous bone.

Their exposure is not considered dangerous because the literature has demonstrated a reepithelisation of the overlying tissue.

Resorbable Membranes The need for a second intervention has provided a stimulus to look for other types of membrane; in fact, resorbable membranes were essentially developed to overcome this main drawback. Moreover, the scientific literature does suggest that the complication of possible exposure is minimal. However, the rate of resorption is not predictable as it depends on individual characteristics. Collagen membranes are the most used–they are produced using animal tissues and their resorption takes from 4 to 8 weeks. The main advantages are the direct participation of such a membrane in the formation of a clot and chemotactic activity.

Nowadays some types of cross-linked collagen membrane have been produced. They demonstrate more resistance to degradation and seem to be a possible way forward to achieve a predictable regeneration.

Biomaterials The main function of a biomaterial is the maintenance of an adequate space between bone and membrane in order to stabilise the clot, and avoiding the collapse of the membrane which represents the most frequent cause of failure. The use of biomaterials should be carefully evaluated considering the goal of intervention. If a surgeon wants to obtain tissue in order to reconstruct the anatomy for aesthetical reasons, he can use any biomaterial provided that it is biocompatible and inert. However, in most cases, the scope of periimplant reconstructive surgery is to obtein functional bone which is able to osteointegrate a dental implant. This means that the ideal biomaterial should be gradually reabsorbable and remodelled by bone.

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Classification Biomaterials for graft procedures can be classified as autogenous, allograft, xenograft and synthetic materials.

Autogenous Grafts Autogenous biomaterials have been used in dentistry and oral maxillofacial surgery for over thirty years. They are used for bone regeneration and currently are considered the gold standard in bone grafts due to their osteogenetic, osteoconductive and osteoinductive features.

Graft integration in a bone defect needs correct vascularisation both through neo-synthesised vessels and via anastomosis between the vessels of the receiving site and newly formed vessels in the bone graft.

There is no immunological response to autologous grafts. The main disadvantages are increased surgical time, need for a second site and limited quantity available to the surgeon.

Allografts Vital bone tissue is obtained from donors and it is stocked in bone banks. The use of homologous grafts is still controversial due to the risk of infection; in particular, the risk of contracting HIV is estimated to be 1:1.6 million, compared with 1:450,000 in blood transfusions.

Rigorous background checks must be made on the donor and his/her family. Homologous grafts, before their use, are tested and treated to prevent any risk of antigenicity or disease transmission.

The bone should be lyophilised and demineralised (Demineralised Freeze-Dried Bone, DFDB) or only lyophilised (Freeze-Dried Bone, FDB).

Xenografts Heterologous materials are obtained from bones of different animal species–bovine bone being the most common source. Xenografts have different properties according to their origin, composition and processing. ●● Bovine grafts. These biomaterials are made of apatite crystals in a reticular form, with an inside surface of about 70 m2/g which induces coagulum synthesis and stability. Many authors have confirmed their osteoconductive properties. Nevertheless, there is always a risk of transmission of CJD or Bovine Spongiform Encephalopathy according to the Food and Drug Administration (FDA) and therefore the origin of the bovine tissues must be carefully selected and evaluated. With these grafts the manufacturer’s preparation should be carefully considered. It is evident that the higher the temperature of sinterization of the bone particles, the more difficult is its capacity to be reabsorbed. ●● Collagenated porcine grafts. This is a xenogeneic bone substitute consisting of sterilised porcine bone in the form of particles with a high porosity: collagen contributes to mineral deposition, vascular ingrowth and growth factor binding, thus providing a favourable environment for bone regeneration. The scientific literature has demonstrated that this biomaterial is similar to human bone, and it has been reported, in humans, to be osteoconductive, well integrated in the host site and incompletely resorbed after 5 months, and with no signs of adverse reactions in a rabbit study. In a previous light microscopy and transmission electron microscopy study, it was found that the material was biocompatible, well integrated in the host bone and osteoconductive.

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Alloplastic Grafts Alloplastic grafts are synthetic bone substitutes that are available in different sizes, forms and textures. The structural characteristics of the alloplastic grafts are similar to bone tissue. ●● Hydroxyapatite allografts. Hydroxyapatite is a natural component of hard tissue (65% in bone tissue, 98% in enamel). Synthetic hydroxyapatite is available in different forms: porous, non-porous, ceramic and non-ceramic. This material has been used in GBR techniques to coat implants, due to its osteointegrative capabilities. Hydroxyapatite is bioinert and biocompatible, but it does not induce significant bone regeneration. ●● Tricalcic phosphate grafts. Ca3(PO4)2 is treated with naphthalene and then is compacted at 1100-1300 °C to obtain a diameter of 100-300 mm. Moreover, during resorption, it provides ion calcium and magnesium to bone tissue and so creates a correct ionic environment, which induces alkaline phosphatase activation–fundamental for bone synthesis. ●● Bioglass grafts. Synthetic glass ceramics are made of silicon dioxide (45%), sodium oxide (24.5%) and phosphorus pentoxide. The bioglass is used mainly in maxillary sinus lifts and is characterised by particles with a diameter of 300-335 mm. Bioglass has osteoconductive properties and their solubility is directly dependent on sodium oxide. ●● Coralline hydroxyapatite grafts. Coralline hydroxyapatite is composed of calcium carbonate (87-98%), strontium, fluoride, magnesium, sodium and potassium (2-13%). It has a porous structure (over 45%) and the pores have a diameter of 150-500 mm. The coralline hydroxyapatite has osteoconductive properties and the resorption of the coralline skeleton is due to the action of the carbonic anhydrase of osteoblasts.

Conclusion There are several key elements which are involved in a successful bone augmentation: the membrane, biomaterial and implant surface used, and the manufacturer’s preparation. First of all, the membrane has to stabilise and protect the blood clot and biomaterial, thus preventing them from detachment and to guarantee new tissue formation. Secondly, the biomaterial plays a crucial role. The clinicians should consider that if the aim of the graft seeks to improve aesthetics, the ideal biomaterial should be slow to be resorbed or non-resorbable, and as a result a high percentage of hydroxyapatite is expected. On the other hand, when the goal of the treatment is to obtain bone a gradually resorbable biomaterial is ideal. Thirdly, the clinicians should consider the manufacturer’s preparation so as to evaluate the temperature of sinterisation of the bone particles: a higher temperature means a difficult resorption. Lastly, the clinician should consider the area surrounding the implant surface. It is surprising that, although commercially pure titanium is the prime material for dental implants, the success rates of different commercially available implants may vary. Several implant-related factors – such as implant surface topography, chemical composition and surface roughness – that influence osteointegration have been studied. Nowadays, the roughness of a biomaterial is considered a crucial parameter for clinical success. Le Guehennec et al. (2007) concluded in their review that surface roughness did enhance osteointegration of dental implants.

In conclusion, clinicians need to be aware that a successful regeneration procedure is dependent on an evaluation of all these factors balanced together.

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CASE REPORT 1

1 - Bone Augmentation after Implant Failure

C1.1 Implant rehabilitation with an asymmetry of gingival scallops.

C1.2 Periapical radiograph showing a peri-implant bone loss.

C1.3 A mucoperiosteal flap has been raised and a peri-implant bone loss has been observed in the vertical direction.

C1.4 Large horizontal bone defect has been observed.

C1.5 Implant was removed and a residual bone defect can be evaluated.

C1.6 Corticocancellous porcine bone was grafted (occlusal view).

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Bone Augmentation after Implant Failure

CASE REPORT 1

C1.7 Corticocancellous porcine bone was grafted (facial view).

C1.8 Collagen membrane was placed and a soft tissue primary closure was obtained.

C1.9 Soft tissue healing after 1 week (occlusal view).

C1.10 Soft tissue healing after 3 weeks (occlusal view).

C1.11 Soft tissue healing after 6 weeks (facial view).

C1.12 Periapical radiograph showing bone healing after 4 months.

➌

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Bone Augmentation after Implant Failure

C1.13 Soft tissue healing after 6 months ( facial view).

C1.14 Bone augmentation after 6 months.

C1.15 Implant placement in augmented bone.

C1.16 Periapical radiograph showing implant placed in augmented bone.

C1.17 Final restoration 1 year after implant placement.

C1.18 Periapical radiograph showing bone healing 1 year after implant placement.

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An Introduction to Guided Bone Regeneration

CHAPTER 1

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Baldini N, De Sanctis M, Ferrari M. Deproteinized bovine bone in periodontal and implant surgery. Dent Mater 2011;27(1):61-70.

Barone A, Crespi R, Aldini NN et al. Maxillary sinus augmentation: histologic and histomorphometric analysis. Int J Oral Maxillofac Implants 2005;20:519-525.

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J Am Acad Orthop Surg 2013;21(1):51-60.

Hammouche S, Khan W et al. Calcium salts bone regeneration scaffolds: a review article. Curr Stem Cell Res Ther 2012;7(5):336-346. Review.

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Monaco E, Bionaz M, Hollister SJ, Wheeler MB. Strategies for regeneration of the bone using porcine adult adipose-derived mesenchymal stem cells. Theriogenology 2011;75(8):1381-1399.

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Orsini G, Scarano A, Piattelli M et al. Histologic and ultrastructural analysis of regenerated bone in maxillary sinus augmentation using a porcine bone derived biomaterial. J Periodontol 2006;77:1984-1990.

Ratcliffe A. The translation of product concept to bone products: a partnership of therapeutic effectiveness and commercialization. Tissue Eng Part B Rev 2011;17(6):443-447.

Retzepi M, Donos N. Guided Bone Regeneration: biological principle and therapeutic applications. Clin Oral Implants Res 2010;21(6):567-576.

Ruff CB, Garofalo E, Holmes MA. Interpreting skeletal growth in the past from a functional and physiological perspective. Am J Phys Anthropol 2013;150(1):29-37.

Sedgley CM, Botero TM. Dental stem cells and their sources. Dent Clin North Am 2012 Jul;56(3):549-561.

Tasoulis G, Yao SG, Fine JB. The maxillary sinus: challenges and treatments for implant placement. Compend Contin Educ Dent 2011;32(1):10-14, 16, 18-19; quiz 20, 34. Review.

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