Post extraction wound healing and physiologic sequelae of third molar surgery can significantly affect the patient’s quality of life2. Various methods have been suggested to improve extraction socket healing and to minimize the postoperative sequelae after third molar surgery4,5. PRF is a second-generation platelet concentrate which is known to stimulate wound healing by releasing growth factors directly to the wound5,8,16,17. Recent studies demonstrated the PRF membrane has a very significant slow sustained release of key growth factors for at least 7 and up to 28 day13. Studies on PRF efficacy in enhancing wound healing have yielded differing results and also there is a divergence of opinion on the activity of PRF. Thus, there is the need for more studies to explore its use in oral and maxillofacial surgery. This study was therefore perceived to determine the effect, if any, that PRF has on postoperative sequelae and enhancement of bone healing after mandibular third molar surgery.
Patients and Methods
The study sample consisted of 15 young adult volunteers 18 to 22 years old presenting with impacted mandibular third molars bilaterally and in similar positions. Patients using systemic drugs or presenting a medical history positive for any systemic pathology or a history of hypersensitivity to any component used in the methodology were not included. Each patient participated as a volunteer after signing an informed consent form on the study for extraction of impacted right and left mandibular third molars. Ethical clearance was obtained from the Ethics Committee prior to the commencement of the study. The following demographic information was collected: age, gender, occupation, marital status, and educational level. Furthermore, the position and type of impaction were recorded. The two operated sides in each patient were randomly divided into 2 study groups: extraction of an impacted mandibular third molar at first side whose socket was filled with blood clot and wound sutured (control group), and extraction of an impacted mandibular third molar on the other side whose socket was filled with PRF gel and wound sutured (PRF group).
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A 10-point visual analog scale (VAS) with a score of 0 equals “no pain” and ten equals “very severe pain” was used to assess pain. Facial swelling was evaluated using a modification of the method described by Schultze-Mosgau et al9, and this entailed measuring the distances from the tragus to the oral commissure and tragus to the pogonion. The arithmetic sum of the two measurements was used to determine the facial swelling at the time point. The percentage facial swelling was calculated from the difference of the measurements made in the preoperative and postoperative periods divided by the value obtained in the preoperative period and multiplied by 100.
(Swelling Postoperatively–Swelling Preoperatively) /Swelling Preoperatively X 100
Digital radiographs were used to evaluate changes in radiographic bone density for each extraction site. Three blinded dental professionals working independently evaluated all radiographs. RVG software was used for radiographic analysis. Radiographs were evaluated by three blinded dental professionals. The radiographs were assessed by obtaining the average density of three independent readings of the 3rd molar extraction socket sites. This was compared to the average of three density outlines of the adjacent tooth. When all radiographs for a patient were assessed, they were normalized to the original radiograph and the same untouched adjacent tooth. The baseline socket average was then subtracted from the normalized average for each tooth extraction socket at the different time points.
The final, normalized socket value differences for each PRF-treated and non-PRF treated site for the various time points were compared. All radiographs were taken by a blinded, certified x-ray dental assistant. They were taken immediately post-operatively and at the following time after the day of surgery: 4th week, 8thweek and 12thweeks.
Preparation of Platelet-Rich Fibrin
PRF was prepared according to the technique described by Choukroun et al1. Twenty minutes before starting surgery, 10 mL of venous blood was collected in a sterilized dry, neutral glass tube without an anticoagulant. After immediate centrifugation at 3000 rpm for 10 minutes, the platelet-poor plasma, which accumulated at the top, was discarded. PRF was removed approximately 2 mm below its connection to the red corpuscle beneath to include remaining platelets, which have been proposed to localize below the junction between PRF and the red corpuscle After 10 minutes, the gel was formed, and autologous PRF was applied immediately in the socket in the PRF group.
To standardize the surgical operations, all patients were operated by the same surgeon. The mandibular third molars of which the extraction sockets would receive PRF treatment were selected randomly before surgery and these molars were operated on first. After tooth extraction, the surgical area in the PRF group was isolated with gauze and the socket was filled with PRF gel. In the control group, the socket was not filled with PRF. The flap was repositioned by an interrupted suture with 3-0 silk suture. The patients received oral and written postoperative guidance, and follow-up was scheduled according to the study periods. Because only the bilateral mandibular third molars similarly impacted were selected for the study, there was no significant difference in the time and surgical trauma associated with surgical extractions.
Immediately after the procedure, details of each procedure were recorded, including the duration of surgery in minutes (from the first incision to insertion of the last suture), and any intraoperative complications. Patients were then recalled at 1, 3, 7, and 14-day postoperative intervals. During such visits, data were recorded for postoperative pain,facial swelling and any untoward complications like infection and alveolar osteitis. Sutures were removed 7 days after surgical operation. Patients were also recalled at the 4th, 8th, and 12th week postoperatively for radiographic bone healing assessment.
The mean age of the sample population was 21.40(range 18 to 35 years). There was no statistically significant difference in the age, gender, and type of impaction between both groups. In both groups, the mean postoperative pain score (VAS) was highest at postoperative day 1 and gradually reduced over the following 14 days. The mean postoperative pain score (VAS) was higher for PRF group than control group at all-time points when compared with the control group and was not statistically significant (P <0.05).
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The percentage facial swelling for the PRF group relative to baseline value was 2.55%, 2.22%, and 0.28% on postoperative days 1, 3, and 7 respectively, whereas it was 1.86%, 1.5%, and 0.29%, respectively, in the non- PRF(control) group for the same period. The percentage facial swelling was highest at postoperative day 1 and gradually reduced over the following days for both groups. The mean percentage swelling was also higher for the PRP group at all-time points when compared with the control. However this difference also was found to be not statistically significant.
The mean bone density score was higher in the PRF group than the non-PRP group over a 12-week period; and the differences were found to be statistically significant. The results of the present study clearly show that the application of autologous PRF in surgical wounds after tooth extraction allows acceleration of bone healing, as indicated by data with statistical differences (p<0.05).
This prospective study evaluated the performance of PRF gel when applied to fresh extraction sites. Third molar extractions are often used as a measurement tool for comparing treatments because they are usually performed electively on a younger population that do not present with significant medical problems (e.g., systemic pathologies, multiple medications). Therefore, this study is especially relevant for healthy 18 to 40 year old patients. This study evaluated the effect of PRF gel on postoperative pain, swelling and bone regeneration potential on third molar extraction sockets.
The mean postoperative pain score (VAS) and swelling were higher for the PRF group at all-time points as compared with the control group, but the differences obtained were found to be statistically non-significant. This suggests that topical application of PRF may not improve the postoperative sequelae after third molar surgery. Choukroun et al5 in a case report found reduced pain and better mouth opening when topical PRF gel was used in molar extraction sockets ,in contrast to this we observed increased pain and swelling when topical PRF gel was used in 3rd molar extraction socket .
Intra-oral digital radiographs taken of the individual surgical sites revealed that the effects of PRF were significantly beneficial (P <0 .05) for increasing bone density following surgery. The increase in bone density suggests a greater volume of new bone formation with PRF treatment. Moreover, the increase in bone density was found to occur at earlier time points than non-PRP treated control sites. Of note was the immediate increase in grayscale readings which indicates enhanced early bone formation. Choukroun et al6,similarly reported that the PRF induced complete bone filling of a residual cystic cavity in 2 months & 2 weeks, a much shorter period than 6 to 12 months of physiologic healing. Choukroun et al7 in a case series on maxillary sinus lifting operations, 3 cases were treated with PRF and freeze-dried bone allograft mixture and 6 cases with freeze-dried bone allograft alone. Histomorphometric results of this study showed that PRF and allograft mixture accelerated bone regeneration, allowing implant placement in 4 months after maxillary sinus lifting procedure. Furthermore, the amount of newly formed bone was equivalent to that achieved with an allograft alone 8 months after surgery. Diss et al10 reported promising results after placing PRF instead of bone graft under the sinus membrane during a closed-sinus lifting technique and demonstrated that an average of 3.2 mm bone gain could be obtained in the sinus after 1-year follow-up.
However the results of our study does not correspond with the study from Gürbüzer et al17 who reported scintigraphically, that platelet-rich fibrin might not bring about promoted activity of osteoblasts in impacted mandibular third molar sockets in 1 or 4 week after extraction.
Accelerated bone formation observed is in contrast to the drop in bone density seen at the control site before bone formation began to take place. It took approximately 6 weeks for the control sites to reach the same bone density that the PRF-treated site had reached by 4 weeks. The PRF-induced acceleration in bone formation may be due to the presence of bone morphogenetic proteins (BMPs) in PRF that stimulates mesenchymal stem cells to begin osteoblast differentiation and subsequent calcification12,14,18. The immediate start of bone formation seen with PRF treatment is of clinical relevance because it is the initial 2 weeks following bone manipulation in oral surgery that are important in preventing infection, loss of the blood clot and/or dry socket formation.
Digital panoramic radiographs might have been a better choice than digital periapical radiographs, as the 2 surgical sites would be represented on 1 film, eliminating the need for normalization between the sites. The disadvantage of digital panoramic radiographs is that these films have a 20 to 25% distortion factor because it is an extra-oral film, as opposed to the intra-oral individual (periapical) radiographs.The digital periapical radiograph was chosen over the panoramic radiograph due to the lower distortion, which results from being in close proximity to the site being evaluated. The CT scans might have exhibited greater differences between the PRF treated sites and the control sites, had they been obtained. Similarly Digital substraction radiography and histomorphometry have provided more sensitive methods of assessing bone healing but are quite invasive and expensive especially in a resource limited environment.
The results of the present study suggest that topical application of autologous PRF gel has a beneficial effect on the osseous healing of extraction sockets after third molar surgery but may not minimize the postoperative sequelae after 3rd molar surgery as its use was found to be associated with increased postoperative pain and swelling . However, a larger sample size in a multicenter study may be necessary before its routine use in extraction socket can be justified
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