**2.1 Biomaterials of synthetic origin**

Biomaterials of synthetic origin are tricalcium phosphate, hydroxyapatites, two-phase ceramics, bioactive glasses, and polymers.

Tricalcium phosphates (ßTCP) Ca3(PO4)2 are produced by heating a mixture of calcium phosphate powder and naphthalene to over a thousand degrees and under pressure, which, after sublimation, leaves a porous structure that gives rise to the osteoconductive properties of the material.

The porous hydroxyapatite Ca10(PO4)6(OH)2 is obtained by the thermal transformation of calcium carbonate. Chemically, this calcium phosphate is the closest to biological apatite crystals. Several porosities are available. The higher the porosity, the better the osteoconduction.

Two-phase ceramics (biphasic calcium phosphate (BCP)) include a combination of hydroxyapatite and tricalcium phosphate in different proportions, which make it possible to combine the qualities of the two materials, in particular to obtain adequate resorption and mechanical qualities.

Bioglasses, SiO2-P2O5-CaO-NaO, are materials called "bioactive". This "bioactivity" would take place due to surface reactions of the bioglass and ion exchanges with biological fluids. The bioactive bone/glass bond would take place through a layer of amorphous silica gel which would exert a chemotactic effect on the osteoblasts. Polymers with, in particular polymethylmethacrylate (PMMA), have excellent biocompatibility.

#### **2.2 Biomaterials of natural origin**

The biomaterials of natural origin are xenogenic bone, natural coral and allogeneic bone.

Xenogenic bone (xenograft) is most often of porcine or bovine origin. Inorganic bovine bone retains a bony spatial structure, giving it osteoconductive properties. These are products presented in freeze-dried form [2]. Natural coral is 99% calcium carbonate. After heat treatment, it retains a porous structure that gives it osteoinductive properties [2].

Allogeneic bone substitutes are produced from femoral head bone taken from human individuals (fresh corpse). Compared to autogenous bone, they have the advantage of not requiring harvesting from the patient (in fact, the harvesting of autogenous bone is accompanied by an increased risk of post-operative morbidity). There are two types of allograft depending on the treatment applied to the harvested bone: freeze-dried allograft called the Freeze Dried Bone Allograft (FDBA) and freeze-dried demineralized allograft called the Demineralized Freeze Dried Bone Allograft (DFDBA) or Demineralized Bone Matric (DBM).

To obtain the FDBA, the bone removed will undergo a series of treatments such as [3]: the elimination of residual musculo-fibrous tissue, size reduction until 5 mm particles are obtained, initial decontamination, microbial treatment with antibacterial, antifungal, and antiviral solutions, freezing in liquid nitrogen at −80°C, dehydration by freeze-drying, a second reduction in particle size, packaging in sterile packaging, and finally sterilization with gamma rays to reduce the risk of contamination. The FDBA will mainly serve as a matrix for bone regeneration: osteoconduction.

For DFDBA, the treatment sequence is similar but with a demineralization phase in a hydrochloric acid bath, which is added following the second reduction in particle size.

Demineralized freeze-dried bone allograft (DFDBA) has osteoconductive properties, that is, it serves as a scaffold for the colonization of the recipient site by different cell types and growth factors, and some authors have shown that it has osteoinductive properties; that is to say that it would allow the neoformation of

#### *The Combined Use of Particulate Allografts (DFDBA) and Platelet Concentrates in Oral… DOI: http://dx.doi.org/10.5772/intechopen.111848*

bone. This would take place due to the presence of Bone Morphogenetic Proteins (BMPs) within the bone matrix [4, 5]. Indeed, as it resorbs, the bone releases growth factors, including BMPs belonging to the transforming growth factor beta (TGF β) superfamily and isolated for the first time in the 1960s by Marshall Urist, an American orthopedic surgeon. BMPs and, in particular, isoforms 2, 3, 4, and 7 play a crucial role in bone healing by stimulating the differentiation of mesenchymal stem cells into bone cells [5].

The ability of DFDBA to be osteoconductive and osteoinductive would be influenced by various factors, such as the age of the donor (best between 41 and 50 years old for a man and 51 and 60 years old for a woman), the size of the particles (which must be between 500 and 710 μm to ensure an optimal effect), the residual calcium level (osteo-induction is optimal when the percentage of residual calcium is 2%) [6], as well as the methods of preparation, sterilization, and conservation [7]. It was shown that there is a large variation in the amounts of proteins extracted within different batches of DFDBA, and the authors hypothesized that proteins could be degraded within certain DFDBA batches or present in too small quantity within the bone matrix and therefore remain undetectable with their method [5].

### **3. Adjuvants to surgery: autologous platelet concentrates**

The purpose of using autologous platelet concentrates (PRP and PRF) in oral and implant surgery is to accelerate and improve the phenomena leading to healing, and in particular during surgical procedures aimed at bone regeneration (for review, see [8]).

Platelet-Rich Plasma (PRP), introduced by Marx et al. in 1998, is obtained following two successive centrifugations in tubes with the anticoagulant citrate dextrose A (avoiding platelet activation and degranulation). Gelation of the platelet concentrate is achieved instantly by adding bovine thrombin, recombinant human thrombin, or recombinant human tissue factor, which triggers platelet activation and fibrin polymerization [9].

Authors have developed a simplified protocol to obtain an autologous platelet concentrate without the use of anticoagulants or thrombin called PRF (Platelet-Rich Fibrin) [10]. Venous blood collected without the addition of anticoagulant is immediately centrifuged for 10–12 minutes at 2700–3000 rpm. The authors obtained three layers successively from the bottom to the surface of the tube: the red blood cells, the PRF clot rich in platelets, and on the surface the acellular plasma rich in fibrin.

The natural coagulation mechanism is triggered when blood comes into contact with the surface of the glass tube and allows the production of a fibrin clot rich in platelets and white blood cells, without biochemical changes, that is without the addition of anticoagulant, thrombin or calcium chloride. PRF can be used in the form of gel or membranes.

Platelet-rich fibrin (PRF) has the advantage over PRP of being completely autologous and has been shown to release platelet growth factors over a period of at least one week [11], unlike PRP that releases them within 1 hour following its preparation [12]. Due to the ease of obtaining it, its purely autologous nature, and the fact that the coagulation cascade takes place physiologically without the addition of bovine thrombin, PRF is currently tending to replace PRP.

Platelet concentrates contain fibrinogen, cell adhesion molecules (fibrin, fibronectin, and vitronectin) playing a role in cell migration and osteoconduction, and

also growth factors such as PDGF (Platelet-Derived Growth Factor), TGF-β, EGF (Epithelial Growth Factor), IGF (Insulin-like Growth Factor), and VEGF (Vascular Endothelial Growth Factor) [13].

In oral implant surgery, platelet concentrates are used as adjuvants to bone reconstruction procedures. The purpose of their use is to accelerate and improve the phenomena leading to healing, and in particular to the integration of bone grafts and bone regeneration [13].

They are used in many clinical applications: maxillary sinus filling, alveolar bone crest augmentation, mandibular reconstructions, treatment of periodontal pockets, filling of post-extraction dental sockets, and osseointegration of dental implants [14–17]. Studies have been able to show the beneficial effects of platelet concentrates such as improved soft tissue healing [18, 19]. However, the improvement of bone regeneration thanks to the contribution of platelet concentrates is still controversial [20, 21]. Lack of standardization in procurement protocols of these platelet concentrates may explain the lack of concordance in the various studies, and in addition, the kinetics of delivery of growth factors is a mechanism that is still poorly understood, and which may show large variations between patients and in the same patient according to the time of day when blood collection takes place (there are circadian variations in platelet concentration) [10, 11]. In addition, the contradictory results noted in the literature concerning the benefits provided by the use of platelet coagulation factors can be partly explained by the fact that these results come from clinical studies for some and from animal studies for others, and that it is difficult to extrapolate the results obtained from one species to another [22, 23].

On the other hand, the minimum concentration of platelets necessary to obtain a blood clot entering into the criteria defining the PRF is not well specified by the authors. However, they agree on the fact that a clinical benefit can be obtained for a platelet concentration of 1 million/μl of plasma (4 to 7 times the basal level) [24].
