Objective: To systematically assess the effects of platelet-rich fibrin (PRF) on in vitro cellular behavior.Methods: A systematic electronic search using MEDLINE database was performed. In vitro studies using PRF were considered and articles published up to June 31, 2018 were screened. Eligible studies were selected based on the use of human PRF.Results: In total, 1746 titles were identified with the search terms, from these 37 met the inclusion criteria and were chosen for data extraction. In addition, 16 new studies, mainly published in 2019, were also included in the analysis resulting in 53 studies. No meta-analysis could be performed due to the heterogeneity of study designs. Included studies show that PRF enhances proliferation, migration, adhesion, and osteogenic differentiation on a variety of cell types along with cell signaling activation. Furthermore, PRF reduces inflammation, suppresses osteoclastogenesis, and increases the expression of various growth factors in mesenchymal cells.Summary and conclusions: Despite some notable differences of the studies, the overall findings suggest a positive effect of PRF on cell proliferation, migration, adhesion, differentiation, and inflammation pointing towards a therapeutic potential in regenerative dentistry.Clinical relevance: PRF serves as a reservoir of bioactive molecules to support wound healing and bone regeneration. Although the cellular mechanisms by which PRF supports the clinical outcomes remain unclear, in vitro research provides possible explanations. This systematic review aims to provide an update of the existing research on how PRF affects basic physiological processes in vitro. The overall findings suggest that PRF induces cell proliferation, migration, adhesion, and differentiation along with possessing anti-inflammatory properties further supporting its therapeutic potential in wound healing and bone regeneration.

Objective: To assess the impact of platelet‐rich fibrin (PRF) on implant dentistry. The primary focused question was as follows: What are the clinical, histological, and radiographic outcomes of PRF administration for bone regeneration and implant therapy?Method: A systematic literature search comprised three databases: MEDLINE, EMBASE, and Cochrane followed by a hand search of relevant scientific journals. Human studies using PRF for bone regeneration and implant therapy were considered and articles published up to December 31, 2017 were included. Eligible studies were selected based on the inclusion criteria. Randomized controlled trials (RCT) and controlled clinical trials (CCT) were included.Results: In total, 5,963 titles were identified with the search terms and by hand search. A total of 12 randomized controlled trials (RCT) met the inclusion criteria and were chosen for data extraction. Included studies focused on alveolar ridge preservation after tooth extraction, osseointegration process, soft tissue management, bone augmentation, bone regeneration after sinus floor elevation and surgical peri‐implantitis treatment. Overall, the risk of bias was moderate or unclear. Nine studies showed superior outcomes for PRF for any of the evaluated variables, such as ridge dimension, bone regeneration, osseointegration process, soft tissue healing. Three studies failed to show any beneficial effects of PRF. No meta‐analysis could be performed due to the heterogeneity of study designs.Conclusions: There is moderate evidence supporting the clinical benefit of PRF on ridge preservation and in the early phase of osseointegration. It remains unclear whether PRF can reduce pain and improve soft tissue healing. More research support is necessary to comment on the role of PRF to improve other implant therapy outcomes.

Background: Platelet‐rich fibrin (PRF) serves as a reservoir of bioactive molecules to support wound healing and bone regeneration. The beneficial action of PRF might involve macrophage polarization from proinflammatory M1 toward pro‐resolving M2 phenotypes. This study aims to evaluate the effect of PRF on macrophage polarization.Methods: Murine primary macrophages and RAW 264.7 cells were exposed to saliva and lipopolysaccharides (LPS) with and without PRF lysates obtained by repeated freeze‐thawing or the secretome of PRF membranes, termed PRF conditioned medium. The expression of the M1 marker genes interleukin 1β (IL1β) and interleukin 6 (IL6) along with the M2 markers arginase‐1 and chitinase‐like 3 (Chil3 or YM1) were evaluated by real time polymerase chain reaction. Immunoassay and immunofluorescence staining were performed for IL6 and p65 translocation, a subunit nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐kB), respectively.Results: We report here that PRF lysates and PRF conditioned medium, the latter containing the secretome, greatly decreased the proinflammatory response of primary macrophages and RAW 264.7 cells as indicated by the expression of IL1β and IL6. The anti‐inflammatory activity of PRF lysates was further confirmed by IL6 immunoassay. Moreover, PRF lysates suppressed the translocation of p65 from the cytoplasm into the nucleus after incubation with saliva. In support of M2 polarization, PRF lysates and PRF conditioned medium enhanced the expression of arginase‐1 and YM1 in primary macrophages.Conclusion: Our results indicate that PRF holds an anti‐inflammatory activity and shifts the macrophage polarization from an M1 toward an M2 phenotype.

Short-chain fatty acids (SCFA), bacterial metabolites released from dental biofilm, are supposed to target the oral epithelium. There is, however, no consensus on how SCFA affect the oral epithelial cells. The objective of the present study was to systematically review the available in vitro evidence of the impact of SCFA on human oral epithelial cells in the context of periodontal disease. A comprehensive electronic search using five databases along with a grey literature search was performed. In vitro studies that evaluated the effects of SCFA on human oral epithelial cells were eligible for inclusion. Risk of bias was assessed by the University of Bristol’s tool for assessing risk of bias in cell culture studies. Certainty in cumulative evidence was evaluated using GRADE criteria (grading of recommendations assessment, development, and evaluation). Of 3591 records identified, 10 were eligible for inclusion. A meta-analysis was not possible due to the heterogeneity between the studies. The risk of bias across the studies was considered “serious” due to the presence of methodological biases. Despite these limitations, this review showed that SCFA negatively affect the viability of oral epithelial cells by activating a series of cellular events that includes apoptosis, autophagy, and pyroptosis. SCFA impair the integrity and presumably the transmigration of leucocytes through the epithelial layer by changing junctional and adhesion protein expression, respectively. SCFA also affect the expression of chemokines and cytokines in oral epithelial cells. Future research needs to identify the underlying signaling cascades and to translate the in vitro findings into preclinical models.

Aim: To test whether the emergence profile (CONVEX or CONCAVE) of implant‐supported crowns influences the mucosal margin stability up to 12 months after insertion of the final restoration.Materials and Methods: Forty‐seven patients with a single implant in the anterior region were randomly allocated to one of three groups: (1) CONVEX (n = 15), implant provisional and an implant‐supported crown both with a convex profile; (2) CONCAVE (n = 16), implant provisional and an implant‐supported crown both with a concave profile; (3) CONTROL (n = 16), no provisional (healing abutment only) and an implant‐supported crown. All patients were recalled at baseline, 6, and 12 months. The stability of mucosal margin along with clinical, aesthetic, and profilometric outcomes as well as time and costs were evaluated. To predict the presence of recession, multivariable logistic regressions were performed and linear models using generalized estimation equations were conducted for the different outcomes.Results: Forty‐four patients were available at 12 months post‐loading. The frequency of mucosal recession amounted to 64.3% in group CONVEX, 14.3% in group CONCAVE, and 31.4% in group CONTROL. Regression models revealed that a CONVEX profile was significantly associated with the presence of recessions (odds ratio: 12.6, 95% confidence interval: 1.82–88.48, p = .01) compared with the CONCAVE profile. Pink aesthetic scores amounted to 5.9 in group CONVEX, 6.2 in group CONCAVE, and 5.4 in group CONTROL, with no significant differences between the groups (p = .735). Groups CONVEX and CONCAVE increased the appointments and costs compared with the CONTROL group.Conclusions: The use of implant‐supported provisionals with a CONCAVE emergence profile results in a greater stability of the mucosal margin compared with a CONVEX profile up to 12 months of loading. This is accompanied, however, by increased time and costs compared with the absence of a provisional and may not necessarily enhance the aesthetic outcomes. Trial registration: German Clinical Trials Register; DRKS00009420.