Comparison of injectable platelet-rich fibrin, titanium platelet-rich fibrin, and 0.8% hyaluronic acid applications versus periodontal dressing alone in wound healing after gingivectomy and gingivoplasty operations: randomized controlled clinical study.

PRP, cPRP, PRF, PRG, PRGF, FC … How to find your way in the jungle of platelet concentrates?

Introduction: Patient centered outcome became of great interest nowadays. Patient’s pain and discomfort following free gingival graft procedure are common complain. Different palatal dressings are suggested to cover and protect the palatal donor site as stents, collagen gelatin scaffolds, platelet rich fibrin (PRF), hyaluronic acid (HA) and Alvogyl. However, in the literature no ideal agent has been emphasized. Objectives: This randomized controlled clinical trial compares for the first-time the effect of PRF versus HA palatal wound dressings on postoperative pain, post-surgical bleeding, and wound healing. Materials and methods: Following sample size calculation, 30 systemically healthy patients requiring palatal mucosal graft harvesting were randomized to receive either PRF or HA (intervention groups) or gelatin sponge (control group) as palatal dressings. Patient-reported visual analogue score (VAS) pain scores as primary outcome. Post-surgical bleeding and wound healing were considered as secondary outcomes. Results: VAS pain scores were reported minimal in PRF group throughout follow up intervals, PRF was statistically significant when compared to HA group at 3 and 7 days postoperative, PRF was statistically significant when compared to control group from 3 to 30 days postoperative and VAS in PRF was nearly 0 in day 14. PRF group showed the highest value of healing index during all the follow up intervals with mean 4.4 at 30 days that indicates a full healing of palatal wound area. Conclusions: Within this study’s limitations, PRF had better outcomes than both HA and gelatin sponge in means of cost, pain reduction, hemostasis and healing properties.

In this study, the authors compared the effects of local application of platelet-rich fibrin (PRF) and hyaluronic acid (HA) bone and soft tissue on wound healing in rats. A total of 30 adult male Wistar Albino rats were used in this study. Twenty-four rats were randomly segregated into 3 groups (n=8 each), namely PRF, HA, and the control group. Six rats were used to obtain PRF. Defects ~8mm in diameter in the frontal region of the rats were created using a trephine burr with an outer diameter of 8mm. HA gel was applied to the defects in the HA group, whereas PRF was placed in the defects of the PRF group. The defects in the control group were left empty. The rats were sacrificed 14 days after the procedure. The calvarial bones and surrounding soft tissues of the rats were analyzed histopathologically and immunohistochemically. In the PRF group, the mean scores for increases in fibrous connective tissue proliferation (P=0.602), osteoblast proliferation (P=0.453), osteoid matrix formation (P=0.380), and osteoid matrix calcification (P=0.084) were consistently higher compared with the HA and control groups although these differences did not reach statistical significance (P>0.05). In addition, osteoprotegerin (OPG) levels were markedly elevated in the PRF group compared with the control and HA groups (P=0.220). Moreover, a higher proportion of samples in the PRF group exhibited elevated RANKL levels compared with the control and HA groups (P=0.183), suggesting an active remodeling state. PRF showed a nonsignificant, yet consistent superiority in enhancing both bone and soft tissue healing parameters and HA have a significant impact on bone and soft tissue healing. However, although both agents seem to impact the healing cascade, the superior OPG expression in the PRF group indicates a potentially stronger anti-resorptive and osteogenic effect. However, further studies are required to comprehensively evaluate their long-term relationship with wound healing.

Chronic periodontitis characterized by a periodontal pocket over 5 mm, alveolar bone resorption accompanied by tooth mobility, requires periodontal surgical treatment. Conventional surgical treatment can not achieve the regeneration of periodontal tissue and thus requires regenerative procedures, such as with the addition of PRF. PDGF-BB is a growth factor that plays an important role in wound healing. Developments in additional bioactive ingredients in surgical procedures are used to regulate inflammation and increase the speed of the healing process. The purpose of this study was to determine the effect of PRF and bone graft (carbonate apatite) on PDGF-BB levels post-surgical flap in patients with chronic periodontitis. The experimental study with open label and consecutive sampling was conducted on 10 subjects of chronic periodontitis who received surgical flap treatment with bone graft and PRF; and 10 subjects without PRF. GCF samples were collected immediately before surgery and 7 days post flap surgery for examination of PDGF-BB levels by ELISA method. The data were calculated statistically by Mann-Whitney test (p <0.05). The results showed that the mean difference of PDGF-BB level in PRF group was 9.44 pg/ml (-1.20 – 37.79 pg/ml) with p value (0.013) and Non-PRF group was 7.97 pg/ml (-6.62 - 44.42 pg/ml) with p value (0.059). The p value in the PRF group > 0.05 means a significant increase in PDGF-BB levels on the 7th day post flap surgery. Examination of PDGF levels, especially PDGF-BB, should be done in each healing phase of the wound from the inflammatory phase to the maturation and remodeling phase, for example on the 3rd, 7th, 14th and 28th days when PDGF levels approach zero and the healing process it's almost over, referring to the results of Alzahrani's research (2018) and also Matsuoka and Grotendorst (1989) which showed higher levels of PDGF-BB and VEGF in GCF on days 1, 3, 7 and 14 after surgery with minimally invasive surgery (MIS) technique. The conclusions of this study showed that the application of Platelet Rich Fibrin (PRF) and bone graft had an effect on the level of Platelet Derived Growth Factor (PDGF-BB) post-surgical flap in patients with chronic periodontitis, and elevated levels of PDGF-BB post-surgical flap with PRF application higher than surgical flap without the PRF application. Increased levels of PGDF-BB in the group applied to the PRF were higher than those that were not applied PRF, although statistically significant differences were not found, there was a tendency for the healing process of the PRF group to be better than the Non PRF group.

Trauma is a common cause of cutaneous surgical disease with an increased risk of secondary infection in cat clinics. Platelet-rich fibrin (PRF), a platelet and leukocyte concentrate containing multiple cytokines and growth factors, is known to accelerate the healing of wounds. However, how PRF affects wound healing in the cat trauma model has not been fully investigated. The study aimed to examine the impact of PRF on skin wound healing in the cat trauma model. In this study, PRF from cats was successfully produced for our investigation. The models of feline trauma were effectively established. A total of 18 cats were randomly divided into 3 groups (n = 6): (1) Control group (CON); (2) PRF group; (3) Manuka honey group (MAN, as a positive control). Experiments were performed separately on days 7, 14, 21, and 28. Our results showed that PRF was a safe and efficient method of wound healing that did not influence the cat’s body temperature, respiration rate, and heart rate (HR). PRF accelerated skin wound healing in the cat trauma model based on the rate and histological observation of wound healing. In addition, PRF promoted the production of growth factors and suppressed inflammation during wound healing. PRF accelerated wound healing by increasing the formation of collagen fibers, as shown by Masson-trichrome staining. The outcomes of the PRF and MAN groups were comparable. In conclusion, PRF improves the healing of skin wounds in cats by boosting the synthesis of growth factors, reducing inflammation, and enhancing the synthesis of collagen fibers.Graphical

Objectives: This study aimed to determine the efficacy of platelet-rich fibrin (PRF) injection on orthodontic pain perception during the 1st week of the alignment and leveling process. Material and Methods: The study sample included 18 patients (11 females and 7 males). The patients were randomly divided into two groups, the PRF group (9 patients) and the control group (9 patients). The mean age of the sample members was 21.9 ± 2.5 and 20.8 ± 2.4 in the control and the PRF group, respectively. Conventional brackets were applied for both groups. PRF was injected into the six upper front teeth at a rate of 0.6 mm for each point before starting the primary wire insertion process. The pain parameters of each patient were evaluated for both groups during the 1st week of the alignment and leveling process by application of the Visual Analog Scale (VAS) at the durations of (2 h, 6 h, 1 day, 2 days, and 7 days) and all patients were followed up until the end of the alignment and leveling process. Results: PRF injection can reduce pain perception in orthodontic patients, overall (P < 0.05), with an effect size of approx. 53 ± 0.13%. The biggest effect was observed 2 h after exposure (P < 0.1) which showed a 50% reduction in pain in the PRF group. No significant effects were observed at later times (P > 0.1). Conclusion: The present study concludes that PRF injection can be an effective alternative for decreasing pain perception levels; however, its efficacy needs to be leveraged immediately after the injection of PRF.

Side effects of zolendronic acid (ZA) and RANKL inhibitors (RANKL-I) include impaired wound healing and osteonecrosis of the jaw. Platelet rich fibrin (PRF) enhances wound healing and bone remodelling in vivo and in vitro. However, the topical use PRF in the surgical treatment of patients with medicament-related osteonecrosis of the jaw is relatively new and not thoroughly investigated. Furthermore, the potential attenuation of the PRF effect following antiresorptive treatment remains unclear. Therefore, we investigated the concentration of growth factors within the PRF in healthy volunteers and in patients with antiresorptive treatment. Blood samples from healthy volunteers and patients were used to produce PRF. The levels of EGF, VEGF, PDGF-BB, TGF-β1, BMP-2, and CD31 in the PRF was investigated by ELISA. ZA treatment induced a significant decrease in EGF and TGF-β1 levels, whereas RANKL-I caused lower TGF-β1 levels. Reduced EGF levels in PRF after ZA treatment may explain the delayed wound healing and question the positive effect of PRF in these patients. PRF use in patients undergoing RANKL-I treatment seems to be more justified.

Leucocyte- and platelet-rich fibrin has been developed to stimulate wound healing response. However, it is currently unknown whether smoking affects the biological responses elicited by leucocyte- and platelet-rich fibrin on periodontal ligament-derived mesenchymal stromal cells. This study analyzes the kinetics of biomolecule release from leucocyte- and platelet-rich fibrin derived from smokers and nonsmokers and their effect on periodontal ligament cell proliferation and migration as essential biological activities during wound healing. Biomolecules present in leucocyte- and platelet-rich fibrin exudates and conditioned media collected from smokers and nonsmokers were analyzed by Luminex arrays. Periodontal ligament-derived mesenchymal stromal cell obtained from one nonsmoker were treated with leucocyte- and platelet-rich fibrin exudates or leucocyte- and platelet-rich fibrin conditioned media derived from both smokers and nonsmokers. The parameters evaluated included cell proliferation, determined by Ki67 immunostaining and migration assessed using transwell assays. Also, cells were treated with nicotine in the presence of fetal bovine serum 10% or leucocyte- and platelet-rich fibrin conditioned media. A similar biomolecular profile was detected in leucocyte- and platelet-rich fibrin exudates and leucocyte- and platelet-rich fibrin conditioned media from smokers and nonsmokers, stimulating (periodontal ligament-derived mesenchymal stromal cell) proliferation, and migration to a comparable degree. Nicotine reduced cell proliferation and migration of periodontal cells; however, this effect was recovered in the presence of leucocyte- and platelet-rich fibrin conditioned media. Leucocyte- and platelet-rich fibrin derived from smokers could be an autologous source of biomolecules to stimulate cell biological activities involved in wound healing in smokers who have difficulties in ceasing this habit. Clinical trials are required to evaluate the impact of leucocyte- and platelet-rich fibrin on healing responses in smokers.

Biomaterials are substances used to restore the anatomical and functional integrity of lost tissues, aiming to improve the patient’s quality of life. Platelet-rich fibrin (PRF), an autologous biomaterial, has gained importance for its regenerative potential. This thesis aims to investigate three specific objectives: Objective 1: to assess the level of knowledge about biomaterials used in periodontics among undergraduate dental students; Objective 2: to critically analyze, through a scoping review, the clinical contexts in which PRF provides the greatest therapeutic benefits; and Objective 3: to evaluate osseointegration in areas grafted with isolated PRF membranes or injectable PRF (i-PRF) combined with deproteinized bovine bone mineral (DBBM) in rat tibias. The results showed that most undergraduate students reported some knowledge of biomaterials (57%). The majority showed interest in the subject, considered the use of biomaterials safe (97%), and did not see the need for specific qualifications (58%). The scoping review included 369 studies. PRF was found to be effective in treating bone defects, root coverage, and keratinized tissue augmentation. It also showed benefits in reducing postoperative complications in tooth extractions and supporting root development in endodontics, although with varied results. For implants and sinus augmentation, long-term stability benefits were limited, and effects on wound healing and periodontitis were inconsistent. Finally, in the in vivo study, no significant differences in removal torque were observed between the groups after 15 and 45 days. In the micro-CT analysis, the SB group (i-PRF + DBBM) showed a greater volume of mineralized tissue and bone trabeculae at 45 days (p<0.05). PRF membranes had the highest bone-to-implant contact (BIC) at 15 days, while DBBM alone led at 45 days. For bone area fraction occupancy (BAFO), PRF demonstrated greater bone formation at 15 days, but DBBM showed the highest values at 45 days. In conclusion, PRF shows promising potential in dentistry, particularly in enhancing the healing and regeneration of both soft and hard tissues. However, despite its versatility, the isolated use of PRF has limited efficacy for bone fill, suggesting that its combination with other materials provides optimized bone regeneration.

Platelet rich plasma (PRP) and platelet rich fibrin (PRF) are considered excellent concentrated sources of growth factors (PDGF, TGF-β, VEGF, bFGF) and cytokines fundamental for wound healing. The aims of this study were to evaluate and compare the effect of PRP and PRF on the second intention wound healing through clinical vision, histopathological examination, and changes in the IL10 and TGF-β genes expression. Fifteen adult dogs were used in this study; induction of a 3cm diameter total thickness cutaneous injury at the right chest region. The animals were divided into three groups equally, and the wounds were treated twice weekly for three successive weeks. The first group (Group A) received only normal saline (control group). The second group was treated by PRP (group B). The third group received PRF treatment (group C). Clinical Evaluation, Molecular studies of interlukin 10 (IL10) and transforming growth factor-β (TGF-β) gene expression, and histopathological examination were used to demonstrate the difference between the three treatment regimens. Results showed a non-significant negative correlation between weight loss and WHR% and showed a significantly high positive correlation between treatment cost either by PRP or PRF with IL10 (0.79*) and WHR% (wound healing rate) (0.994**). The IL10 significantly increased in PRP group, while TGF-b was significantly increased in the PRF group. This study concluded that the PRP and PRF exhibited higher regeneration capacity and accelerates the quality of wound healing

Background and Aims: Platelet-rich fibrin (PRF), rich in growth factors and cytokines, found useful for bone healing in animal studies, has paucity of literature on open fractures in humans. This randomised comparative interventional study aimed to find out the role of PRF in wound healing and fracture union in open fractures of tibia. Material and Methods: Random computerised allocation of 14 open tibial shaft fractures managed with an external fixator were done into PRF and non-PRF groups. Autologous PRF injected at fracture site, with PRF gel over open wounds in the PRF group, was compared with conventional standard treatment in the non-PRF group. Wound assessment on day 3, day 7 and weekly till complete wound healing and radiographs for fracture union at 3, 6, and 12 months were done in both groups. The statistical analysis was done using an unpaired t-test (wound size assessment) and chi-squared test (fracture union), using SPSS version 25. Results: Fractures union in PRF group 7/8 (87.5%) was better than 3/6 (50%) in non-PRF group. External fixators were removed 4 weeks earlier in PRF group. Wound healing time, though not statistically significant, was faster in PRF group (36.25±3.03 days) compared to non-PRF (42±7 days), even with larger wound size in PRF group (7.87±1.43 cm 2 ) than non-PRF group (7.5±1.5 cm 2 ). Conclusions: Results of injectable PRF at fracture site and PRF gel over the wound are encouraging, found to be safe, with faster wound healing and better fracture union in the small sample size of this pilot study.

This study aimed to evaluate and compare the early healing of fresh alveolar sockets treated with or without platelet-rich fibrin (PRF) using laser Doppler flowmetry and tissue spectrophotometry (LDF-TS). The primary outcome was gingival perfusion; secondary outcomes included clinical wound healing (based on the Landry Wound Healing Index) and patient-reported postoperative pain. Sixty-two patients requiring single tooth extraction were randomized into two groups. In the PRF group, an advanced PRF (A-PRF+) plug was placed in the socket before suturing; in the control group, only suturing was performed. Gingival perfusion was measured at four sites preoperatively and on postoperative days 3 and 10 using LDF-TS. Patients rated pain, and wound healing was clinically assessed. Twelve patients were lost to follow-up, leaving 50 for analysis. No significant differences were found between the PRF and control group regarding pain (day 3: p = 0.654; day 10: p = 0.329) or wound healing (day 3: p = 0.178; day 10: p = 0.595). Perfusion parameters also showed no significant group differences between baseline and day 10: oxygen saturation (SO₂: p = 0.884), relative hemoglobin (rHb: p = 0.387), and blood flow (p = 0.072). Gingival perfusion showed no significant group differences over 10 days. PRF did not significantly reduce pain or improve wound healing. PRF does not appear to significantly enhance healing, pain reduction, or perfusion in simple extractions. Future studies should use split-mouth designs and focus on more complex surgeries to better evaluate PRF's effects. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was performed according to the Consolidated Standards of Registered Trial (CONSORT) guidelines. The study was approved by the institutional Clinical Research Ethics Committee (Decision Number 23-105) and by the German Clinical Trials Register (File Number DRKS00032344, registered on October 11, 2023).

Background: Local administration of antibiotics was one of many approaches for the management of localized periodontal infection with the advantages of smaller total dosage delivered into the pocket, avoiding systemic antibiotic side effects, and increasing the exposure of target microorganism to higher concentration. Incorporating antibiotics into platelet concentrates can be considered for local antibiotic administration.Method: The sample in this study used Aggregatibacter actinomycetemcomitans which was divided into 4 partitions on each plate. Each plate was applied with Platelets Rich Fibrin (PRF) and Injectable Platelet rich fibrin (I-PRF) incorporated with metronidazole pre-centrifugation and two negative controls (PRF and I-PRF without metronidazole). The observation was performed after 1 day and 7 days of incubation by measuring inhibition zone diameter using vernier caliper. The data were analyzed using two-way ANOVA followed by post-hoc LSD.Result: I-PRF with metronidazole had the highest bacteria inhibition compared with other groups (p<0,05) on incubation day 1 and 7; I-PRF and PRF with metronidazole showed higher bacteria inhibition compared with I-PRF and PRF without metronidazole (p<0,05).Conclusion: Aggregatibacter actinomycetemcomitans inhibition of PRF and I-PRF incorporated with metronidazole was greater compared to PRF and I-PRF without incorporating metronidazole, and A. actinomycetemcomitans inhibition of I-PRF incorporated with metronidazole was greater than PRF incorporated with metronidazole.

As of a few years ago, platelet concentrates have been applied in a variety of medical and dental procedures. A notable aspect is that platelet-rich fibrin (PRF) is the most commonly utilized platelet concentrate in the field of dentistry. The most significant modification that was used over the years but had the biggest impact was injectable platelet-rich fibrin (I-PRF), which has more special properties. Additionally, the results of this I-PRF have been useful. The solid platelet-rich fibrin (PRF), which is a noticeable feature and has a low speed and duration in centrifugation, is the main advantage of I-PRF. I-PRF is primarily found in liquid form as PRF. It facilitates the quickening of increased vascularization and aids in accelerating the healing of wounds. An autologous blood concentration known as I-PRF has been known for many years.The advantage of I-PRF is that it exhibits constant release of growth factors and promotes cell migration by announcing the expression of type I collagen and transforming growth factor mRNA. The majority of the time, plastic and orthopedic operations use injectable platelet aggregates. It also reduces adverse reactions to transplanted material as compared to other grafting techniques. Additionally, it makes numerous other operations, like regenerative ones, much better options. In circumstances where it has been noticed, I-PRF is helpful and crucial in periodontics for bone regeneration and wound healing. It is therefore not difficult to predict that this fully autologous blood concentrate, which is now being utilized in numerous applications and requires little invasiveness, will become even more frequently used in the future. This review paper contains the differences between platelet-rich plasma (PRP) and PRF, the development of diverse platelets, and the use of I-PRF in periodontal therapy.

Background The aim of the present study was to evaluate postoperative effects of platelet-rich fibrin (PRF) in wound and bone healing, pain, swelling and periodontal complications outcomes after impacted third molars extraction.Material and Methods A prospective, randomized, split-mouth, double-blind clinical trial was conducted. PRF was placed within sockets following tooth removal and before suturing mucoperiosteal flap while no treatment was performed on control group’s sockets. Patients were evaluated considering bone volume which was obtained in the 90-day postoperative period. Other variables included trabecular thickness, trabecular distance and grey values, pain, swelling, and wound healing. A Wilcoxon test and a t-Student test were used at a 5% significance level and a Friedman test was used to multiple comparisons.Results Forty-four surgeries were performed in the present study. The patients’ mean age was 22.41 (± 2.75 years) and 72.73% were women. PRF was associated to increased trabecular thickness and bone volume means (p < 0.001). The experimental group had significantly lower pain scores at 4h, 6h, 8h, 16h, 24h, and 72h (p ˂ 0.05). Mean swelling was lower on the experimental group (p < 0.001). The PRF group showed significant higher wound healing (p ˂ 0.001).Conclusions Alveolar filling with PRF improves wound and bone healing after extractions while also decreasing pain and swelling in the postoperative period. Key words:Third molar surgery, platelet-rich fibrin, bone regeneration, pain.