**5. Platelet concentrate revolution**

Various pathological etiologies may result in oral defects or dysfunction thereby affecting the quality of life in patients. The greatest challenge in clinical research is to develop bioactive surgical additives, that can help to increase the speed of healing process or/and regulate inflammation. Solution to this challenge was found to be *tissue engineering.* This had to be aided with some type of '*biofuel*'. Since the triad forming the base of tissue engineering with a reparative objective is formed by the following: matrices or scaffolds, with various presentations (gels, fibrous matrices, and permeable membranes), progenitor cells (undifferentiated stem cells, or cells with preliminary differentiations) and growth factors. Thus, various platelet-derived products or platelet concentrates have been introduced that act as biological mediators aiding the healing response [43].

In dental implantology**,** the process of osseointegration determines the success of the implanted fixture. The prosthetic loading depends on the stability of the implant attained by osseointegration which is calculated to be complete between 0 and 6 months [44].

To increase bone-implant surface connectivity and accelerate healing few changes in implant surface properties and design can be made that increase primary stability and help the peri-implant tissue remain healthy. Secondly, to accelerate osseointegration, modulation of healing after the placement of the implant can be done. This modulation is achieved by *bioactive molecules* that increase osteoblastic differentiation and accelerate bone healing around the implant [45].

In 1974, platelets regenerative potentiality was introduced, and Ross *et al*, [46] were first to describe a growth factor from platelets. After activation of the platelets which are trapped within fibrin matrix, growth factors were released that could stimulate the mitogenic response in the bone periosteum during normal wound healing for repair of the bone [47].

The platelet-containing preparations derived from human blood contain many growth factors such as bone morphogenetic protein (BMP), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and transforming growth factor-β2 (TGF-β2). These are considered to play a crucial role in bone healing [48, 49]. These growth factors, as explained earlier, attract the undifferentiated mesenchymal cells to the wound site, thus facilitating angiogenesis, chemotaxis, and cell proliferation [44].

C.Pirpir [50] et al. concurred with the above information and he concluded from his study that application of Concentrated growth factor enhanced stability of implants and accelerated osseointegration in the early period. His study demonstrated that CGF has positive effects on the ISQ value at the first week and fourth week.

Many other studies have been undertaken by Ji-Min Kim and Dong-Seok Sohn [51], S. Manoj [52], Andrea Forabosco [53] and Sila Cagri Isler [54] to evaluate bone regeneration around immediate post extraction implants, in sinus floor augmentation and cases of peri-implantitis who have given their affirmation towards increased bone healing with application of platelet containing preparations. Since blood has long been recognized as the torch bearer of healing process in the body, it has potential to accelerate wound healing when added to wounded tissues or surgical sites.

#### **5.1 Platelet rich plasma (PRP)**

Platelet-rich plasma (PRP), also known as autologous conditioned plasma, first introduced in dentistry by Whitman et al. is a concentrate of platelet-rich plasma protein derived from whole blood, centrifuged to remove red blood cells. This concentrate, full of various essential growth factors is introduced to the surgical site, enriching the natural blood clot. This hastens the wound healing and stimulates bone regeneration [55]. Specific protocols and automated systems for preparing PRP have been developed and commercialized, including Ace, PRGF, PRP-Landesber, Curasan, PCCS, Harvest SmartPReP, Vivostat, Friadent-Schutze, Regen, Fibrinet and Plateltex. Dohan Ehrenfest and colleagues offer an excellent comparison between these traditional systems.

A natural human blood clot consists of 95% red blood cells (RBCs), 5% platelets, less than 1% white blood cells (WBCs), and numerous amounts of fibrin strands. A PRP blood clot, on the other hand, contains 4% RBCs, 95% platelets, and 1% WBCs [56].

The PRP preparation protocol requires collection of blood with an anticoagulant, centrifugation in two steps, and induced polymerization of the platelet concentrate using calcium chloride and bovine thrombin [57]. PRP can be used in conjunction with different grafting materials in bone augmentation procedures. However, the addition of bovine-derived thrombin to handle PRP may increase the risk of lifethreatening coagulopathies [58].

#### **5.2 Platelet rich fibrin (PRF)**

PRF represents a step ahead in the platelet revolution. Choukroun *et al*., [59] developed the PRF in 2001 to accumulate platelets and released cytokines in a fibrin clot. Cytokines are immediately used and destroyed in a healing wound. The harmony between cytokines and their supporting fibrin matrix is the magic wand of the or real therapeutic potential of PRF. Also, this technique does not require any gelling agent [60].

Today PRF is increasingly being investigated and used worldwide by clinicians as an adjunctive autologous biomaterial to promote bone and soft tissue healing and regeneration [61]. In surgical procedures, PRF could serve as a resorbable membrane for guided bone regeneration (GBR), preventing the migration of non-desirable cells into bone defect and providing a space that allows the immigration of osteogenic and angiogenic cells and permits the underlying blood clot to mineralize. However, a normal PRF membrane has rapid degradability (1–2 weeks), but if fibers are crosslinked, it could provide resistance against enzymatic degradation and could be more stable during the healing time.

PRF technology has grabbed the attention of clinicians because of its excellent advantages.


It is also concluded and concurred by various authors in their studies, that PRF is a good regenerative option with bone grafts in intra bony defects [62], treatment of peri-implantitis [63], reconstruction of large defects after cancer surgery [64]. Other applications include to accelerate healing in maxillary sinus augmentation, socket healing after tooth extraction, filling of the cyst cavity, treatment of furcation defects in periodontology, and soft tissue injuries [65].

They can be used as an adjunct, as a graft stabilizing membrane or used alone in dental (immediate) implant procedures [66]. Collagen Membrane has been used successfully in these regenerative procedures. An additional use or total replacement with platelet concentrates can provide further regenerative advantages due to the presence of biochemical agents of healing.

Simonpieri A. [67] also stated that, PRF membranes protects the surgical site; promotes soft tissue healing; and when its fragments mixes with graft material, it functions as a "biological connector" between the different elements of graft and acts as a matrix which supports neo angiogenesis, capture of stem cells, and migration of osteoprogenitor cells to the center of graft.

#### **5.3 Concentrated growth factor**

Concentrated growth factor, (CGF) another milestone towards regenerative dentistry was defined by Sacco in 2006 [68]. CGF also has its own centrifugal technique in a manner similar to that of obtaining PRF. It is seen to form rich layers of growth factors that include TGF-β1, VEGF, PDGF, IGF, EGF, FGF, and BMP which are delivered at the site of application. The positive effects of these blood products have triggered the development of various platelet products in different concentrations.

The concentrated growth factor used the advantage of longer and denser fibrin matrix with higher growth factor content. While CGF has been stated to be an improved formulation of PRF, it has also been proposed that a different term is used for CGF because of the use of a different centrifuge machine (MEDIFUGE, Silfradent srl, S. Sofia, Italy) and centrifugation speed (2400 to 3000 rpm). This produces a three layered structure: red blood cell layer at the bottom, plateletdeprived plasma layer (without cell) at the top, and fibrin gel with concentrated growth factor and platelet aggregation in the middle (**Figure 1**) [50]. Furthermore, CGF has been found to be almost identical to self-clotted advanced-PRF (A-PRF) in respect of mechanical and degradation properties [69].

Many studies have now come up with positive effects from local administration of CGF at the defect site. It is proved to increases bFGF or VEGF release. This increases angiogenesis, as well as enhances neutrophil migration by performing integrin release. It has also been shown that CGF contains such growth factors and CD34-positive cells that also provide angiogenesis, neovascularization, and vascular continuity [68].

**Figure 1.** *Freshly prepared concentrated growth factor.*

It is also validated that autogenous bone is the gold standard for grafting in the defects, implant sites or sinus lift procedures, but it is always associated with problems of 'second' surgical site and the associated morbidity of the donor tissue. As

*Growth Factors and Dental Implantology DOI: http://dx.doi.org/10.5772/intechopen.101082*

an alternative, allograft and xenografts are also used, which have the risk of crossinfection [52].

Along with the choice of graft material being a topic of debate, in many procedures like filing the jumping distance, the additional use of a membrane is also a matter of controversy. Various studies have documented some of the complications due to the use of membranes in these sites [70]. The use of CGF has been proposed as a substitute to fill the jumping distance in order to overcome certain disadvantages associated with various graft materials and membranes including increased treatment costs.

One animal study was conducted on CGF, PRF, and PRP placed separately in the defects in the rabbit skull compared with control groups with empty defect or self healing. Histomorphometric analysis revealed statistically significant differences between control and study groups in the growth of new bone formation at 6 and 12 weeks. In the study group, the greatest bone formation was observed in the CGFtreated group but this difference was not statistically significant [71]. In a study by Takeda et al. [72] performed on rats, it was observed that cell proliferation and osteoblastic differentiation in the cell culture from the CGF-treated group was significantly higher than in the other groups.
