|ORIGINAL ARTICLE - COMPARATIVE STUDY
|Year : 2015 | Volume
| Issue : 2 | Page : 213-218
Comparison of platelet rich plasma and synthetic graft material for bone regeneration after third molar extraction
Dipesh B Nathani1, Joyce Sequeira2, B H. Sripathi Rao2
1 Department of Oral and Maxillofacial Surgery, Vaidik Dental College, Daman, Diu, India
2 Department of Oral and Maxillofacial Surgery, Yenepoya Dental College, Mangalore, Karnataka, India
|Date of Web Publication||5-Feb-2016|
Dr. Dipesh B Nathani
404, Sakar Apartment, Near Terapanth Bhavan, City Light Road, Surat - 395 007, Gujarat
Aims: To compare the efficacy of Platelet rich plasma and synthetic graft material for bone regeneration after bilateral third molar extraction. Material and Methods: This study was conducted in 10 patients visiting the outpatient department of Oral & Maxillofacial Surgery, Yenepoya Dental College & Hospital. Patients requiring extraction of bilateral mandibular third molars were taken for the study. Following extraction, PRP (Platelet Rich Plasma) was placed in one extraction socket and synthetic graft material in form granules [combination of Hydroxyapatite (HA) and Bioactive glass (BG)] in another extraction socket. The patients were assessed for postoperative pain and soft tissue healing. Radiological assessment of the extraction site was done at 8, 12 and 16 weeks interval to compare the change in bone density in both the sockets. Results: Pain was less on PRP site when compared to HA site. Soft tissue evaluation done using gingival healing index given by Landry et al showed better healing on PRP site when compared to HA site. The evaluation of bone density by radiological assessment showed the grey level values calculated at 4 months at the PRP site were comparatively higher than HA site. Conclusion: The study showed that the platelet rich plasma is a better graft material than synthetic graft material in terms of soft tissue and bone healing. However a more elaborate study with a larger number of clinical cases is very much essential to be more conclusive regarding the efficacy of both the materials.
Keywords: Bioactive glass, bone density, hydroxyapatite, mandibular third molar extraction, pain, platelet rich plasma
|How to cite this article:|
Nathani DB, Sequeira J, Rao B H. Comparison of platelet rich plasma and synthetic graft material for bone regeneration after third molar extraction. Ann Maxillofac Surg 2015;5:213-8
|How to cite this URL:|
Nathani DB, Sequeira J, Rao B H. Comparison of platelet rich plasma and synthetic graft material for bone regeneration after third molar extraction. Ann Maxillofac Surg [serial online] 2015 [cited 2020 Jun 1];5:213-8. Available from: http://www.amsjournal.com/text.asp?2015/5/2/213/175762
| Introduction|| |
Bone is often subjected to various damages leading to its regeneration or repair. Repair restores the bone to its original form and function. In the case of extraction socket healing, there is resorption of alveolar bone leading to decrease in ridge volume and alteration of ridge contour that consequently impairs prosthetic rehabilitation. Special attention should be given for healing of bone following third molar extraction as it is associated with periodontal defects on the distal surface of an adjacent second molar. Several biocompatible graft materials have been used to combat above healing defects, which include allografts, alloplasts, autografts or xenografts. All these materials are being researched to know their capability of improving clinical outcomes.
Synthetic graft materials mainly comprise of calcium phosphate ceramics, which have a composition similar to bone mineral. Hydroxyapatites (HAs) were considered to be the most useful  until; Larry Hench developed a material using silica (glass) incorporated with calcium and phosphorous to fuse broken bones that came to be known as “bioactive glass”(BG). Both synthetic HA and BG are now combined to be known as “bioactive ceramics.” Both these materials have osteoconductive properties,, The major advantages of these grafts are their biocompatibility and potential to offer an unlimited supply of bone substitutes, the absence of donor site infection and decreased operative time.
Platelet-rich plasma (PRP) has been used and researched extensively for bone regeneration following a breakthrough study done by Marx et al. PRP is an autologous concentration of human platelets in a small volume of plasma. Various growth factors are released by activated platelets which include angiopoietin-2, connective tissue-activating peptide III, epidermal growth factor, factor V, factor XI, factor XIII, fibrinogen, basic fibroblast growth factor, fibronectin, insulin-like growth factor-I, osteocalcin, P-selectin (also called GMP-140), platelet-derived endothelial cell growth factor (or thymidine phosphorylase), platelet-derived growth factor, serotonin, transforming growth factor-b1 (TGF-b1), thrombospondin-1, vascular endothelial growth factor, and von Willebrand factor. All these factors contribute to improve soft- and hard-tissue healing; hence, PRP has been used for bone regeneration by various clinicians.,,
Autologous grafts, demineralized bone matrix, synthetic grafts, and PRP have been used alone or in combination with earlier studies for bone regeneration., Both HA and BG have been used in past synergistically with PRP for the treatment of intrabony defects., The unique feature of this study is that efficacy of PRP and synthetic granules (50% HA and 50% BG) have been evaluated individually for bone regeneration after bilateral third molar extraction.
| Materials and Methods|| |
The present study was undertaken at the Department of Oral and Maxillofacial, Surgery, Yenepoya Dental Hospital. Ethical Committee clearance was procured from University Ethics Committee. A total of 10 subjects requiring bilateral extraction of mandibular third molar were selected. The following criteria were followed in selecting the patients:
- Age group 18–40 years
- Male and female patients
- ASA grade 1 patient
- Subjects having vertical impaction of bilateral mandibular third molars
- Surgical site free from any active infection
- Cases where primary closure of the wound was possible.
An informed consent was taken from each subject.
The synthetic biomaterial used in this study was a new generation composite bioactive material containing silica, calcium and phosphorus made through a nonconventional processing method - “the sol-gel process.” It is an indigenously prepared, resorbable synthetic porous ceramic granular graft with a particle size in the range of 150–500 microns and a pore size range of 100–200 microns. These granules are made up of 50% BG and 50% HA mixture. The material was procured in sterile packs [Figure 1].
|Figure 1: Synthetic granules (50% hydroxyapatite and 50% bioactive glass)|
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Preparation of platelet rich plasma gel
Under all aseptic conditions, 10 ml of blood was drawn intravenously from the antecubital region of patients forearm using disposable syringes. The collected blood was transferred to plastic tubes containing 1 ml of 3.2% sodium citrate solution as an anticoagulant.
PRP was prepared by double centrifugation method using clinical table top centrifugation machine. The whole blood was first centrifuged at 2400 r.p.m. for 10 min. The supernatant formed was platelet poor plasma (PPP) and buffy coat. This PPP and Buffy coat layer were then collected in a fresh tube using 10 ml syringe and centrifuged at 3600 r.p.m. for 15 min. The upper half of the supernatant was discarded, and the lower half was mixed thoroughly to yield PRP. This PRP obtained was in liquid form, so to make it a gel it was mixed with 0.5–1 cc of 10% calcium chloride (CaCl2) [Figure 2].
In this study, both the impacted teeth were removed at same operating day. Under all aseptic conditions and local anesthesia impacted third molars were removed by a single operator. After removal of both the teeth, PRP gel was placed in one socket and HA granules in another socket, which was selected randomly by lottery method. The wound was closed primarily with 3–0 black braided silk.
Patients were recalled on day 1, day 3, day 7, 8 weeks, 12 weeks, and 16 weeks postoperatively for follow-up study. The pain was evaluated at day 1, day 3, and day 7 using the visual analogue scale (VAS).
Evaluation of soft-tissue healing was done at day 1, day 3, and day 7 by healing index given by Landry et al. The scores were given on the basis of tissue color, bleeding on palpation, epithelialization of incision margins and presence or absence of suppuration.
Intraoral periapical radiographs were taken and digitised using the standardized technique as advocated by Peretz et al. Radiographs were obtained at baseline, and at 8th week, 12th week, 16th weeks postoperatively to assess and compare gray level histogram between PRP sites and HA site. X-ray machine was used at 65–70 kVp and 10 mA. These radiographs were placed on a light viewing box and digitalized using canon EOS 1000d camera (ISO 200, F = 8, shutter speed = 1/125). The camera images were taken at same radiograph camera distance with a camera holder jig. The gray level histograms were obtained with the help of ImageJ (National institute of Health) software.,
| Results|| |
After analysis of the data the following observations were made: There were 9 (90%) male subjects and 1 (10%) female subjects who had participated in the study. The subjects who had participated in the study were in the age range from 18 years to 28 years, with a mean age of 22 years.
Assessment of pain
Assessment of pain by VAS on the 1st day showed mean pain score of 1.8 in PRP site and 2.7 in HA site, on 3rd day mean pain score was 1.1 in PRP site and 2 in HA site, on 7th day score was 0 in both PRP and HA site. By doing the Mann–Whitney U-test for comparison of PRP and HA it was found that there was a significant difference in pain on day 1 and day 3 with less pain in PRP site [Graph 1].
Assessment of healing index of soft-tissue
Assessment of soft-tissue healing by healing index showed the mean score on the 1st day of 3.4 in PRP site, 2.7 in HA site, on 3rd day 3.8 in PRP site and 3.1 in HA site, on 7th day mean score of 4.9 in PRP site and 4 in HA site. By doing the Mann–Whitney U-test for comparison of PRP and HA it was found that there was a significant difference in healing on day 1 and day 3 with better healing in PRP site [Graph 2].
At 8 weeks: Blending of bone margins in three patients in PRP site and four patients in HA site [Figure 3]a and [Figure 3]b Chi-square test showed P value of 0.033. The trabecular bone formation was seen in nine patients at PRP site and nine patients at HA site.
|Figure 3: (a) Radiograph (intraoral periapical) at 8 weeks postoperatively-hydroxyapatite site. (b) Radiograph (intraoral periapical) at 8 weeks postoperatively-platelet rich plasma site|
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At 12 weeks: Blending of bone margins was seen in all the 10 patients in both PRP and HA sites [Figure 4]a and [Figure 4]b. The trabecular bone formation was seen in all 10 patients in PRP site and HA site.
|Figure 4: (a) Radiograph (intraoral periapical) at 12 weeks postoperatively-hydroxyapatite site. (b) Radiograph (intraoral periapical) at 12 weeks postoperatively-platelet rich plasma site|
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At 16 weeks: Blending of bone seen in all 10 patients in both PRP site and HA site [Figure 5]a and [Figure 5]b. The trabecular bone formation was seen in all 10 patients in both the sites.
|Figure 5: (a) Radiograph (intraoral periapical) at 16 weeks postoperatively-hydroxyapatite site. (b) Radiograph (intraoral periapical) at 16 weeks postoperatively-platelet rich plasma site|
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Assessment of gray level value at 16 weeks showed that the average gray scale value for PRP site was 144.29 and for HA site it was 138.04 [Graph 3].
| Discussion|| |
Autogenous bone is regarded as the gold standard for the repair of bony defects in the maxillofacial region  as it is the most biocompatible and osteoinductive material. However, the quantity of autogenous bone that can be harvested is limited  and so in large defects, synthetic graft materials do the needful. There are numerable autologous and alloplastic materials available, but PRP and synthetic granules (50% HA and 50% BG) were used individually in this study because both materials increase TGF-beta expression that leads to the rapid bone formation.,
PRP is an autologous concentration of human platelets in a small volume of plasma also known as autologous platelet gel. PRP can be prepared by two methods; one using single centrifugation protocol and the other using double centrifugation protocol. Nagata et al. concluded in their study that double centrifugation protocol resulted in higher platelet concentrations, and so it was used in this study. Activation of PRP leads to the release of various growth factors that promote soft-tissue and bone healing. This activation can be done by various agents such as CaCl2 alone, CaCl2 along with bovine thrombin or human thrombin as reported in the literature. Tsay et al. reported the use of synthetic peptide known as peptide-6 SFLLRN (thrombin receptor activating peptide) for activation of PRP. Some studies indicate the bovine thrombin may cause the development of antibodies to clotting factors V, XI, and thrombin results in the risk of life-threatening coagulopathies. Thus, CaCl2 alone was mixed with PRP to prepare platelet gel.
The granules used in this study are made up of 50% BG and 50% HA mixture. The glassy part (BG) is 17% silicon, 53% calcium (as CaO) and 30% P2O5. The glass is composited with an equal quantity (50%) of synthetic HA. The mixture is processed in the form of porous granules so as to have the desired in vivo bioactivity. Salms et al. and Froum et al. have concluded through their studies that both HA and BG have positive effect on socket healing.,
We carried out a clinical trial to compare the effectiveness of PRP and synthetic granules in terms of better soft-tissue healing and bone regeneration. Several factors affect bone healing that may vary from cases to cases, and so to avoid such bias both materials were placed in different extraction sockets of a single individual in the same sitting. Soft-tissue healing was evaluated using gingival healing index by Landry et al., which showed better soft-tissue healing of extraction sockets with PRP as compared to HA sockets. This finding is supported by the authors who in their study reported that there was decreased the rate of alveolar osteitis, objectively faster soft-tissue flap healing and decreased swelling in the extraction sockets treated with PRP.,
All the procedures were done comfortably under local anesthesia on an outpatient basis. Both the materials not only fill and obliterate the extraction socket defect but also help in gaining height of the alveolar bone. It was observed that both the materials were biocompatible and did not show any exaggerative tissue reaction or any postoperative infection. These findings were in accordance with earlier studies done by Matsui et al. and Shapoff et al.,
Bone density can be measured by calculating the gray level value on the radiograph. All the radiographs were taken and digitalized using the standardised technique as stated by Peretz et al. Gray level values can be measured with the help of different software available such as ImageJ (National Institute of Health), and Adobe Photoshop software (Adobe Systems).,, The radiological assessment in the follow-up period of 4 months showed radiological evidence of osseous ingrowths into both the extraction socket defect. The evaluation of bone density was done by ImageJ software. The radiological assessment showed the grey level values calculated at 4 months at the PRP site 144.29 were comparatively higher than the HA site 138.04.
When comparing, PRP is safer as it is autologous source than homologous like HA. PRP takes care of soft-tissue healing along with bone regeneration that may be the reason that there was no opening of socket margins as seen in this study. However, in cases of HA a proper closure is mandatory, if failed to do so, there might be exfoliation of the material as seen in three of our cases. PRP contains various factors as mentioned earlier, so this could explain the better soft-tissue and bone healing in PRP as seen in our study. PRP is cost-effective than HA.
The limitation of this study was that the sample size was small consisting of 10 patients and 4 months postoperative follow-up is a short duration, as has been reported in the literature where a long-term follow-up of 2–5 years has been done. Hence, a more elaborate study of the materials with a larger number of clinical cases and long-term follow-up is very much essential to be more conclusive regarding the biocompatibility and efficacy of the material in bone regeneration. A further histological sampling following clinical study would be useful to study the nature of the regenerated bone.
| Conclusion|| |
In our study, PRP gave better results than synthetic biomaterial in terms of soft-tissue and bone healing. However, for the success of the procedure, a perfect soft-tissue closure and avoidance of infection are mandatory. Both the materials accelerate bone regeneration in the extraction sockets. PRP is safe, cost-effective when compared to the synthetic biomaterial.
We would like to thank all the staff of Oral and Maxillofacial Surgery Department, Yenepoya Dental College, and Yenepoya Medical College Laboratory. We would also like to thank Dorthom Medi Dents Pvt. Ltd., for providing material.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Intini G. The use of platelet-rich plasma in bone reconstruction therapy. Biomaterials 2009;30:4956-66.
Artzi Z, Tal H, Dayan D. Porous bovine bone mineral in healing of human extraction sockets. Part 1: Histomorphometric evaluations at 9 months. J Periodontol 2000;71:1015-23.
Kugelberg CF, Ahlström U, Ericson S, Hugoson A, Kvint S. Periodontal healing after impacted lower third molar surgery in adolescents and adults. A prospective study. Int J Oral Maxillofac Surg 1991;20:18-24.
Oltramari PV, Navarro Rde L, Henriques JF, Taga R, Cestari TM, Janson G, et al.
Evaluation of bone height and bone density after tooth extraction: An experimental study in minipigs. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:e9-16.
Albanese A, Licata ME, Polizzi B, Campisi G. Platelet-rich plasma (PRP) in dental and oral surgery: From the wound healing to bone regeneration. Immun Ageing 2013;10:23.
Maté-Sánchez de Val JE, Mazón P, Guirado JL, Ruiz RA, Ramírez Fernández MP, Negri B, et al.
Comparison of three hydroxyapatite/β-tricalcium phosphate/collagen ceramic scaffolds: An in vivo
study. J Biomed Mater Res A 2014;102:1037-46.
Costantino PD, Friedman CD. Synthetic bone graft substitutes. Otolaryngol Clin North Am 1994;27:1037-74.
Krishnan V, Lakshmi T. Bioglass: A novel biocompatible innovation. J Adv Pharm Technol Res 2013;4:78-83.
Morio D, Lew D, Krizan K, Keller JC. Short-term bone responses to hydroxyapatite cement. Implant Dent 2002;11:376-82.
Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:638-46.
Soffer E, Ouhayoun JP, Anagnostou F. Fibrin sealants and platelet preparations in bone and periodontal healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:521-8.
Tözüm TF, Keçeli HG, Serper A, Tuncel B. Intentional replantation for a periodontally involved hopeless incisor by using autologous platelet-rich plasma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:e119-24.
Vivek GK, Sripathi Rao BH. Potential for osseous regeneration of platelet rich plasma: A comparitive study in mandibular third molar sockets. J Maxillofac Oral Surg 2009;8:308-11.
Arenaz-Búa J, Luaces-Rey R, Sironvalle-Soliva S, Otero-Rico A, Charro-Huerga E, Patiño-Seijas B, et al.
A comparative study of platelet-rich plasma, hydroxyapatite, demineralized bone matrix and autologous bone to promote bone regeneration after mandibular impacted third molar extraction. Med Oral Patol Oral Cir Bucal 2010;15:e483-9.
Okuda K, Tai H, Tanabe K, Suzuki H, Sato T, Kawase T, et al.
Platelet-rich plasma combined with a porous hydroxyapatite graft for the treatment of intrabony periodontal defects in humans: A comparative controlled clinical study. J Periodontol 2005;76:890-8.
Carvalho MD, Suaid FF, Santamaria MP, Casati MZ, Nociti FH Jr., Sallum AW, et al.
Platelet-rich plasma plus bioactive glass in the treatment of intra-bony defects: A study in dogs. J Appl Oral Sci 2011;19:82-9.
Nagata MJ, Messora MR, Furlaneto FA, Fucini SE, Bosco AF, Garcia VG, et al.
Effectiveness of two methods for preparation of autologous platelet-rich plasma: An experimental study in rabbits. Eur J Dent 2010;4:395-402.
Tözüm TF, Demiralp B. Platelet-rich plasma: A promising innovation in dentistry. J Can Dent Assoc 2003;69:664.
Isik K, Unsal A, Kalayci A, Durmus E. Comparison of three pain scales after impacted third molar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:715-8.
Landry RG, Turnbull RS, Howley T. Effectiveness of benzydamyne HCl in the treatment of periodontal postsurgical patients. Res Clin Forum 1988;10:105-18.
Jankovic SM, Zoran AM, Lekovic MC, Bozidar DS, Kenneyy BE. The use of platelet – Rich plasma in combination with connective tissue grafts following treatment of gingival recessions. Periodontal Pract Today 2007;4:63-71.
Peretz B, Kaffe I, Amir E. Digital images obtained with a digital camera are not associated with a loss of critical information – A preliminary study. Br Dent J 2009;206:E9.
Goes P, Lima AP, Melo IM, Rêgo RO, Lima V. Effect of atorvastatin in radiographic density on alveolar bone loss in wistar rats. Braz Dent J 2010;21:193-8.
Grandi T, Garuti G, Guazzi P, Sapio U, Forabosco A. A longitudinal, multi-centre study on the relationship between insertion torque and peri-implant bone resorption. J Clin Pract Oral Implantol 2010;1:33-40.
Aaboe M, Pinholt EM, Hjørting-Hansen E. Healing of experimentally created defects: A review. Br J Oral Maxillofac Surg 1995;33:312-8.
Nkenke E, Weisbach V, Winckler E, Kessler P, Schultze-Mosgau S, Wiltfang J, et al.
Morbidity of harvesting of bone grafts from the iliac crest for preprosthetic augmentation procedures: A prospective study. Int J Oral Maxillofac Surg 2004;33:157-63.
Salms G, Salma I, Skagers A, Zigurs G, Pilmane M, Vetra J, et al
. Hydroxyapatite ceramics for restoration of alveolar bone. J Craniomaxillofac Surg 2008;36 Suppl 1:S262.
Marx RE. Platelet-rich plasma: Evidence to support its use. J Oral Maxillofac Surg 2004;62:489-96.
Tsay RC, Vo J, Burke A, Eisig SB, Lu HH, Landesberg R. Differential growth factor retention by platelet-rich plasma composites. J Oral Maxillofac Surg 2005;63:521-8.
Zehnder JL, Leung LL. Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. Blood 1990;76:2011-6.
Manitha BN, Varma HK, Kumary TV, Suresh B, Annie J. Cell interaction studies with novel bioglass coated hydroxyapatite porous blocks. Trends Biomater Artif Organs 2006;2:108-14.
Froum S, Cho SC, Rosenberg E, Rohrer M, Tarnow D. Histological comparison of healing extraction sockets implanted with bioactive glass or demineralized freeze-dried bone allograft: A pilot study. J Periodontol 2002;73:94-102.
Mancuso JD, Bennion JW, Hull MJ. Platelet-rich plasma: A preliminary report in routine impacted mandibular third molar surgery and the prevention of alveolar osteitis. J Oral Maxillofac Surg 2003;61:40.
Matsui Y, Ohno K, Michi K, Tachikawa T. Histomorphometric examination of healing around hydroxylapatite implants in 60Co-irradiated bone. J Oral Maxillofac Surg 1994;52:167-72.
Shapoff CA, Alexander DC, Clark AE. Clinical use of a bioactive glass particulate in the treatment of human osseous defects. Compend Contin Educ Dent 1997;18:352-4, 356, 358.
Damante JH, Da S Guerra EN, Ferreira O Jr. Spontaneous resolution of simple bone cysts. Dentomaxillofac Radiol 2002;31:182-6.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
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