|Year : 2019 | Volume
| Issue : 9 | Page : 1189-1195
Potential effects of advanced platelet rich fibrin as a wound-healing accelerator in the management of alveolar osteitis: A randomized clinical trial
E Yüce, N Kömerik
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Biruni University, Istanbul, Turkey
|Date of Acceptance||30-Apr-2019|
|Date of Web Publication||6-Sep-2019|
Dr. E Yüce
Department of Oral and Maxillofacial Surgery, Biruni University, Dentistry Faculty, 34010, Topkapi/İstanbul
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aim: The aim of the present study was to determine whether the use of advanced platelet rich fibrin based on the low speed+ centrifugation concept (A-PRF+) might improve the pain management and healing of delayed wound healing among cases of alveolar osteitis following mandibular third molar extraction. Materials and Methods: The patients (N = 40) with a complaint of alveolar osteitis following third molar extractions were divided into two groups: Group I (control; saline only); and Group II (use of A-PRF+). Pain was evaluated using the visual analogue scale (VAS). Soft tissue healing was assessed by the modified Index of Landry, Turnbull and Howley and bone density was assessed with the i-Dixel 220.127.116.11 software. Inter-group comparisons were analyzed by means of a student t-test and the Mann Whitney U test to identify group samples. Analysis of variance and the Friedman test were applied for repeated measurements. The Wilcoxon test and Bonferroni's test for multiple comparisons were conducted at the time-factor level. Yates Correction was used to compare qualitative data. Results: In regard to pain, A-PRF+ application demonstrated rapidly and continually reduced pain intensity at each respective time in comparison to the control. Statistically, the healing rates of epithelium and hard tissue were significantly faster in the A-PRF+ application group (p: 0.000, P < 0.05). Conclusions: The results show that A-PRF+ might represent an improved and accelerating therapeutic development for hard and soft tissue healing in management of alveolar osteitis that is also effective in reducing pain.
Keywords: Alveolar osteitis, A-PRF, inflammation, platelets, wound healing
|How to cite this article:|
Yüce E, Kömerik N. Potential effects of advanced platelet rich fibrin as a wound-healing accelerator in the management of alveolar osteitis: A randomized clinical trial. Niger J Clin Pract 2019;22:1189-95
|How to cite this URL:|
Yüce E, Kömerik N. Potential effects of advanced platelet rich fibrin as a wound-healing accelerator in the management of alveolar osteitis: A randomized clinical trial. Niger J Clin Pract [serial online] 2019 [cited 2019 Sep 20];22:1189-95. Available from: http://www.njcponline.com/text.asp?2019/22/9/1189/266159
| Introduction|| |
Alveolar osteitis is a widely recognized complication of which well-known clinical manifestations in affected individuals include partial or total disintegrated blood clot within the extraction socket, resulted in inflammation of exposed alveolar bone and delayed healing, accompanied within three days by gradually increasing severity of pain which may radiate to the auricular and temporal regions. The incidence of alveolar osteitis was seen in the range 0.5% to 5% after routine dental extractions; however, this rate has been reported to range from 3.9% up to 29.6% for extractions of mandibular third molars.,
Many predisposing factors have been identified for the occurrence of this phenomenon, such as preexisting systemic diseases, operative technique, reduced local perfusion, mechanical disruption of the blood clot, smoking, bacterial infections, oral contraceptives and menstruation, or oral hygiene, etc.,, In instances whereby the healing process does not follow a linear progression by a number of factors, wound-healing phases are affected regressively, resulting in an impaired healing process and increased risk of serious inflammatory reactions in the alveolar sockets. Therefore, management of alveolar osteitis can pose difficulties for clinicians and also result in severe pain and frequent hospital visits for the patient. In spite of numerous suggested treatment procedures, this continues to pose a challenge in terms of delayed healing.
In the last 20 years, the use of platelet concentrates has been proposed as a potential aid for enhancing regeneration of osseous and epithelial tissues in oral surgery.,, Several in vitro studies, animal experiments and clinical trials have suggested that the platelet rich fibrin (PRF), may effectively trigger a stimulation of angiogenesis, and increase local perfusion during the healing process, resulting in a reduction of inflammation, pain and undesired side effects.,, Therefore, the PRF which is a second generate platelet concentrates is used for a wide range of clinical applications such as extraction socket management, gingival recessions, intrabony defect regeneration and sinus elevation procedures as a simple, minimally invasive and cost-effective method of shaping the healing process. Recently, it is demonstrated that the newer PRF preparations centrifuged at lower g-forces and lower centrifugation times are more potent in releasing several growth factors and facilitating subsequent healing events at the site of application when compared to standard PRF. Promoting delayed extraction wound healing by the use of advanced platelet rich fibrin based on the low speed + centrifugation concept (A-PRF +) in the management of alveolar osteitis may act to reduce the increase in localized inflammation, pain intensity and patient discomfort. The aim of the present study was to determine the effectiveness of A-PRF + in delayed wound healing and pain relief among cases of alveolar osteitis.
| Materials and Methods|| |
The present randomized prospective controlled clinical study was conducted on 40 patients who were referred to the Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Biruni University, with suggestive complaints of alveolar osteitis. Inclusion criteria were as follows: between 18 and 40 years of age; no systemic disease; positively diagnosed and untreated alveolar osteitis in three days after extraction of mandibular third molars of class A and 1 according to the Pell–Gregory classification. In accordance with Blum's definition, positive diagnosis of AO was identified in patients with the presence of increasing postoperative pain severity in and around the lower permanent third molar extraction site in three days after extraction and the total or partial breakdown of the blood clot in the socket with or without halitosis.
Exclusion criteria were: the use of medications that may interfere with the healing process; smoking; pregnancy or lactation; were menstruating; presence of any conditions such as inflammation, periodontitis, gingivitis and dental abscess in the area of the teeth; undergoing antibiotic or anti-inflammatory drug therapies in the 7 days before extraction; using oral contraceptives and radiation therapy or chemotherapy in the 12 months before extraction and would require raising a flap and/or removing bone to remove the tooth.
The study design was approved by the ethics committee of İstanbul Aydın University (n° 2015-11), and was carried out in accordance with the Declaration of Helsinki on medical protocols and ethics. All patients were recruited to the study by request and informed consent was obtained from all participants.
Patients were divided by means of systematic random sampling into two groups each of 20 patients: the control group (Group 1), in which extraction sockets were curetted to remove debris and gently cleaned by irrigation with saline only.; and the study group (Group 2), in which the extraction sockets were packed with A-PRF + after alveolar curettage and irrigation of the socket with saline [Figure 1]. All patients who had only one-third molar extraction and presented alveolar osteitis symptoms in the extraction sockets in three days postoperatively were examined and manipulated by the same surgeon using a standard technique, allowing a blinded study for both participants and evaluators. Initially, plugs and partial breakdown clots were gently removed from the extraction sockets under local anesthesia using articaine HCl 2.5% plus 1:100,000 epinephrine (Ultracaine D-S Forte Ampul; Aventis, Istanbul, Turkey) and the alveolus was irrigated with 20 ml 0.9% saline solution in both groups. Irrigation using saline solution (0.09% NaCl) at similar rates within the same zone was continued for Group 1 patients during postoperative visits on Days 1, 3, 5, and 7.
A-PRF + preparation method was followed by protocol proposed by Kobayashi et al. The required quantity of blood sample (9 ml) was collected from Group 2 patients into 10 ml tubes free from anti-coagulants and immediately centrifuged into three sedimented layers using a centrifuge machine (PRF Duo Centrifuge, Nice, France) at 1300 rpm (RCF: approximately 200 g) for 8 minutes. The resulting A-PRF + clot in the top of 4 ml layer of the centrifuge tube was first separated from red thrombus and placed into the extraction socket and then stabilized with an eight stitch by 3/0 absorbable PTFE suture [Figure 2]. Nonsteroidal anti-inflammatory drugs (NSAIDs; diclofenac sodium 50 mg) were prescribed to all patients, who were instructed to use them only as directed (one tablet every 12 hours) and use only as needed. The intraoral sutures were removed on postoperative Day 7 in Group 2 (before the soft tissue changes were assessed).
|Figure 2: (a) Preoperative clinical view of alveolar osteitis in left mandibular third molar region; (b) After alveolar curettage and irrigation of socket with saline; (c) Placement of A-PRF+ and closure of socket|
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All patients were recalled for follow-up study on postoperative Days 1, 3, 7, and 15, as well as at Months 1, 2, and 3. Pain was evaluated preoperatively using the visual analogue scale (VAS) (Time 1; on the day the alveolar osteitis was diagnosed and manipulated), and postoperatively on Day 1 (Time 2), Day 3 (Time 3), Day 5 (Time 4), and Day 7 (Time 5). Soft tissue healing was assessed preoperatively using the Index of Landry, Turnbull and Howley , (Time 1; on the day the alveolar osteitis was diagnosed and manipulated), and postoperatively on Day 7 (Time 2), Day 15 (Time 3) following the surgical procedure in both groups.
OPTGs were taken preoperatively (Time 1; on the day the alveolar osteitis was diagnosed and manipulated), and at Months 1, 2 and 3 postoperatively, and bone density was assessed using i-Dixel 18.104.22.168 software by the average gray level values [Figure 3]. All clinical assessments and radiological measurements were performed under blind conditions by three independent surgeons who did not perform clinical applications in order to avoid bias.
|Figure 3: Group II: (a) Preoperative (before A-PRF+ gel application) OPTG Image; (b) 2nd month post op, OPTG Image with A-PRF+; (c) 3rd month post op, OPTG Image with A-PRF+. Group I: (d)Preoperative OPTG Image (control group);(e) 2nd month post op, OPTG Image; (f)3rd month post op, OPTG Image|
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The ideal sample size calculation was done using following formula:
Data obtained in this study were analyzed using the SPSS 22 statistical software package. The study included: 2 group-factor levels (control, placement of A-PRF +); five time-factor levels (the day the alveolar osteitis were diagnosed and manipulated; and postoperative Days 1, 3, 5 and 7) for pain; and three time-factor levels for epithelial healing (the day the alveolar osteitis was diagnosed and manipulated, and postoperative Days 7 and 15), and three time-factor levels (the day the alveolar osteitis was diagnosed and manipulated, and postoperative Months 2 and 3) to measure density. The Shapiro Wilks test was used to verify the distribution for normality. Inter-group comparisons were analyzed by means of a student t-test and the Mann Whitney U test to identify group samples that significantly differed from other groups. Analysis of variance and the Friedman test were applied for repeated measurements. The Wilcoxon test and Bonferroni's test for multiple comparisons were conducted at the time-factor level. Yates Correction was used to compare qualitative data. The level of significance was set at P < 0.05.
| Results|| |
About 20 patients were included in each study group, providing a total of 40 patients who established with alveolar osteitis. The female (55%) to male (45%) ratio was 1.22 and the mean age of the patients was 31.2 years. There was no postoperative morbidity. We have experienced no reports of side effects. We found that pain scores following A-PRF + application on post-operative Days 1, 3, 5, and 7 were significantly lower than in the control group (p: 0.000; P < 0.05). The increase in pain levels in the control group at Day 1 (p: 0.049) and pain-level decreases at Day 5 (p: 0.008) and Day 7 (p: 0.000) were significant (p < 0.05) when compared to preoperative pain levels; however, there was no statistically significant change in pain levels on postoperative Day 3 (p > 0.05) when compared to preoperative and postoperative Day 1. Pain was rapidly and continually reduced on Days 1, 3, 5, and 7 in the A-PRF + application group and the difference between measurements at each Time was significant (p: 0.000; P < 0.05) [Table 1]. Total self-medicated analgesic consumption ranged from 2 to 16 tablets over the seven-day follow-up period, and the control group showed significantly higher levels of analgesic usage compared to the A-PRF + application group (p: 0.000; P < 0.05) [Table 2]. In the control group, measurements taken on postoperative Day 7 were nearly identical to Day 3 values in the A-PRF + application group. As well, analgesic intake fell from 2 to 0 after the third day in the A-PRF + application group. This indicates that A-PRF + is effective in reducing postoperative pain.
|Table 1: Pain scores were evaluated between groups and within each group. Values are expressed as the mean|
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There was no statistically significant difference between the preoperative soft tissue values of the two groups (p > 0.05) [Table 3]. The statistical healing rates of epithelium were significantly faster at all times in the A-PRF + application group as compared to the control group (p: 0.000, P < 0.05).
|Table 3: Epithelial healing scores were evaluated between groups and within each group. Values are expressed as the mean|
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There was no statistically significant difference in preoperative gray level pixel values between the two groups (p > 0.05) [Table 4]. Measurements taken at Months 2 and 3 revealed a significant increase in the average pixel values in the A-PRF + application group as compared to the control group (p: 0.000, P < 0.05). In the present study, A-PRF + application proved to be more effective in accelerating soft and hard tissue healing at all-time intervals.
|Table 4: Gray level values were evaluated between groups and within each group. Values are expressed as the mean|
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| Discussion|| |
It is a well-established fact that pain intensity reaches its near maximum for a period of about three to five hours and relief may be achieved within the first 24 hours following tooth removal. The intensity of pain associated with alveolar osteitis is characterized by increasingly severe, debilitative symptoms, which continue throughout the night, respond poorly to over-the-counter analgesics, and subsequently peak at least 72 hours post extraction.,
The goal of conventional treatments involved debridement and irrigation, which is traditionally accomplished by the use of topically applied medicated packing that provides only partial symptom relief., It also remains unclear as to which intra-alveolar dressing is the most effective treatment material for alveolar osteitis. Most studies in the literature describe the topical use of non-resorbable abundant dressing, such as zinc oxide and eugenol, to relieve pain; however, researchers have also warned that these dressings, if not removed, may lead to bone necrosis and impaired socket healing, due to their tendency to adhere to the extraction site., On the other hand, many studies aimed at controlling pain flare have placed more emphasis on the efficacy of drugs (including antibiotics or NSAIDs), vitamins, low-level laser application or processing, than irrigation and removal of debris organic matter using various disinfectant solutions.,,, The application of topical agents or dressings could have a negative effect on the evolution of the wound healing process and increase the risk of developing foreign body reactions for which an objective result cannot be obtained and so was not evaluated in the present study. Additionally, we have experienced no reports of side effects, which is substantially associated with the excellent biocompatibility of A-PRF + because of its derivation from the patient's own blood.
Despite analgesics such as NSAIDs or paracetamol-codeine combinations that are privileged for the adequate treatment of pain, there has been an expression of negative opinion on systemic antibiotic therapy for the treatment of alveolar osteitis unless there is systemic toxicity, a potential risk for developing osteomyelitis, or the patient is immunocompromised. We opted to prescribe only NSAIDs to relive pain. We did not prescribe any antibiotics, taking into account the disadvantages of prophylactic systemic antibiotic therapy, such as the development of resistant bacterial strains and unnecessary destruction of commensal microbiata that promote immune resistance in the host. We experienced no reports of secondary bacterial infection that required the use of antibiotics in this study.
However, the treatment of alveolar osteitis in promoting delayed-extraction wound healing has yet not been fully elucidated and there is no definitive treatment other than palliative methods. In the literature, tremendous advancements have been proposed for the management of delayed wound healing based on strengthened evidence that growth factors foster the healing process.
As to Alexander and Plachokova et al., the use of PRF in the extraction was shown as a potential novel treatment modality for reducing the incidence of alveolar osteitis following routine tooth extraction.,
Chakravarthi assessed reduced pain, and epithelial healing using platelet rich fibrin in the management of alveolar osteitis at 15 days postoperatively, and found that PRF was an effective alternative method to achieve satisfactory healing as well as reduce symptoms and analgesic consumption within 24 hours due to a release of several growth factors and platelet factors that antagonize the kinine released from dry sockets, a phenomenon that is responsible for pain flare.
PRF cloth was selected for this study because: it acts as a healing biomaterial, providing more rapid and denser regeneration by accelerating neovascularization, mitogenic stimulation and fast cicatricial remodeling; it provides microbial inhibition potential at the wound site; and it enhances osteogenic proliferation and differentiation during the early postoperative period., However, modifications to centrifugation speed and time with the low-speed concept were shown to have directly impact on growth factor concentrations within PRF matrix. We also sought to investigate the use of A-PRF + with low speed concept +, using the technique described by Kobayashi et al. due to its advantages over standard PRF (centrifuged at 2700 rpm for 12 minutes), such as its provision of more effective cell migration and proliferation, its synergistic effects on total growth factors resulted in release of additional growth factors, and its ability to favorably influence healing and regeneration due to increase in the mRNA levels of type 1 collagen. Our results provide observation that the use of A-PRF + could represent an improving and accelerating therapeutic development for soft tissue healing in the management of alveolar osteitis while also proving effective in reducing pain and dependence on analgesic intake when compared to recent studies  which have applied the standard PRF protocol to manage alveolar osteitis. Denuded bony walls were successfully covered with healthy granulation tissue in the A-PRF + application group on the 7th day but also, almost complete epithelial healing with flattened epithelial ridges were clinically observed in all cases by the end of the second week postoperatively. Moreover, it may be concluded that besides the release of growth factors from A-PRF + that can accelerate the healing process, the physical properties of A-PRF + may provide support for epithelial coverage of the extraction socket by shielding wounds that feature exposed bone; therefore, wound edges may appear to be touching considerably more rapidly than with saline irrigation.
Where as previous studies on the management of alveolar osteitis have focused on the effect of platelet concentrates on the very early stages of soft tissue healing, the advantages of platelet concentrates in late stages of the healing process (especially new bone formation and mineralization), which would be indispensable in the use of dental implants to replace missing teeth, have not been completely clarified. The current study is the first one evaluating the long term outcome of bone regeneration after the management of alveolar osteitis with platelet concentrates to our knowledge.
Ghanaati et al. demonstrated that by decreasing centrifugation g-force favored an increase in leukocyte number by means of providing uniform distribution of leukocyte cells across the PRF cloth which is critically important for the new bone formation. It was also emphasized that a higher presence of neutrophilic granulocytes in A-PRF + might be related to ensuring the rapid differentiation of monocytes into macrophages thus increasing the effect of bone stimulation. It was confirmed that bone tissue remodeling had an absolute requirement for macrophages which was associated with a marked (23-fold) increase in osteoblast differentiation. In light of this fact, it becomes evident that the significant increase in these key immune cells achieved within the PRF matrix by decreasing centrifugation g forces may directly influence biomaterial integration such as collagen barrier membranes, bone grafting materials and potentially dental implants. Our results provide support that the use of A-PRF+ in the management of alveolar osteitis represent a possible therapeutic mechanism for a more rapid and effective regeneration of hard tissues when compared with curettage and irrigation alone. Further, the management of alveolar osteitis with A-PRF + by changing the speed and duration of centrifugation which is a time-consuming and invasive way to promote bone healing and regeneration, especially through the presence of monocytes/macrophages and their growth factors, could be a great aid in implant rehabilitation at the extraction sites. In order to obtain more reliable results, further studies with larger samples would be required to examine histopathologically.
| Conclusions|| |
In the present study, our results showed that promoting delayed extraction wound healing by the use of A-PRF + in the management of alveolar osteitis may act to reduce pain intensity, patient discomfort and also provide a better opportunity to overcome clinical challenges for clinicians.
This study followed the Declaration of Helsinki on medical protocol and ethics, and the regional ethics review board of Istanbul Aydın University approved the study. (Decision No 2015-11)
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]