Effectiveness of Oroantral Communication Closure Using Solid Platelet-Rich Fibrin Compared to a Conventional Treatment Approach: A Randomized Clinical Trial.

This study aimed to compare the effectiveness of platelet-rich fibrin clot (PRF) and conventional oroantral communication (OAC) repair techniques following tooth extractions from the maxilla. The study involved 22 patients, divided into 2 groups: a study group treated with PRF and a control group undergoing conventional OAC repair. The primary outcome measured was the effectiveness of OAC closure, with pain intensity and postoperative complications as secondary outcomes. Cone-beam computed tomography (CBCT) was used to evaluate post-extraction bone regeneration. Pain was assessed using the Visual Analogue Scale (VAS) on days 0, 1, 7, and 14 postoperatively. The results showed that the PRF group experienced a significant decrease in pain within the first 24 hours and after 7 days (P < .0001; P < .05). In contrast, complications were reported in 45.45% of patients in the conventional repair group and 18.18% in the A-PRF group. Three months postsurgery, CBCT revealed appreciable bone healing in both groups, with no significant difference (P > .05). In conclusion, the study suggests that A-PRF treatment for OACs resulted in fewer complications and quicker pain reduction than traditional repair methods, making it a promising alternative for managing OACs. However, future studies are needed to confirm these findings and establish the full therapeutic potential of PRF.

Hyperspectral Imaging Allows Evaluation of Free Flaps in Craniomaxillofacial Reconstruction.

INTRODUCTION: Treatment of extended defects after tumor resection in oral, maxillofacial, and facial surgery (craniomaxillofacial) is usually performed by free microvascular flaps. Evaluation of flap survival is crucial, especially in the first hours after insertion and connection. For flap evaluation various invasive and noninvasive methods have been developed. This retrospective clinical study examined the ability of a hyperspectral imaging (HSI) camera (Tivita, Diaspective Vision, Germany) to assess postoperative flap properties in comparison to established clinical parameters. MATERIALS AND METHODS: Thirteen patients with tumor resection and free flap reconstruction were included for camera analysis and another 10 patients as control group. For this purpose, at defined time intervals and under standardized conditions, recordings of transplants 3 to 100 hours postoperatively were performed. Images were used to examine oxygenation (StO 2 %), tissue hemoglobin index, tissue water index, near infrared range perfusion index of free flaps quantitatively and qualitatively. RESULTS: HSI provides values differing between patients observed with no intraindividual significant difference. After 24 hours a mean reduction of 16.77% for StO 2 %, 9.16% for tissue hemoglobin index and 8.46% was observed, going in line with no loss of flap was noted in the observation period. CONCLUSION: HSI is suitable as a noninvasive measure for the evaluation of free flaps in craniomaxillofacial surgery in case of stable imaging conditions with respect to light, surrounding and position of the camera. However, clinical measurements are still the method of choice.

In vivo cellular reactions to different biomaterials-Physiological and pathological aspects and their consequences.

Biomaterials are widely used in guided bone regeneration (GBR) and guided tissue regeneration (GTR). After application, there is an interaction between the host immune system and the implanted biomaterial, leading to a biomaterial-specific cellular reaction. The present review focuses on cellular reactions to numerous biomaterials in vivo with consideration of different implantation models and microenvironments in different species, such as subcutaneous implantation in mice and rats, a muscle model in goats and a femur model in rabbits. Additionally, cellular reactions to different biomaterials in various clinical indications within the oro-maxillofacial surgical field were considered. Two types of cellular reactions were observed. There was a physiological reaction with the induction of only mononuclear cells and a pathological reaction with the induction of multinucleated giant cells (MNGCs). Attention was directed to the frequently observed MNGCs and consequences of their appearance within the implantation region. MNGCs have different subtypes. Therefore, the present review addresses the different morphological phenotypes observed within the biomaterial implantation bed and discusses the critical role of MNGCs, their subtypes and their precursors as well as comparing the characteristics and differences between biomaterial-related MNGCs and osteoclasts. Polymeric biomaterials that only induced mononuclear cells underwent integration and maintained their integrity, while polymeric biomaterials that induced MNGCs underwent disintegration with material breakdown and loss of integrity. Hence, there is a question regarding whether our attention should be directed to alternative biological concepts, in combination with biomaterials that induce a physiological mononuclear cellular reaction to optimize biomaterial-based tissue regeneration.

Genotoxic and cytotoxic potential of methacrylate-based orthodontic adhesives.

OBJECTIVES: The biocompatibility of methacrylate-based adhesives is a topic that is intensively discussed in dentistry. Since only limited evidence concerning the cyto- and genotoxicity of orthodontic adhesives is available, the aim of this study was to measure the genotoxic potential of seven orthodontic methacrylate-based adhesives. MATERIALS AND METHODS: The XTT assay was utilized to determine the cytotoxicity of Assure Plus, Assure Bonding Resin, ExciTE F, OptiBond Solo Plus, Scotchbond Universal Adhesive, Transbond MIP, and Transbond XT after an incubation period of 24 h on human gingival fibroblasts. We also performed the γH2AX assay to explore the genotoxic potential of the adhesives within cytotoxic dose ranges after an incubation period of 6 h. RESULTS: The XTT assay showed a concentration-dependent reduction in cell viability. The decrease in cellular viability was in the same dose range most significant for Assure Plus, rendering it the adhesive material with the highest cytotoxicity. Employing the γH2AX assay, a concentration-dependent increase in H2AX phosphorylation was detected, indicating induction of DNA damage. CONCLUSIONS: For most products, a linear correlation between the material concentration and γH2AX foci was observed. The most severe effect on γH2AX focus induction was found for Transbond MIP, which was the only adhesive in the test group containing the co-initiator diphenyliodonium hexafluorophosphate (DPIHP). CLINICAL RELEVANCE: The data indicate that orthodontic adhesives, notably Transbond MIP, bear a genotoxic potential. Since the study was performed with in vitro cultivated cells, a direct translation of the findings to in vivo exposure conditions should be considered with great diligence.

Multinucleated giant cells within the in vivo implantation bed of a collagen-based biomaterial determine its degradation pattern.

OBJECTIVES: The aim of the present study was to characterize the cellular reaction to a xenogeneic resorbable collagen membrane of porcine origin using a subcutaneous implantation model in Wistar rats over 30 days. MATERIALS AND METHODS: Ex vivo, liquid platelet-rich fibrin (PRF), a leukocyte and platelet-rich cell suspension, was used to evaluate the blood cell membrane interaction. The material was implanted subcutaneously in rats. Sham-operated rats without biomaterial displayed physiological wound healing (control group). Histological, immunohistological, and histomorphometric analyses were focused on the inflammatory pattern, vascularization rate, and degradation pattern. RESULTS: The membrane induced a large number of mononuclear cells over the observation period, including lymphocytes, macrophages, and fibroblasts. After 15 days, multinucleated giant cells (MNGCs) were observed on the biomaterial surface. Their number increased significantly, and they proceeded to the center of the biomaterial on day 30. These cells highly expressed CD-68, calcitonin receptor, and MMP-9, but not TRAP or integrin-ß3. Thus, the membrane lost its integrity and underwent disintegration as a consequence of the induction of MNGCs. The significant increase in MNGC number correlated with a high rate of vascularization, which was significantly higher than the control group. Physiological wound healing in the control group did not induce any MNGCs at any time point. Ex vivo blood cells from liquid-PRF did not penetrate the membrane. CONCLUSION: The present study suggests a potential role for MNGCs in biomaterial degradation and questions whether it is beneficial to accept them in clinically approved biomaterials or focus on biomaterials that induce only mononuclear cells. Thus, further studies are necessary to identify the function of biomaterial-induced MNGCs. CLINICAL RELEVANCE: Understanding the cellular reaction to biomaterials is essential to assess their suitability for specific clinical indications and outline the potential benefit of specific group of biomaterials in the respective clinical indications.

Biologization of Pcl-Mesh Using Platelet Rich Fibrin (Prf) Enhances Its Regenerative Potential In Vitro.

INTRODUCTION: Resorbable synthetic scaffolds are promising for different indications, especially in the context of bone regeneration. However, they require additional biological components to enhance their osteogenic potential. In addition to different cell types, autologous blood-derived matrices offer many advantages to enhance the regenerative capacity of biomaterials. The present study aimed to analyze whether biologization of a PCL-mesh coated using differently centrifuged Platelet rich fibrin (PRF) matrices will have a positive influence on primary human osteoblasts activity in vitro. A polymeric resorbable scaffold (Osteomesh, OsteoporeTM (OP), Singapore) was combined with differently centrifuged PRF matrices to evaluate the additional influence of this biologization concept on bone regeneration in vitro. Peripheral blood of three healthy donors was used to gain PRF matrices centrifuged either at High (710× g, 8 min) or Low (44× g, 8 min) relative centrifugal force (RCF) according to the low speed centrifugation concept (LSCC). OP-PRF constructs were cultured with pOBs. POBs cultured on the uncoated OP served as a control. After three and seven days of cultivation, cell culture supernatants were collected to analyze the pOBs activity by determining the concentrations of VEGF, TGF-ß1, PDGF, OPG, IL-8, and ALP- activity. Immunofluorescence staining was used to evaluate the Osteopontin expression of pOBs. After three days, the group of OP+PRFLow+pOBs showed significantly higher expression of IL-8, TGF-ß1, PDGF, and VEGF compared to the group of OP+PRFHigh+pOBs and OP+pOBs. Similar results were observed on day 7. Moreover, OP+PRFLow+pOBs exhibited significantly higher activity of ALP compared to OP+PRFHigh+pOBs and OP+pOBs. Immunofluorescence staining showed a higher number of pOBs adherent to OP+PRFLow+pOBs compared to the groups OP+PRFHigh+pOBs and OP+pOBs. To the best of our knowledge, this study is the first to investigate the osteoblasts activity when cultured on a PRF-coated PCL-mesh in vitro. The presented results suggest that PRFLow centrifuged according to LSCC exhibits autologous blood cells and growth factors, seem to have a significant effect on osteogenesis. Thereby, the combination of OP with PRFLow showed promising results to support bone regeneration. Further in vivo studies are required to verify the results and carry out potential results for clinical translation.

Histomorphometrical assessment of vertical alveolar ridge augmentation using extracted tooth roots in the canine.

OBJECTIVES: To histomorphometrically evaluate the influence of autoclavation on the efficacy of extracted tooth roots (TR) used for vertical alveolar ridge augmentation. MATERIALS AND METHODS: Upper premolars were randomly assigned to either autoclavation (TR-A) or an untreated control group (TR-C) and used as block grafts for vertical alveolar ridge augmentation in both lower quadrants (n = 4 beagle dogs). Tissue biopsies were obtained after 15 weeks of submerged healing. Histological analyses considered gain in ridge height (GRH), augmented area (AA), and the proportion of mineralized (MT) and non-mineralized tissue (NMT). RESULTS: TR-C and TR-A grafts were commonly associated with a complete replacement resorption and a marked gain in ridge height. Significant differences between groups were noted for mean GRH [TR-C: 2.35 ± 0.55 vs. TR-A: 2.46 ± 0.21 mm] and AA [TR-C: 11.88 ± 4.31 vs. TR-A: 8.65 ± 1.59 mm2] values. Within AA, both groups revealed a comparable distribution of mean MT and NMT values. The linear regression analysis pointed to a significant correlation between NMT and AA values. CONCLUSIONS: Both TR-C and TR-A grafts supported vertical alveolar ridge augmentation; however, GRH was improved in the TR-A group. CLINICAL RELEVANCE: TR grafts may serve as a potential alternative for vertical alveolar ridge augmentation.

The Biomaterial-Induced Cellular Reaction Allows a Novel Classification System Regardless of the Biomaterials Origin.

Several different biomaterials are being introduced for clinical applications. However, no current material-specific systematic studies define parameters for evaluating these materials. The aim of this retrospective animal study is to classify biomaterials according to the in vivo induced cellular reaction and outline the clinical consequence of the biomaterial-specific cellular reaction for the regeneration process. A retrospective histologic analysis was performed for 13 polymeric biomaterials and 19 bone substitute materials (BSMs) (of various compositions and origins) that were previously implanted in a standardized subcutaneous model. Semiquantitative analyses were performed at days 3, 15, and 30 after implantation according to a standardized score for the induction of multinucleated giant cells (MNGCs) and vascularization rate. The induced cellular reaction in response to different polymeric materials allowed their classification according to the MNGC score in the following groups: class I induced no MNGCs at any time point, class II induced and maintained a constant number of MNGCs over 30 days, and class III induced MNGCs and provided an increasing number over 30 days. All BSMs induced MNGCs to varying extents. Therefore, the resultant BSM classifications are as follows: class I induced MNGCs with a decreasing number, class II induced and maintained constant MNGCs over 30 days, and class III induced MNGCs with increasing number over 30 days. These observations were mostly related to the biomaterial physicochemical properties and were independent of the biomaterial origin. Consequently, the induction of MNGCs and their increase over 30 days resulted in disintegration of the biomaterial. By contrast, the absence of MNGCs resulted in an integration of the biomaterial within the host tissue. This novel classification provides clinicians a tool to assess the capacity and suitability of biomaterials in the intended clinical indication for bone and soft tissue implantations.

Development of a novel histological and histomorphometric evaluation protocol for a standardized description of the mid-palatal suture - An ex vivo study.

The hard palate and mid-palatal suture are highly important for orthodontic treatment. In cases of transverse maxillary deficiency, palatal expansion is the treatment of choice. As nowadays a growing number of adult patients receive orthodontic treatment, an understanding of suture development throughout life is important to derive tailored orthodontic treatment techniques for each age group. Histological, histochemical and immunohistochemical stains (haematoxylin & eosin, Azan, Movat pentachrome, Masson-Goldner trichrome, Sirius Red, CD 31, osteopontin and TRAP) and histomorphometric analyses were re-established to detect the structural conditions of the mid-palatal suture in human cadavers of three different age groups (20-39, 40-59 and 60-80 years). The mid-palatal suture of the selected age groups (total of n = 12; n = 4 in every group m = f) exhibited marked differences in sutural morphology and metabolism. A wide, interdigitated and well-vascularized suture was observed in younger specimens compared with straighter and smaller sutures with fewer vessels and lower bone density in the 60-80 year group. The fibre composition within the sutural gap differed between the three age groups. Delicate fibres were found in the 20-39 year group, and a tightly interwoven 3D fibre-network was observed in the 40-59 year group. Atrophy primarily characterized the fibres in the 60-80 year group. This evidence demonstrates differences between the evaluated groups. These results suggest that the staining methods used are suitable for the description and evaluation of the morphology and metabolism of mid-palatal sutures. Further investigation is necessary to provide an in-depth description of sutural maturation over a lifetime.

A low-speed centrifugation concept leads to cell accumulation and vascularization of solid platelet-rich fibrin: an experimental study in vivo.

Platelet-rich fibrin (PRF) is generated from the patients' own venous blood by a single centrifugation step without the additional use of anticoagulants. Based on the previously described LSCC (low-speed centrifugation concept), our group showed that modification of the centrifugation setting, that is, reducing the relative centrifugal force (RCF) and mildly increasing the centrifugation time, resulted in modified solid and liquid PRF-matrices with increased number of platelets, leukocytes, and growth factors' concentrations. The aim of this study was to determine whether RCF reduction might also result in different tissue reactions toward the two PRF-based matrices, especially vascularization and cell distribution in vivo. Two centrifugation protocols (PRF-high [719 g] and PRF-medium [222 g]) were compared in a subcutaneous implantation model of SCID mice at 5 and 10 days. Histological and histomorphometrical analyses were performed to quantify lymphocyte, neutrophil, human macrophage, and monocyte populations. CD31 was used to detect newly formed vessels, while all human cells were detected by using human vimentin as a pan-cellular marker. The results demonstrated that PRF-high elicited a dense and stable fibrin structure and prevented cellular penetration of the host tissue. By contrast, PRF-medium was more porous, had a significantly higher in vivo vascularization rate, and included significantly more human cells, especially at day 10, compared to PRF-high. These findings highlight the possibility of modifying the structure and composition of PRF matrices and thus selectively altering their regenerative potential in vivo. Clinical studies now must evaluate the different PRF matrices for bone and soft-tissue regeneration to validate possible benefits using personalized preparation protocols.

Influence of concentration and preparation of platelet rich fibrin on human bone marrow mononuclear cells (in vitro).

Large bone defects have always been a big challenge. The use of bone marrow mononuclear cells (BMCs) combined with an osteoconductive scaffold has been proved a good alternative for the treatment of large bone defects. Another autologous source for tissue engineering is platelet rich fibrin (PRF). PRF is a blood concentrate system obtained through a one-step centrifugation. The generated 3D matrix of the PRF clot serves as a reservoir of growth factors. Those growth factors might support the regenerative response of BMC, and therefore the effect of PRF, centrifuged with either high medium (208 g) or low (60 g) relative centrifugation force (RCF) on BMCs was evaluated in vitro in the present study. The two PRF matrices obtained were initially characterized and compared to human serum. Significantly increased concentrations of insulin-like growth factor (IGF), soluble intercellular adhesion molecule-1 (sICAM1) and transforming growth factor (TGF)-ß were found in PRF compared to human serum whereas VEGF concentration was not significantly altered. A dose-response study revealed no further activation of BMC's metabolic activity, if concentration of both PRF matrices exceeded 10% (v/v). Effect of both PRF preparations [10%] on BMC was analyzed after 2, 7, and 14 days in comparison to human serum [10%]. Metabolic activity of BMC increased significantly in all groups on day 14. Furthermore, gene expression of matrix metalloproteinases (MMP)-2, -7, and -9 was significantly stimulated in BMC cultivated with the respective PRF matrices compared to human serum. Apoptotic activity of BMC incubated with PRF was not altered compared to BMC cultivated with serum. In conclusion, PRF could be used as a growth factor delivery system of autologous or allogeneic source with the capability of stimulating cells such as BMC.

Multiwell three-dimensional systems enable in vivo screening of immune reactions to biomaterials: a new strategy toward translational biomaterial research.

In vivo experiments are accompanied by ethical issues, including sacrificing a large number of animals as well as large costs. A new in vivo 3D screening system was developed to reduce the number of required animals without compromising the results. The present pilot study examined a multiwell array system in combination with three different collagen-based biomaterials (A, B and C) using subcutaneous implantation for 10 days and histological and histomorphometrical evaluations. The tissue reaction towards the device itself was dominated by mononuclear cells. However, three independent biomaterial-specific tissue reactions were observed in three chambers. The results showed a mononuclear cell-based tissue reaction in one chamber (A) and foreign body reaction by multinucleated giant cells in the other two chambers (B and C). Statistical analysis showed a significantly higher number of multinucleated giant cells in cases B and C than in case A (A vs. B; ***P < 0.001), (A vs. C; P < 0.01). These outcomes were comparable to previously published observations with conventional biomaterial implantation. The present data lead to the conclusion that this 3D screening system could be an alternative tool to enhance the effectiveness of in vivo experiments, thus offering a more economic strategy to screen biomaterial-related cellular reactions, while saving animals, without influencing the final outcome.

Allogeneic bone block for challenging augmentation-a clinical, histological, and histomorphometrical investigation of tissue reaction and new bone formation.

OBJECTIVES: The aim of the present study was the histological investigation of an allogeneic spongious bone block for horizontal and vertical ridge augmentation in humans. The amount of new bone, soft tissue, and residual bone substitute were histomorphometrically assessed after a mean healing period of 6 months. MATERIALS AND METHODS: Fourteen patients received augmentation with an allogeneic spongious bone block (Tutobone®, Tutogen Medical, Neunkirchen, Germany). After 6 months of healing, 28 implants were placed with simultaneous harvesting of bone biopsies for histological and histomorphometrical analysis. Moreover, samples from the bone blocks were collected as blanks and analyzed histologically. The formation of new bone, connective tissue, and remaining bone substitute material as well as vascularization and formation of multinucleated giant cells (MNCGs) within the augmentation bed were analyzed. RESULTS: New bone formation could be observed primarily in close proximity to the bone block. Histomorphometrical analyses showed 18.65 ± 12.20% newly formed bone, 25.93 ± 12.36% allogeneic spongious bone block, and 53.45 ± 10.34% connective tissue. MNCGs were observed on the biomaterial surface. Furthermore, organic residues were evident, as donor-related cellular remnants within the osteocyte lacunae were found in the blank bone blocks and in the analyzed biopsies. CONCLUSION: Despite the presence of donor-related organic remnants, the bone block shows the ability to serve as a scaffold for new bone formation. Within the limits of the present study, the detect organic remnants seemed not to affect the bone formation or influence the host in the long term. CLINICAL RELEVANCE: Clinicians have to make a conscious choice of the applied biomaterials with regard to their components and structure to support tissue regeneration and maintain patient safety.

Sugar-based collagen membrane cross-linking increases barrier capacity of membranes.

OBJECTIVES: This study examines the permeability and barrier capacity of a sugar cross-linked resorbable collagen membrane ex vivo and in vivo. MATERIALS AND METHODS: In an ex vivo study, injectable platelet-rich fibrin (i-PRF), a peripheral blood-derived human leukocyte-and-platelet-rich plasma was used to analyze membrane permeability. in vivo subcutaneous implantation in Wistar rats (n = 4 per time point and group) was used to investigate the barrier capacity of the membrane. The induced in vivo cellular reaction was evaluated at 3, 15, and 30 days and compared to sham OP (control) without biomaterial using histological, immunohistochemical, and histomorphometric methods. RESULTS: Ex vivo, the membrane was impenetrable to leukocytes, platelets, and fibrin from peripheral human blood concentrate (PRF). In vivo, the membrane maintained its structure and remained impervious to cells, connective tissue, and vessels over 30 days. CD-68-positive cell (macrophage) numbers significantly decreased from 3 to 15 days, while from day 15 onwards, the number of multinucleated giant cells (MNGCs) increased significantly. Correspondingly, a rise in implantation bed vascularization from 15 to 30 days was observed. However, no signs of degradation or material breakdown were observed at any time point. CONCLUSION: Ex vivo and in vivo results showed material impermeability to cellular infiltration of human and murine cells, which highlights the membrane capacity to serve as a barrier over 30 days. However, whether the induced MNGCs will lead to material degradation or encapsulation over the long term requires further investigation. CLINICAL RELEVANCE: The data presented are of great clinical interest, as they contribute to the ongoing discussion concerning to what extent an implanted material should be integrated versus serving only as a barrier membrane.

Individualized Titanium Mesh Combined With Platelet-Rich Fibrin and Deproteinized Bovine Bone: A New Approach for Challenging Augmentation.

Autologous bone transfer is regarded as the gold standard for ridge augmentation before dental implantation, especially in severe bony defects caused by tumor resection or atrophy. In addition to the advantages of autologous bone, transplantation has several disadvantages, such as secondary operation, increased morbidity and pain. The present study reports, for the first time, a combination of a xenogeneic bone substitute (BO) with platelet-rich fibrin (PRF), which is a fully autologous blood concentrate derived from the patient's own peripheral blood by centrifugation. Solid A-PRF+ and liquid i-PRF together with an individualized 3-D planned titanium mesh were used for reconstruction of a severe tumor-related bony defect within the mandible of a former head and neck cancer patient. The BO enriched with regenerative components from PRF allowed the reconstruction of the mandibular resective defect under the 3-D mesh without autologous bone transplantation. Complete rehabilitation and restoration of the patient's oral function were achieved. Histological analysis of extracted bone biopsies confirmed that the new bone within the augmented region originated from the residual bone. Within the limitations of the presented case, the applied concept appears to be a promising approach to increase the regenerative capacity of a bone substitute material, as well as decrease the demand for autologous bone transplantation, even in cases in which autologous bone is considered the golden standard. PRF can be considered a reliable source for increasing the biological capacities of bone substitute materials.

Fifteen Years of Platelet Rich Fibrin in Dentistry and Oromaxillofacial Surgery: How High is the Level of Scientific Evidence?

Platelet-rich fibrin is a blood concentrate system used for soft tissue and bone tissue regeneration. In the last decade, platelet rich fibrin (PRF) has been widely used in different indication fields, particularly in oral and maxillofacial surgery. This review investigates the level of scientific evidence of published articles related to the use of PRF for bone and soft tissue regeneration in dentistry and maxillofacial surgery. An electronic literature research using the biomedical search engine "National Library of Medicine" (PubMed-MEDLINE) was performed in May 2017. A total of 392 articles were found, 72 of which were classified for each indication field. When comparing PRF with biomaterials vs biomaterial alone in sinus lift (5 studies; IIa), no statistically significant differences were detected. Socket preservation and ridge augmentation using PRF significantly enhanced new bone formation compared to healing without PRF (7 studies Ib, IIa, IIb). Reepithelialization and bone regeneration was achieved in 96 of 101 patients diagnosed with medication-related osteonecrosis of the jaw (5 studies, III). In periodontology, PRF alone (6 studies; Ib, IIa, IIb) or its combination with biomaterials (6 studies; Ib, IIa, IIb) significantly improved the pocket depth and attachment loss compared to a treatment without PRF. Over 70% of the patients were part of studies with a high level of scientific evidence (randomized and controlled prospective studies). This published evidence (38 articles), with a high scientific level, showed that PRF is a beneficial tool that significantly improves bone and soft tissue regeneration. However, the clinical community requires a standardization of PRF protocols to further examine the benefit of PRF in bone and soft tissue regeneration in reproducible studies, with a higher scientific level of evidence.

Reduction of the relative centrifugal force influences cell number and growth factor release within injectable PRF-based matrices.

Platelet rich fibrin (PRF) is a blood concentrate system obtained by centrifugation of peripheral blood. First PRF matrices exhibited solid fibrin scaffold, more recently liquid PRF-based matrix was developed by reducing the relative centrifugation force and time. The aim of this study was to systematically evaluate the influence of RCF (relative centrifugal force) on cell types and growth factor release within injectable PRF- in the range of 60-966 g using consistent centrifugation time. Numbers of cells was analyzed using automated cell counting (platelets, leukocytes, neutrophils, lymphocytes and monocytes) and histomorphometrically (CD 61, CD- 45, CD-15+, CD-68+, CD-3+ and CD-20). ELISA was utilized to quantify the concentration of growth factors and cytokines including PDGF-BB, TGF-ß1, EGF, VEGF and MMP-9. Leukocytes, neutrophils, monocytes and lymphocytes had significantly higher total cell numbers using lower RCF. Whereas, platelets in the low and medium RCF ranges both demonstrated significantly higher values when compared to the high RCF group. Histomorphometrical analysis showed a significantly high number of CD61+, CD-45+ and CD-15+ cells in the low RCF group whereas CD-68+, CD-3+ and CD-20+ demonstrated no statistically significant differences between all groups. Total growth factor release of PDGF-BB, TGF-ß1 and EGF had similar values using low and medium RCF, which were both significantly higher than those in the high RCF group. VEGF and MMP-9 were significantly higher in the low RCF group compared to high RCF. These findings support the LSCC (low speed centrifugation concept), which confirms that improved PRF-based matrices may be generated through RCF reduction. The enhanced regenerative potential of PRF-based matrices makes them a potential source to serve as a natural drug delivery system. However, further pre-clinical and clinical studies are required to evaluate the regeneration capacity of this system.

Three Milliliters of Peripheral Blood Is Sufficient for Preparing Liquid Platelet-Rich Fibrin (PRF): An In Vitro Study.

Platelet-rich fibrin (PRF) has assumed an important role in supporting tissue regeneration in different fields. To date, the standard protocol for liquid PRF requires at least 10 mL of peripheral blood. The present study aimed to analyze the composition, growth factor release, and effects on the cell proliferation of PRF samples produced using 3 mL vs. 10 mL of peripheral blood in vitro. Peripheral venous blood from six healthy donors was used to prepare liquid PRF using either 3 mL or 10 mL tubes. Three different centrifugation protocols were used according to the low-speed centrifugation concept. The cellular distribution was evaluated using immunohistology and automated cell count. ELISA was used to determine the release of different growth factors (EGF, TGF-ß1, and PDGF) and interleukin 8 at different time points. Primary human osteoblasts (pOBs) were cultivated for 7 days using PRF-conditioned media acquired from either 3 mL or 10 mL of peripheral blood. The results showed that 3 mL of peripheral blood is sufficient to produce a liquid PRF concentrate similar to that acquired when using 10 mL blood. The concentrations of platelets and leukocytes were comparable regardless of the initial blood volume (3 mL vs. 10 mL). Similarly, the release of growth factors (EGF, TGF-ß1, and PDGF) and interleukin 8 was often comparable in both groups over 7 days. The cultivation of pOBs using PRF-conditioned media showed a similar proliferation rate regardless of the initial blood volume. This proliferation rate was also similar to that of pOBs treated with 20% FBS-conditioned media. These findings validated the use of 3 mL of peripheral blood to generate liquid PRF matrices according to the low-speed centrifugation concept, which may open new application fields for research purposes such as in vivo experiments and clinical applications such as pediatric surgery.

Fucoidan/chitosan hydrogels as carrier for sustained delivery of platelet-rich fibrin containing bioactive molecules.

Platelet-rich fibrin (PRF), derived from human blood, rich in wound healing components, has drawbacks in direct injections, such as rapid matrix degradation and growth factor release. Marine polysaccharides, mimicking the human extracellular matrix, show promising potential in tissue engineering. In this study, we impregnated the self-assembled fucoidan/chitosan (FU_CS) hydrogels with PRF obtaining PRF/FU_CS hydrogels. Our objective was to analyze the properties of a hydrogel and the sustained release of growth factors from the hydrogel that incorporates PRF. The results of SEM and BET-BJH demonstrated the relatively porous nature of the FU_CS hydrogels. ELISA data showed that combining FU_CS hydrogel with PRF led to a gradual 7-day sustained release of growth factors (VEGF, EGF, IL-8, PDGF-BB, TGF-ß1), compared to pure PRF. Histology confirmed ELISA data, demonstrating uniform PRF fibrin network distribution within the FU_CS hydrogel matrix. Furthermore, the FU_CS hydrogels revealed excellent cell viability. The results revealed that the PRF/FU_CS hydrogel has the potential to promote wound healing and tissue regeneration. This would be the first step in the search for improved growth factor release.

Current Knowledge on the Healing of the Extraction Socket: A Narrative Review.

The concept of extraction socket healing has been severally researched and reported over the years, since tooth extraction remains one of the most common procedures performed in the dental clinic. Understanding this healing process is of utmost importance because the outcome has a direct bearing on future prosthetic rehabilitation and, by extension, on patients' esthetics and masticatory function, among others. This mini review, therefore, summarized the current knowledge on the different stages of socket healing, including the biologic and clinical events that occur following tooth extraction up until the complete closure of the socket. Additionally, the modeling of the alveolar bone/process post extraction, and the resultant dimensional changes that, altogether, shape the bone, were reviewed and documented. The effects of various socket preservation interventions to mitigate these dimensional changes, and therefore preserve the alveolar process in a condition suitable for future prosthetic rehabilitation, were highlighted. Finally, a review of some of the factors that influence the entire process was also carried out.