*2.2.4 Types of grafting materials*

Various types of grafting materials are available for use in bone augmentation procedures (**Figure 5**). With different action mechanisms and regeneration potentials, there is no definitive recommendation specific to any procedure. Results vary depending on the regenerative approaches in conjunction with grafting materials. The most common classification for bone graft materials is as follows [3]:


#### **Figure 5.**

*Restoration of missing maxillary incisors (clinical view in* **Figure 1***) via GBR and titanium dental implants. (a) tomogram reveal severe bone atrophy, (b) dental implants showing insufficient bone coverage, (c) GBR procedure covering the area of missing bone volume stabilized on to the dental implants, (d) final prosthetic restoration.*

**149**

*Alveolar Ridge Augmentation Techniques in Implant Dentistry*

Autogenous grafts, also known as autografts, are type of grafts transferred from one site to another within the same individual. These grafts are harvested in the form of bone blocks or particulates. Main intraoral donor sites are mandibular symphisis, ramus buccal shelf and maxillar tuberosity. They can either be harvested from iliac crest, calvaria, tibial plates and costae extraorally when larger volumes of

Containing viable osteoblast cells, these materials are the only grafting materials with osteogenic properties. Therefore they have capacity of bone growth in the recipient site when vascularized. During incorporation growth factors, such as bone morphogenetic proteins, are released and induce bone growth through osteoinduction mechanism. Subsequently, a part of autograft becomes nonviable and acts as a scaffold with its calcium phosphate matrix. Surrounding bone is conducted by this matrix to regenerate. So autografts acts in all three mechanisms: osteogenesis,

Main advantages of autografts are low cost, unique osteogenic properties and early vascularization. Although autografts are considered to be a golden standard for augmentation procedures, search and evaluation for new grafting materials continue due to secondary surgical site for harvesting, limited source, morbidity and infection risk at the donor site. In contrast, a number of comparative studies reported autografts to remain golden standard for augmentation procedures due to their rapid stimulation of new bone formation compared to other bone grafting

Allografts are transferred from an individual to another within the same species.

Since there is no need for a secondary surgical site to obtain allografts, reduced morbidity is one of the advantages brought by use of this graft. Unlimited source is another advantage over autografts. Although allografts have no osteogenic properties, they stimulate bone growth via osteoconduction and incorporation of osteoinductive growth factors. There are strict sterilization and decontamination protocols regarding these materials due to the risk of disease transmission and host immune response. Donors are carefully evaluated and graft materials are gradually processed to avoid any risks. Some studies reported that certain allografts are less osteoinductive than others because of the sterilization protocols and the variability of their content. Schwartz et al. studied on different allografts taken from various tissue banks and stated wide range of variability related to donor's age, preparation

There are four forms of allografts: fresh frozen bone, freeze-dried bone allograft, demineralized free-dried bone allograft and deproteinized bone allograft. Freeze-dried bone allografts (FDBA) and demineralized freeze-dried bone allografts (DFDBA) are more frequently in use. DFDBA is demineralized with hydrochloric acid to provide easier access to growth factors such as BMP thus increase osteoinductive potential. Due to the lack of mineralized content, disadvantage of rapid resorption arises with DFDBA use. For this reason, FDBA is utilized more routinely in bone augmentation procedures. Compared to DFDBA, it's easier

*DOI: http://dx.doi.org/10.5772/intechopen.94285*

• Xenografts (animal source)

• Alloplasts (synthetic source)

*2.2.4.1 Autografts*

autograft is required [2, 3].

materials [3, 5, 13].

*2.2.4.2 Allografts*

osteoinduction and osteoconduction [2, 24].

method and sterilization protocols [2, 3].


### *2.2.4.1 Autografts*

*Oral and Maxillofacial Surgery*

agent [5, 21, 22].

*2.2.3 Osteoconduction*

*2.2.4 Types of grafting materials*

• Autografts (same individual)

• Allografts (human cadaver source)

Urist et al. performed the landmark study on osteoinductive grafting materials

isolating bone morphogenetic protein (BMP), a growth factor from the transforming growth factor (TGF)-β family, and described it as the main inductive

Osteoconduction refers to bone growth into a scaffold formed by the grafting material [5]. It's characterized by resorption of the grafting material and apposition of the new bone which is called "creeping substitution" process. Osteoconductive graft materials are biocompatible and contains osteoconductive surfaces such as pores, tubes and ducts so that the surronding bone can grow into these spaces. This type of grafting materials have no potential of bone growth by itself but take part in

Various types of grafting materials are available for use in bone augmentation procedures (**Figure 5**). With different action mechanisms and regeneration potentials, there is no definitive recommendation specific to any procedure. Results vary depending on the regenerative approaches in conjunction with grafting materials.

*Restoration of missing maxillary incisors (clinical view in* **Figure 1***) via GBR and titanium dental implants. (a) tomogram reveal severe bone atrophy, (b) dental implants showing insufficient bone coverage, (c) GBR procedure covering the area of missing bone volume stabilized on to the dental implants, (d) final prosthetic* 

The most common classification for bone graft materials is as follows [3]:

the regeneration process as a supporting structure [3, 5, 22, 23].

**148**

**Figure 5.**

*restoration.*

Autogenous grafts, also known as autografts, are type of grafts transferred from one site to another within the same individual. These grafts are harvested in the form of bone blocks or particulates. Main intraoral donor sites are mandibular symphisis, ramus buccal shelf and maxillar tuberosity. They can either be harvested from iliac crest, calvaria, tibial plates and costae extraorally when larger volumes of autograft is required [2, 3].

Containing viable osteoblast cells, these materials are the only grafting materials with osteogenic properties. Therefore they have capacity of bone growth in the recipient site when vascularized. During incorporation growth factors, such as bone morphogenetic proteins, are released and induce bone growth through osteoinduction mechanism. Subsequently, a part of autograft becomes nonviable and acts as a scaffold with its calcium phosphate matrix. Surrounding bone is conducted by this matrix to regenerate. So autografts acts in all three mechanisms: osteogenesis, osteoinduction and osteoconduction [2, 24].

Main advantages of autografts are low cost, unique osteogenic properties and early vascularization. Although autografts are considered to be a golden standard for augmentation procedures, search and evaluation for new grafting materials continue due to secondary surgical site for harvesting, limited source, morbidity and infection risk at the donor site. In contrast, a number of comparative studies reported autografts to remain golden standard for augmentation procedures due to their rapid stimulation of new bone formation compared to other bone grafting materials [3, 5, 13].

#### *2.2.4.2 Allografts*

Allografts are transferred from an individual to another within the same species. Since there is no need for a secondary surgical site to obtain allografts, reduced morbidity is one of the advantages brought by use of this graft. Unlimited source is another advantage over autografts. Although allografts have no osteogenic properties, they stimulate bone growth via osteoconduction and incorporation of osteoinductive growth factors. There are strict sterilization and decontamination protocols regarding these materials due to the risk of disease transmission and host immune response. Donors are carefully evaluated and graft materials are gradually processed to avoid any risks. Some studies reported that certain allografts are less osteoinductive than others because of the sterilization protocols and the variability of their content. Schwartz et al. studied on different allografts taken from various tissue banks and stated wide range of variability related to donor's age, preparation method and sterilization protocols [2, 3].

There are four forms of allografts: fresh frozen bone, freeze-dried bone allograft, demineralized free-dried bone allograft and deproteinized bone allograft.

Freeze-dried bone allografts (FDBA) and demineralized freeze-dried bone allografts (DFDBA) are more frequently in use. DFDBA is demineralized with hydrochloric acid to provide easier access to growth factors such as BMP thus increase osteoinductive potential. Due to the lack of mineralized content, disadvantage of rapid resorption arises with DFDBA use. For this reason, FDBA is utilized more routinely in bone augmentation procedures. Compared to DFDBA, it's easier

to track FDBA on radiographs with it's mineralized and radiopaque characteristics. Therefore, it's easier document this material's follow-up and resorption rates [5, 24].

#### *2.2.4.3 Xenografts*

Grafts obtained from different species like bovine animals are called xenografts. This type of grafts are deproteinized to avoid the risk of disease transmission and they are present in spongeous form. Deproteinized bovine bone mineral (DBBM) is the most utilized and well-documented type of xenograft. Since it's highly purified, anorganic and protein-free, it has no osteogenic potential nor osteoinductive properties. DBBM contains natural calcium phosphate which facilitates osteoconduction. Mineral content of this graft material provides low rates of resorption over time. Due to their long-term low resorption features, there is a widespread use of xenografts in augmentation procedures where the healing period is long and space maintenance is needed during this time. Sinus augmentations, contour augmentations, augmentation of horizontal and vertical defects are among the procedures xenografts can be preferred. Several studies demonstrated that DBBM particulates are present in the regeneration site up to 10 years after the placement [7, 13, 25]. In a study conducted by Mendoza-Azpur et al., GBR cases utilizing xenografts alone and along with autogenous block bones are evaluated. Results demonstrated statistically no significant difference between two groups in terms of implant survival rates. Higher rate of complications and post-operative discomfort is reported in the group receiving autogenous block bones, though [26].

#### *2.2.4.4 Alloplasts*

Alloplastic biomaterials are produced in the laboratories synthetically to avoid the disadvantages of allografts and xenografts. Providing space maintenance and acting as a scaffold, they stimulate osteoconduction. Biocompatibility, zero risk for disease transmission and availability are important advantages of these biomaterials. There are resorbable and non-resorbable forms of alloplasts. For resorbable alloplasts, porosity of the material is the main factor that affects resorption rate; increased micro-porosity leads to faster turnover. Although non-resorbable alloplasts are seldomly used alone as the grafting material in augmentation procedures, resorbable alloplasts show good results used either alone or in combination with other grafting materials since they act as a scaffold and provide stability to the regeneration site. These materials are derived from the combinations of hydroxyapatite (HA), β-TCP, polymers and/or bioactive glasses [5, 24].

Synthetic hydroxyapatites are biomaterials similar to the human bone in terms of chemical composition. Therefore they cause minimal inflammation and foreign body reactions. With their high levels of chemical stability and biocompatibility, they can be used in many clinical applications such as ridge preservation following extraction or ridge augmentation to reconstruct bone defects. One of the important advantages of this material is the possibility of altering the microstructure and new bone formation accordingly [3, 5, 13].

Calcium phosphate ceramics are promising biomaterials considering their high level of biocompatibility, low risk of foreign body reactions and possibility of combination with bioactive molecules and therapeutic agents. Hydroxyapatite layer forms after the placement of calcium phosphate ceramics faciliating osteoinduction in addition to osteoconduction mechanism. Although alloplastic materials have many advantages, these materials demonstrate lower regenerative potential in comparison with other grafting materials [3]. Further studies are required to document these biomaterials [3, 27].

**151**

*Alveolar Ridge Augmentation Techniques in Implant Dentistry*

Bone augmentation procedures are advanced and complex surgical interventions. Since there are multiple factors affecting the treatment outcomes, growth factors which promote healing and regeneration are mostly used along with the grafting materials and membranes. These agents are widely utilized especially when bone healing mechanisms are affected by the patient's medical conditions such as diabetes mellitus or osteoporosis. Growth factors used in dentistry are divided in two categories: platelet concentrates and recombinant growth factors [3, 5, 28].

Platelet concentrates are obtained by centrifuging autologous blood to concentrate platelets, cells taking part in the active secretion of growth factors. These concentrates have two forms as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) [3]. PRP is the first generation of platelet concentrates consisting %95 platelets, %4 red blood cells and %1 white blood cells. Although PRP has been widely used for it's healing enhancing properties for a long time, it's observed to have some major drawbacks. Several studies reported that incorporation of bovine thrombin or calcium chloride as anticoagulants decelerates the healing process and poses a risk for infection transmission or host immune response. It's preparation method is demanding and technique-sensitive. Furthermore, there are studies showing rapid release of growth factors from PRP whereas the desired release process is extended and gradual to cover the regenerative phase. PRF is developed to overcome these

PRF is obtained without any anticoagulant use, therefore it's a fibrin matrix containing the full set of growth factors in it's matrix. Fibrin form of this platelet concentrate facilitates a slow release of growth factors over time as desired. PRF, later called as L-PRF, is rich in leukocytes and platelets. High levels of leukocytes contribute in wound healing and vascular formation along with their contribution in host defense to pathogens at the regeneration site as they are anti-infectious and

L-PRF is easily prepared compared to PRP. Once the blood sample is collected,

With it's fibrin matrix structure acting as a scaffold for tissue ingrowth, rich content in cells recruiting future regenerative cells to the site and gradual delivery of growth factors make L-PRF attractive for use in regeneration procedures (**Figure 6**) [31, 32].

Bone morphogenetic protein (BMP) is a well-documented recombinant growth factor with it's recruiting, proliferating and differentiating effect on mesenchymal progenitor cells. Studies show osteoinductive properties of BMP activates osteoblast differentiation pathway MAPK/ERK. It's capacity of osteoinduction is at higher levels compared to other known growth factors therefore BMP can be utilized to promote bone regeneration especially in complex augmentation procedures like

Platelet-derived growth factor (PDGF) is the second most utilized growth factor in augmentation procedures. It's responsible for cell migration and proliferation to

it's put in glass tubes and centrifuged at 750 g for 12 minutes. It's important to centrifuge the collection quickly, since the sample's contact with glass tube walls starts the coagulation process rapidly. When the centrifugation is complete, there are three layers in the tube: red blood cells in the bottom, cells plasma at the top and

*DOI: http://dx.doi.org/10.5772/intechopen.94285*

**2.3 Growth factors**

*2.3.1 Platelet concentrates*

limitations [28].

immune modulating cells [29].

L-PRF in the middle [13, 30].

*2.3.2 Recombinant growth factors*

vertical augmentation [13, 33].

#### **2.3 Growth factors**

*Oral and Maxillofacial Surgery*

receiving autogenous block bones, though [26].

apatite (HA), β-TCP, polymers and/or bioactive glasses [5, 24].

bone formation accordingly [3, 5, 13].

these biomaterials [3, 27].

*2.2.4.3 Xenografts*

*2.2.4.4 Alloplasts*

to track FDBA on radiographs with it's mineralized and radiopaque characteristics. Therefore, it's easier document this material's follow-up and resorption rates [5, 24].

Grafts obtained from different species like bovine animals are called xenografts. This type of grafts are deproteinized to avoid the risk of disease transmission and they are present in spongeous form. Deproteinized bovine bone mineral (DBBM) is the most utilized and well-documented type of xenograft. Since it's highly purified, anorganic and protein-free, it has no osteogenic potential nor osteoinductive properties. DBBM contains natural calcium phosphate which facilitates osteoconduction. Mineral content of this graft material provides low rates of resorption over time. Due to their long-term low resorption features, there is a widespread use of xenografts in augmentation procedures where the healing period is long and space maintenance is needed during this time. Sinus augmentations, contour augmentations, augmentation of horizontal and vertical defects are among the procedures xenografts can be preferred. Several studies demonstrated that DBBM particulates are present in the regeneration site up to 10 years after the placement [7, 13, 25]. In a study conducted by Mendoza-Azpur et al., GBR cases utilizing xenografts alone and along with autogenous block bones are evaluated. Results demonstrated statistically no significant difference between two groups in terms of implant survival rates. Higher rate of complications and post-operative discomfort is reported in the group

Alloplastic biomaterials are produced in the laboratories synthetically to avoid the disadvantages of allografts and xenografts. Providing space maintenance and acting as a scaffold, they stimulate osteoconduction. Biocompatibility, zero risk for disease transmission and availability are important advantages of these biomaterials. There are resorbable and non-resorbable forms of alloplasts. For resorbable alloplasts, porosity of the material is the main factor that affects resorption rate; increased micro-porosity leads to faster turnover. Although non-resorbable alloplasts are seldomly used alone as the grafting material in augmentation procedures, resorbable alloplasts show good results used either alone or in combination with other grafting materials since they act as a scaffold and provide stability to the regeneration site. These materials are derived from the combinations of hydroxy-

Synthetic hydroxyapatites are biomaterials similar to the human bone in terms of chemical composition. Therefore they cause minimal inflammation and foreign body reactions. With their high levels of chemical stability and biocompatibility, they can be used in many clinical applications such as ridge preservation following extraction or ridge augmentation to reconstruct bone defects. One of the important advantages of this material is the possibility of altering the microstructure and new

Calcium phosphate ceramics are promising biomaterials considering their high

level of biocompatibility, low risk of foreign body reactions and possibility of combination with bioactive molecules and therapeutic agents. Hydroxyapatite layer forms after the placement of calcium phosphate ceramics faciliating osteoinduction in addition to osteoconduction mechanism. Although alloplastic materials have many advantages, these materials demonstrate lower regenerative potential in comparison with other grafting materials [3]. Further studies are required to document

**150**

Bone augmentation procedures are advanced and complex surgical interventions. Since there are multiple factors affecting the treatment outcomes, growth factors which promote healing and regeneration are mostly used along with the grafting materials and membranes. These agents are widely utilized especially when bone healing mechanisms are affected by the patient's medical conditions such as diabetes mellitus or osteoporosis. Growth factors used in dentistry are divided in two categories: platelet concentrates and recombinant growth factors [3, 5, 28].

#### *2.3.1 Platelet concentrates*

Platelet concentrates are obtained by centrifuging autologous blood to concentrate platelets, cells taking part in the active secretion of growth factors. These concentrates have two forms as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) [3].

PRP is the first generation of platelet concentrates consisting %95 platelets, %4 red blood cells and %1 white blood cells. Although PRP has been widely used for it's healing enhancing properties for a long time, it's observed to have some major drawbacks. Several studies reported that incorporation of bovine thrombin or calcium chloride as anticoagulants decelerates the healing process and poses a risk for infection transmission or host immune response. It's preparation method is demanding and technique-sensitive. Furthermore, there are studies showing rapid release of growth factors from PRP whereas the desired release process is extended and gradual to cover the regenerative phase. PRF is developed to overcome these limitations [28].

PRF is obtained without any anticoagulant use, therefore it's a fibrin matrix containing the full set of growth factors in it's matrix. Fibrin form of this platelet concentrate facilitates a slow release of growth factors over time as desired. PRF, later called as L-PRF, is rich in leukocytes and platelets. High levels of leukocytes contribute in wound healing and vascular formation along with their contribution in host defense to pathogens at the regeneration site as they are anti-infectious and immune modulating cells [29].

L-PRF is easily prepared compared to PRP. Once the blood sample is collected, it's put in glass tubes and centrifuged at 750 g for 12 minutes. It's important to centrifuge the collection quickly, since the sample's contact with glass tube walls starts the coagulation process rapidly. When the centrifugation is complete, there are three layers in the tube: red blood cells in the bottom, cells plasma at the top and L-PRF in the middle [13, 30].

With it's fibrin matrix structure acting as a scaffold for tissue ingrowth, rich content in cells recruiting future regenerative cells to the site and gradual delivery of growth factors make L-PRF attractive for use in regeneration procedures (**Figure 6**) [31, 32].

#### *2.3.2 Recombinant growth factors*

Bone morphogenetic protein (BMP) is a well-documented recombinant growth factor with it's recruiting, proliferating and differentiating effect on mesenchymal progenitor cells. Studies show osteoinductive properties of BMP activates osteoblast differentiation pathway MAPK/ERK. It's capacity of osteoinduction is at higher levels compared to other known growth factors therefore BMP can be utilized to promote bone regeneration especially in complex augmentation procedures like vertical augmentation [13, 33].

Platelet-derived growth factor (PDGF) is the second most utilized growth factor in augmentation procedures. It's responsible for cell migration and proliferation to

**Figure 6.** *Prepared human blood-derived PRF in the centrifuge tubes.*

the defect site. Several studies reported PDGF to be highly effective on regeneration in advanced periodontal osseous defects [3].
