• Sonuç bulunamadı

Effect of locally applied bfgf on implant stability biomechanical evaluation of 2 different implant surfaces in rabbits

N/A
N/A
Protected

Academic year: 2021

Share "Effect of locally applied bfgf on implant stability biomechanical evaluation of 2 different implant surfaces in rabbits"

Copied!
8
0
0

Yükleniyor.... (view fulltext now)

Tam metin

(1)

Effect of Locally Applied bFGF on Implant

Stability: Biomechanical Evaluation of 2

Different Implant Surfaces in Rabbits

Yasemin Kartal, DDS, PhD,* Cahit Ucok, DDS, PhD,† Ozkan Ozgul, DDS, PhD,‡ _Ismail Doruk Kocyigit, DDS, PhD,§ and Berkay Tolga Suer, DDS, PhDk

D

ental implants have recentlybecome an ideal treatment modality for treating tooth loss; however, treatment outcome is depen-dent on successful osseointegration during the recovery period. Given the expectation that implant surface will have an effect on healing regardless of the bone quality, quantity, or ana-tomical region, recent research has focused on implant surface character-istics with the aim of shortening the length of time required for osseointe-gration.1 Studies have shown that the

relationship between implant surface and bone-making osteoblasts has an effect on implant bioconsistency with long-term implant success dependent on a stable connection between the biomaterial surface and surrounding bone tissue.2Although average

rough-ness is known to affect the implant success, roughness provides biome-chanical adhesion only, which is less effective over time when compared

with osseointegration that entails bio-mechanical and biochemical adhe-sion.3

Growth factors are basically poly-peptides in structure that can either inhibit or encourage cellular prolifera-tion, differentiaprolifera-tion, migraprolifera-tion, and adhesion or gene expression.4 Basic fibroblast growth factor (bFGF) plays an important role in wound healing and morphogenesis process5 and also

has the potential to stimulate osteoblas-tic proliferation.6–8 Mayahara et al9

reported that systemically administra-tion of bFGF in rats resulted in

increased endosteal bone formation. Chen et al10found that local application

of FGF-2 in bone fracture model had substantial positive effects on bone healing in rats. A diabetic animal model study performed by Santana and Trackman11 reported that the loading of FGF-2 in the cranial fossa surround-ing implants showed better osseointe-gration with highly increased new bone formation in the study group than the control group in rats.

Several techniques can be used to measure the implant stability; these techniques include biomechanical tests *Private Practice, Oral and Maxillofacial Surgery, Ankara, Turkey.

†Professor, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ankara University, Ankara, Turkey. ‡Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Ufuk University, Ankara, Turkey.

§Associate Professor, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Kirikkale University, Kirikkale, Turkey.

kAssistant Professor, Department of Oral and Maxillofacial Surgery, GATA Haydarpasa Teaching Hospital, Istanbul, Turkey.

Reprint requests and correspondence to: Ozkan Ozgul, DDS, PhD, Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Ufuk University, Konya Yolu, Mevlana Blv, Balgat, Ankara 06520, Turkey, Phone: 903122044000, Fax: +903122872390, E-mail: ozkanozgul@yahoo.com

ISSN 1056-6163/14/02304-463 Implant Dentistry

Volume 23 Number 4

Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/ID.0000000000000104

Objectives: The aim of this study was to evaluate the implant stability with the addition of local application of basic fibroblast growth factor (bFGF) during the osseointegration of 2 different dental implant surfaces using rabbit tibia model.

Materials and Methods: Fifty-six dental implants, 28 of hydrophilic surface (SLActive) and 28 of hydro-phobic surface (OsseoSpeed), were placed in 14 mature New Zealand rabbits. The rabbits each received both SLActive and OsseoSpeed im-plants per tibia, and bFGF was applied locally on 1 randomly selected tibia. Half of the subjects were killed at the fourth week of healing period, and the other half were killed at the twelfth week. Stabilization was assessed using

res-onance frequency analysis (RFA) and removal torque value (RTV).

Results: The local application of bFGF was found to enhance os-seointegration, especially at the fourth week of healing period after application (P ¼ 0.046). RFAs and RTVs were found to be higher in bFGF-treated implant with hydro-philic surfaces when compared with both bFGF-treated hydrophobic im-plants and nontreated hydrophilic controls.

Conclusion: Local application of bFGF seems to increase the stabilization values in implants with hydrophilic surfaces and those with hydrophobic surfaces. (Implant Dent 2014;23:463–470)

Key Words: bFGF, osseointegra-tion, implant surface

(2)

The mounting peg has a magnet at the top where it is excited by magnetic pulses. The RFA is expressed electro-magnetically as an implant stability quotient (ISQ) with units ranging from 1 to 100.

Besides these biomechanical tests, histomorphometric evaluation can be used to evaluate implant-bone interface. Although histomorphomet-ric assessment technique and removal torque measurements are more accu-rate than nondestructive biomechani-cal measurements, such as RFA, they both have destructive nature. Because of this destructive nature, they can be applied only once. However, with the use of RFA, it is possible to measure the degree of implant stability at any time during the course of osseointegra-tion without sacrificing the implant-bone interface. Thus, the application of RFA is used in clinical practice. How-ever, the use of RFA is also limited because of many clinical- and operator-related factors such as high-density bone and high variability of this instrument’s application during examination.12

To evaluate the degree of osseoin-tegration, removal torque value (RTV) has been mostly used in the scientific studies. It provides a quantitative mea-sure of implant-bone interface breaking point. Because of its very invasive and destructive nature, this technique can-not be used for a routine clinical testing. Therefore, it is commonly used for research purposes.13

The purpose of this study was to investigate the effects of local bFGF application on the implant stability val-ues with different surface characteristics. Implant stabilization was assessed by using RFA and reverse torque tests at the fourth and twelfth week after implantation.

ment to allow them to adapt to the environment, protect them against infection, and maintain optimal health conditions. In this study, each animal (n¼ 14) was received 4 dental implants on their tibias, 2 implants for each tibia as 1 Standard Plus SLActive (Straumann, Basel, Switzerland) (3.3 mm in diameter and 8.0 mm long) and 1 OsseoSpeed (Astra-Tech AB, Mölndal, Sweden) (3.5 mm in diameter and 8.0 mm long). Randomly selected 1 tibia of each animal was received FGF-2 treatment along with the 2 dental implants (SLActive and OsseoSpeed) and served as experimental group, whereas the other tibia of the same animal served as control group and also received 2 implants, 1 SLActive and 1 OsseoSpeed. As a result, in this experimental design, each rabbit had its own controls. A total of 56 dental implants (28 SLActive and 28 OsseoSpeed) were placed to 14 animals. According to study, design rabbits were divided into 2 sacrificial groups as 4 and 12 weeks. Seven animals were killed at the fourth week after the implant insertion, and the other 7 animals were killed at the end of the twelfth week after the implant insertion (Fig. 1).

Preparation of the Basic Fibroblast Growth Factor

In this study, bFGF (known as recombinant FGF-2 [Code No. 233-FB/001MG/CF, R&D Systems]) that was produced by genetic recombination that introduced the gene for human FGF-2 into Escherichia Coli was used. To improve the operability of the solu-tion and to avoid any damage to the solution before administration to the implant cavities, 0.2 mL of the bFGF solution with a protective phosphate buffer containing bovine serum albu-min protein at a concentration of 100

Operative sites were prepped with betadine and draped in the usual sterile surgical fashion to allow for implant placement. Articaine HCl was administered locally into surgical sites (1:100,000 epinephrine, Ultracaine D-S Fort, Sanofi Avantis San. Tic., Istanbul, Turkey).

Starting from medial to the proxi-mal tibial metaphysis to the distal side, 3- to 4-cm long surgical incision was made using 15 blades. After the skin incision, subcutaneous tissue and mus-cle layers of the leg were bluntly dissected to the periosteum, and the periosteal layer of the tibia was incised using 15 blades. For each tibia, 2 implant holes were drilled as a proximal and distal fashion. During the drilling of the tibia, the physiodispenser (KaVo Dental GmbH, Wien, Austria) was set to 750 rpm, and also copious irrigation was used not to overheat the tibial bone. Approximately 10-mm distance was created between the 2 implant cavities. Each rabbit received 4 implants, 2 in each tibia, as 1 OsseoSpeed and 1 SLActive implant on each side. Before the implant insertion, according to the study protocol, only 1 randomly as-signed tibia on each subject had received 100mL of the prepared bFGF solution locally (50mL for each implant hole) using micropipette (Gilson Inc., Middleton, WI, USA) (Fig. 2). Five sec-onds after the placement of the bFGF into implant holes, the implants were inserted to subjects’ tibia using a physi-odispenser unit set to 50 rpm (Fig. 3). Before the closure of the surgical sites, the first RFA tests were conducted using a smart peg (a metal rod) mount. The smart peg mount was connected to each implant by means of screw con-nection. Then, RFA values were mea-sured using an Osstell Mentor device (Integration Diagnostics AB,

(3)

Gothenburg, Sweden); the results were recorded. The periosteum and subcuta-neous tissue were sutured with 4/0 vicryl (Ethicon; Johnson & Johnson Interna-tional Brussels, Belgium), and the skins were closed with 3/0 Prolene suture (Ethicon; Johnson & Johnson Int.). Each subject recovered without any complication and received prophylac-tic antibioprophylac-tic (50 mg/kg of Cefazolin) and analgesic (1 mg/kg of Tramadol Hcl) through IM injection per day for 5 days postoperatively.

Resonance Frequency Analysis

Fourteen subjects (4 and 12 weeks of healing groups) were used for RFA analysis to measure changes in implant stability during study. For the RFA evaluation, the values were measured at the time of implant insertion and before killing of the subjects. During the killing of the subjects, the top part of the implants was exposed, and the cover screws were removed. Then, smart peg mount was inserted onto implants, and the ISQ values were measured by Osstell Mentor (Integration Diagnostics AB). Because the different directions where transducer is applied could yield differ-ent ISQ values, transducer was kept in the same direction, and 5 different measurements were taken for each implant. And then, for each implant, 2 ISQ values were recorded. At the end of

the study, insertion ISQ values were compared with the ISQ values at kill for the each implant site separately.

Removal Torque Values

Removal torque tests were per-formed for both groups. Fourteen rabbits were used: 7 rabbits (4 weeks of healing) and 7 rabbits (12 weeks of healing). After the general anesthesia was admin-istered to the subjects, full-thickness mucoperiostealflap was raised to expose implants (Fig. 4). The cover screws were removed, and RFA tests were con-ducted. After obtaining the RFA meas-urements for both groups, removal torque tests were conducted using a dig-ital torque meter (DTM) (Mark-10, MGT 12, Mark-10 Corp., Copiague, NY, USA) (Fig. 5). Implant mount parts (moving parts) were securely connected to the implant by means of screw con-nection. After immobilizing the DTM’s jaws onto the implant mount, a slowly increasing counter-clockwise extraction force was applied. The highest torque value measurement to initiate reverse rotation was recorded, and the highest reverse torque value at the break-up time was logged as Newton centimeter.

After torque testing, animals were sedated with 40 mg/kg of ketamine HCl (Alfamine) and 5 mg/kg of xylazine (Alfazine) and killed using an intracardiac injection of 20 mg of

suxamethonium chloride (Lystenon Fort 2%, Fako, Istanbul, Turkey).

Statistical Analysis

Statistical analyses were performed using SPSS software version 15.0 (SPSS Inc., Chicago, IL). RFAs and RTVs were summarized as mean and SDs (average and minimum-maximum, where necessary). We applied the

Fig. 1. Schematic view of the animal study (time line, groups, and the evaluation criteria).

Fig. 2. The bFGF was applied only in 1 leg that assigned as a test group using micro-pipette.

Fig. 3. Dental implants placed using physi-odispenser set to 50 rpm, and 10-mm dis-tance was created between each implant holes.

Fig. 4. All implants were exposed to mea-sure ISQs and RTVs at the end of the experiment.

(4)

Mann-Whitney U test for paired com-parisons. The Wilcoxon test was used for comparisons of 2 dependant varia-bles that do not show regular distribu-tion. P values, 0.05 was considered statistically significant.

R

ESULTS

During the experimental time of this study, subjects’ good general health was maintained. No pathology, such as weight reduction in animals, dehis-cence, or inflammation in the area of operation, was observed.

Resonance Frequency Analysis

ISQ values at 4 weeks of healing. Mean ISQ values for the bFGF + OsseoSpeed test group were 65.66 33.3 at baseline and 71.46 2.6 at 4 weeks. Mean ISQ statistically increased significantly after 4 weeks (P ¼ 0.017) for this group. Mean ISQ values for the OsseoSpeed control group (without bFGF) were 62.06 8.1 at baseline and 65.6 6 3.2 at 4 weeks. When compared with base-line, although ISQ values also increased, there was no statistical significance (P ¼ 0.310) for control group.

For the bFGF + SLActive test group, the mean ISQ values were 65.46 4.0 at baseline and 74.9 6 3.4 at 4 weeks of healing period. There was

a statistically significant increase in the ISQ values (P¼ 0.017). The mean ISQ values for SLActive control group at baseline were 66.96 2.7 and 71.1 6 3.2 at 4 weeks. Increase in ISQ values was also statistically significant (P ¼ 0.017) in this group.

Comparisons of the 2 main test groups showed that the mean ISQ values for the bFGF + SLActive test group at 4 weeks were significantly higher than for the bFGF + OsseoSpeed test group (P¼ 0.046). The mean ISQ values for the SLActive control group were also significantly higher than the OsseoSpeed control group (P¼ 0.018).

When we compare bFGF-treated test groups with control groups, mean ISQ values were higher for the bFGF-treated SLActive and OsseoSpeed test groups. The difference was significant for the bFGF + OsseoSpeed test groups (P ¼ 0.005) but not for the bFGF + SLActive test groups (P¼ 0.071). ISQ values at 12 weeks of healing. When compared with baseline ISQ val-ues, significant increases in the mean ISQ values were observed at the time of 12 weeks of healing periods in the bFGF + OsseoSpeed test group (from 68.66 1.7 to 72.76 3.0; P ¼ 0.018), the bFGF + SLActive test group (from 69.16 2.9 to

Fig. 5. DTM (Mark-10, MGT 12) was used to measure RTVs.

Fig. 6. Boxplot display shows the distributions of the ISQ values of the both implant surfaces (at the baseline, 4 weeks, and 12 weeks). ISQs were significantly higher with the test groups than the control groups for both implant surfaces, but, overall, the bFGF + SLActive surface showed the higher ISQ values compared with the bFGF + OsseoSpeed group and the control groups.

Fig. 7. Boxplot display shows the distribution of the RTVs at the baseline, fourth week, and twelfth week for both test and control groups. Results showed that the RTVs at the fourth week were significantly higher compared with baseline for both implant surfaces, but, at the twelfth week, RTVs lost their significance compared with controls.

(5)

75.96 3.4; P , 0.018), and the SLA control group (from 65.9 6 4.9 to 72.06 2.7; P ¼ 0.028). Mean ISQ values also increased in the OsseoSpeed control group (from 67.76 2.6 to 69.7 6 4.0), but the difference was not statistically significant (P ¼ 0.107).

The mean ISQ value for the bFGF + SLActive test group was higher than the bFGF + OsseoSpeed test group, but the difference was not statistically significant (P ¼ 0.075). However, mean ISQ value for the SLActive con-trol group was significantly higher than the OsseoSpeed control group (P¼ 0.047).

Mean ISQ values were higher for the bFGF-treated test groups in com-parison with control groups. The dif-ference was significant for the SLA groups (P ¼ 0.033) but not for the OsseoSpeed groups (P¼ 0.156). Comparison of ISQ values at the time of 4 and 12 weeks of healing periods. When we compare the relationship between ISQ values at different periods of healing, mean ISQ values at the time of 12 weeks of healing period was higher than the ISQ values at the time of 4 weeks of healing period in the all groups. However, the only statistically significant difference was found in the bFGF + OsseoSpeed test group (P ¼ 0.040) (Fig. 6).

Removal Torque Values

At the 4 weeks of healing. Mean RTV was significantly higher in the bFGF + OsseoSpeed test group (13.54 6 2.8 N/cm) in comparison with the Osseo-Speed control group (7.45 6 1.4 N/cm, P ¼ 0.01) and in the bFGF + SLActive test group (15.99 6 4.2 N/cm) in comparison with the SLActive control group (11.03 6 3.0 N/cm, P, 0.025).

Comparisons of the 2 main test groups revealed that the mean RTV for the bFGF + SLActive test group was significantly higher than the bFGF + OsseoSpeed test group (P ¼ 0.034). Similarly, the mean RTV for the SLAc-tive control group was significantly higher than the OsseoSpeed control group (P¼ 0.018).

At the 12 weeks of healing. Mean RTV was higher in the bFGF + OsseoSpeed

test group (14.586 4.5 N/cm) in com-parison with the OsseoSpeed control group (11.696 3.7 N/cm), but the dif-ference was not statistically significant (P¼ 0.179). Similarly, mean RTV was higher in the bFGF + SLActive test group (17.596 5.5 N/cm) in compari-son with the SLActive control group (13.076 4.2 N/cm), but the difference was not statistically significant (P ¼ 0.084).

Mean RTV for the bFGF + SLAc-tive test group was significantly higher than the bFGF + OsseoSpeed test group (P¼ 0.001). Similarly, the mean RTV for the SLActive control group was sig-nificantly higher than the OsseoSpeed control group (P¼ 0.018).

Comparison of RTVs at the time of 4 and 12 weeks of healing. Although there was no statistically significant difference, the results of the comparison of the 4- and 12-week healing test groups and also the control groups showed that all mean RTVs at the 12-week healing period groups were high-er than those of at 4-week healing period groups (Fig. 7).

D

ISCUSSION

One of the most serious drawbacks of the dental implant treatment is that there is a relatively long waiting time requirement for osseointegration process to take place. During this waiting period, the patient may remain edentulous, which adversely affects function, phona-tion, aesthetics, and the psychology of the patient. Therefore, whenever dental implant treatment is planned, faster and improved osseointegration is a crucial factor.14In the last decade, concentrated

efforts to provide faster osseointegration have been tried to achieve. Scientific lit-erature has shown that the quality of os-seointegration depends on the chemical, physical, mechanical, and topographic characteristics of the implant surface.15

Because early and/or immediate loading protocols entail a stable bone-to-implant contact, several different mechanical, physical, or chemical methods for sur-face modifications have been proposed.16

Among them, surface topography, sur-face charge, and wettability are consid-ered to be the key factors to achieve enhanced bone response.17 Regarding

the surface topography, Albrektsson and Wennerberg18reported that an

aver-age surface roughness of 1.0 to 2.0mm resulted in the greatest adhesion between implant and bone, and that no adhesion occurred with smooth surfaces of 0.0 to 0.4mm. Wennerberg and Alberktsson2

published a study on implant surface characteristics in which their aim was to find common mechanism behind the strong bone responses to novel implant surfaces from different commercial companies (among them, SLActive and OsseoSpeed). They concluded that although SLActive and OsseoSpeed implants have different physiochemi-cal surface effects, possibility of a com-mon mechanism behind the strong bone response of these novel implants may be attributable to their altered nanorough surface pattern.

In this study, 2 different commer-cial oral implant systems (SLActive from Straumann and OsseoSpeed from Astra-Tech) were used. SLActive implant system, a novel hydrophilic surface, has an acid-etched, grit-blasted, and chemically modified tita-nium surface.2 Based on the animal

studies, this novel surface shows stronger bone response than the pre-decessor SLA implant.1 OsseoSpeed

(Astra-Tech), a novel hydrophobic and bioactive surface, has an acid-etched, small-micronized titanium dioxide blasted (TiOblast), andfluoride ions– treated titanium surface. According to the clinical study conducted Stanford,19

OsseoSpeed implant showed a good result over a 3-year follow-up period in the posterior maxilla. Regarding surface roughness, both implant systems used in this study have an average nanometer-level rough titanium surfaces.

Rupp et al20conducted a research

on dynamic wettability of some of the marketed implants that they measured the wettability of an implant surface as a dynamic contact angle (DCA). They suggested that, if the DCA is less than 90 degrees, surface of an implant has a hydrophilic property, and if the DCA is more than 90 degrees, implant has a hydrophobic property. Their study showed that the DCA of the SLActive implant is 0 degree representing superhydrophilicity, and the DCA of

(6)

tative of hydrophilic surface implant and OsseoSpeed as a representative of hydrophobic surface implant. Our sec-ond aim for this study was to evaluate whether bFGF has an augmented effect on early bone response with these 2 implant systems, which have already been shown in the literature that they have early bone response and faster osseointegration time compared with their predecessors on the market.

Numerous studies have looked at the effects of bFGF on tissue regener-ation, bone healing, and osseointegra-tion. The bFGF is known to participate in the key steps and sequential cellular and molecular cascades in the bone healing process. The effect of this sub-stance is achieved by elevation of cell proliferation or recruitment of mesen-chymal stem cells, osteoblasts, and endothelial cells.21–23 Mayahara et al9

showed that bFGF regulates extracellu-lar bone matrix production by osteo-blastic cells in vitro experiment. Park et al24 reported that bFGF plays an

important role in bone healing process and is a potent stimulator of osteoblastic proliferation. Inui et al25reported that

the application of bFGF mini pellets induced healing of segmental bone de-fects in rabbit models. Franke Stenport et al26reported that a single application

of localfibroblast growth factor stimu-lated bone formation around titanium implants. For these reasons, bFGF was adopted for use in this study. Regarding the amount of bFGF, Hayashi et al27in

an experimental animal study, com-pared different amount of bFGF usage in the bone defects around titanium den-tal implants. They placed bFGF-gelatin hydrogel complex with 0, 0.1, 1, 10, 100mg bFGF or autogenous bone as a control around the exposed screws. The 10 mg group showed the higher values of bone height around bony

searchers mentioned above used micro-spheres as a carrier to parcel drugs to lengthen the sustained release time of bFGF.

In this study, we used recombinant FGF-2 (R&D Systems) as bFGF. Ac-cording to manufacturer’s technical product profile, half-life of recombinant proteins in culture is between 48 and 72 hours. However, that does not mean the protein active for entire incubation period. Because the authors did not use any carrier system to provide sus-tained release of bFGF, they chose to apply 50-mL bFGF in the implant cav-ities for practical reasons. An underly-ing assumption in this study was that 10 mg of bFGF could be optimum for bone defects around implant treats when used with carrier system such as gelatin hydrogen complex; however, it could not be enough to enhance the bone response around whole implant-tissue level.

The effects of local application of bFGF on implant stability in this study were evaluated using RTV and RFA. RTV was measured at the time of killing of subjects for both test and control groups. Implants in both test groups had significantly higher RTVs at 4 weeks after insertion compared with control groups (P¼ 0.025, P ¼ 0.01), which was interpreted as more rapid and favorable bone response to bFGF-treated implants. In addition, the RTVs of the hydrophilic surface test group were significantly higher than the hydrophobic surface test group. Other studies found similar results when com-paring bFGF treatment versus no treat-ment in the bone healing process (all studies related bFGF). One possible explanation for observing significantly higher RTVs in the hydrophilic surface implants is that the effect of the bFGF with hydrophobic surfaces is

minishing in the later phase.

In this study, the implant stability was also measured at the time of implant placement, fourth and twelfth week of insertions using RFA to assess changes that may occur around im-plants during different phases of heal-ing period.

Although RFA might not be the best test for evaluating implant stability or the bone-tissue interface, in the literature, some studies showed strong correlation between ISQ values and measured micromotion around im-plants14 and between ISQ values and

insertion torque values, or between ISQ values and RTVs.30–32

At the fourth week, RFA values increased significantly in comparison with initial RFA values in the test and control groups of hydrophilic implants (P ¼ 0.017 and P ¼ 0.017, respec-tively). Test group of hydrophobic im-plants had significantly higher ISQ values at the fourth week after insertion, but there were no statistically signifi-cant differences between ISQ values at the insertion and at the fourth week of healing. However, implants with hydrophilic surfaces showed greater stabilization in comparison with im-plants with hydrophobic surfaces. These findings show the positive impact of hydrophilic surfaces on early osseointegration. In the literature, the expected pattern of ISQ values shows a decrease between the third and fourth week followed by an increase between the sixth and eighth week. According to the histological study performed by Berglundh and Lindhe,33

osseointegra-tion is a dynamic process in that early phase is characterized by bone resorp-tion between implant and surrounding bone tissue, followed by a maintenance phase characterized by new bone for-mation around the implant surface.

(7)

They suggested that the decrease of ISQ values in the third week corre-sponds to the biological phenomenon that is characterized as early osteo-clastic activity, which affects initial mechanical stability.

In this study, our findings at the fourth week of early healing phase were not in accordance with the results of the studies mentioned above. We con-cluded that the bFGF treatment of the implant cavities yields to faster bone response and faster stabilization at the early healing phase of osseointegration period.

At the twelfth week, RFA values were higher for test implants with hydrophilic surface (P ¼ 0.018) and hydrophobic surface (P¼ 0.018) when compared with baseline ISQ values. The difference in ISQ values between the fourth and twelfth week were higher for both hydrophilic and hydrophobic implant test groups compared with con-trol groups; however, the difference was not significant for the hydrophilic implant group because of the high values obtained in the fourth week after insertion. These findings can be similar to those described by Makary et al,14who found continuous increasing

ISQ values for implants over 6-week follow-up.

In our study, local application of bFGF resulted in significantly higher values in both RFA and RTV in com-parison with nontreated controls at the fourth week after implant placement. Regardless of implant surface, bFGF was shown to have a positive effect on osseointegration, although higher ISQ values were observed for implants with hydrophilic surfaces than for those with hydrophobic surfaces.

Moreover, RFA values of the fourth week test groups of hydrophobic implants are higher than those of the twelfth week values of control groups. Thesefindings indicate that the combi-nation of local application of bFGF and hydrophilic surfaces achieved rapid onset of osseointegration at the fourth week after implant insertion.

A variety of procedures can be used to assess implant stabilization, includ-ing percussion, Periotest, RFA, and removal torque tests. Regarding RFA measurement, Meredith et al12reported

that RFA showed a strong correlation with histomorphometric values during the osseointegration period. Rasmusson et al34reported that RFA values showed

increases in new bone formed around implants during the osseointegration period. Turkyilmaz et al35reported that

obtained high torque values in high bone quality and in low quality bone torque values decreased remarkably in their research and that RFA values supported these results. In this study, RFA and RTVs were consistent with one another.

A limitation of this study is the only biomechanical testing methods used for the evaluation of the implant stability. Although RTV measurement is one of the efficient representative tests in studying the nature of implant-tissue interface, it measures the shear forces of the interface between bone and implant. Although greater forces may be inter-preted as an increase in the strength of osseointegration, the results do not necessarily show a direct relation with bone response at the implant-bone interface.

C

ONCLUSION

In conclusion, with the limitations of this study, we demonstrate that local application of FGF-2 has a positive effect on implant stability for both hydrophilic and hydrophobic surface dental implants. According to ISQ and RTVs, we further postulated that this increased implant stability from locally applied FGF-2 found higher for im-plants with hydrophilic surfaces com-pared with implants with hydrophobic surfaces. Our results showed that the local application of the FGF-2 could initiate early osseointegration of dental implants regardless of their surface properties. Further research is antici-pated, in particular, tofind the amount and delivery method for FGF-2 in dental implant placement.

D

ISCLOSURE

The authors claim to have no financial interest, either directly or indirectly, in the products or informa-tion listed in the article.

R

EFERENCES

1. Buser D, Schenk RK, Steinemann S, et al. Influence of surface characteristics on bone integration of titanium implants. A histomorphometric study in miniature pigs. J Biomed Mater Res. 1991;25: 889–902.

2. Wennerberg A, Albrektsson T. On implant surfaces: A review of current knowledge and opinions. Int J Oral Maxil-lofac Implants. 2010;25:63–74.

3. Wennerberg A, Albrektsson T. Suggested guidelines for the topographic evaluation of implant surfaces. Int J Oral Maxillofac Implants. 2000;15:331–344.

4. Zou GK, Song YL, Zhou W, et al. Effects of local delivery of bFGF from PLGA microspheres on osseointegration around implants in diabetic rats. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 114:284–289.

5. Vemuri S, Beylin I, Sluzky V, et al. The stability of bFGF against thermal dena-turation. J Pharm Pharmacol. 1994;46: 481–486.

6. Okada-Ban M, Thiery JP, Jouanneau J. Fibroblast growth factor-2. Int J Biochem Cell Biol. 2000;32:263–267.

7. Bikfalvi A, Klein S, Pintucci G, et al. Biological roles of fibroblast growth factor-2. Endocr Rev. 1997;18:26–45.

8. Claus P, Werner S, Timmer M, et al. Expression of thefibroblast growth factor-2 isoforms and the FGF receptor 1-4 transcripts in the rat model system of Par-kinson’s disease. Neurosci Lett. 2004; 360:117–120.

9. Mayahara H, Ito T, Nagai H, et al. In vivo stimulation of endosteal bone forma-tion by basic fibroblast growth factor in rats. Growth Factors. 1993;9:73–80.

10. Chen M, Song K, Rao N, et al. Roles of exogenously regulated bFGF expression in angiogenesis and bone regeneration in rat calvarial defects. Int J Mol Med. 2011;27:545–553.

11. Santana RB, Trackman PC. Con-trolled release offibroblast growth factor 2 stimulates bone healing in an animal model of diabetes mellitus. Int J Oral Maxillofac Implants. 2006;21:711–718.

12. Meredith N, Alleyne D, Cawley P. Quantitative determination of the stability of the implant-tissue interface using reso-nance frequency analysis. Clin Oral Im-plants Res. 1996;7:261–267.

13. Sullivan DY, Sherwood RL, Collins TA, et al. The reverse-torque test: A clinical report. Int J Oral Maxillofac Implants. 1996;11:179–185.

14. Makary C, Rebaudi A, Sammartino G, et al. Implant primary stability deter-mined by resonance frequency analysis: Correlation with insertion torque, histologic

(8)

17. Cochran DL, Buser D, ten Bruggenkate CM, et al. The use of reduced healing times on ITI implants with a sandblasted and acid-etched (SLA) sur-face: Early results from clinical trials on ITI SLA implants. Clin Oral Implants Res. 2002;13:144–153.

18. Albrektsson T, Wennerberg A. Oral implant surfaces: Part 1: Review focusing on topographic and chemical properties of different surfaces and in vivo responses to them. Int J Prosthodont. 2004;17:536–543. 19. Stanford CM. Surface modi fica-tions of implants. Oral Maxillofac Surg Clin North Am. 2002;14:39–51.

20. Rupp F, Scheideler L, Eichler M, et al. Wetting behavior of dental implants. Int J Oral Maxillofac Implants. 2011;26: 1256–1266.

21. Gospodarowicz D. Fibroblast growth factor. Chemical structure and bio-logic function. Clin Orthop Relat Res. 1990;231–248.

22. Tabata Y, Ikada Y. Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with

differ-25. Inui K, Maeda M, Sano A, et al. Local application of basicfibroblast growth factor minipellet induces the healing of segmental bony defects in rabbits. Calcif Tissue Int. 1998;63:490–495.

26. Franke Stenport V, Johansson CB, Sawase T, et al. FGF-4 and titanium im-plants: A pilot study in rabbit bone. Clin Oral Implants Res. 2003;14:363–368.

27. Hayashi K, Kubo T, Doi K, et al. Development of new drug delivery system for implant bone augmentation using a basicfibroblast growth factor-gelatin hy-drogel complex. Dent Mater J. 2007;26: 170–177.

28. Akagawa Y, Kubo T, Koretake K, et al. Initial bone regeneration around fen-estrated implants in Beagle dogs using basic fibroblast growth factor-gelatin hy-drogel complex with varying biodegrada-tion rates. J Prosthodont Res. 2009;53: 41–47.

29. Perets A, Baruch Y, Weisbuch F, et al. Enhancing the vascularization of three-dimensional porous alginate scaf-folds by incorporating controlled release

surface modifications and implant diame-ter. Clin Oral Implants Res. 2010;21: 605–611.

32. Glauser R, Sennerby L, Meredith N, et al. Resonance frequency analysis of implants subjected to immediate or early functional occlusal loading. Successful vs. failing implants. Clin Oral Implants Res. 2004;15:428–434.

33. Berglundh T, Lindhe J. Healing around implants placed in bone defects treated with Bio-Oss. An experimental study in the dog. Clin Oral Implants Res. 1997;8:117–124.

34. Rasmusson L, Meredith N, Sennerby L. Measurements of stability changes of titanium implants with exposed threads subjected to barrier membrane induced bone augmentation. An experi-mental study in the rabbit tibia. Clin Oral Implants Res. 1997;8:316–322.

35. Turkyilmaz I, Sennerby L, McGlumphy EA, et al. Biomechanical as-pects of primary implant stability: A human cadaver study. Clin Implant Dent Relat Res. 2009;11:113–119.

Şekil

Fig. 2. The bFGF was applied only in 1 leg that assigned as a test group using  micro-pipette.
Fig. 7. Boxplot display shows the distribution of the RTVs at the baseline, fourth week, and twelfth week for both test and control groups

Referanslar

Benzer Belgeler

İçinde bulunduğumuz yüzyıl dijital çağ olarak adlandırılmaktadır. Gelişen teknoloji, eğitimde de kendine yer bulmaktadır. Gerek öğretmenler gerekse öğrenciler

Björk gibi şarkıcılar ve Gorillaz gibi müzik grupları çeşitli formlarda sanal konser deneme- leri yapmıştı ancak ilk kez bir bilgisayar oyununda bu kadar geniş katılımlı

Hâdimizâde Enver efendide mevcud türkçe daha mufassal bir Karaman Tarihi de yine A rifi Paşa tarafından İbrahim Aczî isminde birine istinsâh et­ tirilmiştir ki,

(1) Even under increasing returns to scale in production, price taking equilibrium may exist in a dynamic model with 'nance constraints,.. (2) Standard Euler equations may continue

approach are that a) driver actions are not assumed to be known a priori but determined based on a human decision making process, b) multiple interactions between drivers, vehicles

The focus of this paper is to present a game theoretical modeling and simulation frame- work for the integration of Unmanned Aircraft Systems (UAS) into the National Airspace

Different from Carraro and Siniscalco model that concludes differences in the strictness of environmental regulation is the reason of trade, Sartzetakis and Constantatos

Relying on evidence from Turkey, this study proposes three alternative factors adding nuance to these propositions in the general literature: the restrictions imposed by the 1980