Evaluation of different platelet-rich concentrates effects on early soft tissue healing and socket preservation after tooth extraction

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JORMAS-748; No. of Pages 6 J Stomatol Oral Maxillofac Surg xxx (2019) xxx–xxx

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Original Article

Evaluation of different platelet-rich concentrates effects on early soft tissue healing and socket preservation after tooth extraction G. Ustaog˘lu a,*, D. Go¨ller Bulut b, K.C¸. Gu¨mu¨s¸ a a b

Department of Periodontology, Faculty of Dentistry, Bolu Abant I˙zzet Baysal University, Bolu, Turkey Department of Dentomaxillofacial Radiology, Faculty of Dentistry, Bolu Abant I˙zzet Baysal University, Bolu, Turkey

A R T I C L E I N F O

A B S T R A C T

Article history: Received 27 June 2019 Accepted 4 September 2019

Background: The present study aimed to analyze the early soft tissue healing characteristics and Fractal Dimension (FD) of extraction sockets preserved by Leukocyte-platelet-rich fibrin (L-PRF) and titanium prepared platelet-rich fibrin (T-PRF). Materials and methods: 57 single-tooth extraction sockets were included in the study, three groups were prepared: post-extraction sockets filled with L-PRF (n = 19) and T-PRF (n = 19), and control group; naturally healing sockets (n = 19). Three months after tooth extraction, FD measurement was made in the center of the healing socket. The Landry Wound Healing Index (LWHI) and H2O2 bubbling test results for the complete wound epithelization (CWE) rates were recorded 1 and 2 weeks postoperatively. All patients were asked to record a visual analog scale (VAS) value for pain and the number of analgesics taken during the 3 days after the extraction. Results: CWE using H2O2 test result showed a significantly lower rate in the controls than in L-PRF and TPRF groups at 1st week. At 2nd weeks, both of the test groups showed 100% CWE compared with only 40.7% in the control group. The VAS pain score was significantly higher in the control group than in L-PRF and T-PRF groups on the 1st day. However, no significant difference was found among the groups on 2nd day. FD value of control group was significantly lower than the L-PRF group and T-PRF group. Conclusions: T-PRF and L-PRF similarly enhanced wound epithelization and reduced postoperative discomfort at extraction sockets. The T-PRF procedure resulted in higher FD compared to the L-PRF and control group.

C 2019 Elsevier Masson SAS. All rights reserved.

Keywords: Extraction Fractals Platelet-rich fibrin Post-extractional healing preservation Radiography Socket preservation

1. Introduction Tooth extractions may be needed due to traumatic dental injury, unrestorable tooth caries, and progressive periodontal disease [1]. Extraction socket healing leads to vertical and horizontal ridge resorption that can make difficult implant installation in a prosthetically driven position and affect the functional and aesthetic outcomes negatively [2]. The most volumetric alterations of alveolar bone occur in the first three months after tooth extraction and result in a 50% reduction in the buccolingual dimension of the alveolar ridge during 1 year after tooth extraction. Decrement of the buccal wall is more significant than the lingual wall because the buccal bone is mostly composed of bundle bone and it loses its function after tooth extraction and is resorbed by osteoclasts [3]. The reduction of the alveolar bone volume may cause difficulty in placing the implant fixture in a * Corresponding author. E-mail address: [email protected] (G. Ustaog˘lu).

prosthetically suitable position and influence the functional and aesthetic outcomes negatively. To preserve or improve the original alveolar ridge dimensions and to provide an ideal implant location, alveolar socket preservation (ASP) procedures are often required [4]. Alveolar socket preservation (ASP) is a procedure in which biomaterials are placed in the socket of the extracted tooth at the time of extraction to minimize dimensional changes of hard and soft tissue after tooth loss [5]. Numerous different methodologies and materials have been reported, including autogenous, allogeneic, xenogeneic, and alloplastic bone grafts, barrier membranes due to the success in space maintenance, rapid bone turnover, biocompatibility and other materials like bone morphogenetic protein (BMP), platelet-rich plasma, platelet-rich fibrin (PRF), titanium prepared platelet-rich fibrin (T-PRF), and Emdogain [6– 11]. Leukocyte-Platelet-rich fibrin (L-PRF) first defined by Choukroun et al. [12] in France, has been attributed to as a secondgeneration platelet concentrate and has a simplified preparation

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Please cite this article in press as: Ustaog˘lu G, et al. Evaluation of different platelet-rich concentrates effects on early soft tissue healing and socket preservation after tooth extraction. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.09.005

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protocol without biochemical blood handling. It has several advantages in comparison traditionally prepared platelet-rich fibrin (PRF). Slow polymerization of PRF allows the accumulation of numerous growth factors like Platelet-Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), Transforming Growth Factor beta (TGFb), Insulin-like Growth Factor (IGF), cytokines such as; IL-1b, IL-4, IL-6 and Tumour necrosis factor-a (TNF-a) into the fibrin mesh. This fibrin mess allows more potent cell migration, proliferation, and tissue healing. By the slow and gradual release of these factors, hard and soft tissue healing is enhanced. Its chief advantages involve ease of preparation, low cost and lack of biochemical handling of harvested blood [13]. T-PRF method developed by Tunalı et al. [14] is based upon the hypothesis that titanium may activate platelets more effective than the silica activators used with glass tubes. It has a denser and thicker fibrin network than L-PRF. This fibrin structure provides prolonging intra-tissue fibrin resorption and releasing growth factors in a longer period [14]. T-PRF also has osteoinductive properties similar to those of bone and preserves tissue volume [15]. Rapid, complete soft tissue healing after tooth extraction minimizes surgical complications and enables subsequent implant placement. Thus, the post-extraction dimensional changes of the alveolar ridge have been largely researched in humans using clinical, histologic, histomorphometric and radiographic examinations [16–18]. The osseous fractal dimension (FD) analysis is a useful method to identify the trabecular bone microarchitecture by using readily available image analysis software, regions of interest (ROI) to be examined over the radiograph can be selected and the fractal analysis can be done easily and quickly [19]. A mathematical and morphological image processing system has been used in this method [20]. FD analysis has been used to identify and appreciate most structures on dental radiographs [21]. The authors want to contribute to the literature by assessing the efficiency of FD measurement on two-dimensional radiography in assessing wound healing with different socket protection methods. Thus, this study aimed to compare the early soft tissue healing characteristics and FD values of three different groups of healing extraction sockets filled with L-PRF, T-PRF, and control group on periapical intraoral radiographs taken 3 months after extraction.

the study were periodontal disease, severe decay, root fracture, endodontic complications, or trauma. Patients were recalled for a follow-up examination on the 3rd, 7th, 14th and 90th day after tooth extraction. Patients were advised to record their pain level using a visual analog scale (VAS) and the number of analgesics taken for 3 days after tooth extraction. The Landry wound healing index (LWHI) and H2O2 epithelization test were performed after 1 and 2 weeks by a blinded examiner. Fractal analysis was performed at 3 months after tooth extraction. 2.2. Randomization and blinding The extraction sites were randomly divided into three groups (two tests and one control) with the aid of digital software (RANDOM.ORG). The group was allocation concealed for each participant throughout the study to avoid bias. The investigators who performed clinical and radiographic measurements were blinded as to which treatment group the patient was assigned. 2.3. Landry Wound Healing Index (LWHI) The LWHI evaluates the extraction region based on tissue color, response to touch, the marginality of the incision line, and extent of the area. The rating is from 1 = very poor to 5 = excellent [22]. 2.4. H2O2 epithelization test Complete wound epithelization (CWE) was evaluated clinically using the H2O2 bubbling test, which is based on the principle that if the epithelium is discontinuous, H2O2 will diffuse into the connective tissue and catalase will act on the H2O2 to release water and oxygen, producing bubbles in the wound. The area to be evaluated is dried and 3% H2O2 is applied on the wound using a syringe. The appearance of bubbles suggests that the surgical site is not completely epithelialized. If there is no bubble, it is assumed that CWE has occurred. The rate of CWE is calculated as follows: CWE (%) = the number of sites with CWE (+)  100/total number of sockets. 2.5. Surgical procedures

2. Materials and methods 2.1. Study design Fifty-seven patients (29 women and 28 men) participated in this randomized, controlled clinical trial, which took place in the Department of Periodontology, Faculty of Dentistry, XX University. Patients subjected to single-tooth extraction were allocated to 3 groups: group 1: control group; naturally healing sockets (n = 19), L-PRF group; post-extraction socket filled with L-PRF (n = 19) and T-PRF group; post-extraction socket filled with T-PRF (n = 19). Before surgical procedures, all patients underwent a rigorous oral hygiene regimen, including non-surgical periodontal treatment to provide a suitable oral environment for wound healing sockets. Patients were included if: they were 18 years or older; needed a single-rooted tooth extraction with the persistence of 50% or more of bone support (anterior or premolar teeth); demanded a single implant-supported prosthetic restoration in a premolar or anterior site. Patient in lactating period or pregnant, use anticoagulant drugs or steroid, have bleeding disorders, autoimmune or immune proliferative disorders, smoking habit, poor oral hygiene and motivation and with an acute inflammation have were excluded from the study. The reasons for the extraction of teeth included in

To reduce study bias, a single examiner performed all surgical procedures. Following local anesthesia, the tooth was extracted using a flapless technique with as little trauma to the bone and soft tissue. After the tooth extraction, the granulation tissues were removed by bone curettes. A periodontal probe was then used to affirm the integrity of the extraction socket bone walls. L-PRF or TPRF was placed in the extraction socket and stabilized with 4-0 non-resorbable sutures (Trofilen, Dog˘san1, Turkey). Patients were prescribed 500 mg paracetamol for use if needed and disinfectant mouthwash (0.12% chlorhexidine) two times per day, for one week. All patients were told to follow a soft, warm and liquid diet, avoiding hot environment in the following hours. The sutures were removed after 7 to 10 days. 2.6. L-PRF and T-PRF preparation protocol The L-PRF was produced through single centrifugation of blood according to the protocol of Dohan Ehrenfest et al. [13] (Intra-Spin System, L-PRF kit, Intra-Lock, Boca-Raton, FL, USA) for 12 minutes at 2700 rpm. Blood was taken in 9 mL tubes, 30 minutes before the surgery, immediately centrifuged. For T-PRF, Blood was drawn into a 20mL injector and divided immediately into two grade IV sterile titanium tubes, each of which received 10 mL of blood. The tubes were positioned opposite one another and centrifuged at 2800 rpm

Please cite this article in press as: Ustaog˘lu G, et al. Evaluation of different platelet-rich concentrates effects on early soft tissue healing and socket preservation after tooth extraction. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.09.005

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for 12 min at room temperature. The L-PRF and T-PRF clot were carefully pulled out from the underlying layer containing red blood cells and put between two sterile gauze pads with adequate compression were applied to separate them from the serum to get the fibrin membranes. The sockets were fully filled with two or three fibrin membranes according to the space size. 2.7. Imaging procedure Intraoral periapical radiography was obtained 3 months after the ridge preservation procedure. All periapical radiographs were obtained using D-speed intraoral Photo Stimulable Phosphor Plates (PSPs) with the same intraoral X-ray Generator (CARESTREAM CS 2100). Exposure geometry was standardized using an apparatus that allowed the vertical angle of the X-ray to reach both the long axis of the tooth and the image receptor at 908, and the images were taken in parallel technique. Then, radiographs scanned with the same plate scanner (Du¨rr VistaScan mini view) and recorded as high-resolution Joint Photographic Experts Group (JPEG) format. 2.8. Fractal measurements FD analysis of each socket was performed using the boxcounting proposed method by White and Rudolph [22]. The measurement was made in the area corresponding to the center of the healing socket 3 months after tooth extraction and surgical procedures (Fig. 1). High-resolution periapical radiographs in JPEG formats were converted into tagged image file formats (TIFF). Each ROI is selected in a dimension of 18  19 pixels, cropped and duplicated. Gaussian Blur was used to remove the brightness changes, depending on the upper soft tissues and varying bone thicknesses. The resulting image was then subtracted from the original image. Bone marrow voids and trabeculae were separated by adding 128 gray values for each pixel location. After binary, erode, dilate, invert and skeletonize operations were performed, the FD was calculated (Fig. 2). All measurements were performed independently by an oral and maxillofacial radiologist with 6 years of experience and periodontist with 5 years of experience. To standardize the FD measurements, the observers were calibrated at the beginning of the study by re-evaluating randomly selected 10 periapical radiography images again after 2 weeks. The correlation coefficient

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for the assessment of intra-observer and inter-observer reliability were 0.832 and 0.897 respectively. 2.9. Statistical analysis Statistical analyses were done with SPSS for Windows SPSS1 v. 16.0 (IBM Corp., New York, NY; formerly SPSS Inc., Chicago, IL). Multiple comparisons were made by one way ANOVA-test and differences between the groups were evaluated by post-hoc Tukey test. Differences between men and women were assessed by independent sample t-test. Chi2-test was used to analyze the differences between independent categorical variables Numerical variables were compared by the Wilcoxon test. P < 0.05 was accepted as a statistical significance level.

3. Results A total of 57 patients (mean age 35.4  5.6) were included in the study, 29 of who were female (age mean 35.9  4.8) and 28 of who were male (mean age 34.9  6.4). According to LWHI results, in all groups, better values were found at 2nd weeks than 1st weeks (P < 0.05). But, no significant difference was found among the three groups in each week (Table 1). The results of complete wound epithelization using H2O2 test was shown in Table 1. At the 1st week, the rate was significantly lower in the controls than in L-PRF and T-PRF groups (P = 0.047). At 2nd weeks, both of the test groups showed 100% CWE compared with only 40.7% in the control group (P = 0.041). The VAS scores decreased gradually in all groups (Table 2). On the 1st day, the score was significantly higher in the control group than in L-PRF and T-PRF groups (P = 0.047). However, no significant difference was found among the groups on 2nd day (P = 0.054). There was no significant difference in the number of analgesics among the groups at any period (P > 0.05). The descriptive statistical values of the distribution of individuals according to groups, age, and fractal measurement are shown in Table 3. A significant difference was found between the fractal values of the 3 groups when we assessed all individuals without discrimination between male and female (P < 0.001). The FD value of the control group was lowest (FD value = 1.247), followed by the L-PRF group (FD value = 1.331) and the T-PRF group had the highest FD (FD value = 1.401).

Fig. 1. A. Periapical radiography of the socket taken on the day of extraction. B. Measurement of FD at the socket center on periapical radiography taken 3 months after tooth extraction.

Please cite this article in press as: Ustaog˘lu G, et al. Evaluation of different platelet-rich concentrates effects on early soft tissue healing and socket preservation after tooth extraction. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.09.005

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Fig. 2. Steps of fractal dimension analysis: blurred image of the cropped and duplicated region of interest (A), subtracted blurred image from the original image (B), addition of a gray value of 128 to each pixel location (C), binarization (D), erosion (E), dilatation (F), inversion (G), skeletonization (H).

Table 1 Landry Wound Healing Indexes and H2O2 test results (Complete Wound Epithelization). Groups Landry Wound Healing Indexes (mean  SD) Control L-PRF T-PRF P Complete Wound Epithelization (%) Control L-PRF T-PRF P

1st week

2nd week

P

3.21  0.66 3.58  0.63 3.69  0.51 0.058

4.38  0.49 4.59  0.51 4.71  0.50 0.061

0.046 0.045 0.040

10.1a 54.9b 70.1b 0.047

40.7 100 100 0.041

Statistically significance level is P < 0.05; a,b,c: different superscript letters indicate a significant difference between groups; SD: standard deviation.

Table 2 The VAS pain scores and the number of analgesics.

Groups

n

Mean age

Mean fractal

Min fractal

Max fractal

Std dev.

P

Control groupa L-PRF groupb T-PRF groupc

19 19 19

36.93 35.00 34.40

1.247a 1.331b 1.401c

1.115 1.220 1.311

1.350 1.399 1.487

0.151 0.107 0.135

< 0.001

Min: minimum; Max: maximum; Std Dev: standard deviation; different superscript letters indicate a significant difference between groups; statistically significance level is P < 0.05.

No significant difference was found between the mean age of the three groups (P = 0.451). The number of males and females were similar in the three groups. There was no significant difference between male and female in FD of all groups (P > 0.05). Also, there was no significant difference between genders in terms of LWHI and CWE values (Table 4). 4. Discussion

Parameters

Groups

1st day

2nd day

3rd day

VAS pain scores

Control L-PRF T-PRF P Control L-PRF T-PRF P

5.11  1.60a 3.30  2.07b 3.29  1.85b 0.047 1.47  1.11 0.89  0.84 0.79  0.65 0.061

1.01  1.44 0.48  0.92 0.47  0.62 0.054 0.32  0.70 0.07  0.33 0 0.069

0 0 0

The number of analgesics

Table 3 Descriptive values of the Fractal measurements according to groups.

0 0 0

a,b,c: different superscript letters indicate a significant difference between groups; statistically significance level is P < 0.05.

Currently, various techniques are used to prepare the socket after tooth extraction and these techniques require a certain amount of time to wait and may delay implant placement. Rapid resorption of autogenous grafts and lack of apposition and resorption synchronization of allogeneic materials are the most common problems in guided tissue regeneration [12]. Besides, radiological evaluation after graft membrane application may not give accurate results because the resorption time of the graft varies from person to person and can sometimes remain

Please cite this article in press as: Ustaog˘lu G, et al. Evaluation of different platelet-rich concentrates effects on early soft tissue healing and socket preservation after tooth extraction. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.09.005

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Table 4 Comparison of the descriptive values of the Fractal measurements, LWHI and CWE according to genders and group. Gender

Groups

n

Mean age

Fractal value Mean  SD

P

Mean  SD

P

%

P

Female

Control groupa L-PRF groupb T-PRF groupc Total Control groupa L-PRF groupb T-PRF groupc Total

9 10 10 29 10 9 9 28

38.71 37.14 32.50 35.90 35.38 33.13 36.57 34.91

1.25  0.71 1.31  0.64 1.40  0.56 1.31  0.91 1.24  0.61 1.34  0.28 1.39  0.62 1.33  0.76

< 0.001

4.35  0.48 4.50  0.50 4.70  0.50 4,51  0.49 4,41  0.50 4,68  0.51 4,72  0.50 4,60  0.50

> 0.05

40.5 100 100

> 0.05

Male

LWHI 2nd week

< 0.001

CWE 2nd week

40.9 100 100

Statistically significance level is P < 0.05; P-values indicate differences between genders; SD: standard deviation; a,b,c: different superscript letters indicate a significant difference between groups.

unresolved for months [23,24]. It affects the results of radiological measurement and assessment by radiopaque imaging on the radiograph when the graft is not resorbed. So, in the present study, we preferred L-PRF and T-PRF because they don’t give an image on radiography, they are autogenous and have regenerative properties, they do not cost like grafts and membrane applications, do not require second surgery area for acquisition of autogenous grafts and invasive procedures are not necessary except blood collection [15]. In this study, we compared the early soft tissue healing and trabecular structure of extraction sites treated with L-PRF, T-PRF, and untreated control sites. In the literature, studies reported that soft tissue healing was statistically better for sockets treated with Autologous Platelet Concentrates (APCs) at the seventh postoperative day [25,26]. Suttapreyasr and Leepong [9] applied L-PRF to the final extraction sockets and found that soft tissue healing was faster at four weeks than control. Dutta et al. [27] observed that the extraction sockets which L-PRF placed were associated with less pain, swelling and faster soft tissue healing on the third, seventh and fourth day compared to hydroxyapatite. Similarly, in our study, L-PRF and T-PRF groups showed higher Landry recovery scores, but not statistically significant. Most of the studies measured pain through VAS of ten points. While some studies reported statistical differences in pain reduction for the APC group [28,29], some studies showed no statistical differences [30,31]. In our study, VAS of T-PRF and L-PRF groups were lower than the control group. These may be related to the anti-inflammatory and antimicrobial activity of the platelet concentrates [32]. In socket healing, a secondary wound is formed, which may cause pain and discomfort until the connective tissue is completely covered by epithelium. We used L-PRF and T-PRF membranes to fill the socket. As a result, the area of secondary healing covered by the platelet concentrates showed a pattern similar to primary wound healing. In the literature, there were studies, which researched xenograft methods with the use of PRF or L-PRF in socket preservation by clinical and radiographic parameters [33,34]. De Angelis et al. [33] researched three clinical protocols: L-PRF alone, L-PRF mixed with a bone xenograft, and bone xenograft alone for alveolar ridge preservation on single posterior teeth. The L-PRF plus bone xenograft group had less vertical and horizontal bone resorption than the bone xenograft alone group at 6 months postoperatively. Kollati et al. [34] searched the effectiveness of naturally derived bovine hydroxyapatite combined with PRF matrix in socket preservation. They reported that the addition of PRF released growth factors that enhanced the wound healing process and maintained the dimensions. In the present study, we used L-PRF and T-PRF alone without any graft materials and found that they promoted early soft tissue healing and socket preservation by releasing numerous growth factors.

In previous studies, CBCT [17], panoramic radiography [18], periapical radiography [35], scintigraphy, and histopathologic methods [6–8,14] were used to assess the quality of bone. In recent years, FD analysis which provides information on whether there is a variation in bone microarchitecture like resorption, thickening or density changes in the trabeculae has become a popular method in evaluating the bone trabecular structure [36]. The high FD value indicates a more complex and dense bone structure, whereas the lower FD indicates a more porous bone structure [37]. It is easy to measure and calculate FD and the measurement region is subjectively determined. The obtained numerical values give objective information about the texture of the bone or bone-like structure. There are several studies evaluated FD on different patient groups [36,38]. In cases with osteoporotic changes in bone metabolism, FD values were found to be lower when compared to the control group [20,39]. Similarly, in the present study, significant differences were found between mean FD values of study groups; the mean FD in the control group was the lowest and the T-PRF group had the highest FD value. This indicates that L-PRF and T-PRF affect healing and bone remodeling positively. In our study, although soft and hard tissue changes after socket preservation revealed with clinical and radiographic evaluations, histological studies are needed to support these results. 5. Conclusion The results demonstrated that L-PRF and T-PRF accelerated early soft tissue healing and the T-PRF stimulated better maturation of bone or bone-like structures as compared with PRF and controls. Ethical statement The study protocol was approved by the Ethics Committee for Human Research of Bolu Abant I˙zzet Baysal University (number 2017/165). Informed consent was taken from all patients before the beginning of the study. Funding The authors declare that this study received no financial support. Disclosure of interest The authors declare that they have no competing interest.

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Please cite this article in press as: Ustaog˘lu G, et al. Evaluation of different platelet-rich concentrates effects on early soft tissue healing and socket preservation after tooth extraction. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.09.005