Platelet derivatives represent a rich source of growth factors, including platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF), which are essential for osteogenesis and angiogenesis (Burnouf et al., 2013). The term “Platelet-rich plasma” was at first introduced by Marx et al. (1998) after which it became widely adopted in the literature. The first generation of platelet concentrates, represented by PRP, is obtained by centrifuging whole blood with the addition of anticoagulants and subsequent activators (Marx et al., 1998). However, the use of chemical additives in this process may interfere with the healing process (Miron and Zhang, 2018).

The second generation, PRF, eliminates anticoagulants, allowing the blood to clot naturally and forming a three-dimensional fibrin matrix (Shah et al., 2017). More recently, third-generation protocols based on low-speed centrifugation (LSCC), such as advanced PRF (A-PRF) and injectable PRF (i-PRF), have been developed. Recent studies highlight conflicting results in bone regeneration, and we also observe numerous preparation protocols referred to by different authors as PRF, PRP, CGF, PRFG, etc.

Due to the variability in preparation protocols used, some authors have been concerned with standardizing the quality of the product obtained. PRP is better characterized based on three parameters that take into account platelet concentration compared to baseline, platelet activation method, and total white blood cell (WBC) content, with particular attention to the inclusion or exclusion of neutrophils (DeLong et al., 2012).

This approach led to the development of the PAW classification system (Platelets, Activation, and White blood cells), which provides a more quantitative assessment of the cellular components present (DeLong et al., 2012). Another classification is called PLRA and based on the on four key variables: platelet concentration, presence or absence of leukocytes, red blood cells (RBC), and activation method (Mautner et al., 2015). Subsequently, in 2016, Magalon et al. proposed the DEPA classification system, which considers the quality of PRP preparation through four key factors: dose, efficiency, purity, and activation, thus providing a comprehensive framework for evaluating both the composition and bioactivity of PRP products (Magalon et al., 2016).

The aim of this mini review is to provide an overview of the applications of Autologous Platelet Concentrates (APCs) and their clinical application.

Platelet concentrates were initially used for the treatment of patients suffering from severe thrombopenia, and the first studies, due to a lack of an organized terminology, referred to them generically such as platelet -fibrinogen-thrombine mixture (Rosenthal et al., 1975), platelet-derived wound healing factors (PDWHF) (Knighton et al., 1986), or gelatine platelet (Alidadi et al., 2017). When we talk about Platelet Concentrates (PCs), we should primarily refer to the classification proposed by Dohan et al. (2009), which considers the presence of leukocytes and the organization of the fibrin matrix (liquid or solid). Based on this, we have: Pure Platelet-Rich Plasma (P-PRP) (low leukocytes, liquid/gel), Leukocyte-Platelet-Rich Plasma (L-PRP) (high leukocytes, liquid/gel), Pure Platelet-Rich Fibrin (P-PRF) (no leukocytes, dense fibrin matrix), and Leukocyte-Platelet-Rich Fibrin (L-PRF) (high leukocytes, dense fibrin matrix) (Figure 1). Therefore, we essentially have four families of platelet concentrates. In dentistry, several preparation protocols for PCs have been developed, considering that variables such as centrifugal force (CF) and the type of tube used influence the final product (Figure 1). In dentistry and maxillofacial surgery, PRF is widely used because it also serves as a scaffold and filler. Platelet concentrates (PCs) are employed because, once applied to the bone defect, they provide a quantity of growth factors such as PDGF, IGF, EGF, and VEGF at a concentration higher than what platelets arriving from blood could offer (Egierska et al., 2023). These growth factors promote cell migration, proliferation, and differentiation, mechanisms that are considered the basis of their positive effect on tissue regeneration.

The growth factors contained in PCs act like “conductors,” recruiting the cells responsible for tissue regeneration. The presence of leukocytes, once considered undesirable due to the risk of triggering inflammation, is now believed to play an important role in bone healing, particularly in reducing infections through immune system regulation (Anitua et al., 2021). They also contribute to pain reduction and promote neoangiogenesis (Blanco et al., 2000).

This naturally raises the question: how do we produce PRP with or without leukocytes? Technology provides us with manual and automated systems that help minimize production errors. Manual systems use centrifuges to separate the blood components (Figure 2). For tubes that generate PRF, three main layers can be identified: red blood cells at the bottom, followed by a solid fibrin architecture that traps platelets and leukocytes, and finally platelet-poor plasma (PPP) at the top.

In the case of PRP, where the fibrin is liquid, it is difficult to accurately collect the platelet concentrate with or without the buffy coat (which contains leukocytes) using pipetting (Figure 2). Typically, in manual procedures, this is done by visual inspection, the operator, based on experience, identifies the whitish layer containing white blood cells (Figure 2). Obviously, this procedure is subject to individual error depending on the operator’s level of expertise. Automatic systems help reduce the error in collecting the platelet concentrate with greater precision because they can identify the buffy coat using optical systems. In our opinion, the variability in results reported by some authors may be attributed precisely to the ability to extract the buffy coat accurately during pipetting.

The scientific literature shows conflicting results, making the data difficult to organize and interpret. For example, while many studies demonstrate significant benefits of using PCs in tissue regeneration (Scarano et al., 2021), others report modest or no results, creating uncertainty about the actual clinical usefulness of these PCs (Franchini et al., 2019). To clarify the concept of heterogeneity in results due to the method used, imagine preparing a dish without specifying the cooking time, temperature, or exact ingredient quantities. Even if the main ingredient is blood, each operator will produce a different dish: some will be perfect, others undercooked or burnt. Without a standard recipe, it is impossible to ensure that the patient always receives the same therapeutic benefit.

Currently, we have numerous devices available to obtain PCs with specific and characteristic features of each method, such as APG, PRF, PRGF, CGF, etc. On one hand, this wide range of options offered by companies creates confusion; on the other hand, it allows us to have systems that provide a uniform product for all operators by standardizing centrifugal force, type of vial used, its inclination, and rotation time.

It is also true that there is no consensus on the optimal preparation methods, and a clear and complete categorization of these final products is difficult to find in the literature.

Every small variation in these parameters results in changes in platelet composition, leukocyte profile, and the 3D architecture of fibrin, producing a new and completely different PC.

The positive aspect is that each manual system has a well-defined protocol, which helps clinicians obtain a product that is clearly characterized and studied by various research groups. On the other hand, automatic systems are precise but expensive and bulky to use in a dental office, and current Italian regulations are still unclear as to whether these systems can be used in a dental clinic.