## 4 Discussion
In another three-arm trial, [PERSON] et al. compared CGF, low-level laser therapy (LLLT) and conventional treatment (gentle socket curettage and saline irrigation) for the management of dry sockets [36]. They found that the beneficial effects of CGF were superior to those of LLLT with respect to control in healing rate and pain control. It is difficult to compare these studies with the present one, due to different protocols, but the advantages of CGF in both healing and pain relief after tooth extraction were in line with our findings. In vitro studies showed that, as compared to L-PRP and P-PRP, L-PRF releases greater amounts of TGF-1, shows a longer-term and steady release of growth factors up to at least 10 days, and displays a stronger induction of mesenchymal stem cell migration [20; 37; 38; 39]. Such differences were attributed to the different composition and architecture of PRP and PRF, particularly to the denser and stronger fibrin network of the latter. The fibrin mesh of PRF, which forms through a natural polymerization during centrifugation, in the absence of anticoagulants, may entrap platelets and cells inside the clot, and modulate the growth factors release over time. The degradation of the fibrin mesh of L-PRF occurs more slowly than in PRP, and it is believed to correlate with the longer duration of growth factors released from L-PRF [20; 37; 38; 39]. The Concentrated Growth Factor is the most recently introduced system for producing platelet concentrates [16]. Blood is drawn in tubes without anticoagulant, similar to L-PRF, but CGF is characterized by a peculiar blood centrifugation process, carried out at a constant temperature and at strictly controlled alternating speeds. Additionally, there is a gradual speed increase and decrease at the start and the end of the process, to avoid violent acceleration and deceleration, with the aim of preserving as much as possible the cellular integrity. The importance of the centrifuge characteristics and the centrifugation protocol have been underlined by recent in vitro studies that compared different commercially available centrifuges for the production of L-PRF [31; 40]. These studies pointed out that different centrifugation systems produce clots with different sizes and mechanical consistence, fibrin matrix strength, cellular content, growth factors release profile, and bioactivity. According to these studies, the system producing the best-quality L-PRF clot is the one that was used in the present study, namely the Intra-Spin, manufactured by Intra-Lock [31; 40]. Recent in vitro studies compared the features and the biological activity of the advanced PRF clot obtained with the original protocol, and the CGF clot obtained with the Medifuge System, manufactured by Silfradent [21; 41]. The study by [PERSON] et al. found extremely similar composition, mechanical strength, degradation, fibrin fibers thickness and crosslink density of PRF and CGF, in spite of marked differences in the centrifugation process between the two products [21]. The study by [PERSON] et al. found higher tensile strength, higher concentration and amount of PDGF-BB and EGF in CGF, as compared to PRF [41]. In addition, osteoblasts proliferation in cultures enriched with PRF or CGF clots at different % (5%, 10%, and 50%) was comparable to cultures with the medium enriched with fetal bovine serum (FBS, 10%). Osteoblast number, as well as gingival fibroblasts number, independent of the preparation (10% and 50%), was significantly greater with CGF than with PRF [33]. According to the results of these preliminary in-vitro comparative studies, the biological features and activity of CGF were not inferior to those obtained with PRF. Clearly, the result of in vitro investigations need to be confirmed by comparative clinical studies. In 2019, a case report was published of a 21-year old patient with bilateral multiple gingival recession, treated by coronally advanced flap [42].