**3.1 Fibrin glue**

The fibrin glue is a precursor to platelet concentrates, application of which in medicine started 50 years ago. It is packed in two bottles with different content. One bottle contains lyophilized human fibrinogen, while another one contains either bovine or human thrombin. The mandatory ingredients are calcium salts. Proper usage entails mixing the contents of the two bottles, whereby the coagulation process is imitated, and a gel-like formulation is formed (fibrin clot) that can further be used as a topical hemostatic, tissue adhesive (glue), as well as to join bone graft particles. Although they do have broad applications, fibrin glues have several disadvantages, among which is costly manufacture that makes them less popular in comparison to platelet concentrates [6].

#### **3.2 Platelet-rich plasma**

Platelet-rich plasma (PRP) belongs to the first generation of platelet concentrates that were put into practice by Robert Marx in 1998. PRP is an autologous human platelet concentrate in a small plasma volume. Precisely, it consists of 1 million platelets per 1 microliter in a total volume of 5 milliliters of plasma. Platelet activation in PRP leads to a release of a variety of growth factors that have an important role in the regulation and stimulation of healing.

The PRP preparation process can be divided into the following phases (**Figure 1**):


#### **Figure 1.**

*The PRP preparation process. (A) Blood drawing into 3.2% sodium citrate vacuum test tubes. (B) First centrifugation. (C) Transferring the supernatant to a sterile test tube. (D) Second centrifugation. (E) Removal of two-thirds of the supernatant (PPP). (F) Final product platelet-rich plasma (PRP).*


When prepared accordingly, the PRP is in a liquid state due to the anticoagulant presence and can be stored for up to 8 hours in sterile conditions. Before using the PRP, calcium chloride and bovine thrombin should be added, thereby activating platelets that trigger coagulation processes, which, in return, results in a PRP transition from liquid to gel-like state. Activated thrombocytes release the granules growth factors and cytokines.

Activated growth factors interact with the cell membrane. They never enter the cell or the nucleus. Consequently, they do not have a mutagenic potential; rather, they stimulate physiological healing processes only [8–10].

When in a liquid state, PRP can be injected into a tissue, or it can be mixed with biomaterials that serve as a substitute for bone. In contact with tissue collagen, platelet activation ensues. Activated PRP transitions to a gel, so it can be used as a membrane, or it can be mixed with bone grafts to obtain a graft with a specific shape.

A disadvantage to PRP is a complicated preparation as well as the presence of foreign substances such as anticoagulants (sodium citrate) and procoagulants (calcium chloride and bovine thrombin). Each of these substances can have an antigenic effect albeit, according to Marx, bovine thrombin does not have any contact with systemic circulation and is used in small quantities.
