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.
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.
Objectives
The aim of the study was to investigate the impact of two hyaluronan (HA) formulations on the osteogenic potential of osteoblast precursors.
Materials and methods
Proliferation rates of ...HA-treated mesenchymal stromal ST2 and pre-osteoblastic MC3T3-E1 cells were determined by 5-bromo-20-deoxyuridine (BrdU) assay. Expression of genes encoding osteogenic differentiation markers, critical growth, and stemness factors as well as activation of downstream signaling pathways in the HA-treated cells were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunoblot techniques.
Results
The investigated HAs strongly stimulated the growth of the osteoprogenitor lines and enhanced the expression of genes encoding bone matrix proteins. However, expression of late osteogenic differentiation markers was significantly inhibited, accompanied by decreased bone morphogenetic protein (BMP) signaling. The expression of genes encoding transforming growth factor-β1 (TGF-β1) and fibroblast growth factor-1 (FGF-1) as well as the phosphorylation of the downstream signaling molecules Smad2 and Erk1/2 were enhanced upon HA treatment. We observed significant upregulation of the transcription factor Sox2 and its direct transcription targets and critical stemness genes, Yap1 and Bmi1, in HA-treated cells. Moreover, prominent targets of the canonical Wnt signaling pathway showed reduced expression, whereas inhibitors of the pathway were considerably upregulated. We detected decrease of active β-catenin levels in HA-treated cells due to β-catenin being phosphorylated and, thus, targeted for degradation.
Conclusions
HA strongly induces the growth of osteoprogenitors and maintains their stemness, thus potentially regulating the balance between self-renewal and differentiation during bone regeneration following reconstructive oral surgeries.
Clinical relevance
Addition of HA to deficient bone or bony defects during implant or reconstructive periodontal surgeries may be a viable approach for expanding adult stem cells without losing their replicative and differentiation capabilities.
Objective
To develop a novel in vitro periodontal pocket model for evaluating the effect of two different root surface instrumentation modalities on biofilm-epithelial cell interactions.
Materials ...and methods
An artificial periodontal pocket model was created using an impression material. Dentin discs were prepared and incubated for 3.5 days with a biofilm consisting of 12 bacterial strains. Then, the discs were inserted into the pocket model and instrumented for 10 s or 10 strokes either with ultrasonics (US) or hand instruments (HI). Subsequently, a glass slide coated with epithelial cells was placed in close vicinity to the discs. After incubation of the pocket model in a 5% CO
2
atmosphere for 6 h, residual bacteria of the biofilm as well as bacteria adhering to or invaded into epithelial cells were determined using colony-forming unit (cfu) counts and real-time PCR. Further, as a parameter of the pro-inflammatory cell response, interleukin (IL)-8 expression was determined by ELISA.
Results
Compared to untreated control, HI reduced the cfu counts by 0.63 log10 (not significant) and US by 1.78 log10 (
p
= 0.005) with a significant difference between the treatment modalities favoring US (
p
= 0.048). By trend, lower detection levels of
Tannerella forsythia
were detected in the US group compared to HI. Concerning the interaction with epithelial cells, half of the control and the HI samples showed epithelial cells with attaching or invading bacteria, while US displayed bacteria only in two out of eight samples. In addition, US resulted in significantly lower IL-8 secretion by epithelial cells compared to the untreated control. Between HI and controls, no statistically significant difference in IL-8 secretion was found.
Conclusion
This newly developed in vitro model revealed in terms of biofilm-epithelial cell interaction after root surface instrumentation that compared to hand curettes, ultrasonic instrumentation appeared to be more effective in removing bacterial biofilm and in decreasing the inflammatory response of epithelium to biofilm.
Clinical relevance
Ultrasonic instrumentation might be more advantageous to reduce cellular inflammatory response than hand instruments.
The aim of the present study was to investigate the influence of a novel volume-stable collagen matrix (vCM) on early wound healing events including cellular migration and adhesion, protein ...adsorption and release, and the dynamics of the hemostatic system. For this purpose, we utilized transwell migration and crystal violet adhesion assays, ELISAs for quantification of adsorbed and released from the matrix growth factors, and qRT-PCR for quantification of gene expression in cells grown on the matrix. Our results demonstrated that primary human oral fibroblasts, periodontal ligament, and endothelial cells exhibited increased migration toward vCM compared to control cells that migrated in the absence of the matrix. Cellular adhesive properties on vCM were significantly increased compared to controls. Growth factors TGF-β1, PDGF-BB, FGF-2, and GDF-5 were adsorbed on vCM with great efficiency and continuously delivered in the medium after an initial burst release within hours. We observed statistically significant upregulation of genes encoding the antifibrinolytic thrombomodulin, plasminogen activator inhibitor type 1, thrombospondin 1, and thromboplastin, as well as strong downregulation of genes encoding the profibrinolytic tissue plasminogen activator, urokinase-type plasminogen activator, its receptor, and the matrix metalloproteinase 14 in cells grown on vCM. As a general trend, the stimulatory effect of the vCM on the expression of antifibrinolytic genes was synergistically enhanced by TGF-β1, PDGF-BB, or FGF-2, whereas the strong inhibitory effect of the vCM on the expression of profibrinolytic genes was reversed by PDGF-BB, FGF-2, or GDF-5. Taken together, our data strongly support the effect of the novel vCM on fibrin clot stabilization and coagulation/fibrinolysis equilibrium, thus facilitating progression to the next stages of the soft tissue healing process.
Objectives
The aim of this systematic review and meta-analysis was to compare the use of platelet-rich fibrin (PRF) with other commonly utilized treatment modalities for root coverage procedures.
...Materials and methods
The eligibility criteria comprised randomized controlled trials (RCTs) comparing the performance of PRF with that of other modalities in the treatment of Miller class I or II (Cairo RT I) gingival recessions. Studies were classified into 5 categories as follows: (1) coronally advanced flap (CAF) alone vs CAF/PRF, (2) CAF/connective tissue graft (CAF/CTG) vs CAF/PRF, (3) CAF/enamel matrix derivative (CAF/EMD) vs CAF/PRF, (4) CAF/amnion membrane (CAF/AM) vs CAF/PRF, and (5) CAF/CTG vs CAF/CTG/PRF. Studies were evaluated for percentage of relative root coverage (rRC; primary outcome), clinical attachment level (CAL), keratinized mucosa width (KMW), and probing depth (PD) (secondary outcomes).
Results
From 976 articles identified, 17 RCTs were included. The use of PRF statistically significantly increased rRC and CAL compared with CAF alone. No change in KMW or reduction in PD was reported. Compared with PRF, CTG resulted in statistically significantly better KMW and RC. No statistically significant differences were reported between the CAF/PRF and CAF/EMD groups or between the CAF/PRF and CAF/AM groups for any of the investigated parameters.
Conclusions
The use of CAF/PRF improved rRC and CAL compared with the use of CAF alone. While similar outcomes were observed between CAF/PRF and CAF/CTG for CAL and PD change, the latter group led to statistically significantly better outcomes in terms of rRC and KTW. In summary, the use of PRF in conjunction with CAF may represent a valid treatment modality for gingival recessions exhibiting adequate baseline KMW.
Clinical relevance
The data indicate that the use of PRF in conjunction with CAF statistically significantly improves rRC when compared with CAF alone but did not improve KMW. Therefore, in cases with limited baseline KMW, the use of CTG may be preferred over PRF.
Objectives
The aim was to compile the current knowledge about the efficacy of different soft tissue correction methods around osseointegrated, already uncovered and/or loaded (OU/L) implants with ...insufficient soft tissue conditions. Procedures to increase peri-implant keratinized mucosa (KM) width and/or soft tissue volume were considered.
Materials and methods
Screening of two databases: MEDLINE (PubMed) and EMBASE (OVID), and manual search of articles were performed. Human studies reporting on soft tissue augmentation/correction methods around OU/L implants up to June 30, 2016, were considered. Quality assessment of selected full-text articles to weight risk of bias was performed using the Cochrane collaboration’s tool.
Results
Overall, four randomized controlled trials (risk of bias = high/low) and five prospective studies (risk of bias = high) were included. Depending on the surgical techniques and graft materials, the enlargement of keratinized tissue (KT) ranged between 1.15 ± 0.81 and 2.57 ± 0.50 mm. The apically positioned partial thickness flap (APPTF), in combination with a free gingival graft (FGG), a subepithelial connective tissue graft (SCTG), or a xenogeneic graft material (XCM) were most effective. A coronally advanced flap (CAF) combined with SCTG in three, combined with allogenic graft materials (AMDA) in one, and a split thickness flap (STF) combined with SCTG in another study showed mean soft tissue recession coverage rates from 28 to 96.3 %. STF combined with XCM failed to improve peri-implant soft tissue coverage.
Conclusions
The three APPTF-techniques combined with FGG, SCTG, or XCM achieved comparable enlargements of peri-implant KT. Further, both STF and CAF, both in combination with SCTG, are equivalent regarding recession coverage rates. STF + XCM and CAF + AMDA did not reach significant coverage.
Clinical relevance
In case of soft tissue deficiency around OU/L dental implants, the selection of both an appropriate surgical technique and a suitable soft tissue graft material is of utmost clinical relevance.
Platelet-rich fibrin (PRF) contains a broad spectrum of bioactive molecules that can trigger several cellular responses. However, these molecules along with their upstream responses remain mostly ...uninvestigated. By means of proteomics we revealed that PRF lysates contain more than 650 proteins, being TGF-β one of the few growth factors found. To uncover the major target genes regulated by PRF lysates, gingival fibroblasts were exposed to lysates obtained from PRF membranes followed by a whole genome array. We identified 51 genes strongly regulated by PRF including IL11, NOX4 and PRG4 which are characteristic TGF-β target genes. RT-PCR and immunoassay analysis confirmed the TGF-β receptor I kinase-dependent increased expression of IL11, NOX4 and PRG4. The PRF-derived TGF-β activity was verified by the translocation of Smad2/3 into the nucleus along with the increased phosphorylation of Smad3. Considering that PRF is clinically used in combination with dental implants and collagen membranes, we showed here that PRF-derived TGF-β activity adsorbs to titanium implants and collagen membranes indicated by the changes in gene expression and immunoassay analysis. Our study points towards TGF-β as major target of PRF and suggest that TGF-β activity released by PRF adsorbs to titanium surface and collagen membranes.
Objectives
The potential effect of enamel matrix derivative (EMD) on wound healing following recession coverage surgery is still controversially discussed in the literature. The aim of this ...randomised, controlled, single blinded clinical study was, therefore, to investigate clinically and immunologically the potential effects of EMD on early wound healing and clinical results following treatment of single and multiple gingival recessions by the modified coronally advanced tunnel technique (MCAT) and subepithelial connective tissue graft (sCTG).
Materials and methods
A total of 40 systemically healthy patients with Miller class I, II or III single or multiple gingival recessions were treated with MCAT + sCTG with or without EMD. Patients were consecutively enrolled and randomly assigned to test or control treatment. Inflammatory markers (interleukin (IL)-1β, IL-8, IL-10 and matrix metalloprotease (MMP)-8) were measured at baseline, 2 days and 1 week postoperatively. The following clinical parameters were assessed at baseline and at 6 months postoperatively: Recession Depth (RD), Recession Width (RW), Width of Keratinized Tissue (KT) and Probing Depth (PD). Patient-reported outcomes were analysed by means of a visual analogue scale.
Results
No statistically significant differences were detected between the 2 groups in terms of inflammatory markers and patient-reported outcomes during early wound healing. In the test group, RD was reduced from 4.0 ± 1.2 mm at baseline to 0.9 ± 1.3 mm at 6 months (
p
< 0.001), while the corresponding values in the control group were 4.5 ± 2.0 mm at baseline and 1.0 ± 1.0 mm at 6 months, respectively. At 6 months, mean root coverage measured 78 ± 26% in the test group and 77 ± 18% in the control group, respectively.
Conclusion
Within their limits, the present data have failed to show an influence of EMD on the clinical and immunological parameters related to wound healing following recession coverage surgery using MCAT and sCTG.
Clinical relevance
Early wound healing following recession coverage by means of MCAT and sCTG does not seem to be influenced by the additional application of EMD.
Objective
To evaluate and compare the effects of laser monotherapy with non-surgical mechanical instrumentation alone in untreated periodontitis patients.
Materials and methods
A focused question was ...formulated based on the Population, Intervention, Comparison, Outcome, and Study design criteria (PICOS): in patients with untreated periodontitis, does laser mono-therapy provide adjunctive effects on pocket probing depth (PPD) changes compared with non-surgical instrumentation alone? Both randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) were included. The results of the meta-analyses are expressed as weighted mean differences (WMD) and reported according to the PRISMA guidelines.
Results
The search yielded 1268 records, out of which 8 articles could be included. With respect to PPD changes, a meta-analysis including 5 articles (
n
= 148) failed to identify statistically significant differences in favor of laser monotherapy for PPD change (WMD = 0.14 mm; 95% CI: − 0.04/0.32;
z
= 1.51;
p
= 0.132) nor for clinical attachment level (CAL) (WMD = 0.04 mm; 95% CI: − 0.35/0.42;
z
= 0.19;
p
= 0.850). Data on cost-effectiveness are lacking. One study reported patient-related outcome measures (PROMS).
Conclusions
In untreated periodontitis patients, laser monotherapy does not yield superior clinical benefits compared with non-surgical mechanical instrumentation alone.
Clinical relevance
In untreated periodontitis patients, mechanical instrumentation with hand and/or ultrasonic instruments remains the standard of care.
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