YBJOM-4663; No. of Pages 5
ARTICLE IN PRESS Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Platelet-rich fibrin: the benefits Yuvika Raj Kumar a,∗ , Sujata Mohanty a , Mahesh Verma b , Raunaq Reet Kaur b,1 , Priyanka Bhatia c , Varun Raj Kumar c , Zainab Chaudhary a a b c
Department of Oral & Maxillofacial Surgery, Maulana Azad Institute of Dental Sciences, New Delhi, 110002, India Maulana Azad Institute of Dental Sciences, New Delhi, 110002, India Private Dental Practice, New Delhi, India
Accepted 14 October 2015
Abstract Current published data presents confusing results about the effects of platelet-rich fibrin on bone, and there is a need for studies that throw light on its effect. Our main objective therefore was to evaluate (by fractal analysis) osseous regeneration in extraction sockets with and without platelet-rich fibrin in a study with a substantial sample and a reliable technique to calibrate its effects on bone cells. We also assessed the soft tissue response. Thirty-four patients had their bilaterally impacted third molars (68 surgical sites) extracted in this split-mouth study, following which platelet-rich fibrin was placed in one of the sockets. Patients were followed up clinically and radiographically, and a pain score and fractal analysis were used to evaluate healing of soft tissue and bone, respectively. We conclude that platelet-rich fibrin improves healing of both soft and hard tissues. Although osseous healing did not differ significantly between the groups, healing of soft tissue as judged by the pain score was significantly better in the experimental group. © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Platelet rich fibrin (PRF); Fractal analysis; Osseous regeneration
Introduction Biological additives regulate inflammation and increase healing postoperatively,1 and the use of fibrin adhesives has been well-documented during the past three decades. However, their use has been controversial because of the risk of cross-infection and the tedious protocols involved in their preparation.
∗
Corresponding author. Tel.: +91 8860724307. E-mail addresses: [email protected] (Y.R. Kumar), [email protected] (S. Mohanty), [email protected] (M. Verma), [email protected] (R.R. Kaur), [email protected] (P. Bhatia), [email protected] (V.R. Kumar), [email protected] (Z. Chaudhary). 1 Present address: UCLA School of Dentistry, Los Angeles, California, USA.
The difficulties encountered in manufacturing fibrin adhesives led to the evolution of platelet-rich plasma and further simplification of the procedure resulted in platelet-rich fibrin, which has all the components that permit optimal recovery and healing. Numerous studies have been conducted in which platelet-rich fibrin has been used at different sites including implants, extraction sockets, and bone grafts. Most of these concluded that it seems to accelerate physiological healing.2,3 After in-depth evaluation of the established literature, the authors have tried to answer the following questions: how much does platelet-rich fibrin help, and if it accelerates physiological healing, then at what stage of the postoperative period does it affect it? Although recent studies have evaluated the efficacy of platelet-rich fibrin, there is a dearth of evidence about the actual amount of benefit a healing site gets from it. The pioneers have stressed the inadequate documentation of
http://dx.doi.org/10.1016/j.bjoms.2015.10.015 0266-4356/© 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kumar YR, et al. http://dx.doi.org/10.1016/j.bjoms.2015.10.015
Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),
YBJOM-4663; No. of Pages 5
2
ARTICLE IN PRESS Y.R. Kumar et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
interaction between fibrin and osseous cells,3 and Sunitha and Munirathnam called for more studies to evaluate its effects.4 Gurbuzer et al wondered if it might improve bony healing in impacted third molars, and suggested that further investigation is required about the effect of crystal-like particles on the outer surface of the platelet-rich fibrin,5 and another study complained that papers about platelet-rich fibrin and its subtypes are confusing.6 To answer these questions and to provide more information we have evaluated the quantity of bone formed with and without the addition of platelet-rich fibrin at third molar extraction sites by applying fractal analysis. We have also evaluated the soft tissue response by measuring the pain score, and studied a sample of sufficient size, which was lacking in previous studies. Fractal analysis gives a numerical value to the quality of bone formed and so helps to give a more accurate interpretation of the results. It is a method for describing complex shapes and structural patterns and is expressed numerically as the fractal dimension, which has been used on periapical radiographs as a simple descriptor of the complex architecture of cancellous bone7 and seems to be relatively insensitive to the alignment and exposure of the film.8 It is a non-invasive indicator of bony regeneration and remodelling,7 and is a convenient and economical way to assess the results of treatment. To our knowledge this is one of the first papers to combine the use of platelet-rich fibrin in extraction sockets and fractal analysis to evaluate the regeneration of bone.
Fig. 1. Bilateral extraction sockets with and without platelet-rich fibrin.
Fig. 2. Fractal analysis (D value=quantity of bone).
Patients and methods The main criterion for inclusion of patients in this study was bilateral impacted mandibular third molars of similar difficulty. The initial sample consisted of 66 patients aged 18-40 years, and those with routine laboratory tests and platelet counts within the reference ranges were included in the study. Patients gave their informed consent for the procedure and for withdrawal of blood for preparation of platelet-free fibrin. In accordance with inclusion and exclusion criteria 42 of the 66 patients were included in the study and further underwent radiographic examinations. All patients had bilateral mandibular third molars removed, which involved a Terrence-ward incision followed by raising of a flap and removal of an adequate amount of bone depending on the type of impaction. Subsequently, platelet-rich fibrin was prepared according to Choukroun’s protocol,1 and placed in one of the sockets chosen at random (Fig. 1); the sockets were closed primarily. To avoid bias, a single surgeon did all the operations. All patients were prescribed antibiotics and analgesics, and sutures were removed a week later. Patients were followed up for the assessment of pain (numerical pain score), 9 infection, and extrusion of the graft on postoperative days 1 and 3, and weeks 1 and 4. Please cite this article in press as: Kumar YR, et al. http://dx.doi.org/10.1016/j.bjoms.2015.10.015
Fig. 3. Intraoral periapical view immediately postoperatively.
Radiographs were taken immediately postoperatively, and 2, 4, and 6 months later. Radiographic evaluation by fractal analysis Radiographic evaluation was made by taking digital radiographs (Radiovisiograph-RVG) with a lead mesh that help to locate the region of interest at the same place for each follow-up intraoral periapical film (Figs. 2 and 3). These digital images were saved in JPEG format, and the calculations of the fractal dimension for analysis were made using Image J 1.38x software.10 The reference for selecting the same region of interest was a definite point on the second molar (the cementoenamel junction of the distal surface). On every follow-up digital image, equal numbers of boxes were counted from this reference point towards the centre of the extraction socket. These images were subsequently processed according to the method described by White and Rudolph.11
Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),
YBJOM-4663; No. of Pages 5
ARTICLE IN PRESS Y.R. Kumar et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
3
Table 1 Median (IQR) pain scores (n = 34 in each group)
Fig. 4. Intraoral periapical view six months postoperatively.
Finally, a box-counting method 12 was used to calculate the D value that indicated the quantity of bone (Fig. 4).
Time
Experimental
Control
1 day 3 days 1 week 4 weeks
3.0 (2.0 – 3.25) 1 (0 to 2) 0 (0 to 0) 0 (0 to 0)
6.0 (5.7 to 7.0) 4 (3 to 5) 1 (1 to 2) 0 (0 to 0)
The pain score as a reflection of healing of soft tissue differed significantly between the control and experimental group (p = 0.00) at all follow-up intervals (day 1, day 3, and week 1) except the 4th week (Table 1). There was only one case of infection and that was in the control group. Discussion
Statistical analysis Data are expressed as mean (SD) or median (IQR), as appropriate. A linear mixed model with first order autoregressive correlation structure was applied to calculate the results for D values obtained from the software. To remove the baseline effect on values from fractal analysis, the baseline value was subtracted from these time points at each subsequent time point. We calculated 95% CI or used the Wilcoxon rank sum test for analysis, as appropriate. Probabilities of less than 0.05 were accepted as significant.
Results Of the 42 patients included in the study, eight were lost to follow-up at different times, which left us with a study sample of 34 patients. After the baseline effect had been removed, we found no significant difference between the experimental and control group (p=0.24). The values for fractal analysis were 0.03 (95% CI -0.02 to 0.08) higher in the experimental group across the time points compared with the control, but the difference was not significant. The mean (SD) change in D value for the control group at 2, 4, and 6 months was 0.11(0.10), 0.16(0.11) and 0.19(0.12), respectively, and for the experimental group 0.13(0.12), 0.19(0.13) and 0.23(0.12) (Fig. 5).
Fig. 5. Graph showing results of fractal analysis at 2, 4, and 6 months postoperatively. Blue=experimental, red=control.
Please cite this article in press as: Kumar YR, et al. http://dx.doi.org/10.1016/j.bjoms.2015.10.015
Our aim was to conduct a study that would contribute to the existing body of evidence about the beneficial effects of platelet-rich fibrin on healing of bone and soft tissue. Numerous papers have mentioned the inadequacy of data about its effects, although some have shown the favourable effect on soft tissue which is consistent with our results. However, the interaction between osseous cells and fibrin has not been clear. The highlights of our study were the use of fractal analysis to evaluate the osseous healing of extraction sockets, and a good sample size, comprising 68 surgical sites. The fractal dimension offers a potential means of quantifying changes in alveolar bone mineral content in dental radiographs13 and an increase in the fractal dimension indicated an increase in the complexity of the trabecular bone.14 We found that the D value for the experimental group was higher by 0.02 at 2 months compared with the D value in the immediate postoperative period. At 4 and 6 months the values were higher by 0.03 and 0.04, respectively, compared with the control group. These numbers show that plateletrich fibrin gradually increases the osseous healing at every follow-up, and the mean value remains consistently higher in the experimental group. Singh et al15 did similar research on 40 surgical sites, where they observed acceleration in healing of both soft tissue and bone. They used a method different from ours for the assessment of bone, and the patients were followed up for 3 months. They suggested a longer follow-up period with a larger study sample and our study provides this. Gurbuzer et al made a scintigraphic evaluation of osteoblastic activity in extraction sockets treated with platelet-rich fibrin. Their study was done on 28 surgical sites with four weeks’ follow-up. They concluded that platelet-rich fibrin might not lead to improved bony healing but suggested further investigations and more studies to evaluate it.5 The results of the pain score showed that patients in the experimental group experienced significantly less pain and discomfort (p = 0.00) than those in the control group. There
Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),
YBJOM-4663; No. of Pages 5
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ARTICLE IN PRESS Y.R. Kumar et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
was only one case of infection and that was in the control group. Our results are in accordance with a study conducted by Hoaglin et al, who evaluated the prevention of localised osteitis with and without platelet-rich fibrin in mandibular third molars. Although the sample size in their study was large, the assessment was limited to the soft tissue component, with a follow-up of 7-10 days. The results showed a significant reduction in the incidence of localised osteitis in the platelet-rich fibrin group.16 In another study conducted by Gassling et al17 the results showed that platelet-rich fibrin has a supportive effect on the immune system, because it is able to stimulate defence mechanisms. This could be the reason that we had no case of infection in the experimental group. An in vitro study of Choukron’s platelet-rich fibrin also reported less infection with its use.18 There has been an ongoing debate about which platelet product is most effective, particularly platelet-rich plasma and platelet-rich fibrin. Analyses have shown that plateletrich plasma incorporates more platelets/ml than platelet-rich fibrin, but recent studies have shown that the latter has a strong fibrin structure and mechanical properties that optimally support the transplanted mesenchymal cells and allow for slow release of growth factors over a period of 7 days.18,19 Platelet-rich plasma, however, provides a sudden release of growth factors after which the concentrations of growth factor fall. In addition, platelet-rich plasma is more expensive and involves addition of foreign agents such as thrombin. All these factors make it inconvenient to use. Platelet-rich fibrin is the new biomaterial with many applications. It is an autogenous material with an inherent strength to support growth factors for timely and optimum release. It is user-friendly and economical, and has huge potential to be used routinely to reduce postoperative discomfort. It may also be used to hasten natural healing in immunocompromised patients, those taking drugs that interfere with natural healing, and those with a history of radiotherapy. As minimal cost is involved, it can be used for all types of patients. In conclusion, the results of our study add weight to those that advocate the use of platelet-rich fibrin. We found definite clinical advantages with respect to the healing of soft tissues. As far as bone was concerned, there was an increase in quantity in the experimental group throughout the study period. Platelet-rich fibrin offers a natural way of augmenting soft and hard tissues. The authors recommend more studies that evaluate it’s nature and effects. With further clarity, wider applications can be discovered for platelet-rich fibrin for enhancement of hard and soft tissue healing.
Conflict of interest None Please cite this article in press as: Kumar YR, et al. http://dx.doi.org/10.1016/j.bjoms.2015.10.015
Ethics statement/confirmation of patients’ permission The study was conducted according to the principles of the Declaration of Helsinki. All patients gave written informed consent to participation.
Acknowledgement The study was financed by the Government of India Department of Science and Technology DST-WOS(A), New Delhi, India.
References 1. Dohan DM, Choukroun J, Diss A, et al. Platelet-rich fibrin (PRF): a second generation platelet concentrate. Part I: technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;10:E37–44. 2. Choukroun J, Diss A, Simonpieri A, et al. Platelet-rich fibrin (PRF): a second generation platelet concentrate. Part IV: clinical effects on tissue healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:E56–60. 3. Sammartino G, Tia M, Marenzi G, et al. Use of autologous platelet rich plasma (PRP) in periodontal defect treatment after extraction of mandibular third molars. J Oral Maxillofac Surg 2005;63: 766–70. 4. Sunitha Raja V, Munirathnam Naidu E. Platelet-rich fibrin: evolution of a second generation platelet concentrate. Indian J Dent Res 2008; 19:42–6. 5. Gurbuzer B, Pikdoken L, Tunali M, et al. Scintigraphic evaluation of osteoblastic activity in extraction sockets treated with platelet-rich fibrin. J Oral Maxillofac Surg 2010;68:980–9. 6. Del Corso M, Vervelle A, Simonpieri A, et al. Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 1: Periodontal and dentoalveolar surgery. Curr Pharm Biotechnol 2012;13: 1207–30. 7. Bollen AM, Taguchi A, Hujoel PP, et al. Fractal dimension on dental radiographs. Dentomaxillofac Radiol 2001;30:270–5. 8. Shrout MK, Potter BJ, Hildebolt CF. The effect of image variations on fractal dimension calculations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:96–100. 9. McCaffery M, Beebe A. Pain: clinical manual for nursing practice. St. Louis: Mosby; 1989. 10. ImageJ 1.38x software (US National Institutes of Health, http://rsb.info.nih.gov/nih-image) (last consulted 12 October 2015). 11. White SC, Rudolph DJ. Alterations of the trabecular pattern of the jaws in patients with osteoporosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:628–35. 12. Ergun S, Saracoglu A, Guneri P, et al. Application of fractal analysis in hyperparathyroidism. Dentomaxillofac Radiol 2009;38:281–8. 13. Southard TE, Southard KA, Jakobsen JR, et al. Fractal dimension in radiographic analysis of alveolar process bone. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:569–76. 14. Heo MS, Park KS, Lee SS, et al. Fractal analysis of mandibular bony healing after orthognathic surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:763–7. 15. Singh A, Kohli M, Gupta N. Platelet rich fibrin: a novel approach for bone regeneration. J Oral Maxillofac Surg 2012;11:430–4. 16. Hoaglin DR, Lines GK. Prevention of localized osteitis in mandibular third-molar sites using platelet-rich fibrin. Int J Dent 2013; 2013:875380.
Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),
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17. Gassling VL, Acil Y, Springer IN, et al. Platelet-rich plasma and plateletrich fibrin in human cell culture. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:48–55. 18. Dohan Ehrenfest DM, Diss A, Odin G, et al. In vitro effects of Choukroun’s PRF (platelet-rich fibrin) on human gingival fibroblasts, dermal prekeratinocytes, preadipocytes, and maxillofacial osteoblasts in
Please cite this article in press as: Kumar YR, et al. http://dx.doi.org/10.1016/j.bjoms.2015.10.015
5
primary cultures. Oral Surg Oral Med Oral Pathol Oral Radiod Endod 2009;108:341–52. 19. He L, Lin Y, Hu X, et al. A comparative study of platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) on the effect of proliferation and differentiation of rat osteoblasts in vitro. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:707–13.
Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),
ARTICLE IN PRESS Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Platelet-rich fibrin: the benefits Yuvika Raj Kumar a,∗ , Sujata Mohanty a , Mahesh Verma b , Raunaq Reet Kaur b,1 , Priyanka Bhatia c , Varun Raj Kumar c , Zainab Chaudhary a a b c
Department of Oral & Maxillofacial Surgery, Maulana Azad Institute of Dental Sciences, New Delhi, 110002, India Maulana Azad Institute of Dental Sciences, New Delhi, 110002, India Private Dental Practice, New Delhi, India
Accepted 14 October 2015
Abstract Current published data presents confusing results about the effects of platelet-rich fibrin on bone, and there is a need for studies that throw light on its effect. Our main objective therefore was to evaluate (by fractal analysis) osseous regeneration in extraction sockets with and without platelet-rich fibrin in a study with a substantial sample and a reliable technique to calibrate its effects on bone cells. We also assessed the soft tissue response. Thirty-four patients had their bilaterally impacted third molars (68 surgical sites) extracted in this split-mouth study, following which platelet-rich fibrin was placed in one of the sockets. Patients were followed up clinically and radiographically, and a pain score and fractal analysis were used to evaluate healing of soft tissue and bone, respectively. We conclude that platelet-rich fibrin improves healing of both soft and hard tissues. Although osseous healing did not differ significantly between the groups, healing of soft tissue as judged by the pain score was significantly better in the experimental group. © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Platelet rich fibrin (PRF); Fractal analysis; Osseous regeneration
Introduction Biological additives regulate inflammation and increase healing postoperatively,1 and the use of fibrin adhesives has been well-documented during the past three decades. However, their use has been controversial because of the risk of cross-infection and the tedious protocols involved in their preparation.
∗
Corresponding author. Tel.: +91 8860724307. E-mail addresses: [email protected] (Y.R. Kumar), [email protected] (S. Mohanty), [email protected] (M. Verma), [email protected] (R.R. Kaur), [email protected] (P. Bhatia), [email protected] (V.R. Kumar), [email protected] (Z. Chaudhary). 1 Present address: UCLA School of Dentistry, Los Angeles, California, USA.
The difficulties encountered in manufacturing fibrin adhesives led to the evolution of platelet-rich plasma and further simplification of the procedure resulted in platelet-rich fibrin, which has all the components that permit optimal recovery and healing. Numerous studies have been conducted in which platelet-rich fibrin has been used at different sites including implants, extraction sockets, and bone grafts. Most of these concluded that it seems to accelerate physiological healing.2,3 After in-depth evaluation of the established literature, the authors have tried to answer the following questions: how much does platelet-rich fibrin help, and if it accelerates physiological healing, then at what stage of the postoperative period does it affect it? Although recent studies have evaluated the efficacy of platelet-rich fibrin, there is a dearth of evidence about the actual amount of benefit a healing site gets from it. The pioneers have stressed the inadequate documentation of
http://dx.doi.org/10.1016/j.bjoms.2015.10.015 0266-4356/© 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kumar YR, et al. http://dx.doi.org/10.1016/j.bjoms.2015.10.015
Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),
YBJOM-4663; No. of Pages 5
2
ARTICLE IN PRESS Y.R. Kumar et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
interaction between fibrin and osseous cells,3 and Sunitha and Munirathnam called for more studies to evaluate its effects.4 Gurbuzer et al wondered if it might improve bony healing in impacted third molars, and suggested that further investigation is required about the effect of crystal-like particles on the outer surface of the platelet-rich fibrin,5 and another study complained that papers about platelet-rich fibrin and its subtypes are confusing.6 To answer these questions and to provide more information we have evaluated the quantity of bone formed with and without the addition of platelet-rich fibrin at third molar extraction sites by applying fractal analysis. We have also evaluated the soft tissue response by measuring the pain score, and studied a sample of sufficient size, which was lacking in previous studies. Fractal analysis gives a numerical value to the quality of bone formed and so helps to give a more accurate interpretation of the results. It is a method for describing complex shapes and structural patterns and is expressed numerically as the fractal dimension, which has been used on periapical radiographs as a simple descriptor of the complex architecture of cancellous bone7 and seems to be relatively insensitive to the alignment and exposure of the film.8 It is a non-invasive indicator of bony regeneration and remodelling,7 and is a convenient and economical way to assess the results of treatment. To our knowledge this is one of the first papers to combine the use of platelet-rich fibrin in extraction sockets and fractal analysis to evaluate the regeneration of bone.
Fig. 1. Bilateral extraction sockets with and without platelet-rich fibrin.
Fig. 2. Fractal analysis (D value=quantity of bone).
Patients and methods The main criterion for inclusion of patients in this study was bilateral impacted mandibular third molars of similar difficulty. The initial sample consisted of 66 patients aged 18-40 years, and those with routine laboratory tests and platelet counts within the reference ranges were included in the study. Patients gave their informed consent for the procedure and for withdrawal of blood for preparation of platelet-free fibrin. In accordance with inclusion and exclusion criteria 42 of the 66 patients were included in the study and further underwent radiographic examinations. All patients had bilateral mandibular third molars removed, which involved a Terrence-ward incision followed by raising of a flap and removal of an adequate amount of bone depending on the type of impaction. Subsequently, platelet-rich fibrin was prepared according to Choukroun’s protocol,1 and placed in one of the sockets chosen at random (Fig. 1); the sockets were closed primarily. To avoid bias, a single surgeon did all the operations. All patients were prescribed antibiotics and analgesics, and sutures were removed a week later. Patients were followed up for the assessment of pain (numerical pain score), 9 infection, and extrusion of the graft on postoperative days 1 and 3, and weeks 1 and 4. Please cite this article in press as: Kumar YR, et al. http://dx.doi.org/10.1016/j.bjoms.2015.10.015
Fig. 3. Intraoral periapical view immediately postoperatively.
Radiographs were taken immediately postoperatively, and 2, 4, and 6 months later. Radiographic evaluation by fractal analysis Radiographic evaluation was made by taking digital radiographs (Radiovisiograph-RVG) with a lead mesh that help to locate the region of interest at the same place for each follow-up intraoral periapical film (Figs. 2 and 3). These digital images were saved in JPEG format, and the calculations of the fractal dimension for analysis were made using Image J 1.38x software.10 The reference for selecting the same region of interest was a definite point on the second molar (the cementoenamel junction of the distal surface). On every follow-up digital image, equal numbers of boxes were counted from this reference point towards the centre of the extraction socket. These images were subsequently processed according to the method described by White and Rudolph.11
Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),
YBJOM-4663; No. of Pages 5
ARTICLE IN PRESS Y.R. Kumar et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
3
Table 1 Median (IQR) pain scores (n = 34 in each group)
Fig. 4. Intraoral periapical view six months postoperatively.
Finally, a box-counting method 12 was used to calculate the D value that indicated the quantity of bone (Fig. 4).
Time
Experimental
Control
1 day 3 days 1 week 4 weeks
3.0 (2.0 – 3.25) 1 (0 to 2) 0 (0 to 0) 0 (0 to 0)
6.0 (5.7 to 7.0) 4 (3 to 5) 1 (1 to 2) 0 (0 to 0)
The pain score as a reflection of healing of soft tissue differed significantly between the control and experimental group (p = 0.00) at all follow-up intervals (day 1, day 3, and week 1) except the 4th week (Table 1). There was only one case of infection and that was in the control group. Discussion
Statistical analysis Data are expressed as mean (SD) or median (IQR), as appropriate. A linear mixed model with first order autoregressive correlation structure was applied to calculate the results for D values obtained from the software. To remove the baseline effect on values from fractal analysis, the baseline value was subtracted from these time points at each subsequent time point. We calculated 95% CI or used the Wilcoxon rank sum test for analysis, as appropriate. Probabilities of less than 0.05 were accepted as significant.
Results Of the 42 patients included in the study, eight were lost to follow-up at different times, which left us with a study sample of 34 patients. After the baseline effect had been removed, we found no significant difference between the experimental and control group (p=0.24). The values for fractal analysis were 0.03 (95% CI -0.02 to 0.08) higher in the experimental group across the time points compared with the control, but the difference was not significant. The mean (SD) change in D value for the control group at 2, 4, and 6 months was 0.11(0.10), 0.16(0.11) and 0.19(0.12), respectively, and for the experimental group 0.13(0.12), 0.19(0.13) and 0.23(0.12) (Fig. 5).
Fig. 5. Graph showing results of fractal analysis at 2, 4, and 6 months postoperatively. Blue=experimental, red=control.
Please cite this article in press as: Kumar YR, et al. http://dx.doi.org/10.1016/j.bjoms.2015.10.015
Our aim was to conduct a study that would contribute to the existing body of evidence about the beneficial effects of platelet-rich fibrin on healing of bone and soft tissue. Numerous papers have mentioned the inadequacy of data about its effects, although some have shown the favourable effect on soft tissue which is consistent with our results. However, the interaction between osseous cells and fibrin has not been clear. The highlights of our study were the use of fractal analysis to evaluate the osseous healing of extraction sockets, and a good sample size, comprising 68 surgical sites. The fractal dimension offers a potential means of quantifying changes in alveolar bone mineral content in dental radiographs13 and an increase in the fractal dimension indicated an increase in the complexity of the trabecular bone.14 We found that the D value for the experimental group was higher by 0.02 at 2 months compared with the D value in the immediate postoperative period. At 4 and 6 months the values were higher by 0.03 and 0.04, respectively, compared with the control group. These numbers show that plateletrich fibrin gradually increases the osseous healing at every follow-up, and the mean value remains consistently higher in the experimental group. Singh et al15 did similar research on 40 surgical sites, where they observed acceleration in healing of both soft tissue and bone. They used a method different from ours for the assessment of bone, and the patients were followed up for 3 months. They suggested a longer follow-up period with a larger study sample and our study provides this. Gurbuzer et al made a scintigraphic evaluation of osteoblastic activity in extraction sockets treated with platelet-rich fibrin. Their study was done on 28 surgical sites with four weeks’ follow-up. They concluded that platelet-rich fibrin might not lead to improved bony healing but suggested further investigations and more studies to evaluate it.5 The results of the pain score showed that patients in the experimental group experienced significantly less pain and discomfort (p = 0.00) than those in the control group. There
Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),
YBJOM-4663; No. of Pages 5
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ARTICLE IN PRESS Y.R. Kumar et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
was only one case of infection and that was in the control group. Our results are in accordance with a study conducted by Hoaglin et al, who evaluated the prevention of localised osteitis with and without platelet-rich fibrin in mandibular third molars. Although the sample size in their study was large, the assessment was limited to the soft tissue component, with a follow-up of 7-10 days. The results showed a significant reduction in the incidence of localised osteitis in the platelet-rich fibrin group.16 In another study conducted by Gassling et al17 the results showed that platelet-rich fibrin has a supportive effect on the immune system, because it is able to stimulate defence mechanisms. This could be the reason that we had no case of infection in the experimental group. An in vitro study of Choukron’s platelet-rich fibrin also reported less infection with its use.18 There has been an ongoing debate about which platelet product is most effective, particularly platelet-rich plasma and platelet-rich fibrin. Analyses have shown that plateletrich plasma incorporates more platelets/ml than platelet-rich fibrin, but recent studies have shown that the latter has a strong fibrin structure and mechanical properties that optimally support the transplanted mesenchymal cells and allow for slow release of growth factors over a period of 7 days.18,19 Platelet-rich plasma, however, provides a sudden release of growth factors after which the concentrations of growth factor fall. In addition, platelet-rich plasma is more expensive and involves addition of foreign agents such as thrombin. All these factors make it inconvenient to use. Platelet-rich fibrin is the new biomaterial with many applications. It is an autogenous material with an inherent strength to support growth factors for timely and optimum release. It is user-friendly and economical, and has huge potential to be used routinely to reduce postoperative discomfort. It may also be used to hasten natural healing in immunocompromised patients, those taking drugs that interfere with natural healing, and those with a history of radiotherapy. As minimal cost is involved, it can be used for all types of patients. In conclusion, the results of our study add weight to those that advocate the use of platelet-rich fibrin. We found definite clinical advantages with respect to the healing of soft tissues. As far as bone was concerned, there was an increase in quantity in the experimental group throughout the study period. Platelet-rich fibrin offers a natural way of augmenting soft and hard tissues. The authors recommend more studies that evaluate it’s nature and effects. With further clarity, wider applications can be discovered for platelet-rich fibrin for enhancement of hard and soft tissue healing.
Conflict of interest None Please cite this article in press as: Kumar YR, et al. http://dx.doi.org/10.1016/j.bjoms.2015.10.015
Ethics statement/confirmation of patients’ permission The study was conducted according to the principles of the Declaration of Helsinki. All patients gave written informed consent to participation.
Acknowledgement The study was financed by the Government of India Department of Science and Technology DST-WOS(A), New Delhi, India.
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