Assessment of Platelet Rich Fibrin Combined With Bioactive Glass on Healing Of Bony Defect after Cyst Enucleation

Yahia Atef Koraiem^1, Aliaa M Habib², Laila Mostafa Omara³, Mohammad Ibrahim El-Faramawey⁴

^{1.Postgraduate student "master degree" In Oral & Maxillofacial Surgery, Faculty of Oral and Dental medicine, Cairo University.}

^{2.Associate lecturer Department of Oral & Maxillofacial Surgery, Faculty of Oral and Dental medicine, Cairo University.}

^{3.Professor, Department of Oral & Maxillofacial Surgery, Faculty of Oral and Dental medicine, Cairo University.}

^{4.Lecturer, Department of Oral & Maxillofacial Surgery, Faculty of Oral and Dental medicine, Cairo University.}

*Corresponding Author: Aliaa M Habib. Associate lecturer Department of Oral & Maxillofacial Surgery, Faculty of Oral and Dental medicine, Cairo University.

Received Date:  March 16, 2021

Publication Date: April 01, 2021

DOI:10.1027/mards.2021.0151

Abstract

The purpose of this study is to clinically and radiographically evaluate the osteoconductive effect of platelet-rich fibrin (PRF) combined with bioactive glass as graft material on repairing the surgically created bony defects following cysts enucleation. The study was conducted on twelve patients suffering from cystic lesions. The cystic lesions were surgically enucleated according to the standard techniques and the resulting surgical defects were grafted using bioactive glass. The patients were divided randomly into two groups of six patients each. The first group was grafted with bioactive glass along with platelet-rich fibrin (PRF) while the second group which is the control group was grafted using bioactive glass only. Data were collected and statistically analyzed by applying a T-test. The bioactive glass exhibits bioactive behavior, without escape or migration of the granules from the cystic defects. The addition of PRF to bioactive glass allograft accelerates the regenerative capacity of bone Comparing the two groups, the Independent sample t-test showed no statistically significant difference in the bone density between the two groups throughout the study period.

Introduction & Review

Surgical removal of cysts is applied by two clinical methods, either enucleation and marsupialization. Many materials help to increase the strength of the bone replacement material such as the bioactive glass. Bioactive glass is one of the bioactive ceramics, mainly used in the form of granules as bone fillers.(1,3)

Bone and bioactive ceramics are bonded together by the appetite layer found on the surface which is in contact with interstitial fluids. (4,5) The glass surface on the bioactive glass can stimulate the formation of the bone when it comes in direct contact with the bone. (6) The bioactive glass has a positive effect on the osteoblasts, and this effect is demonstrated by the calcium phosphate layer on the formation of the bone matrix. (7)

Recent studies have revealed new bone production on the bioactive glass granules that were found away from the deficient walls, this could reveal that the bone repair is not only achieved through the osteoconductive feature of the bone substitute material but also the cellular differentiation in the particles internal chamber, because there is no bond between the newly formed bone and the preexisting bone. It was found that there was active deposition on the particle surface. (8) PRF was first developed in France by Choukroun (9) et al. for specific use in oral and maxillofacial surgery. It’s a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. (10) Fibrin sealing mimics the last phases of the coagulation cascade, where fibrinogen is converted to fibrin. This supports the natural wound healing process. Platelets contain potent growth factors that stimulate new tissue synthesis, e.g. platelet-derived growth factor (PDGF) PRF preparation. (11)

This technique requires neither anticoagulant nor bovine thrombin (nor any other gelling agent). It’s centrifuged blood without any addition. To obtain PRF, a table centrifuge and a collection kit from Process are needed. (9)

PATIENTS AND METHODS

The present study was conducted on twelve patients suffering from cystic lesions. They were selected from the outpatient clinic; Oral and Maxillofacial Surgery Department, Faculty of Oral and Dental Medicine, Cairo University.

The cystic lesions were surgically enucleated according to the standard techniques and the resulting surgical defects were grafted using bioactive glass. The patients were divided randomly into two groups’ six patients each. In the recent work cystic lesions of at least 2x1 cm size as measured on a digital panoramic x-ray were corrected to 1:3

• Group I: was grafted with bioactive glass along with platelet rich fibrin (PRF).
• Group II: The control group was grafted using bioactive glass only.

All the patients were entailed about the cyst enucleation and a bone substitute implantation in the bony cavity and they gave their approval to participate in the written consent.

Patients were informed about unfavorable conditions for cyst enucleation and given the necessary information about the procedure including its prognosis, potential hazards, and complications.

Criteria for patients’ selection

Patients were physically healthy and with no known history of systemic or local disease that might affect bone grafting and the healing process.

Pre-operative Evaluations

Medical & Dental Evaluation

Clinical Examination: Extra-oral & intra-oral examinations were carried out.

Radiographic Examination: Preoperative digital panoramic radiographs were obtained for each patient to Determine the cyst dimensions and reveal the proximity of the cyst margins to the maxillary sinus and the nasal floor in the maxilla as well as the proximity to the inferior dental canal and its contents in the mandible.

Surgical Procedure

Surgical access by enucleation was obtained through trans-oral flap design in all cases. (Fig.1 A)

In group No. I (PRF+ Bioactive glass)

The PRF prepared as follows:  blood samples were taken according to the PRF protocol without anticoagulant in 10 ml tubes which are immediately centrifuged.

Circulating thrombin transforms it into fibrin. A fibrin clot is then obtained in the middle of the tube (Fig.3 A). 

PRF is then separated from the red corpuscles and the acellular plasma layers by a scissor or any sharp instrument and mixed with the bioactive glass (Fig.3 B, C).

The mixture of bioactive glass and PRF is added to the bony cavity (Fig.1 C).

In group no. II (Bioactive glass only)

Bioactive glass granules were mixed with saline and the mix was used to fill up the cavity (Fig.2 C)

The mucoperiosteal flap was repositioned back and sutured in position using three zero black silk sutures.

Radiographic Evaluation

The radiographic evaluation was performed for each Patient by obtaining a digital panorama. All digital radiographs were taken with the same machine and the same parameters, under the slandered instructions & recommendations.

All radiographs were performed at the following intervals: immediate postoperative, 3 months, and 6 months.

Radiographic Image Analysis

Panoramic images were analyzed by one radiologist. Each image was analyzed twice by the same examiner at two different sessions with two weeks interval in between.

Radiodensitometric analysis obtained by measurement of the relative bone density using the sigma view, Digora software.

Statistical Analysis

Statistical analysis was performed using STATA special edition version 10, Stata Corp., U.S.A.  Data were represented as mean + standard deviation. Paired Student t-test was used to compare two variables within the same group. Independent samples t-test was used to compare variables between the two studied groups. The result was considered statistically significant if the p-value was less than 0.05.

Results

A total of 12 patients (4 males and 8 females) suffering from jaw cysts of almost (2x1cm) in dimensions. Patients underwent surgical enucleation of the cystic lesions and the bony cavities had been obliterated using Bioactive glass only in Group II (The control group), while Group I (The study group) was grafted with Bioactive glass and platelet-rich fibrin (PRF).

All patients were included for statistical analysis. Data were reported as mean + standard deviation. Patients age, gender, site, and cyst type were shown in the following tables and figures:

Descriptive Statistics

Age:

   Group I: Table (1) represents patients’ age of group I. Group I age ranged between 17 and 43  years old with mean age of approximately 32.3± 9.7 years old.

There was no statistically significant difference between the two studied groups regarding the age P=0.64.

The study consisted of cyst lesions of different types and in both the maxilla and mandible. It was found that the maxilla is a more common site for the oral cysts with a percentage of 91.7% compared to the mandible which had a percentage of 8.3% only. All the cases of this study were maxillary cysts except one case only of a mandibular cyst. All the cysts in this study were found to be radicular cysts except one case of a dentigerous cyst. The percentage of radicular cysts was 97.1% while the percentage of the dentigerous cysts was 8.3% only.

Radiodensity Results

Group I

The mean value of the bone density measured immediately postoperatively was 149.514 + 29.757HU. By the end of the third month, it was reduced to 138.2 + 3.49HU. While, after six months at the end of the follow-up period, it reached 146.93 + 33.22HU. 

The percentage change of the bone density throughout the study was -7.56% and –1.7% by the end of the third and the sixth months respectively. There was no statistically significant difference in the mean values of the bone density three months postoperatively p= 0.12 as well as six months postoperatively p= 0.71 (Table 5) (fig.4).

Group II

The mean value of the bone density measured immediately postoperatively was 131.78 + 21.99HU. Three months postoperative, it was reduced to 126.42 + 29.19HU. While by the end of the follow-up period in the sixth month it reached 138.05 + 16.36HU. The percentage change of the bone density at three months was   -4.07%, where it was 4.76% at the sixth months postoperatively. There was no statistically significant difference in the mean values of the bone density three months postoperatively p= 0.73 as well as six months postoperatively p= 0.49 (Table 4) (fig.5).

Comparing the two groups

Independent sample t-test showed no statistically significant difference in the bone density between the two groups throughout the study. p=0.5, 0.1, 0.1 immediate, three and six months postoperative respectively (Table 5) (Fig.6).

Discussion

Cauley et al., (2003)12, reports concluded that jaw cysts were observed to be affecting both males and females constantly. However, In the present study females were more affected than males, unlike what was found in the other studies by Jones et al., (2006)13, Avelar et al., (2009)14, and Açikgöz et al., (2012)15, who concluded that males are usually more affected than females because men customarily have worse oral hygiene habits and are more susceptible to trauma than women.

According to the location & type of the cystic lesion, our findings reported 91.7% of radicular cystic lesions in the maxilla, except one case was located in the mandible. All the cystic lesions were found to be radicular cysts except one case was a dentigerous cyst. In agreement with Bodner et al (2011)16, a retrospective study of 27 cystic jaw lesions in edentulous patients showed that the maxilla was more affected than the mandible, with radicular/residual cysts being the most common. Also, El-Gehani et al., (2008)17, reported that the maxilla was found to be more affected by cystic lesions than the mandible with a ratio of (1.3:1); especially the anterior part of the maxilla, which coincides with our findings.

The prevalence of odontogenic cysts was reported to be (54.7%) radicular as reported by the findings of Açikgöz et al., (2012)15, which were in agreement with our findings reported (100%), radicular cysts were the most common type. However, there was a disagreement with the above-mentioned studies, in the work done by Avelar et al (2009)14, who reported that the mandible was the most prevalent site by (56%). Regarding the ethnic background, almost 40% of the patients were of African descent, which was in agreement with the recent study, where all the subjects were African.

Bioactive glasses have high potential as scaffold materials as they stimulate bone cells to produce new bone, they are degradable in the body and they bond to bone. (Jones et al., 2007, Hench et al., 1993 & Oliveira et al., 1995)18-20. Bioglass is a scaffold that is thought to be required for three-dimensional tissue growth, our findings were in agreement with Jones’s study as the application of bioactive glass in the three-walled cystic defects stimulated the bone cells to produce new bone.

Platelet-rich fibrin matrix represented a simple and effective means of accelerating new bone growth in a variety of oral and dental applications without the disadvantages of barrier membranes, non-vital graft materials, or exogenous thrombin associated with other PRP systems9, 21.

The combined use of PRF and (β-TCP or demineralized bone matrix ) for bone augmentation in the treatment of periapical defects was an alternative for faster healing than using tricalcium phosphate or Osseograft alone 22, 23  However, the results gained in the present study have shown no statistically significant differences between using bioactive glass alone or when combined with platelet-rich fibrin.

 Zhao et al., (2012)24, reported that the combination of PRF and bioactive glass is an effective modality of regenerative treatment for radicular cysts at 4 months postoperatively. In the present study, clinical & radiographic assessment at 6 months post-operatively has shown a promising approach for augmenting cystic defects, whereas, no statistically significant difference was reported with the use of bioactive glass alone Bioactive glass particles mixed with saline were applied after cyst enucleation to fill intrabony cystic defects in the present study.

Upon implantation of the bioactive glass particles inside the intrabony defect, the material seemed to be coherent in the defect, easy to be manipulated and has a hemostasis effect. This is by the results stated by Abd-el azym and El Sherbiny, (1999)25 which proved the coherence of the glass inside the bony defect.

The test group patients were grafted with platelet-rich fibrin (PRF) along with bioactive glass.

It is hypothesized that the PRF has a natural fibrin framework that can protect growth factors from proteolysis according to Dohan et al., (2006)26. It is organized as a dense fibrin scaffold with a specific slow release of growth factors27.

The target of this study was to evaluate clinically and radiographically the efficacy of filling cystic defects with bioactive glass in combination with or without PRF. During the whole follow-up period, there were no signs of mucosal dehiscence, infection, or graft rejection were detected. Wound stability and infection control were of prime importance. This goes with the results stated by Nasr (2000)28.

The findings of the present study using direct digital radiography to measure the changes in the density of the grafted cystic bony defects in both groups through the specific follow-up periods: immediately, three then six months post-operatively. Direct digital radiography made both qualitative and quantitative visualization of bone density changes easy to be detected.29, 30.

As proven to be a more accurate, sensitive, and reliable alternative technique to routine x-rays, in the present study. Also, it offers a lower level of irradiation to the patient and decreases the time consumption for both the patient and operator.

Radiodensitometric analysis was obtained by measurement of the relative bone density using Digora software. The computerized image analysis system was found to be an appropriate tool in detecting changes in bone density as it provides numeric values for the progression of the healing process. This goes with the present study & the results confirmed by Delano et al., (2001)31 and Yoshioka et al., (2002)32.

Postoperative digital orthopantomography was taken immediately, 3 months than 6 months postoperatively to evaluate the bone density changes in the grafted former cyst cavity. Radio density measurement throughout the study showed a decrease in bone density after three months in both groups. This decrease in density was due to the formation of a soluble silica layer that is readily absorbed and excreted from the body. Also, excavation of the granule core by phagocytosis and early osteoid formation within the excavated chambers. That was coincident with the studies of Gaisser et al., (2002)33.

In both groups, the radiodensity raised again at the 6th month radiographic assessment. That increase in radiodensity was thought to be because of new bone formation after the invasion of osteoblasts as a result of the osteostimulatory effect of bioactive glass which is coincident with the studies of Schepers et al., (1991)34, Schepers et al., (1997)35, Furusawa et al., (1998)36, and Froum et al., (2002)37.

Comparing the two groups, the Independent sample t-test showed no statistically significant difference in the bone density between the two groups throughout the study. p=0.5, 0.1, 0.1 immediate, three and six months postoperative respectively. There are no many studies to compare these results with, however, Zhao et al., (2012)24, found out after grafting two cases of radicular cysts and bioactive and a follow-up of 7 months that PRF can improve periapical osseous healing as the fibrin matrix can guide the healing processes, but no statistical data was available to compare with. From the results gained in the recent study, bioactive glass can be used alone to augment the 3-walled cystic defects.

Conclusion

From the results of this study it could be concluded that:

1. The bioactive glass exhibits bioactive behavior, without escape or migration of the granules from the cystic defects. The formation of hydroxycarbonate apatite transformed, remodeled, and replaced by newly formed osseous tissue.

2. The addition of PRF to bioactive glass allograft accelerates the regenerative capacity of bone. Utilizing bioactive glass in conjunction with platelet-rich-fibrin membranes may be a reliable choice for osseous regeneration in cases of bony defects.

3. Platelet-rich fibrin matrix acts as a membrane with the property of healing benefits. Platelet-rich fibrin is an autologous preparation and found to be clinically effective and economical than any other available regenerative materials. It is cheap, easy manipulative as a bone defect filler.

4. The direct digital radiography system used in this study (digital system) proved to be an appropriate tool in assessing the density of the cystic bony defects. Direct digital radiographs can be used reliably in tracing the healing process in the cystic bony defects of the jaws.

References

1.Turunen T, Peltola J, Urpo A, Happonen RP: “Bioactive glass granules as a bone adjunctive material in maxillary sinus floor augmentation”. Clan Oral Impl Res; 15:259, 2004.

2.Hench LL, Ducheyne P: Bioactive ceramics: “In material characteristics versus in vivo behavior”. New York Academy of Sciences, New York; p.54, 1988.

3.Gatti AM, Valdrè G, Andersson ÖH: “Analysis of the in vivo reactions of a bioactive glass in soft, hard tissue”. Biomaterials; 15: 208, 1994.

4.Beckham CA, Greenlee Jr, Crebo AR: “Bone formation at a ceramic implant interfacing”. Calcified Tissue Research; 8:165, 1971.

5.Vrouwenvelder CA, Groot CG, Groot K: “Histological, biochemical evaluation of osteoblasts cultured on bioactive glass, hydroxyaptite, titanium alloy, stainless steel”. J Bomed Mater Res; 27:465, 1993.

6.Beckham CA, Greenlee Jr, Crebo AR: “Bone formation at a ceramic implant interfacing”. Calcified Tissue Research; 8:165, 1971.

7.Vrouwenvelder CA, Groot CG, Groot K: “Histological, biochemical evaluation of osteoblasts cultured on bioactive glass, hydroxyaptite, titanium alloy, stainless steel”. J Bomed Mater Res; 27:465, 1993.

8.Villaça HJ, Arthur B. Novaes Jr, De Souza LS, Taba Jr, Molina OG, Carvalho LT: “Bioactive- glass efficacy in the periodontal healing of intrabony defects in Monkeys”. Braz Dent, J.vol.16 no.1 Jan./Apr.2005.

9.Choukroun J, Diss A, Simonpieri A, Girard MO, Schoeffler C, Dohan SL: Platelet-rich fibrin (PRF): A second generation platelet concentrate, Part I: “Technological concepts and evolution”. Oral Surg Oral Med Oral Pathol Oral Radiol Endod; 37:101, 2006.

10.Raja S, Naidu E: Platelet rich fibrin: ”Evolution of a second generation platelet concentrate”. Indian J Dent Res; 19:42, 2008.

11.Clark RA: “Fibrin, wound healing, Ann N Y Acad Sci; 36:355, 2001”.

12.Cauley JA, Robbins J, Chen Z: Effects of estrogen plus progestin on risk of fracture and bone mineral density: “the Women's Health Initiative randomized trial”. JAMA; 290: 1729-38, 2003.

13.Jones JR, Gentleman E, Polak J: Medical Mineralogy and Geochemistry: “Bioactive Glass Scaffolds for Bone Regeneration ELEMENTS, V”. 3, p. (6): 393-399, 2007.Cawson RA, Odel EW: Cysts of the jaw: Cawson’s essentials of oral pathology and oral medicine, Churchill livingstone an imprint of Elesiver science limited Publishers,  spain; 102, 2002.

14.Avelar RL, Antunes AA, Carvalho RW, Bezerra PG, Oliveira Neto PJ, Andrade ES. “Odontogenic cysts: a clinicopathological study of 507 cases”. J Oral Sci; 51:581–586, 2009.

15.Açikgöz A., Uzun-Bulut E., Özden B., Gündüz K.: “Prevalence and distribution of odontogenic and nonodontogenic cysts in a Turkish Population”. Med Oral Patol Oral Cir Bucal.; 17(1): e108–e115, January 2012.

16.Bodner L, Manor E, Glazer M, Brennan PA: “Cystic lesions of the jaws in edentulous patients: analysis of 27 cases”. Br J Oral Maxillofac Surg.; 49(8):643-6, 2011 Filipowicz FJ, Page DG: The lateral periodontal cyst isolated periodontal defects. J. Periodontol; 53(3):145, 1982.

17.El Gehani R., Krishnan B., and Orafi H: “The Prevalence of Inflammatory and Developmental Odontogenic Cysts in a Libyan Population”. Libyan J Med; 3(2): 75–77, 2008.

18.Jones JR, Gentleman E, Polak J: “Medical Mineralogy and Geochemistry: Bioactive Glass Scaffolds for Bone Regeneration ELEMENTS, V”. 3, p. (6): 393-399, 2007.

19.Hench LL, Wilson J: “An introduction to bioceramics, 1st ed”. World Sci¬entific, Singapore; 1993.

20.Oliveira JM, Correia RN, Fernades MH: “Surface modifications of a glass and a glass-ceramic of the MgO-3CaO.P2O5-SiO2 system in a simulated body fluid”. Biomaterials; 16(11):849, 1995.

21.Lynch SE, de Castilla GR, Williams RC: “The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing”. J Periodontol; 62, (7):458–67, 1991.

22.Jayalakshmi KB, Agarwal S, Singh MP, Vishwanath BT, Krishna A, and Agrawa R: “Platelet-Rich Fibrin with β-Tricalcium Phosphate”. A Noval Approach for Bone Augmentation in Chronic Periapical Lesion: A Case Report. Case Reports in Dentistry Volume 2012, 2012.

23.Bhandari S, Ashwini TS, Naik R, Bandiwadekar T, Makandar S: Regenerative periapical surgery: “A case report”, Dental Hypotheses, Volume 4, Issue 2,p. 61-66, 20, 2013.

24.Zhao JH, Tsai CH, Chang YC: ”Management of radicular cysts using platelet-rich fibrin and bioactive glass: A report of two cases”. Journal of the Formosan Medical Association, 5, June 2012.

25.Abdel-Azym A and El-Sherbiny M: “Direct digital radiography and SPECT for evaluation of bioactive glass coated dental implants”. Egyptian Dental J; 45: 4189, 1999.

26.Dohan DM, Choukroun J, Diss A: Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part II: “Platelet-related biologic features”. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.101, (3) :e45-50, 2006.

27.Dohan DM, de Peppo GM, Doglioli P: Slow release of growth factors and thrombospondin-1 in Choukroun’s platelet-rich fibrin (PRF): “a gold standard to achieve for all surgical platelet concentrates technologies”. Growth Factors 27, (1):63-9, 2009

28.Nasr TA: “Clinical and digital radiographic evaluation of surface conditioned bioglass as an osteoconductive material in osseous defects in the jaw bone”. Thesis for Master Degree in Oral Surgery, Cairo University, 2000.

29.Kullrndroff B, Nilsson M: “Diagnostic accuracy of direct dental radiography for the detection of peripheral bone lesions”. Oral Surg. J Oral Surg Oral Med Oral Pathol.; 82:585, 1996.

30.Bardbet J, Messer HH: “Detectability of artificial periapical lesions using direct digital and conventional radiography”. J. Endod.; 24(12):837, 1998.

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