Maxillary Sinus Augmentation Using Autologous Platelet Concentrates (Platelet-Rich Plasma, Platelet-Rich Fibrin, and Concentrated Growth Factor) Combined with Bone Graft: A Systematic Review

Background: The current review aims to provide an overview of the most recent research on the potentials of concentrated growth factors used in the maxillary sinus lift technique. Materials and methods: “PRP”, “PRF”, “L-PRF”, “CGF”, “oral surgery”, “sticky bone”, “sinus lift” were the search terms utilized in the databases Scopus, Web of Science, and Pubmed, with the Boolean operator “AND” and “OR”. Results: Of these 1534 studies, 22 publications were included for this review. Discussion: The autologous growth factors released from platelet concentrates can help to promote bone remodeling and cell proliferation, and the application of platelet concentrates appears to reduce the amount of autologous bone required during regenerative surgery. Many authors agree that growth factors considerably enhance early vascularization in bone grafts and have a significantly positive pro-angiogenic influence in vivo when combined with alloplastic and xenogeneic materials, reducing inflammation and postoperative pain and stimulating the regeneration of injured tissues and accelerating their healing. Conclusions: Even if further studies are still needed, the use of autologous platelet concentrates can improve clinical results where a large elevation of the sinus is needed by improving bone height, thickness and vascularization of surgical sites, and post-operative healing.


Introduction
The balance of bone resorption and bone creation is critical for the preservation and regeneration of alveolar bone and supporting structures surrounding teeth and dental implants [1]. Tissue regeneration in the oral cavity is influenced by a variety of cell types, signaling systems, and matrix interactions [1,2]. Severe bone defects in the areas where the implant is to be placed might restrict the surgery; as a result, numerous bone regeneration techniques have been designed [3]. Maxillary sinus floor elevation (MSFE) is one of these procedures meant to increase bone volume in the atrophic posterior maxilla [4,5]. MSFE aims to increase bone height in the posterior maxilla by raising the Schneiderian membrane and inserting graft material into the surgically generated gap in the maxillary sinus floor [1]. Clinical trials of MSFE and other bone grafting methods, including biomaterial grafting,

Data Processing
The screening procedure, which was carried out by reading the article titles and abstracts chosen in the earlier identification step, allowed for the exclusion of any publications that varied from the themes looked at. The complete text of publications that had been determined to match the predetermined inclusion criteria was then read. Reviewer disagreements on the choice of the article were discussed and settled.

Results
Keyword searches in the Web of Science (307), Scopus (362) and Pubmed (1333) databases yielded a total of 2002 articles. The subsequent elimination of duplicates (468) resulted in the inclusion of 1534 articles. Of these 1534 studies, 1512 were excluded because they deviated from the previously defined inclusion criteria. The screening phase ended with selecting 22 publications for this work (Figure 2). The results of each study were reported in Table 2.

Authors (Year) Type of the Study Aim of the Study Materials Results
Anitua et al., 2012 [24] A report of five cases In five consecutive patients who had bilateral sinus lift augmentation, the prospective effects of (PRGF) technology were assessed.
-Five patients; -One side treated with bovine bone and PRGF, and the other only with bovine bone; -Lateral wall technique; -Two stage implants; -Five-month histomorphometrical analysis.
PRGF may play a role in lowering tissue inflammation during surgery, boosting the production of new bone, and encouraging the vascularization of bone tissues.

Authors (Year) Type of the Study Aim of the Study Materials Results
Kaarthikeyan et al., 2019 [33] A randomized controlled trial To compare bone growth in the elevated maxillary sinus using an implant as a tent pole and PRF or blood clot alone as the only sinus-filling material.
-Seven patients; -Lateral bony window; -Implant used as a tent pole; -One side PRF, other side only blood; -Twelve-month follow-up.
As the only material to fill the sinuses, PRF might be a better option than a blood clot. During the OSFE procedure and implantation, using PRF and bone graft material is a safe and efficient alternative.

Different Platelet Derivates
Based on different centrifugation parameters, platelet concentrates are classified into PRP, PRF and CGF [42,43].
PRP is a rich source of growth factors and platelets, and it is found in low-volume plasma. PRP includes FGF, TGF-β, IGF, PDGF-like growth factors and cell adhesion molecules such as vitronectin, fibrin and fibronectin. Because of this content, PRP accelerates wound healing [44].
Venous blood is drawn, and an anticoagulant agent is mixed in to prevent the blood from clotting. The mixture is centrifuged at 2400 rpm for 10 min. At the end of the first centrifugation, the blood in the tube is divided into two parts (upper part yellow plasma, lower part erythrocytes accumulate). The whole mixture, using the cannulation technique, is transferred to a second tube and subjected to a second centrifugation at 3600 rpm for 15 min to collect the platelet fraction at the bottom of the tube. What you get is PRP to be used for the surgical procedure [44].
Because of the limitations of PRP arising from its anticoagulant content, further studies by Joseph Choukroun in the early 2000s focused on the development of a second-generation platelet concentrate without the use of anticoagulant factors [45].
In this way, it was observed for the first time that in a single centrifugation cycle at 2700 rpm (750 g), a platelet concentration was collected that did not carry clotting factors to the top of the centrifuge tubes. This formulation is called PRF [46,47].
PRF is a second-generation platelet product that enables the formation of growth factors and platelet-rich membranes. PRF also contains leukocytes (WBCs) within the fibrin matrix (L-PRF) [46,48].
Peripheral venous blood is collected and centrifuged in glass-lined plastic tubes free of anticoagulants at 2700 rpm for 12 min or 3000 rpm for 10 min. Since there is no anticoagulant in PRF, coagulation begins when the blood is collected in the tube [8]. After centrifugation, a layer of cell-free plasma is formed at the top, a layer at the base rich in erythrocytes, and an intermediate layer of PRF clot. The PRF clot consists of a strong fibrin matrix in which platelets and leukocytes are concentrated [46,47].
CGF is a leukocyte-and platelet-rich fibrin structure first used by Sacco in 2006 [50]. As in PRF, CGF is obtained by a single centrifugation method. Plastic tubes without anticoagulants lined with red-capped silica particles are required, and no exogenous substances need to be added in this process [50].
The blood is centrifuged at low and controlled speeds for 12 min at 2400-2700 rpm. The resulting clot is divided into three layers (the upper layer contains platelet-poor plasma; the middle layer includes polymerized dense fibrin blocks containing fibrin and CGF; and the lower layer contains erythrocytes). The upper and lower layers are discarded, and CGF is collected in the buffy coat layer [51].
In 2006, Sacco first developed CGFs [52]. CGFs have stiffer fibrin structures than PRP and PRF [53]. In addition, CGF is more effective in bone regeneration and breast augmentation as it promotes osteogenesis [53,54].
A study by Dai et al. evaluated the efficacy of CGFs combined with MC in GBR [19]. Patients in whom CGF+MC was used and patients with MC alone were compared. It was seen that all implants healed, and the CGF+MC group had less swelling and less pain. The complex of CGF and MC seems to be appropriate and efficient as a biomaterial for bone augmentation [19].
The double-blind study by Ghasemirad et al. evaluated the effect of CGF on bone healing in a maxillary sinus lift [29]. A bovine xenograft was applied on one side and CGF on the other side. Staining with alizarin red and hematoxylin-eosin showed that the percentage of bone formed in the CGF group was significantly higher than in the control group [29].
So, the percentage of newly formed bone in the CGF group was significantly higher than in the control group (xenograft) after 6 months [29].
Zhang et al. evaluate the influence of PRF on bone regeneration in a xenograftassociated sinus lift (deproteinized bovine bone) [41]. On histological examination, no statistically significant differences were found between patients treated with PRF and patients treated only with xenograft. In conclusion, the study showed no differences of the application of PRF associated with deproteinized bovine bone in sinus augmentation 6 months after surgery [41].

Different Bone Graft Materials Used in Combination with Platelet Derivates
The "gold standard" for bone tissue regeneration is an autograft taken from an adjacent site in the same patient [57]. This procedure has negative effects such as a second surgical procedure, unpredictable extent of resorption, and shortage of donor sites [58,59]. So, bone substitutes can be applied to avoid these disadvantages.
The maxillary sinus has been augmented using a variety of graft materials, including autograft, xenografts and allografts, each of which has advantages and disadvantages [60]. PRF has greater advantages than other graft materials since platelets are essential for the development and repair of soft tissue and bone [61,62].
PRP is a plasma concentrate high in platelets produced by centrifuged peripheral venous blood from the patient and used as a bone-grafting material. PDGF, TGF-β, and VEGF are three growth factors that are particularly abundant in PRP, and they have a potential range of cellular activities that includes cell differentiation, tissue healing, angiogenesis and increasing collagen formation [61,62]. This approach had already been applied in other fields of medicine such as in dermatology up until the late 1990s when Marx et al. discovered that the use of PRP in conjunction with autologous bone might result in a noticeably better outcome [63].
The following cellular processes are stimulated by PRP three days after grafting in the recipient site: proliferation of osteoblasts and fibroblast, neoangiogenesis, and stimulation of the mineralization of the newly created bone matrix [1,64].
In implantology, GBR operations frequently employ PRP to repair edentulous regions that need an increase in bone volume [61].
A study by Inchingolo et al. involved a cohort of 127 patients requiring a maxillary sinus lift. Half of the patients received PRP in combination with anorganic, organic or autogenous bone; the control group received only grafting material without PRP. In all cases, authors obtained successful results, but the test group with PRP showed a statistically significant enhancement in osseointegration in terms of primary stability and peri-implant bone quality evaluated in tomographic sections with a 3D software [1].
Another strategy is to insert the implants during the sinus lift to save time and prevent a second surgery; Inchingolo et al. assessed the efficacy of PRP with deproteinized bovine oss (Bio-OSS) and beta-tricalcium phosphate (SINT-Oss) for a sinus lift and simultaneous implant placement in patients with sinus pathology [31]. The PRP prepared with Choukroun's technique was used in two different ways: a portion was blended with Bio-Oss and Sint-Oss; the remaining was modelled as a resistant fibrin membrane that could be transferred to the Schneiderian membrane, and the other portion was transferred to the material used before closing the lateral window created with the use of piezosurgery. The soft tissues around the implants in all patients showed no signs of tissue damage; the implants had optimal primary stability, and the density of the bone around the implants had increased. There was no unfavorable progression of the sinusitis. The authors concluded that the combination of PRF and Piezosurgery decreased the healing time, favored optimum bone regeneration, and allowed sinus membrane integrity to be preserved during surgical treatments [31].
Instead, Kempraj et al. compared the use of Choukroun's PRP as a single-graft material to Xenograft (BIO-OSS) for a sinus lift [34]. The sample size was constituted by 22 interventions performed with the lateral window technique. Compared to the use of PRP alone, radiological results revealed an important rise in bone density and in bone height in the Bio-oss group. This could be caused by the sinus membrane's collapse of the PRF plug due to the absence of a structure that support it, as also reported by Lundgren et al. [65].
Promising results were shown by Powell et al., who experimented with L-PRF using three different methods: in the first case, L-PRF was employed to support a maxillary hybrid denture by bilateral sinus augmentation. In the second patient, it emphasized the use of L-PRF associated with an elevation of the Schneiderian membrane. In the third patient's implant placement after L-PRF/xenograft sinus augmentation, a histological examination was provided six months later [40]. Dental implants were successfully placed in every patient; in the second case, freeze-dried bone allograft offered around 4 mm of extra vertical height for implant insertion. Six months after sinus augmentation, histology from the third case showed that there was fresh, viable bone in contact with the xenograft [40].
Simonpieri et al. stated that literature findings regarding PRP's efficacy could have been clearer because different PRPs were tried in several different combinations with varied bone materials [9].
Despite being an excellent way to manage bone graft material during the incision in the subsinus cavity, and despite having the potential to speed up bone healing, the degree of proof for this technique was still just marginal because the surgical treatment already had a very high success rate even without PRP [9]. Surgical methods and how PRP and bone grafts were combined varied between research, so Simonpieri et al. asserted that because of the many methodological variations, it could appear hard to draw broad conclusions from the diverse research present in literature [9] (Figures 3 and 4). PRF plug due to the absence of a structure that support it, as also reported by Lundgren et al. [65]. Promising results were shown by Powell et al., who experimented with L-PRF using three different methods: in the first case, L-PRF was employed to support a maxillary hybrid denture by bilateral sinus augmentation. In the second patient, it emphasized the use of L-PRF associated with an elevation of the Schneiderian membrane. In the third patient s implant placement after L-PRF/xenograft sinus augmentation, a histologica examination was provided six months later [40]. Dental implants were successfully placed in every patient; in the second case, freeze-dried bone allograft offered around 4 mm of extra vertical height for implant insertion. Six months after sinus augmentation, histology from the third case showed that there was fresh, viable bone in contact with the xenograft [40].
Simonpieri et al. stated that literature findings regarding PRP s efficacy could have been clearer because different PRPs were tried in several different combinations with varied bone materials [9].
Despite being an excellent way to manage bone graft material during the incision in the subsinus cavity, and despite having the potential to speed up bone healing, the degree of proof for this technique was still just marginal because the surgical treatment already had a very high success rate even without PRP [9]. Surgical methods and how PRP and bone grafts were combined varied between research, so Simonpieri et al. asserted that because of the many methodological variations, it could appear hard to draw broad conclusions from the diverse research present in literature [9] (Figures 3 and 4).

Surgical Techniques for Sinus Augmentation Using Platelet Derivatives
Tatum, in 1976, modified the Caldwell-Luc technique and performed the first maxillary sinus lift procedure. Through the lateral window, the membrane of the sinus was dissected and elevated ( Figure 5); in this case, autogenous bone was used as a bone substitute in the sinus, and the implant was placed after 6 months [66]. Boyne and James proposed the Caldwell-Luc sinus revision and the lateral window sinus floor elevation, and implant placement was performed in 3 months [66]. Since the first sinus floor elevation, numerous graft techniques and materials have been proposed.

Surgical Techniques for Sinus Augmentation Using Platelet Derivatives
Tatum, in 1976, modified the Caldwell-Luc technique and performed the first maxillary sinus lift procedure. Through the lateral window, the membrane of the sinus was dissected and elevated ( Figure 5); in this case, autogenous bone was used as a bone substitute in the sinus, and the implant was placed after 6 months [66]. Boyne and James proposed the Caldwell-Luc sinus revision and the lateral window sinus floor elevation, and implant placement was performed in 3 months [66]. Since the first sinus floor elevation, numerous graft techniques and materials have been proposed.

Surgical Techniques for Sinus Augmentation Using Platelet Derivatives
Tatum, in 1976, modified the Caldwell-Luc technique and performed the first maxillary sinus lift procedure. Through the lateral window, the membrane of the sinus was dissected and elevated ( Figure 5); in this case, autogenous bone was used as a bone substitute in the sinus, and the implant was placed after 6 months [66]. Boyne and James proposed the Caldwell-Luc sinus revision and the lateral window sinus floor elevation, and implant placement was performed in 3 months [66]. Since the first sinus floor elevation, numerous graft techniques and materials have been proposed. In 1986, Tatum Jr. developed the transalveolar sinus floor elevation to minimize pain and suffering after surgery [67]. Summers modified this approach in 1994 [68].
The Summer's osteotomy, which used no grafting material even in thin residual bone height, has been associated with developing the idea of limited grafting. The bone's and the sinus membrane's osteogenic potential is well-protected and effective in a closed space like an elevated sinus [69,70].
Simonpieri et al. applied a sinus lift with the lateral window technique in 24 patients, and the follow-up time for these patients from the placement of the implants was 2-6 years ( Table 2). The patients had a subantral augmentation category 4 (SA4) sinus morphology where the height of the crestal bone from the floor of the sinus is <5 mm. A PRF membrane was used for the Schneiderian membrane protection, and the implant served as "tent pegs" for the L-PRF-patched Schneiderian membranes. In this study, the height of the peri-implant crestal bone was consistent, and the floor level of the reconstructed sinus was always continuous with the apical edge of the implant [71] (Figure 6). In 1986, Tatum Jr. developed the transalveolar sinus floor elevation to minimize pain and suffering after surgery [67]. Summers modified this approach in 1994 [68].
The Summer s osteotomy, which used no grafting material even in thin residual bone height, has been associated with developing the idea of limited grafting. The bone s and the sinus membrane s osteogenic potential is well-protected and effective in a closed space like an elevated sinus [69,70].
Simonpieri et al. applied a sinus lift with the lateral window technique in 24 patients and the follow-up time for these patients from the placement of the implants was 2-6 years ( Table 2). The patients had a subantral augmentation category 4 (SA4) sinus morphology where the height of the crestal bone from the floor of the sinus is <5 mm. A PRF membrane was used for the Schneiderian membrane protection, and the implant served as "ten pegs" for the L-PRF-patched Schneiderian membranes. In this study, the height of the peri-implant crestal bone was consistent, and the floor level of the reconstructed sinus was always continuous with the apical edge of the implant [71] (Figure 6). In fact, if the preservation of the Schneiderian membrane is achieved at the righ height with the help of immediate implantation, this technique has given successfu results [72]. But this technique does not accept tears of the sinus membrane and presents difficulties in filling the base of the sinus cavity with a blood clot [71]. Kaarthikeyan et al concluded that PRF is an effective biomaterial when used alone for filling the maxillary sinus with an implant as a tentacle (Table 3), but perforation of the sinus membrane during the procedure may lead to unsatisfactory results [33].
Other authors have shown that the lateral approach can be performed in a full sinus lift only with whole blood and no other graft material [73,74]. Chitsazi et al. (Table 2) used only PRF as bone graft material for raising the maxillary sinus with an open window on one side and did not use graft material on the other side. Implants were placed in one session. This study (Table 3) stated that PRF may improve both the quantity and quality of bone resorption [27].
The fibrin network found in PRF has the tendency to develop a three-dimensiona structure comparable to the place of insertion, promoting the healing process. A three dimensional scaffold is created by the accumulation of fibrin monomers, creating a thin In fact, if the preservation of the Schneiderian membrane is achieved at the right height with the help of immediate implantation, this technique has given successful results [72]. But this technique does not accept tears of the sinus membrane and presents difficulties in filling the base of the sinus cavity with a blood clot [71]. Kaarthikeyan et al. concluded that PRF is an effective biomaterial when used alone for filling the maxillary sinus with an implant as a tentacle (Table 3), but perforation of the sinus membrane during the procedure may lead to unsatisfactory results [33].
Other authors have shown that the lateral approach can be performed in a full sinus lift only with whole blood and no other graft material [73,74]. Chitsazi et al. (Table 2) used only PRF as bone graft material for raising the maxillary sinus with an open window on one side and did not use graft material on the other side. Implants were placed in one session. This study (Table 3) stated that PRF may improve both the quantity and quality of bone resorption [27].
The fibrin network found in PRF has the tendency to develop a three-dimensional structure comparable to the place of insertion, promoting the healing process. A threedimensional scaffold is created by the accumulation of fibrin monomers, creating a thin mesh of soft porous material that enables the quick cell colonization of the site and surrounding tissues [9,75,76].
Molemans et al. also conducted a study using only L-PRF as filler material in a maxillary sinus lift. Only in cases when the crestal height was <5 was the lateral window technique performed; in contrast, the preference was for the crestal technique ( Table 2). The results showed that this biomaterial can be used in lateral sinus surgery with success. Implant failure was seen only in the crestal technique; it is possible that the membrane was perforated during the procedure [37].
Choudhary et al.'s goal was to assess the effects of simultaneous implant insertion with PRF and indirect sinus lift with hydraulic pressure when the average mean height at the beginning was 5.573 ± 0.66 mm ( Table 3). The average pretreatment mean height significantly increased after surgery ( Table 2). A six-month postoperative period saw an increase in the implant stability quotient [28]. These results were in line with earlier research that showed a considerable rise in residual alveolar ridge height after indirect sinus lift and concurrent PRF implant insertion [77,78].
During Summer's osteotomy, the use of PRF membranes offered a good result as filling material. PRF servs as a cushion shock absorber during osteotomy and supports healing in case of a damaged Schneiderian membrane [79]. Huang et al. showed how the PRF membrane can be used to repair the perforation of Schneider's membrane caused by the maxillary sinus lift procedure with the lateral window technique. The Schneiderian membrane's perforation could be repaired by a PRF membrane [30]. The PRF membrane's fibrin and platelet contents may both play a role in this impact [65,80,81].
Independently of whether a procedure was 1-stage or 2-stage, Rosen et al., for the osteotomy sinus floor elevation, found that the success of implant placement was better when the ridge bone height was ≥5 mm [82]. Other authors had shown that when the bone crest is less than 5 mm, the failure rate increases [83]. However, Li [84] asserts that if primary stability has been attained, the osteotomy procedure can be applied even in residual ridges with heights of 3-4 mm. Krasny et al., in 26 patients with a residual bone height of 3-5 mm using the transalveolar sinus lift technique in two stages, successfully reconstructed the maxillary sinus [85].
Aoki et al. presented the results of histopathological analyses performed in two case reports wherein sinus elevation was conducted-in one case with a lateral window and with only PRF as bone filling material and placement of implants in two stages, and in the second case a crestal approach with PRF as a bone-filling material ( Table 2). The residual bone height in both cases was <2.7 mm. The histopathological results showed that the presence of PRF in the sinus cavity induced the formation of new bone [25].
The Schneiderian membrane has a high potential for osteogenesis, which explains why the majority of graft materials result in bone development [86][87][88]. Without the use of graft material, a sinus floor elevation can still be performed with enough bone development and implant longevity [72,89,90]. However, in an animal study, Kim et al. shown that bone development is restricted when no material for grafts is used in sinus lift surgery [91]; also, Sul et al. asserted that without graft material, bone formation may be constrained and that the implant apex could get caught with the Schneiderian membrane [92]. But in the study by Simonpieri et al., it was thought that the presence of the PRF membrane does not allow the implant apex to be enmeshed with the sinus membrane [71].
Anitua et al. conducted a study of bilateral maxillary sinus elevation where one side was treated with bovine bone and plasma rich growth factor (PRGF) and the other side as a control group only with bovine bone ( Table 2). The results showed that the side where PRGF was used with bovine bone created new bone faster and was denser and more compact than that of the control group; in addition, the side that was treated only with bovine bone was more inflamed compared to the side where PRGF was used. Patients indicated pain on the side where only bovine bone was placed [24]. Platelet products have been found to inhibit monocyte cytokine release and restrict inflammation [93]. Additionally, new findings imply that platelets initially block the release of interleukin-1 (IL-1) from activated macrophages. Broad implications for the description of a process by which platelet-rich products may operate as an anti-inflammatory agent could result from the first reduction of the inflammatory response [3].
According to Lv et al., the flapless endoscope-supported osteotome sinus floor elevation using sole (PRF) has a lower incidence of postoperative pain and edema than sinus elevation with lateral windows filled with bovine bone and is more bearable for patients ( Table 2). But compared to the transcrestal approach with PRF alone (Table 3), the lateral window technique with bovine bone seems to offer more peri-implant bone height and density [35].
Rapone et al. observed over a period of 7 years the results obtained from the elevation of the maxillary sinus with the lateral window technique [3]. Patients were divided in two groups, and as grafting material, the natural porous fluorohydroxyapatite combined with PRF was used in one group, and bovine bone with autogenous bone (50:50) combined with PRP was used for the other group. For both groups, this study revealed predictable outcomes over time ( Table 2). Compared to implanting an ungrafted maxillary, this method offers a better long-term prognosis and a greater survival rate [3,94].
Irdem et al. stated that over a four-month period, the combination of bovine bone and liquid PRF helped create new bone, although this effect was not statistically significant compared to bovine bone alone [32]. Nizam et al. (Table 2) also came to the conclusion that under histological and histomorphometric examination, the addition of L-PRF to particle DBBM did not increase the amount of regenerated bone or the degree to which the graft was integrated into the newly created bone [39].
Narang et al. [38], in a case report, used PRF with bone graft material to reach a height >10 mm in the maxillary sinus area when the patient had residual ridge heights of 1.49 mm and 1.47 mm. The technique followed was the modified Summer's. The results showed that this method is successful in raising the maxillary sinus and placing the implants (Table 2). This procedure often only needs 3-4 months of recovery compared to other techniques, which typically need at least 6-9 months. One explanation would be the smaller access hole established in the sinus cavity. Blood flow is rarely affected by this approach. The main benefit of this technique, unlike the lateral window technique, is that the implant and bone grafts obtain most of their blood supply from buccal [38] (Figure 7). other techniques, which typically need at least 6-9 months. One explanation would be the smaller access hole established in the sinus cavity. Blood flow is rarely affected by this approach. The main benefit of this technique, unlike the lateral window technique, is that the implant and bone grafts obtain most of their blood supply from buccal [38] (Figure 7). Also according to Merli et al. (Table 2), lateral sinus floor elevation using CGFs as the only grafting material resulted in implant success rates and slight changes in bone level that were comparable to demineralized bovine bone grafting [36], Between the CGF and the DBBM groups, there was no statistically significant difference in marginal bone loss (Table 3).
In fact, CGF is considered a new generation of platelet products that have dense fibrin networks and a high concentration of GF and are important in cell proliferation [95]. The CD34+ cells have been discovered at both levels (CGF-RBC) and are entrapped in the CGF matrix in large numbers. Due to its promotion of osteogenic cell differentiation and proliferation, the CGF seems to have more promise for tissue regeneration. As a result, the CGF greatly boosts alkaline phosphatase (ALP) activity [52,96].
According to Chen et al., in patients with a residual bone height of 4-6 mm before surgery (Table 3), the osteotome sinus floor elevation with a CGF approach is safe and dependable, whether bone grafting is used or not. Individuals who had bone grafting experienced postoperative discomfort and pain compared to individuals who did not get bone grafting. For the two groups, there was no big difference in marginal bone loss [26].
According to some studies, the survival rate of implants inserted in augmented sinuses is not improved by autogenous bone alone [97][98][99][100]. The disappointing 82% implant success rate once autogenous block graft is employed was also highlighted in two of these reviews [98,99].
On the other hand, when xenograft was utilized instead of autogenous bone, two reviews found that 96% of 10,000 studied implants survived after sinus augmentation [97,98]. Also according to Merli et al. (Table 2), lateral sinus floor elevation using CGFs as the only grafting material resulted in implant success rates and slight changes in bone level that were comparable to demineralized bovine bone grafting [36], Between the CGF and the DBBM groups, there was no statistically significant difference in marginal bone loss (Table 3).
In fact, CGF is considered a new generation of platelet products that have dense fibrin networks and a high concentration of GF and are important in cell proliferation [95]. The CD34+ cells have been discovered at both levels (CGF-RBC) and are entrapped in the CGF matrix in large numbers. Due to its promotion of osteogenic cell differentiation and proliferation, the CGF seems to have more promise for tissue regeneration. As a result, the CGF greatly boosts alkaline phosphatase (ALP) activity [52,96].
According to Chen et al., in patients with a residual bone height of 4-6 mm before surgery (Table 3), the osteotome sinus floor elevation with a CGF approach is safe and dependable, whether bone grafting is used or not. Individuals who had bone grafting experienced postoperative discomfort and pain compared to individuals who did not get bone grafting. For the two groups, there was no big difference in marginal bone loss [26].
According to some studies, the survival rate of implants inserted in augmented sinuses is not improved by autogenous bone alone [97][98][99][100]. The disappointing 82% implant success rate once autogenous block graft is employed was also highlighted in two of these reviews [98,99].
On the other hand, when xenograft was utilized instead of autogenous bone, two reviews found that 96% of 10,000 studied implants survived after sinus augmentation [97,98].
In the study developed by Forabosco et al., in the group using only xenograft, a 96.1% survival rate was recorded; in the group using a combination of CGF and xenograft, a 96.4% survival rate was recorded [101].
Chen et al., reported a 100% implant success rate in the two groups, which had either CGF with bone graft or CGF without bone graft [26]. Other studies that have used only CGF as graft material in maxillary sinus elevation [54] state that the bone level obtained and the success of the implants can be compared to that of a bovine bone graft [36].

Conclusions
In conclusion, there are different surgical methods for the treatment of peri-and preimplant defects, from the use of zygomatic implants to the use of biomaterials capable of increasing and accelerating bone formation. Following tooth extraction, a process of bone resorption occurs, making it necessary to increase bone, especially with a view to implant-supported rehabilitation. MSFE has become a standard surgical procedure to solve the reduced levels of bone, allowing the positioning of dental implants. Different biomaterials have been proposed from synthetic products up to heterologous or autologous grafts for the purpose of bone conservation and regeneration.
Histological analyses reveal an enhanced vascularization and the early formation of new bone thanks to the use of growth factors. The significant positive pro-angiogenic influence of PRF combined with bone grafts favors regeneration processes, exploiting the body's natural ability to repair injured bony tissue with new bone cells. The improved vascularization of the surgical site through neoangiogenesis promotes the healing of surgical wounds, and this is particularly advantageous, especially in surgical areas with reduced vascularization, such as in sinus lifts. Pre-treatment with PRP provides primary stability, improving in a statistically significant way implant-prosthetic rehabilitation. Comparing other bone substitutes, the sinus floor elevation performed with the use of CGFs alone showed implant survival and marginal bone level changes comparable to a demineralized bovine bone matrix.
Even if further studies are still needed, the use of CGF, PRF and PRP seems to have the ability to improve clinical results by improving the vascularization of surgical sites, and they can improve the post-operative quality of life of patients.
Platelet derivatives will certainly see further developments in the near future, which will above all improve costs, preparation time, and surgical efficiency, given that clinicians often complain of having minimal clinical advantages in the face of an expensive and complex procedure.
Furthermore, it will certainly be necessary to work towards making these procedures less operator-dependent, given that nowadays the effectiveness of these surgical procedures is very much linked to the surgical skills of the clinician, their knowledge of these materials and their ability to use them in the right way.