**6. Membranes**

the receiving site to reduce morbidity. Using a bone scraper may reduce the treatment time

Allografts are bone grafts collected for transplantation purposes from one person to another and have widespread use. They are important for the treatment of congenital, traumatic, degenerative, and neoplastic bone defects. The advantages of allografts include availability and reduced morbidity, since harvesting bone from an intraoral site is no longer required. The main disadvantage is the possibility of transmission of infection from the donor to the recipient. Possible transmittable infections include malignant neoplasms, degenerative bone diseases, hepatitis B, hepatitis C, and HIV. Donors are carefully screened, and graft materials are meticulously processed to reduce disease transmission. Allografts are not osteogenic and thus, healthy bone formation takes longer compared to that with autogenous bone grafts. There are two main forms of allografts: mineralized freeze-dried bone allografts (MFDBA) and DFDBA. In FDBA, the graft is dried at low temperatures throughout the entire process. In DFDBA, the mineralized phase of MFDBA is removed so that collagen and BMPs are exposed. If this mineral phase is not removed, the bone induction process is not observed. MFDBA is mainly used for its osteoconductive properties and space maintenance. Cortical bone chips are generally preferred for allografts because of their low antigenic activity and high levels

Grafts obtained from a donor in a different species are xenografts (also called heterogeneous grafts). Xenografts are composed of deproteinized spongiform bones naturally obtained from other species such as horses or cows. Heterogeneous bone grafts have been proposed to fill bone defects; many clinicians have reported that these grafts have little to no osteogenic potential and may instead be used as scaffolds for space maintenance and long-term bone formation. Bovine bone is the best and most commonly preferred source of xenografts. The risk of transmission of diseases, such as spongiform encephalopathy in cattle, is insignificant due to the grafts deproteinization process. Inorganic and protein-free bones are materials in which only the natural calcium phosphate in the bone is retained. This material consists of unsaturated calcium apatite crystals, and provides long-term low resorption space maintenance, shown to remain 10 years postoperatively. Xenografts inhibit resorption of the grafted site but may negatively impact healing by decreasing the rate at which the implant surface area is integrated with the newly formed bone. Used in cystic cavities, alveolar ridge augmentation, extraction sites for implant placement, and sinus lifting, xenografts are viable materials, when a high osteogenic potential is not imperative. Xenografts can also be mixed with autogenous bone grafts. Such a composite graft material with osteogenic properties can be successfully

Alloplastic biomaterials are synthetic graft materials. Biocompatible synthetic graft materials have been used for the last two decades to avoid the disadvantages of allografts and xenografts. Alloplastic materials are not osteoinductive, but they can provide space maintenance and act as a scaffold for new bone formation; this means that they are osteoconductive. Advantages of alloplastic materials include being risk free in terms of cross infection, their availability, being sterilizable, and their biocompatibility. Alloplasts used in augmentations are solid or porous polymers, hydroxyapatite (HA), and calcium triphosphate ceramics, or

and simplify harvesting of the autogenous bone [37].

used for horizontal and vertical ridge augmentations [19].

combinations of these materials [20].

of collagen [36].

148 Tissue Regeneration

Various types of membranes have been used for tissue regeneration, with the aims of support and maintenance of the treatment area. The barrier membrane allows the migration of regenerative cells within the confinement area, while this technique prevents the migration of undesired cells into the wound area. There are two main groups of membranes: resorbable and nonresorbable.

#### **6.1. Resorbable membranes**

Graft materials have been used with resorbable membranes for guided bone regeneration. Ever since resorbable membranes have no stable fixed shape, it is feasible to utilize them for GBR. Resorbable membranes that are developed nowadays are prepared from glycosides and lactic polymers. Absorption of these membranes by hydrolysis takes a minimum of 6 weeks and is completed in exactly 8 months. Traditional resorbable membranes, using polymers like polylactic acid, demonstrated therapeutic problems due to their inflammatory properties and reaction to foreign bodies upon degradation. Due to premature membrane resorption, minimal inflammatory reaction may occur, but clinical observations show that the inflammation does not prevent healing. Resorbable membranes possess qualities such as low possibility of complication, membrane subtraction after healing, reduced morbidity, and easy manipulation. These types of membranes as effective as conventional expanded polytetrafluoroethylene (e-PTFE) in recent experiments [37].

Polymers have had long and widespread use as biomaterials. Resorbable polymers have a remarkable advantage since they do not require a second operation after implant placement. The body can absorb these materials over time. Polylactic acid membranes can retain their long-term durability. They can be prepared in small sizes and yield more moderate foreign body reactions. Furthermore, slow degradation makes the substance less aggressive. Thus, the surrounding tissue produces less reactions. The clinical use of polylactic acid membranes is that they can serve as barrier materials that can guide the periodontal ligament and bone cells that in turn can be shaped according to the morphology of the defect when manipulation is evaluated. When evaluated in terms of membrane reliability and toxicity, any negative tissue reaction that can be attached to this membrane in surgically created defects does not show any anatomical defects in the regenerated portions [38].

Collagen membranes have recently been preferred due to their biological advantages. They are strong and resistant to deformation and have high-calcium-binding properties. In addition, collagen membranes are biocompatible and are as matrix materials in guided tissue regeneration and with hydroxyapatites. Collagen membranes do not possess immunogenicity; they are well-qualified and have demonstrated excellent long-term clinical outcomes (**Figures 5** and **6**) [39].

space unless supported by graft material. The most important disadvantage is that it requires a second surgical operation because it cannot be resurfaced. It has become preferable to use membranes that are resorbed because of the risk of tissue damage and economic damages to the patients due to a second operation. In addition, nonresorbable e-PTFE membranes are disadvantageous because these membranes involve a high incidence of soft tissue problems,

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Comparison of e-PTFE and resorbed membranes reveals that bone regeneration with e-PTFE membranes is greater, if no exposures occur [40]. Because e-PTFE has no tolerance to exposure, e-PTFE membranes must be completely healed during the primary healing procedure. Currently, because of the complications related to membrane exposure, e-PTFE membranes are not commonly used in GBR treatments. Instead, d-PTFE membranes, which are titaniumreinforced nonresorbable membranes, are used for the reconstruction of critically sized defects. A d-PTFE membrane is used because unlike e-PTFE, d-PTFE continues to be functional even if exposed to the oral cavity. Nano-PTFE membrane is more flexible than e-PTFE; therefore, manipulation and adaptation in this type of membrane is easier. Nano-PTFE has 0, 2–0, and 3 pores. These small pores limit the access of epithelial growth and bacterial infiltra-

The advantage of strengthening membranes with titanium is that it maintains regeneration of the region and obstructs pressure on graft material, soft tissue subsidence, and resorption. Its surface structure and pores are designed to prevent bacterial migration and retention. Soft tissue provides a suitable environment for bone formation and neovascularization in the region by reducing migration to the defect site. They are strained membranes and do not bend but

Recently, there has been increasing interest to promote bone formation. Platelet-rich plasma (PRP), growth factors, and BMPs are used to accelerate bone augmentation [43]. Coagulated

such as exposure, especially when compared to resorbable membranes [41].

**Figure 6.** Stabilization of collagen membrane with miniscrews.

are also resilient enough to prevent perforation of the soft tissue [42].

tion in the augmentation area [41].

**7. Platelet concentrates**

blood acts as a scaffold for bone formation [44].

Synthetic barriers, such as collagen and PTFE barriers, also yield successful clinical results. They occur in the form of lactic acid and glycolic acid polymers. Although directed tissue regeneration membranes are widely accepted as a treatment modality, their clinical use should be approached with care. These membranes may cause problems such as exposures, risk of bacterial infiltration, and incomplete closure of the operative site. Degradation is usually through hydrolysis when membranes that are resorbed are used. This leads to the formation of an acid cycle, which is a negative effect on bone formation [40].

#### **6.2. Nonresorbable membranes**

Reinforced nonabsorbable membranes are used when higher bone augmentation is required. e-PTFE, titanium-reinforced e-PTFE, dense polytetrafluoroethylene (d-PTFE), nano-PTFE, and titanium mesh membranes are known as nonresorbable membranes. Nonresorbable membrane barriers require a second surgical procedure to remove them from the site of augmentation. In large bone defects, the e-PTFE membrane cannot adequately cover the existing

**Figure 5.** Horizontal augmentation of alveolar ridge, application of xenograft and collagen membrane.

**Figure 6.** Stabilization of collagen membrane with miniscrews.

The body can absorb these materials over time. Polylactic acid membranes can retain their long-term durability. They can be prepared in small sizes and yield more moderate foreign body reactions. Furthermore, slow degradation makes the substance less aggressive. Thus, the surrounding tissue produces less reactions. The clinical use of polylactic acid membranes is that they can serve as barrier materials that can guide the periodontal ligament and bone cells that in turn can be shaped according to the morphology of the defect when manipulation is evaluated. When evaluated in terms of membrane reliability and toxicity, any negative tissue reaction that can be attached to this membrane in surgically created defects does not show

Collagen membranes have recently been preferred due to their biological advantages. They are strong and resistant to deformation and have high-calcium-binding properties. In addition, collagen membranes are biocompatible and are as matrix materials in guided tissue regeneration and with hydroxyapatites. Collagen membranes do not possess immunogenicity; they are well-qualified and have demonstrated excellent long-term clinical outcomes

Synthetic barriers, such as collagen and PTFE barriers, also yield successful clinical results. They occur in the form of lactic acid and glycolic acid polymers. Although directed tissue regeneration membranes are widely accepted as a treatment modality, their clinical use should be approached with care. These membranes may cause problems such as exposures, risk of bacterial infiltration, and incomplete closure of the operative site. Degradation is usually through hydrolysis when membranes that are resorbed are used. This leads to the forma-

Reinforced nonabsorbable membranes are used when higher bone augmentation is required. e-PTFE, titanium-reinforced e-PTFE, dense polytetrafluoroethylene (d-PTFE), nano-PTFE, and titanium mesh membranes are known as nonresorbable membranes. Nonresorbable membrane barriers require a second surgical procedure to remove them from the site of augmentation. In large bone defects, the e-PTFE membrane cannot adequately cover the existing

**Figure 5.** Horizontal augmentation of alveolar ridge, application of xenograft and collagen membrane.

tion of an acid cycle, which is a negative effect on bone formation [40].

any anatomical defects in the regenerated portions [38].

(**Figures 5** and **6**) [39].

150 Tissue Regeneration

**6.2. Nonresorbable membranes**

space unless supported by graft material. The most important disadvantage is that it requires a second surgical operation because it cannot be resurfaced. It has become preferable to use membranes that are resorbed because of the risk of tissue damage and economic damages to the patients due to a second operation. In addition, nonresorbable e-PTFE membranes are disadvantageous because these membranes involve a high incidence of soft tissue problems, such as exposure, especially when compared to resorbable membranes [41].

Comparison of e-PTFE and resorbed membranes reveals that bone regeneration with e-PTFE membranes is greater, if no exposures occur [40]. Because e-PTFE has no tolerance to exposure, e-PTFE membranes must be completely healed during the primary healing procedure. Currently, because of the complications related to membrane exposure, e-PTFE membranes are not commonly used in GBR treatments. Instead, d-PTFE membranes, which are titaniumreinforced nonresorbable membranes, are used for the reconstruction of critically sized defects. A d-PTFE membrane is used because unlike e-PTFE, d-PTFE continues to be functional even if exposed to the oral cavity. Nano-PTFE membrane is more flexible than e-PTFE; therefore, manipulation and adaptation in this type of membrane is easier. Nano-PTFE has 0, 2–0, and 3 pores. These small pores limit the access of epithelial growth and bacterial infiltration in the augmentation area [41].

The advantage of strengthening membranes with titanium is that it maintains regeneration of the region and obstructs pressure on graft material, soft tissue subsidence, and resorption. Its surface structure and pores are designed to prevent bacterial migration and retention. Soft tissue provides a suitable environment for bone formation and neovascularization in the region by reducing migration to the defect site. They are strained membranes and do not bend but are also resilient enough to prevent perforation of the soft tissue [42].

## **7. Platelet concentrates**

Recently, there has been increasing interest to promote bone formation. Platelet-rich plasma (PRP), growth factors, and BMPs are used to accelerate bone augmentation [43]. Coagulated blood acts as a scaffold for bone formation [44].

## **7.1. Platelet rich plasma (PRP)**

The plasma rich in thrombocytes obtained from autogenous blood tissue is called PRP. PRP contains high proportions of thrombocytes as well as growth factors and other components [45]. PRP is obtained by centrifugation of blood, and 95% of the platelets comprise 4% red blood cells and 1% white blood cells. The most common advantage of PRP is that it accelerates hard and soft tissue healing. PRP can be injected directly into the wound area to accelerate tissue healing or it can be used with graft materials [46].

repairs the pulp to form new dentin [54]. However, half of the morphogenesis is achieved due

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An ideal carrier has not yet been identified, since the cost for this is high. These factors directly influence gene therapy instead of being applied along with morphogenesis, which is a desir-

This chapter is concerning the dental implant placement. It is one of the most reliable and predictable treatment choices in modern oral surgery. The ways to regenerate the bone to place the implants with the desired dimensions are as follows: (1) guided bone regeneration, (2) socket grafting, (3) allograft bone block grafting, (4) intra- and extraoral autogenous bone block grafting. There are many scaffold biomaterials available that are used as templates for new bone formation. In recent years, biomaterial usage for the reconstruction of hard tissue defects has dramatically increased. Combination of scaffold biomaterials with growth factors presents promising results. In the future, there is no doubt that autologous bone usage will be

\* and Gamze Zeynep Adem Siyli2

1 Istanbul University, Faculty of Dentistry, Department of Oral Implantology, Istanbul,

2 Okmeydani Dental and Oral Health Hospital, Department of Periodontology, Istanbul,

[1] Leite-Cavalcanti A, Menezes SA, Granville-Garcia AF, Correia-Fontes LB. Prevalence of early loss of primary molars: Study retrospective. Acta Sci. Health Sciences. 2008;**30**:139-143 [2] Cetiner S, Zor F. The factors affecting success in dental implantology. GU Journal of

\*Address all correspondence to: alpergultekin@hotmail.com

to the limited lifetime of the carrier at very high concentrations [55].

able treatment approach [55].

replaced with artificial tissue engineering.

There is no conflict of interest in this study.

**8. Conclusions**

**Conflict of interest**

**Author details**

Turkey

Turkey

**References**

Dentistry. 2007;**24**(1):51-56

Bahattin Alper Gultekin1

PRP has a long shelf life, but it should be used quickly. This is because 95% of the growth factors available in PRP are released within 1 h and the activity lasts for 7 days [47].

The use of PRP in oral maxillofacial surgery has been increasing. PRP secreted by growth factors accelerate the healing mechanism of the bone tissue. It has been shown that PRP increases mature bone density by 15–30% [48].

Furthermore, PRP allows a nonspecific immunoreaction to occur. Leukocytes in this context and interleukins secreted from these leukocytes are also activated by the activation of macrophages. Bacteria exhibiting antimicrobial activity of PRP are *Escherichia coli*, *Staphylococcus aureus*, *Candida albicans*, and *Cryptococcus neoformans* [49].

#### **7.2. Platelet rich fibrin (PRF)**

The PRF protocol was developed by Choukroun in 2001. The goal of PRF is to obtain a membrane that is rich in plagioclase-like factors. The acquisition protocol is not dependent on a specialized medical device but can easily be implemented by clinicians. PRF is obtained by removing autogenous venous blood from the dry glass tubes and then centrifuging it at low speed.

Since no anticoagulant is added to the blood in PRF, blood coagulation mechanism begins. PRF has three layers: red blood cell at the bottom, cells plasma at the top, and PRF clot in the middle. This clot is a 3D strong fibrin matrix structure, in which leukocytes and platelets are present in high concentrations [50].

Previous studies have reported the positive clinical and radiographic results for the efficacy of PRF in intrabony and mandibular defects [51].

Platelets help repair damaged tissues by releasing growth factors such as PDGF, TGF-β, VEGF, IGF-1, FGF, and EGF. The granules in the platelets also stimulate cellular growth and proliferation; similarly, chemokines and cytokines are involved in the regulation of tissue regeneration and treatment of inflammation. Platelet granules are important protein sources for the activation of other cells [52].

#### **7.3. Bone morphogenetic protein (BMP)**

Recombinant human bone morphogenetic proteins (rhBMP) are used in osteogenic regenation in addition to its use in pulp amputation treatment for new osteodentin formation in the presence of inflammation [53]. It has been reported that the recombinant human proteins repairs the pulp to form new dentin [54]. However, half of the morphogenesis is achieved due to the limited lifetime of the carrier at very high concentrations [55].

An ideal carrier has not yet been identified, since the cost for this is high. These factors directly influence gene therapy instead of being applied along with morphogenesis, which is a desirable treatment approach [55].
