Contemporary Overview of Blood Concentrates in Oral and Maxillacial Surgery

*Onur Gönül, Ahmet Usame Çiçek, Murat Afat, Onur Atali and Faysal Uğurlu*

## **Abstract**

It has always been a target to shorten and improve the healing process in medical field. Platelets with cytokines and growth factors in their structure have great importance on wound healing. Features of platelets gave the clinicians the idea of using platelet concentrates to promote the healing process. For this reason, many platelet-derived biomaterials have been tried in the medical field over the years. When approaching today, platelet concentrates have been found to be used medically, especially with the use of platelet rich plasmas (PRPs) and then platelet rich fibrins (PRFs). In particular, several studies conducted in recent years have revaled different blood concentrates. This chapter summarizes the develoment over time, properties and usage areas of blood concentrates in dentistry.

**Keywords:** platelet rich fibrin, platelet rich plasma, sinus lifting, growth factor, graft, regeneration, oral and maxillofacial surgery

#### **1. Introduction**

Platelets are the smallest, colorless blood cells which paly a majör role in coagulation cascade and prevent excessive blood loss. Plateletsb diameters varies between 1-3 microns and they appear in a bright blue color under the microscope. Low platelet rate causes an increase in the tendency to bleed, and high platelet rate causes a clot (thrombosis) formation in the vein [1].

Platelets provide their functions with secretory granules in which there is a reservoir in its structure and freshly synthesized mediators. These granules consists ATP, ADP, serotonin, fibrinogen, plasminogen, platelet derived growth factor (PDGF), transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin like growth factor (IGF), etc. The growth factors have stimulating effect on wound healing by means of potential for matrix remodeling, cell proliferation and angiogenesis [2, 3].

Accordong to several researches, main task of platelets in the body is hemostasis and final clot formation in bleeding areas. In addition to their hemostatic duties, they are also effective in the tissue repair process due to the long term effects of these growth factors in theri structure [2, 3].

**58**

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Mosby; 1979

*Oral and Maxillofacial Surgery*

1-4614-5221-8

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Platelets are counted among the potential cells of regenerative therapy. For the fact that they consist a large number of growth factors and are easy to obtain, has increased the interest in platelets. Tissue regeneration enginering is a field that many studies and attempts have been made about repairing a diseased tissue, regenerating or restoring a damaged tissue. Initially, studies have included allografts, xenografts, synthetic-based alloplasts, etc. However, most of these materials were observed to cause foreign body reaction in the body, which lead the studies to the human bodys's own tissues [4–7].

Ideas based on the use of human blood proteins as sources for regeneration arise from the idea that blood-derived proteins are a source of growth factors that can support angiogenesis and tissue growth for tissue regeneration. The healing process required for regeneration consists of hemostasis, inflammation, proliferation and maturation phases. Each phase requires its own specific proteins and cell types. However, since the non-human biomaterials used are avascular, the use of blood concentrates becomes more prominent [4–7].

As mentioned earlier, wound healing is a process that occurs as a result of hemostasis, inflammation, proliferation and maturation phases. Platelets are essential components that play an active role in the stages of hemostasis and fibrin formation, that is, in the early phases of the tissue regeneration process. Platelets secrete and contain some growth factors such as PDGF (Platelet derived growth factor), VEGF (Vascular endothelial growth factor), cytokines, etc., as well as angiogenetic factors that stimulate proliferation and activate the wound healing cells such as fibroblasts, neutrophils and mesenchymal stem cells [3, 8].

#### **2. History of blood concentrates**

The use of blood concentrates in medical field for various purposes is common for a long period of time. When we look at its historical background, the idea was used in the 1970s to be used for nerve tissue repair. The first use of platelet-rich plasma was reported in 1987 by Ferrari et al. during cardiac surgery and PRP was used to repair damaged cardiovascular tissues [9].

Looking at its use in dentistry, in the late 1990s, Whitman et al. suggested using PRP in oral surgical procedures, observing that PRP enhanced osteoprogenitor cells in bone graft and bone tissue. However, it is reported that depending on the use of bovine thrombin, coagulopathies and immune reactions can be observed [9, 10].

PRF is considered as the current platelet concentrate and has been used in oral and maxillofacial surgery since 2001. According to Choukroun et al. who first described PRFs in literature, PRFs have some advantages compared to PRPs, such as easier preparation and no chemical intervention to blood concentrates [11].

According to leukocyte and fibrin content, Verma et al. divided the platelet concentrates into 4 basic categories. They categorized platelet concentrates as P-PRP, L-PRP, P-PRF, and L-PRF [12].

Choukroun, the first person to report the use of PRF in 2001, described A-PRF, a new form of PRF, containing higher amounts of leukocytes in 2014. According to Choukroun, this new type of PRF has more potential than the original PRF [13].

#### **3. Classification of blood concentrates**

The story of blood concentrates is usually examined in 2 parts/generations. Here we see the PRPs first, and the PRFs as the second generation. Classification is simply done as follows:

**61**

minute [4, 19–23].

*Contemporary Overview of Blood Concentrates in Oral and Maxillacial Surgery*

**4. Preparation procedures and clinical features of PRPs**

disadvantage of their liquid structures during use [9, 14–18].

**5. Preparation procedures and clinical features of PRFs**

Despite the high platelet and growth factor ratios provided by PRPs, the observed negativities pushed clinicians to new researches. As a result, PRFs, which are the second generation blood concentrates and have the advantages of being prepared more quickly, have emerged. PRFs appeared mainly as blood concentrates created without using additive anticoagulants. A single, high-speed return is achieved in obtaining the PRF. In the most basic centrifuge method that provides the PRFs, single centrifugation is performed for 12 minutes at 2700-3000 rpm per

Basically, the aim of the formation of blood concentrates is to achieve higher platelet density and high level of growth hormones. PRPs are also tried to be prepared for this purpose. PRPs are basically condensed plasma with a higher platelet concentration than the normal state of the blood. PRPs show high platelet and growth factor levels compared to normal blood. It has been determined that PRPs have positive effects on periodontal cells, osteoblasts, etc. after their use [9, 14–18]. Despite their benefits, PRPs have some disadvantages. They are obtained in a multi-stage and long process, difficult to handle and expensive to obtain. PRPs usually have two basic centrifuge steps. Ethylenediaminetetraacetic acid (EDTA) or citric acid can be used in the first slow centrifuge step. Then comes the second centrifuge step, which is applied faster. At this stage, additional substances such as calcium chloride or/and bovine thrombin can be used. These additives, in fact, cause blood concentrates, which are of interest as being autologous, to loose their full autologous feature. In addition, foreign substances -especially bovine thrombinwhich are included in the PRPs, increase the potential of PRPs to create a foreign body reaction. Accordingly, the natural inflammatory process of the body can be disrupted. In addition, artificial clotting is provided while obtaining PRP. Accordingly, the fibrin matrix structure formed is different from the structure obtained naturally. The fibrin matrix structure obtained in this way is more rigid. Due to this rigid structure, it does not release the growth factors in the PRP in a controlled and long term and releases all at once. Also bovine thrombin can cause the risk of coagulopathy as well as foreign body reaction. It also increases the cost of preparing PRPs with special kits and spending a lot of time. PRPs are often used by mixing with grafts due to the

*DOI: http://dx.doi.org/10.5772/intechopen.93865*

• P-PRP (1. GENERATION)

• L-PRP (1. GENERATION)

• P-PRF (2. GENERATION)

• L-PRF (2. GENERATION)

• I-PRF (2. GENERATION)

• A-PRF (2. GENERATION)

• T-PRF (2 GENERATION)

*Contemporary Overview of Blood Concentrates in Oral and Maxillacial Surgery DOI: http://dx.doi.org/10.5772/intechopen.93865*


#### **4. Preparation procedures and clinical features of PRPs**

Basically, the aim of the formation of blood concentrates is to achieve higher platelet density and high level of growth hormones. PRPs are also tried to be prepared for this purpose. PRPs are basically condensed plasma with a higher platelet concentration than the normal state of the blood. PRPs show high platelet and growth factor levels compared to normal blood. It has been determined that PRPs have positive effects on periodontal cells, osteoblasts, etc. after their use [9, 14–18].

Despite their benefits, PRPs have some disadvantages. They are obtained in a multi-stage and long process, difficult to handle and expensive to obtain. PRPs usually have two basic centrifuge steps. Ethylenediaminetetraacetic acid (EDTA) or citric acid can be used in the first slow centrifuge step. Then comes the second centrifuge step, which is applied faster. At this stage, additional substances such as calcium chloride or/and bovine thrombin can be used. These additives, in fact, cause blood concentrates, which are of interest as being autologous, to loose their full autologous feature. In addition, foreign substances -especially bovine thrombinwhich are included in the PRPs, increase the potential of PRPs to create a foreign body reaction. Accordingly, the natural inflammatory process of the body can be disrupted. In addition, artificial clotting is provided while obtaining PRP. Accordingly, the fibrin matrix structure formed is different from the structure obtained naturally. The fibrin matrix structure obtained in this way is more rigid. Due to this rigid structure, it does not release the growth factors in the PRP in a controlled and long term and releases all at once. Also bovine thrombin can cause the risk of coagulopathy as well as foreign body reaction. It also increases the cost of preparing PRPs with special kits and spending a lot of time. PRPs are often used by mixing with grafts due to the disadvantage of their liquid structures during use [9, 14–18].

#### **5. Preparation procedures and clinical features of PRFs**

Despite the high platelet and growth factor ratios provided by PRPs, the observed negativities pushed clinicians to new researches. As a result, PRFs, which are the second generation blood concentrates and have the advantages of being prepared more quickly, have emerged. PRFs appeared mainly as blood concentrates created without using additive anticoagulants. A single, high-speed return is achieved in obtaining the PRF. In the most basic centrifuge method that provides the PRFs, single centrifugation is performed for 12 minutes at 2700-3000 rpm per minute [4, 19–23].

In this way, three layers are obtained:


As studies based on PRF progressed, it was understood that the amount of leukocytes in the content had an important effect on ideal wound healing. This is the reason why leukocyte content is also taken into account in the classification of PRFs. The presence of leukocytes has been found to be effective in obtaining clinical results ideally and achieving lower infection rates. PRFs are structures that contain important cells for healing process of the body, but it is also important that they form a three-dimensional matrix and contain significant growth factors [4, 12, 19–23].

PRFs, of course, did not remain as they first appeared, but were developed in time. PRFs with different contents were obtained by applying different centrifuge methods. The first obtained P-PRF consisted of a solid fibrin matrix structure and did not contain leukocytes. Later, L-PRF appeared, known as leukocyte and plateletrich fibrin. The A-PRFs were produced by Choukroun, the first revealer of PRFs. This type of PRF has a better handling than other types of PRFs. It is obtained by low speed centrifuge. 14-minute centrifuge process at 1500 rpm is required for the A-PRF acquisition. A-PRFs are blood concentrates containing high amounts of leukocytes. In addition, I-PRFs, an injectable form of PRFs, have emerged. I-PRFs are a type of PRF that can also contain stem cells. To obtain it, centrifuge should be applied for 3-4 minutes at 800 rpm. Another type of PRF is T-PRF. The main difference is that

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fibrin content [4, 19–23].

**Figure 2.**

given below [4, 19–23]. ENDODONTICS:

coated tube to perform the process [19–23].

**6. Application fields in dentistry**

• Can be used for pulp regeneration

• It can be used for apex formation procedures.

• It can be used in the treatment of periapical cysts.

*Contemporary Overview of Blood Concentrates in Oral and Maxillacial Surgery*

the tubes are made of titanium. According to some studies fibrin matrix obtained in this method is considered to be more successful (**Figures 1** and **2**) [4, 12, 19–23]. PRFs have been of great interest and improved platelet concentrates for many years. The reason for this is of course their advantages. Unlike the PRPs we mentioned earlier, PRFs are produced completely autogenously. There is no need for extra biochemical interventions. It has an easy application procedure. The method is inexpensive since there is no kit requirement or extra process requirement mentioned in PRPs. Since there is no substance added from the outside, fibrinogen turns into fibrin thanks to the thrombin that is found in the blood spontaneously. In this way, the mechanism operates slowly and in accordance with its natural state. The fibrin thus formed is also a close to nature fibrin. Cell migration and proliferation increased compared to PRP. There are studies showing that it positively affects osteoblast activity. Also, when compared with PRP, it is seen that PRFs have higher

In addition to the many advantageous features described, PRFs also have some disadvantages. Blood is required to be applied. This situation creates anxiety in patients or increases the tendency to refuse treatment. When it is desired to obtain high amounts of PRF, serious blood intake is needed. There is a need for a glass-

PRFs have been used in many fields of medicine and dentistry since its occurrence. It is used in general medicine especially in orthopedic field and for the healing of open wounds and ulcers. In dentistry, it is used in endodontics, periodontology and oral and maxillofacial surgery. Main fields of clinical usage are

*DOI: http://dx.doi.org/10.5772/intechopen.93865*

*PRF membrane after pressing PRF clot between two sterile surfaces.*

**Figure 1.** *PRF clot just after centrifuge.*

*Contemporary Overview of Blood Concentrates in Oral and Maxillacial Surgery DOI: http://dx.doi.org/10.5772/intechopen.93865*

**Figure 2.** *PRF membrane after pressing PRF clot between two sterile surfaces.*

the tubes are made of titanium. According to some studies fibrin matrix obtained in this method is considered to be more successful (**Figures 1** and **2**) [4, 12, 19–23].

PRFs have been of great interest and improved platelet concentrates for many years. The reason for this is of course their advantages. Unlike the PRPs we mentioned earlier, PRFs are produced completely autogenously. There is no need for extra biochemical interventions. It has an easy application procedure. The method is inexpensive since there is no kit requirement or extra process requirement mentioned in PRPs. Since there is no substance added from the outside, fibrinogen turns into fibrin thanks to the thrombin that is found in the blood spontaneously. In this way, the mechanism operates slowly and in accordance with its natural state. The fibrin thus formed is also a close to nature fibrin. Cell migration and proliferation increased compared to PRP. There are studies showing that it positively affects osteoblast activity. Also, when compared with PRP, it is seen that PRFs have higher fibrin content [4, 19–23].

In addition to the many advantageous features described, PRFs also have some disadvantages. Blood is required to be applied. This situation creates anxiety in patients or increases the tendency to refuse treatment. When it is desired to obtain high amounts of PRF, serious blood intake is needed. There is a need for a glasscoated tube to perform the process [19–23].
