OBJECTIVE: To explore the feasibility of injectable platelet-rich fibrin (i-PRF) in regenerative endodontics by comparing the effect of i-PRF and platelet-rich fibrin (PRF) on the biological behavior and angiogenesis of human stem cells from the apical papilla (SCAPs).
METHODS: i-PRF and PRF were obtained from venous blood by two different centrifugation methods, followed by hematoxylin-eosin (HE) staining and scanning electron microscopy (SEM). Enzyme-linked immunosorbent assay (ELISA) was conducted to quantify the growth factors. SCAPs were cultured with different concentrations of i-PRF extract (i-PRFe) and PRF extract (PRFe), and the optimal concentrations were selected using the Cell Counting Kit-8 (CCK-8) assay. The cell proliferation and migration potentials of SCAPs were then observed using the CCK-8 and Transwell assays. Mineralization ability was detected by alizarin red staining (ARS), and angiogenesis ability was detected by tube formation assay. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of genes related to mineralization and angiogenesis. The data were subjected to statistical analysis.
RESULTS: i-PRF and PRF showed a similar three-dimensional fibrin structure, while i-PRF released a higher concentration of growth factors than PRF ( P <.05). 1/4× i-PRFe and 1/4× PRFe were selected as the optimal concentrations. The cell proliferation rate of the i-PRFe group was higher than that of the PRFe group ( P <.05), while no statistical difference was observed between them in terms of cell mitigation ( P >.05). More importantly, our results showed that i-PRFe had a stronger effect on SCAPs than PRFe in facilitating mineralization and angiogenesis, with the consistent result of RT-qPCR ( P <.05).
CONCLUSIONS: This study revealed that i-PRF released a higher concentration of growth factors and was superior to PRF in promoting proliferation, mineralization and angiogenesis of SCAPs, which indicates that i-PRF could be a promising biological scaffold for application in pulp regeneration.

BACKGROUND: This study evaluated the clinical benefits of adding NanoBone® with split-crest technique and simultaneous implant placement covered with platelet-rich fibrin membrane in horizontally deficient maxillary ridges in terms of crestal and horizontal bone changes and patient morbidity.
METHODS: Forty patients indicated for maxillary ridge splitting and simultaneous implant placement were assigned randomly to the study groups: control group (Platelet Rich Fibrin membrane) and test group (Platelet Rich Fibrin membrane + Nanobone®). The Cone Beam Computed Tomography Fusion technique was utilized to assess crestal and horizontal bone changes after five months of the surgical procedure. Patient morbidity was recorded for one week post-surgical.
RESULTS: Five months post-surgical, buccal crestal bone resorption was 1.26 ± 0.58 mm for the control group and 1.14 ± 0.63 mm for the test group. Lingual crestal bone resorption was 1.40 ± 0.66 mm for the control group and 1.47 ± 0.68 mm for the test group. Horizontal bone width gain was 1.46 ± 0.44 mm for the control group and 1.29 ± 0.73 mm for the test group. There was no significant statistical difference between study groups regarding crestal and horizontal bone changes and patient morbidity.
CONCLUSIONS: The tomographic assessment of NanoBone® addition in this study resulted in no statistically significant difference between study groups regarding crestal and horizontal bone changes and patient morbidity. More randomized controlled clinical trials on gap fill comparing different bone grafting materials versus no grafting should be conducted.
RESULTS:
UNASSIGNED: NCT02836678, 13th January 2017.

BACKGROUND: The effectiveness of alveolar ridge preservation on bone regeneration and tissue healing has been thoroughly documented in the literature. This study aimed to evaluate the peri-implant soft and hard tissue changes after alveolar ridge preservation using either platelet-rich fibrin (PRF) or freeze-dried bone allograft (FDBA) over a 12-month period following the prosthetic loading of implants.
METHODS: In this randomized clinical trial, 40 individuals were recruited for alveolar ridge preservation using (1) FDBA or (2) PRF in incisal/premolar areas. At two follow-up sessions (six- and 12-months post-implant insertion), radiographic imaging and clinical examinations assessed marginal bone loss and soft tissue factors, including gingival recession and bleeding on probing. The differences between study groups were analyzed using Generalized estimating Equations, the Binary logistic regression model, and Cochran\'s Q test.
RESULTS: There was a statistically significant difference regarding gingival recession at both follow-up evaluations; values in the PRF group were considerably lower compared to the FDBA group (p < 0.05). The mean values for vertical marginal bone loss and bleeding on probing showed no significant differences between the two study groups (p > 0.05).
CONCLUSIONS: Except for gingival recession, applying PRF yielded comparable clinical results to FDBA after one year of implant loading and could be recommended as a potential biomaterial for alveolar ridge preservation following tooth extractions.
BACKGROUND: The research protocol was registered in the Protocol Registration and Results System on 13/08/2021, available at https://clinicaltrials.gov/ (NCT05005377).

This study aimed to determine the contribution of titanium prepared platelet-rich fibrin (T-PRF) with open flap debridement (OFD) on clinical, biochemical and radiographic measurements of periodontal regeneration. Twenty periodontitis patients with bilateral intrabony defects and stage III grade A periodontitis were included in the study. A total of 40 defects were randomly selected for OFD alone (control group, n = 20) or combined OFD+ T-PRF (test group, n = 20). Clinical and radiographic parameters (at baseline and nine months after surgery), and growth factor levels in gingival crevicular fluid (at baseline and at two, four, six, and twelve weeks after surgical treatment) were also evaluated. Considering the clinical parameters, alterations in probing pocket depth, gingival marginal level and clinical endpoint in the test regions treated with T-PRF significantly improved (P<0.05). Fibroblast growth factor-2 and platelet-derived growth factor-BB levels between the two groups in the second and fourth weeks were also significantly different (P<0.05). Furthermore, the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio between the groups was significantly different in the second, fourth, sixth, and twelfth weeks (P<0.05). The bone-filling rate was also significantly greater in the test group than in the control group (P <0.001). Compared with OFD alone, combining T-PRF with the procedure was more successful with regards to clinical, radiographic, and biochemical measurements of periodontal regeneration.

The sagittal split ramus osteotomy (SSRO) carries potential risks and complications. A double-blind, split-mouth, randomized clinical trial was performed, involving 30 patients undergoing mandibular setback. Advanced platelet-rich fibrin (A-PRF) was applied to one side, and the other side served as a control. The volume of postoperative drainage over 24 h was recorded. At 1, 2, and 5 days, and 3 months postsurgery, nerve recovery was assessed using the two-point discrimination test (TPD), while pain was evaluated using a visual analogue scale (VAS pain). Facial swelling was evaluated by taking linear measurements from facial reference points at the same time intervals. In the treatment group, the 24-hour drainage volume was lower (P = 0.011), pain was better on day 5 (P = 0.011), and TPD was better on day 2 (P = 0.011), day 5 (P = 0.007), and 3 months postoperatively (P = 0.020) than in the control group. There was also less facial swelling in the treatment group when compared to the baseline of 3 months postoperative (day 1, P = 0.012; day 2, P = 0.001; day 5, P = 0.011). The difference in bone mineral density (HU) at 3 months between the treatment group (469.7 ± 134.2) and the control group (348.3 ± 127.2) was statistically significant (P = 0.011), in favour of the treatment group. A-PRF may reduce postoperative complications such as neurosensory disturbance of the inferior alveolar nerve, pain, swelling, and drainage while enhancing bone healing in the osteotomy gap following SSRO. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Register (ChiCTR2200064534).

OBJECTIVE: The aim of the present pilot study was to assess the effectiveness of the platelet-rich fibrin (PRF) apical barrier for the placement of MTA for the treatment of teeth with periapical lesions and open apices.
METHODS: A total of thirty teeth on twenty-eight patients with open apices and periapical periodontitis were enrolled and divided into two groups in the present pilot study. In the PRF group (fourteen teeth in thirteen patients), nonsurgical endodontic treatment was performed using PRF as an apical matrix, after which the apical plug of the MTA was created. For the non-PRF group (fourteen teeth in fourteen patients), nonsurgical endodontic therapy was performed using only the MTA for an apical plug with no further periapical intervention. Clinical findings and periapical digital radiographs were used for evaluating the healing progress after periodic follow-ups of 1, 3, 6, and 9 months. The horizontal dimension of the periapical lesion was gauged, and the changes in the dimensions were recorded each time. The Friedman test, Dunn-Bonferroni post hoc correction, and Mann-Whitney U test were used for statistical analysis, with P < 0.05 serving as the threshold for determining statistical significance.
RESULTS: All patients in both groups in the present pilot study had no clinical symptoms after 1 month, with a significant reduction in the periapical lesion after periodic appointments. The lesion width of the PRF group was significantly smaller than that of the non-PRF group in the sixth and ninth month after treatment.
CONCLUSIONS: PRF is a promising apical barrier matrix when combined with MTA for the treatment of teeth with open apices and periapical periodontitis. Small number of study subjects and the short time of follow-up period limit the generalizability of these results.
BACKGROUND: TCTR, TCTR20221109006. Registered 09 November 2022 - Retrospectively registered, https://www.thaiclinicaltrials.org/show/TCTR20221109006 .

OBJECTIVE: Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes. Leukocyte- and platelet-rich fibrin (L-PRF) is a second-generation autologous platelet-rich plasma. This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice.
METHODS: Patients with DFU who received L-PRF treatment and standard of care (SOC) from 2018 to 2019 in Tongji Hospital were enrolled. The clinical information including patient characteristics, wound evaluation (area, severity, infection, blood supply), SOC of DFU, and images of ulcers was retrospectively extracted and analyzed. L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction (PVR) greater than 80%. Therapeutic effectiveness, including overall PVR and the overall and weekly healing rates, was evaluated.
RESULTS: Totally, 26 patients with DFU were enrolled, and they had an ulcer duration of 47.0 (35.0, 72.3) days. The severity and infection of ulcers varied, as indicated by the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) scores of 2-6, Wagner grades of 1-4, and the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) scores of 2-4. The initial ulcer volume before L-PRF treatment was 4.94 (1.50, 13.83) cm3, and the final ulcer volume was 0.35 (0.03, 1.76) cm3. The median number of L-PRF doses was 3 (2, 5). A total of 11 patients achieved complete epithelialization after the fifth week of treatment, and 19 patients achieved at least an 80% volume reduction after the seventh week. The overall wound-healing rate was 1.47 (0.63, 3.29) cm3/week, and the healing rate was faster in the first 2 weeks than in the remaining weeks. Concurrent treatment did not change the percentage of complete epithelialization or healing rate.
CONCLUSIONS: Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index, SINBAD score, or Wagner grade, indicating that this method is appropriate for DFU treatment under different clinical conditions.

Gingival recession treatment is one of the major clinical challenges in periodontics, and various surgical techniques have been proposed to correct it. Most of these techniques are suitable for isolated recession sites and involve harvesting an autogenous tissue graft, which increases patient morbidity and might result in inferior esthetics due to incision design. This study assessed the benefit of adding platelet-rich fibrin (PRF) to the vestibular incision subperiosteal tunneling approach (VISTA) in treating multiple gingival recession compared to using VISTA alone. A total of 41 teeth with Miller Class I and II defects were randomized in a split-mouth design. Multiple clinical parameters were tested, including the change in gingival thickness over time, keratinized tissue width, and gingival phenotype (using the transparency of a periodontal probe). Patient-centered outcomes were also assessed via visual analog scale. Multiple Miller Class I and II recessions in the maxilla can be effectively treated with VISTA. However, when used in conjunction with PRF, no significant differences were detected in any parameter. VISTA has been shown to be associated with a low level of postsurgical pain for patients and can be used for patients with high esthetic demands.

This clinical trial investigated the efficacy of platelet-rich fibrin (PRF) as an adjunct to conventional scaling and root planing (SRP) in non-surgical periodontal therapy. In a split-mouth randomized controlled trial with 13 patients and 26 periodontal pocket sites, PRF was inserted in test group pockets alongside SRP, while control group pockets received SRP alone. Measurements at baseline and six weeks included probing pocket depths (PPDs), clinical attachment loss (CAL), gingival recession (GR), the plaque index, and the gingivitis index. The wound healing index was assessed at six weeks. The results show statistically significant improvements in the SRP+PRF group compared to SRP alone, demonstrating a better CAL gain (SRP+PRF group: 2.69 ± 0.63; SRP alone group: 4.15 ± 0.69-p-value: 0.001), PPD reduction (SRP+PRF group: 2.62 ± 0.65; SRP alone group: 3.85 ± 0.80-p-value: 0.001), and GR minimization (SRP+PRF group: 0.46 ± 0.62; SRP alone group: 0.81 ± 0.72-p-value: 0.21). The adjunctive use of PRF enhanced healing, reduced pocket depths, decreased tissue morbidity, and minimized gingival recession. This study concludes that PRF placement is effective in 5-6 mm pockets, potentially reducing the number of periodontal treatment sessions needed for pocket closure.

OBJECTIVE: This study aims to develop a compound biomaterial to achieve effective soft tissue regeneration.
METHODS: Compound hyaluronic acid (CHA) and liquid horizontal-platelet-rich fibrin (H-PRF) were mixed at a ratio of 1:1 to form a CHA-PRF gel. Human gingival fibroblasts (HGFs) were used in this study. The effect of CHA, H-PRF, and the CHA-PRF gel on cell viability was evaluated by CCK-8 assays. Then, the effect of CHA, H-PRF, and the CHA-PRF gel on collagen formation and deposition was evaluated by qRT‒PCR and immunofluorescence analysis. Finally, qRT‒PCR, immunofluorescence analysis, Transwell assays, and scratch wound-healing assays were performed to determine how CHA, H-PRF, and the CHA-PRF gel affect the migration of HGFs.
RESULTS: The combination of CHA and H-PRF shortened the coagulation time of liquid H-PRF. Compared to the pure CHA and H-PRF group, the CHA-PRF group exhibited the highest cell proliferation at all time points, as shown by the CCK-8 assay. Col1a and FAK were expressed at the highest levels in the CHA-PRF group, as shown by qRT‒PCR. CHA and PRF could stimulate collagen formation and HGF migration, as observed by fluorescence microscopy analysis of COL1 and F-actin and Transwell and scratch healing assays.
CONCLUSIONS: The CHA-PRF group exhibited greater potential to promote soft tissue regeneration by inducing cell proliferation, collagen synthesis, and migration in HGFs than the pure CHA or H-PRF group. CHA-PRF can serve as a great candidate for use alone or in combination with autografts in periodontal or peri-implant soft tissue regeneration.