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Inter- and intraobserver reproducibility of buccal bone measurements at dental implants with cone beam computed tomography in the esthetic region

Inter- and intraobserver reproducibility of buccal bone measurements at dental implants with cone beam computed tomography in the esthetic region

  • Kirsten W Slagter,
  • Gerry M Raghoebar,
  • Arjan Vissink and
  • Henny J A Meijer
International Journal of Implant Dentistry 2015 1:8

Received: 24 December 2014

Accepted: 19 February 2015

Published: 18 April 2015


Abstract

Background

Sufficient buccal bone is important for optimal esthetic results of implant treatment in the anterior region. It can be measured with cone beam computed tomography (CBCT), but background scattering and problems with standardization of the measurements are encountered. The aim was to develop a method for reliable, reproducible measurements on CBCTs. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Methods

Using a new method, buccal bone thickness was measured on ten CBCTs at six positions along the implant axis. Inter- and intraobserver reproducibility was assessed by repeated measurements by two examiners.

Results

Mean buccal bone thickness measured by observers 1 and 2 was 2.42 mm (sd: 0.50) and 2.41 mm (sd: 0.47), respectively. Interobserver intraclass correlation coefficient was 0.96 (95% CI 0.93 to 0.98). The mean buccal bone thickness of the first measurement and the second measurement of observer 1 was 2.42 mm (sd: 0.50) and 2.53 mm (sd: 0.49), respectively, with an intraobserver intraclass correlation coefficient of 0.93 (95% CI 0.88 to 0.96). The mean buccal bone thickness of the first measurement and the second measurement of observer 2 was 2.41 mm (sd: 0.47) and 2.52 mm (sd: 0.47), respectively, with an intraobserver intraclass correlation coefficient of 0.96 (95% CI 0.93 to 0.97). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Conclusions

Applying the methods used in this study, CBCTs are suitable for reliable and reproducible measurements of buccal bone thickness at implants. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Keywords

Dental implantsEsthetic regionCBCTBone thickness

Background

Single-tooth implant placement in the esthetic zone is a highly reliable treatment option for replacing a failing tooth [14]. Yet, research interest has shifted from implant survival towards optimal preservation of soft and hard tissues [57]. Especially in the esthetic region, buccal bone and its preservation is one of the key factors in esthetic outcome [8].

Computerized tomography (CT) scans and cone beam CTs (CBCTs) are commonly used for presurgical planning and to predict bone density and potential stability of dental implants [9]. Next to this, CTs and CBCTs also allow for measuring bone at dental implants during follow-up [10,11]. The quality and accuracy of a three-dimensional (3D) model derived from a (CB)CT is dependent on scanner-related factors such as type of scanner, field of view (FoV), artifacts, and voxel size [12]. In addition, patient-related factors such as patient position and metal artifacts [13] and operator-related factors such as the segmentation process or interpretation of the (CB)CT are of influence [14]. It has been reported that buccal bone thickness at implant sites can be measured with CBCT, but background scattering and problems with standardization of the measurements are frequently encountered [15]. In view of the aforementioned factors, there is need for a reliable, reproducible method to facilitate measurements. The use of 3D image diagnostic and treatment planning software programs in combination with software programs for tracking and registration of the exact position of existing dental implants in radiographs can be of help [16].

The aim of the current study was to develop a reproducible method based on 3D image diagnostic and treatment planning software programs for buccal bone measurements at implants on CBCTs.

Methods

Ten patients with a dental implant in the esthetic zone (regions 13 to 23) were included (Figures 1 and 2). Research was carried out in compliance with the Helsinki Declaration. Patients were part of a randomized controlled trial on esthetics; the study was approved by the Medical Ethic Board of the University Medical Center Groningen, University of Groningen (METC 2010.246) as well as that written informed consent was obtained from all patients. The CBCT scans were made with an iCAT 3D exam scanner (KaVo Dental GmbH, Biberach, Germany), which scanner was validated for measuring bone thickness by Fourie et al. [17]. The method error of this scanner is very small, i.e., 0.05 mm (95% CI 0.03 to 0.07). The standard used voxel size was 0.30 and FoV was 100 × 100 mm on the CBCT scans. Bone measurements at implants on the CBCT scans was done using 3D image diagnostic and treatment planning software (NobelClinician, version 2.1 (Nobel Biocare – Guided Surgery Center, Mechelen, Belgium). A novelty is that this program, regularly used preoperatively, was employed to measure the buccal bone thickness (in mm), after implant surgery. To allow for reproducible measurements, a CBCT imaging and software protocol was developed. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

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Figure 1

Clinical photograph of implant-supported restoration at position 21.

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Figure 2

Conventional intra-oral radiograph of same patient with implant-supported restoration at position 21.

CBCT imaging and software protocol

Acquired CBCT Digital Imaging and Communications in Medicine (DICOM) datasets were transferred to a computer. The CBCT images were exported in DICOM multi-file format and imported into Maxilim, version 2.3 (Medicim, Sint-Niklass, Belgium). Maxilim is a medical image computing program assessing the patients head anatomy and is used for diagnostics and preoperative planning of maxillofacial surgery. The input information for Maxilim is a 3D dataset, often (CB)CT data. The DICOM files of all patients were set continuously on Hounsfield unit (HU) isovalue 280. The implant used was set on HU isovalue 130. With Multimodality Image Registration using Information Theory (MIRIT), which has an accuracy of a subvoxel, the exact position of the implant could be recognized, determined and implemented in the patients DICOM files [16]. The MIRIT procedure is based on recognizing image similarities. The degree of similarity between intensity patterns in two images is determined, and consequently, the recognized image is registered automatically into one coordinate system. Image similarities are broadly used in medical imaging to enhance diagnostics. In the software program NobelClinician, the patients DICOM files were opened with the same HU isovalue of 280. An extra research tool was added to this software program by the program makers, so that the DICOM file from Maxilim was recognized by this program and the exact position of the implant, as determined in Maxilim, could be aligned with a planning implant in NobelClinician. Due to the alignment of a planning implant (with a known configuration) and an actual inserted implant into one image, measurements could take place at the exact buccal midline of the implant (Figure 3). The display of the implant and surrounding structures was set on bone value, so that the outline of the bony structures could be seen and measured. The buccal bone measurements at midline of the implant were performed with the standard provided measurement tools in the software program of NobelClinician.

Figure 3

Implant position. Due to the alienation of the patients’ DICOM files by MIRIT, the exact position of the implant was defined. As such, the measurements could take place in the exact correct buccal direction.

Measuring procedure

The implant and patient dataset were exactly aligned by the MIRIT method, so that the distance from the central axis of the implant to the outer contour of the buccal bone could be measured. Area of interest was the upper 5 mm section of the implant, beginning at the neck of the implant towards the apical direction. Exact dimensions along the implant axis of each implant configuration used in the study were provided by the manufacturer. Buccal bone measurements (in mm) were performed calculating the distance to the buccal bone outline minus the radius of the interior contour of the implant. These buccal bone measurements were done for 5 mm at each millimeter along the axis, beginning at the neck of the implant (Figure 4). Measurements were repeated twice (with time interval to prevent recollection) by two independent operators (HJAM and KWS, both dentists) in a random order. Flow diagram of the consecutive steps has been depicted in Figure 5مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

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Figure 4

Implant measurements. Measurements were performed at each millimeter along the axis of the implant for 5 mm, beginning at the neck of the implant.

Figure 5

Flow diagram of CBCT imaging and measurements to calculate bone thickness buccally of implants.

Statistical analysis

Continuous variables were expressed as a mean with standard deviation. Interobserver and intraobserver variability was assessed using two-way mixed intraclass correlation coefficient single measures analysis [18]. All analyses were performed using SPSS software (version 20.0). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Results

The mean buccal bone thickness measured by observers 1 and 2 was 2.42 mm (sd: 0.50) and 2.41 mm (sd: 0.47), respectively. Interobserver intraclass correlation coefficient was 0.96 (95% CI 0.93 to 0.98). The mean buccal bone thickness of the first measurement and the second measurement of observer 1 was 2.42 mm (sd: 0.50) and 2.53 mm (sd: 0.49), respectively, with an intraobserver intraclass correlation coefficient of 0.93 (95% CI 0.88 to 0.96). The mean buccal bone thickness of the first measurement and the second measurement of observer two was 2.41 mm (sd: 0.47) and 2.52 mm (sd: 0.47), respectively, with an intraobserver intraclass correlation coefficient of 0.96 (95% CI 0.93 to 0.97). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Discussion

Intraobserver and interobserver agreement was very high with measurements on CBCTs of bone buccally of dental implants. Apparently, the method is clear and measurements can be performed reproducibly. Moreover, measurements are not observer dependent, meaning that results of different observers in different studies can be compared with each other. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

In previous studies, buccal bone thickness was also measured, but the exact position of these measurements at the surface of the implant was not determined by 3D image-based diagnostic and treatment planning software programs [10,11,15]. It is important to perform measurements of bone thickness at the same position at implants to make comparison in time possible. Because of the cylindrical contour of the implant, thickness of bone can vary considerably in the mesio-distal direction. The combination of the software programs MIRIT (for determination and registration of the implant position in Maxilim) and Research Tool in NobelClinician (for alignment of planning implant and registered implant) makes the method reproducible.

Scattering of the titanium dental implant makes it difficult to perform measurements from the bone-to-implant boundary to the buccal outer contour of the bone [19]. The combination of Research Tool in NobelClinician (exact positioning of the planning implant) and Measurement Tool in NobelClinician (for measurements from central axis of the implant) makes it possible to bypass the scattering area. Measurements are corrected by subtraction of the known radius of implant, resulting in the actual thickness of bone.

Measurements are not directly possible in NobelClinician, because the image-recognizing program MIRIT can only be executed in the configuration of Maxilim. It would be desirable if the total procedure could be carried in one program, being NobelClinician. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Conclusions

When applying 3D image-based software programs according to the set-up used in this study, CBCTs are suitable for reliable and reproducible measurements of buccal bone thickness at implants.

Abbreviations

3D: 

three-dimensional

CBCT: 

cone beam computed tomography

CT: 

computerized tomography

DICOM: 

Digital Imaging and Communications in Medicine

FoV: 

field of view

HU: 

Hounsfield unit

MIRIT: 

Multimodality Image Registration using Information Theory

Declarations

References

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  10. Kan JY, Roe P, Rungcharassaeng K, Patel RD, Waki T, Lozada JL, et al. Classification of sagittal root position in relation to the anterior maxillary osseous housing for immediate implant placement: a cone beam computed tomography study. Int J Oral Maxillofac Implants. 2011;26:873–6.PubMedGoogle Scholar
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  18. Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull. 1979;86:420–8.View ArticlePubMedGoogle Scholar  مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا
  19. Parsa A, Ibrahim N, Hassan B, Syriopoulos K, van der Stelt P. Assessment of metal artefact reduction around dental titanium implants in cone beam CT. Dentomaxillofac Radiol. 2014;43:20140019.View ArticlePubMedGoogle Scholar مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

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Temperature rise during removal of fractured components out of the implant body: an in vitrostudy comparing two ultrasonic devices and five implant types

Temperature rise during removal of fractured components out of the implant body: an in vitrostudy comparing two ultrasonic devices and five implant types

  • Eric W Meisberger
  • Sjoerd J G Bakker and
  • Marco S Cune
International Journal of Implant Dentistry 2015 1:7

Received: 19 December 2014

Accepted: 2 March 2015

Published: 20 March 2015


Abstract

Background

Ultrasonic instrumentation under magnification may facilitate mobilization of screw remnants but may induce heat trauma to surrounding bone. An increase of 5°C is considered detrimental to osseointegration. The objective of this investigation was to examine the rise in temperature of the outer implant body after 30 s of ultrasonic instrumentation to the inner part, in relation to implant type, type of ultrasonic equipment, and the use of coolants in vitroمقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Methods

Two ultrasonic devices (Satelec Suprasson T Max and Electro Medical Systems (EMS) miniMaster) were used on five different implant types that were provided with a thermo couple (Astra 3.5 mm, bone level Regular CrossFit (RC) 4.1 mm, bone level Narrow CrossFit (NC) 3.3 mm, Straumann tissue level regular body regular neck 3.3 mm, and Straumann tissue level wide body regular neck 4.8 mm), either with or without cooling during 30 s. Temperature rise at this point in time is the primary outcome measure. In addition, the mean maximum rise in temperature (all implants combined) was assessed and statistically compared among devices, implant systems, and cooling mode (independent t-tests, ANOVA, and post hoc analysis).

Results

The Satelec device without cooling induces the highest temperature change of up to 13°C, particularly in both bone level implants (p < 0.05) but appears safe for approximately 10 s of continuous instrumentation, after which a cooling down period is rational. Cooling is effective for both devices. However, when the Satelec device is used with coolant for a longer period of time, a rise in temperature must be anticipated after cessation of instrumentation, and post-operational cooling is advised. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Conclusions

The in vitro setup used in this experiment implies that care should be taken when translating the observations to clinical recommendations, but it is carefully suggested that the EMS device causes limited rise in temperature, even without coolant. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Keywords

ImplantAbutmentComplicationFracture

Background

Complications in implant dentistry are generally divided into biological and mechanical complications. Mechanical complications include fracture of the implant body or prosthetic components such as chipping of ceramic material as well as loosening or fracture of implant abutments or fixation screws. This has a documented prevalence of 6 to 13% and 0.4 to 2% respectively after 5 years [17].

With respect to the etiology of screw loosening, several causes are to be considered [8]. Screw-nut systems generally become unstable when the load that is applied to the system exceeds that of the preload of the screw that causes a clamping force preventing separation of the joint [9]. Preload is proportional to the tightening torque at placement. Hence, tightening torque on the one hand has a significant effect on screw loosening [10]. Embedment relaxation or settling can be overcome by retorquing abutment screws after a certain period of time, increasing joint stability [9,11]. On the other hand, the magnitude of forces applied to the system is of major influence. The transfer of high forces can be generated by bruxers, through non-occlusal loading or because of a non-passive fit of suprastructures [8,1215]. Other factors that are of influence of a systems’ resistance to screw loosening include lubrication, screw design, screw material, and surface characteristics [1620]. Especially implant designs with an external hex configuration are prone to abutment screw loosening [21].

Fracture of abutments or abutment screws can be contributed to acute trauma, chronic overload, production flaws, or errors in screw-nut design. If fractured screw components cannot be removed, it may render the implant unrestorable or forces the dentist to creative solutions, such as cementable components. Fortunately, fractured screw components will generally be loose because the preload has not been retained. In that case, they may be removed by manipulating them counter clockwise with a straight probing instrument. On occasion, screw remnants cannot be mobilized, and removal remains a clinical challenge. Careful instrumentation when attempting to remove them should prevent damage to the internal thread of the implant and its surrounding tissues. The use of a fine-tipped hand instrument, a round burr turning counter clockwise, or drilling a slot in the screw in order to get more grip can be attempted to loosen the fragment. Specific instrumentation to remove broken screws from implants is available from most implant suppliers. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

The use of ultrasonic equipment under adequate magnification may facilitate removal. It generates heat. Instrumentation without a coolant likely increases the temperature of the implant body and could cause tissue damage, in particular be harmful to osseointegration. The use of a coolant could be effective, but compromises visibility considerably, hence increases the risk of damaging the internal configuration of the implant.

Results from an experimental heat conduction model investigating the ranges of temperature gradients occurring in implants demonstrate that a 60°C heat source causes a heat front exceeding 47°C and advances more than 3 mm down an implant within 1 s [22]. Temperatures over 47°C for more than a minute cause necrosis of cortical bone [2325]. Some studies investigating the potential harmfulness of intraoral abutment preparation or plaster on implants to osseointegration mention this threshold as harmful [2628]. It has been postulated that a rise in temperature to 42°C causes denaturation of osteoblasts and should be considered the temperature threshold of transient changes in bone [25]. This threshold was used by others when investigating the potentially damaging effect to the implant-bone interface as a result of drinking hot beverages [2931]. Also from endodontic literature regarding the removal of metal endodontic posts, concerns have been raised based on observations from in vitro experiments with respect to potentially detrimental heat transformation through dentine while ultrasonically manipulating the post [3237]. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

The objective of this investigation is to examine the rise in temperature of the outer surface of an implant body after 30 s of ultrasonic instrumentation of its inner part in relation to type of ultrasonic equipment, implant type, and the use of coolants in vitroمقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Methods

Two different types of commercially available ultrasonic devices, set at their lowest intensity for endodontic purpose, were used to instrument the internal portion of five different implant types, either with or without cooling. Intermittent anti-clockwise strokes were made, assuring that the tip was constantly in contact with the inner implant wall, as much as possible mimicking the motion that would have been used in clinical practice.

The ultrasonic devices used were the Satelec Suprasson T Max (Acteon Group, Merignac, France) and the EMS miniMaster (EMS, Electro Medical Systems SA, Nyon, Switzerland) with non-diamant, non-cutting tips ET 20, Satelec, and Instrument A (EMS). The device allowed for internal cooling of the tip with the cooling liquid at 31°C during instrumentation.

The implants used were from different brands; all 8-mm long but with various diameters and designs: Astra 3.5 mm (Dentsply Implants, Mölndal, Sweden), bone level Regular CrossFit (RC) 4.1 mm, bone level Narrow CrossFit (NC) 3.3 mm, Straumann tissue level regular body regular neck 3.3 mm (Straumann, Basel, Switzerland), and Straumann tissue level wide body regular neck 4.8 mm (Straumann AG, Basel, Switzerland). A single implant per group was used. They were embedded in epoxy resin, with a thermocouple (TC-08, Pico Technology, St. Neots, Great Britain) glued to the outer implant surface, at a level corresponding with the anticipated marginal bone level in uncompromised conditions. The change in temperature was registered for 30 s, followed by a 30-s cooling down period, at 5-s intervals (Figure 1).

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Figure 1

Implant embedded in epoxy resin with thermocouple at the outer surface.

Statistical analysis

The primary outcome variable was defined as the difference in temperature between the start of instrumentation and after 30 s when comparing the different implants and the maximum rise in temperature (deltaTmax) where results were averaged per experimental condition (type of device, with or without coolant). All tests were performed three times, and the results were averaged per condition. Differences between several experimental conditions were analyzed by means of independent t-tests and univariate analysis of variance, after verification of normal distribution by human eyeballing and the Kolmogorov-Smirnov test. Where appropriate, post hoc analysis was performed using the Student-Newman-Keuls multiple comparison test. The value for α was set at 0.05 to distinguish statistical significancy. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Results

The results for all implants instrumented with the two tested ultrasonic devices, either with or without cooling, are presented in Figure 2a,b,c,d.

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Figure 2

Results for all implants instrumented with two tested ultrasonic devices, either with or without cooling. (a) Temperature rise when instrumenting with the Satelec ultrasonic device without cooling. The horizontal dotted line denotes the assumed critical rise in temperature. Temperature rise at 30 s: bone level 3.3 mm > bone level 4.1 mm > Straumann regular neck 3.3 mm = Astra 3.5 mm = Straumann regular neck 4.8 mm. (b) Temperature rise when instrumenting with the Satelec ultrasonic device with cooling. The horizontal dotted line denotes the assumed critical rise in temperature. Temperature rise at 30 s: bone level 3.3 mm = Astra 3.5 implant > Straumann regular neck 3.3 mm = Straumann regular neck 4.8 mm. Temperature rise at the bone level 4.1 implant lies in between the bone level 3.3 mm and Astra 3.5 mm implant and both Straumann implants, but not significantly different from either of these implants. (c) EMS without cooling. Temperature rise at 30 s: bone level 3.3 mm = bone level 4.1 mm > Straumann regular neck 3.3 mm = Astra 3.5 mm = Straumann regular neck 4.8 mm. (d) EMS with cooling. No statistically significant differences between the implant types at 30 s. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

For the Satelec device, applied without coolant, only the temperature of the Straumann wide body regular neck implant never exceeded the 50 threshold. The data proved normally distributed (Kolmogorov-Smirnov test, p > 0.05). Analysis of variance indicated statistically significant differences among the implant types (F = 33.3, df 4, p < 0.001). The highest mean temperature increase at 30 s was seen around the 3.3-mm bone level implant (13.0°C), followed by the 4.1-mm bone level implant (9.5°C), and subsequently by the other three implant types (Student-Newman-Keuls (SNK) test, Figure 2a). When coolant was used during instrumentation, an increase of temperature exceeding 5°C was not seen. There were some differences between the implant types (ANOVA, F = 6.4, df 4, p < 0.01), primarily between the bone level 3.3 mm and Astra 3.5-mm implant on the one hand and both Straumann tissue level implants on the other hand (SNK test). Interestingly, when instrumentation and cooling had stopped, the outer temperature of all implants raised markedly above the 5°C critical threshold during the following 10 s, for both bone level implant types up to approximately 10°C (Figure 2b).

For the EMS device when applied without cooling, an increase at 30 s above the threshold was only seen for the 3.3- and 4.1-mm bone level implant types (approximately 6°C), which was statistically significantly higher than the rise in temperature seen in the other three implant types (ANOVA, F = 3.4, df = 4, p = 0.04, and SNK test, Figure 2c). Cooling the EMS device proved pretty efficient at 30 s, without differences between the groups. Only a mild increase of the outer temperature was observed to a maximum of 2°C. It takes some time for cooling to take effect. When instrumentation and cooling is stopped, no increase of outer implant temperature occurs, which contrasts the findings with the Satelec device (Figure 2d).

The mean maximum rise in temperature (deltaTmax, all implants averaged per experimental condition) was reached at 30 to 40 s for all conditions. There was a significant difference for the Satelec device without cooling (mean 9.6, SD 1.6°C) and the EMS device without cooling (mean 4.3, SD 2.0°C) (t-test, t(28) = 4.7, p < 0.001). When using coolant, the deltaTmax for the Satelec device (mean 8.3, SD 1.3°C) was significantly higher than for the EMS device (mean 1.6, SD 0.6°C) (t-test, t(28) = 17.9, p < 0.001). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Discussion

Several techniques have been described to deal with biomechanical complications. Acquiring adequate visibility and access is essential to success which will require the use of a dental microscope.

Several mechanical approaches to remove screw remnants can be employed. Generally, after identifying the position and condition of the screw remnant, it can be carefully removed using manual instrumentation. A fine-tipped hand instrument may be wedged between screw and implant. If this fails to do the trick, the use of a round burr applying occlusal pressure and turning counter clockwise may loosen the fragment. When a flared burr is wedged between implant and screw remnant, the drill should make a clockwise action, to direct the screw in the counterclockwise direction. Cutting a deep slot in the screw and subsequently removing it with a bladed screw driver has also been advised. The use of rotary instrumentation may cause damage to the cranial inner portion of the implant body. If that occurs, even when the fragment (finally) loosens, it will not screw out, and this complicates matters considerably. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Most implant suppliers, and also some third parties, provide specific instrumentation to remove broken screws from implants (i.e., Certain screw removal kit, Biomet 3I, Palm Beach Gardens, United States; screw removal kit NobelReplace, Nobel Biocare, Göteborg, Sweden; Neo screw remover kit, Neobiotech Co, South Korea). In general, they screw into the center of the screw remnant, which facilitates another burr to grip it and remove it counter clockwise or fragmentate the screw remnant. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

The use of ultrasonic equipment has also proven to be effective in dislodging fixed screw remnants at the risk of damaging the inner portion or overheating the implant. Hence, the use of magnification is a must and cooling may be advisable, but compromises the vision of the operator. The present study evaluated heat accumulation in vitro and the efficiency of cooling when using two types of ultrasonic equipment to the inner portion of several implants. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

The degree to which a material is able to transfer heat is called thermal conductivity. It can be defined as the time rate of transfer by conduction, through unit thickness, across unit area for unit temperature gradient. Differences in design and wall thickness of the implants used in the present study account for the variation in outcome (i.e., Straumann tissue level 4.8 implant less effected), considering the fact that all implant types used are made from the same material: grade 4 commercially pure (CP) titanium. The thermal conductivity of CP titanium is relatively low compared to, for instance, that of steel (1/4) and aluminum (1/13). On the other hand, it is approximately 60% higher than that of grade 5 titanium alloy (16.3 W · m−1 · K−1 for grade 4 CP titanium compared to 7.2 W · m−1 · K−1 for grade 5 Ti-6Al-4 V). The former material is used in several other implant brands than the ones used here [38], and as a consequence, the results cannot be extrapolated to those systems. The data from this in vitro experiment can only be generalized to the clinical situation bearing in mind some inherent limitations and assumptions. The epoxy resin used does not resemble alveolar bone, its structure, water content, and potential to cope with thermal challenges. It is unlikely that wall thickness, design, and material between different implants from the same implant type will vary because of the high degree of current precision and standardization achieved during the fabrication of implants. Consequently, only one specimen per brand was used. To correct for variation during the instrumentation of the ultrasonic device, the experiment was performed three times.

The results show that both 1. the type of implant and 2. the type of ultrasonic device (and in especially the use of coolant) affect the amount of temperature rise to the outer implant surface. Both bone level implants in particular appear to heat up the most. Without the use of coolant, the heat accumulation was much higher with the Satelec compared to the EMS device and exceeded the theoretical threshold for permanent biological damage after 10 to 15 s of continuous instrumentation (Figure 2a,c) and differed statistically significant at deltaTmax. There may be several explanations for this, but most likely, the produced energy at the point of the tip for the Satelec device was higher. Both devices were set at their lowest possible level. The present authors have not been able to verify what energy levels are actually produced. The former is presumed linear to the frequency and the deflection/amplitude of the tip. The frequency is mentioned in the product documentation (Satelec: 27 to 33 kHz and the EMS: 24 to 32 kHz) but the amplitudes differ per tip and are not disclosed. The effect of the difference in coolant spray between the two instruments is also a factor that needs considering when interpreting the data.

Cooling proves effective for both systems, increasing the outer implant temperature by an acceptable 1°C to 3°C during continued instrumentation; however, as already stated, the spray will blur the vision of the operator.

One would expect the temperature to drop immediately after cessation of instrumentation and cooling, but the peak temperature is reached some seconds later for all experimental conditions, so regardless of device, use of coolant, or implant type (Figure 2a,b,c,d). Others, instrumenting endodontic posts in natural teeth [32,33], also saw a ‘lag’ period with a rise in temperature after cessation that lasted up to 9 s post-instrumentation. They left it unexplained. We offer two possible explanations. Firstly, ultrasonic instrumentation causes the implant wall and its surrounding tissues (in this case, resin and thermocouple, but in vivo, this would be surrounding alveolar bone) to vibrate and generate heat. Vibration continues some time after cessation of instrumentation, explaining the continued rise in temperature. Secondly, after cooling has stopped, generated and stored heat in the surrounding ‘tissues’ may flow back to the outer wall of the implant that is no longer cooled from the inside and raises the temperature. The potentially damaging rise in temperature (‘explosion’) seen for the Satelec device, but not for the EMS device when instrumentation and cooling was stopped, could be explained by these phenomena on the one hand and by the fact that energy produced by the Satelec device was presumably higher on the other hand (Figure 2b).

Conclusions

It is concluded from this in vitro study that heat accumulation and transfer is dependent on the type of ultrasonic device, the use of coolant, and the implant type. The highest rise in temperature is seen when using the Satelec device without coolant on the smaller diameter implants. The EMS device causes limited rise in temperature when used without coolant for less than 10 s, but presumably delivers less energy to the tip, and consequently may be not as effective. A cooling down period is sensible. When used with coolant for a longer period of time, the clinician should anticipate a considerable rise in temperature after cessation of instrumentation, and post-operational cooling is advised. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Declarations

Acknowledgements

The input of Prashant K. Sharma PhD, material scientist of the Department of Biomedical Engineering (Kolff Institute) of the UMC Groningen is greatly appreciated for his help interpreting the data. Michael Kars, DDS assisted during the collection of the data. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

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Efficacy of intravenous sedation and oral nifedipine in dental implant patients with preoperative hypertension – a retrospective study of 516 cases — International Journal of Implant Dentistry 2015 1:6

Efficacy of intravenous sedation and oral nifedipine in dental implant patients with preoperative hypertension – a retrospective study of 516 cases

  • Motoshi Kimura
  • Yoshihiro Takasugi,
  • Shigeyoshi Hanano,
  • Katsuyuki Terabe and
  • Yuko Kimura
International Journal of Implant Dentistry 2015 1:6

Received: 8 October 2014

Accepted: 14 January 2015

Published: 18 March 2015


Abstract

Background

To examine the effects of intravenous sedation and oral nifedipine on blood pressure and pulse rate in patients with perioperative high blood pressure undergoing implant surgery, the clinical records of dental implant patients managed by intravenous sedation at our outpatient dental offices were retrospectively evaluated.

Methods

A total of 516 clinical charts were evaluated. The subjects were divided into two groups: a normotensive group with no history of hypertension and a hypertensive group with a history of hypertension. The patients in the hypertensive group were further divided into two subgroups: with or without nifedipine administration before operation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), and rate pressure product (RPP) were assessed. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Results

In 30 patients (33%) of the hypertensive group, the high blood pressure on arrival obviously declined to around or less than 160 mmHg; in the remaining patients in the group who showed a mean SBP of 182.1 ± 13.8 mmHg on arrival, the blood pressure did not decrease after a 30-min rest. Oral nifedipine administered to the patients with sustained high blood pressure decreased SBP to 144.7 ± 23.1 mmHg in 28.1 ± 9.3 min after administration, comparable to that in hypertensive patients without nifedipine.

Conclusions

For patients with stage 2 hypertension before operation, it may be difficult to maintain the recommended blood pressure during surgery by only intravenous sedation; reduction of blood pressure by antihypertensive drugs may be necessary. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Keywords

Oral surgeryDental implantHemodynamicsIntravenous sedationNifedipine administration

Background

Osseointegrated dental implants were introduced in Japan in 1983, and the procedures are now performed very frequently. Dental implants are placed in a wide age range of patients, including elderly patients with hypertension. Patients with very high blood pressure are at great risk for acute medical problems when undergoing stressful dental procedures, such as oral surgery, periodontal surgery, and placement of dental implants [1].

Patients with normal blood pressure (<120/80 mmHg), prehypertension (120 to 139/80 to 89 mmHg), or stage I hypertension (140 to 159/90 to 99 mmHg) may receive regular dental care, but those with stage 2 hypertension (≥160/≥100 mmHg) should receive noninvasive treatment only and be referred to the physician for immediate follow-up [2]. Normotensive individuals may develop signs of hypertensive encephalopathy at blood pressures as low as 160/100 mmHg, whereas chronically hypertensive patients can tolerate higher blood pressure and may not do so until the blood pressure rises to 220/110 mmHg or above [3]. Although no recommendation has been presented on the optimal level of blood pressure to avoid hypertensive complications during invasive dental treatments, blood pressure in hypertensive patients should be maintained below 160/100 mmHg.

Pain, stress, or anxiety-related dental procedures can raise blood pressure in both hypertensive and normotensive patients [4]. We have employed intravenous sedation to manage patients with hypertension as well as dental anxiety and phobia. The oral antihypertensive agent nifedipine is mainly administered to patients with high systolic blood pressure (SBP) ≥160 mmHg prior to implant placement. To examine the effects of intravenous sedation and oral nifedipine on blood pressure and pulse rate in patients with perioperative high blood pressure, the clinical records of dental implant patients managed by intravenous sedation at our outpatient dental offices were retrospectively evaluated. The purpose of this clinical study is to examine whether intravenous sedation and oral administration of nifedipine is efficient for the hemodynamic for the patient with hypertension. The authors expect that it is possible not only to obtain a hemodynamic blood stable but also to prevent the medical sequelae by performing intravenous sedation and oral nifedipine for patients with hypertension.

Methods

A retrospective review of the clinical records was conducted for 336 patients who received dental implant-related surgeries combined with intravenous sedation between January 2008 and February 2012 at our outpatient dental offices. Among the patients, 125 patients received multiple surgeries during the observation period: 4 patients underwent surgery five times, 7 patients four times, 29 patients three times, 85 patients twice, and others once. The following surgical procedures were performed in a total of 516 patients: dental implant placement (466 patients), sinus lift surgery and dental implant (28 patients), socket lift and dental implant (10 patients), and guided bone regeneration and dental implant (12 patients). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

We performed surgeries after medical consultation when patients had a history of hypertension or cardiovascular or cerebrovascular diseases. History of ischemic heart disease, renal dysfunction, diabetes mellitus, cerebral infarction, or articular rheumatism was documented in 17 patients in the hypertensive group and 16 patients in the normotensive group. They were confirmed stable and well controlled for implant surgery. For patients who received therapeutic drugs, surgery was performed following daily medication.

The patients were allowed to have water or snacks until 2 h before the visit. On arrival at the office, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) were measured using an automatic blood pressure monitor with an oscillometric method (HEM-1010, Omron Healthcare, Kyoto, Japan). The cephalic vein was cannulated with a 22-G disposable intravenous catheter. Nifedipine capsule (10 mg) was orally administered to patients with sustained increases in SBP ≥160 mmHg for 30 min from baseline measurement. A noninvasive blood pressure monitoring system with electrocardiogram (ECG) monitor and pulse oximeter (Moneo BP-88, Omron Healthcare, Kyoto, Japan) was mounted, and blood pressure was measured at 2- to 5-min intervals. In patients with a history of cardiovascular disease, ECG was continuously monitored. Following confirmation of a definite decline of blood pressure or SBP <160 mmHg, infiltration anesthesia and/or conduction anesthesia was administered using 1 to 3 cartridges (1.8 to 5.4 ml) of 2% lidocaine containing 1/80,000 epinephrine.

Following confirmation of a sufficient anesthetic effect, intravenous sedation with continuous infusion of propofol 1 to 2 mg/kg/h and midazolam 20 to 40 μg/kg bolus together with inhalation of oxygen 3 L/min via nasal cannula was initiated. After confirming Verrill sign, implant surgery was initiated. During operation, the propofol dose was adjusted to maintain the optimum conscious sedative condition (level 2 on the Ramsay sedation scale) [5], and local anesthesia was added when the patient complained of pain. On completion of surgery, administration of oxygen and propofol were terminated and the patient was observed for about 1 h, until normal cognitive and motor functions were restored. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

The subjects were divided into two groups: a normotensive group with no history of hypertension and a hypertensive group with a history of hypertension. Thirteen patients who had no history of hypertension were included in the hypertensive group, since they indicated SBP ≥160 mmHg on arrival at the office and were later diagnosed with essential hypertension by cardiologists. Furthermore, the patients in the hypertensive group were divided into two subgroups: with or without nifedipine administration.

From the clinical chart, data of SBP, DBP, PR, and percutaneous oxygen saturation (SpO2) were sampled at the point of arrival to the office, prior to the initiation of sedation, 30 min after the initiation of operation, and on completion of operation. Furthermore, rate pressure product (RPP: SBP × PR) was calculated.

There were two primary outcome measures: (1) incidence of improved hypertension following oral nifedipine and (2) incidence of normal ranges of hemodynamic parameters during surgery. The secondary outcome variable was incidence of hypertension related to perioperative complications. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Statistical analysis

In this study, we used data from all cases (516 cases) for statistical analysis.

Data were described as mean ± standard deviation. The unpaired t test was used to compare demographic variables between groups. Fisher’s exact test was used to compare ratios of patients in hypertensive group between subgroups. One-way analysis of variance (ANOVA) followed by Tukey’s multiple comparison test was performed to examine the change in the values of parameters. Repeated measures ANOVA followed by Dunnett’s multiple comparison test was used to compare the values of parameters in groups at each time point. Statistical analysis was performed using Prism 5 for Windows Ver. 5.01 (GraphPad Software Inc., San Diego, CA, USA). The significance level was set at p < 0.05. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Ethical approval

This study protocol was approved by the ethics committee of Japanese Dental Society of Anesthesiology (No. 2015–4).

Results

Patient demographics and clinical characteristics are summarized in Table 1. There were significant differences in age (p < 0.0001) and duration of surgery (p = 0.025) between normotensive and hypertensive groups. On arrival at the office, values of all hemodynamic parameters, including SBP, DBP, PR, and RPP, were higher in the hypertensive group than in the normotensive group (p < 0.0001).

Table 1

Demographic and clinical characteristics

Normotensive group

Hypertensive group

p value

Number (male: female)

410 (127: 283)

106 (37: 69)

0.170

Age (year mean ± SD)

59 ± 11

65 ± 10

<0.0001

Weight (kg)

54.5 ± 9.2

57.1 ± 10.9

0.204

Values of circulation parameters on arrival at office

 SBP (mmHg)

133 ± 19

165 ± 22

<0.0001

 DBP (mmHg)

76 ± 13

99 ± 20

<0.0001

 PR (bpm)

79 ± 13

90 ± 19

<0.0001

 RPP (bpm × mmHg)

10,574 ± 2,614

12,367 ± 5,771

<0.0001

Preoperative oral nifedipine

0

44 (42%)

<0.0001

Duration of surgery (min)

40 ± 20

35 ± 17

0.025

Duration of sedation (min)

69 ± 25

65 ± 22

0.114

SBP, systolic blood pressure; DBP, diastolic blood pressure; PR, pulse rate; RPP. rate pressure product.

Tables 2 and 3 indicate incidences of patients with SBP ≥160 mmHg and RPP ≥12,000 bpm × mmHg, and perioperative hemodynamic changes, respectively. On arrival at the office, 66 patients (62%) in the hypertensive group and 41 patients (10%) in the normotensive group revealed high SBP ≥160 mmHg. Thirty minutes later, SBP declined to less than 160 mmHg in most of the patients in the normotensive group. On the other hand, in 30 patients (33%) in the hypertensive group, high blood pressure on arrival obviously declined to around or less than 160 mmHg, while in the remaining patients in the group who showed a mean SBP of 182.1 ± 13.8 mmHg on arrival, the blood pressure did not clearly decrease after 30 min of rest. Oral nifedipine administered to patients with sustained high blood pressure decreased SBP to 144.7 ± 23.1 mmHg by 28.1 ± 9.3 min after administration, which was similar to that in hypertensive patients without nifedipine.

Table 2

Incidence of high blood pressure and high rate pressure product

SBP (>160 mmHg)

RPP (>12,000 bpm × mmHg)

Normotensive group (N = 410)

 On arrival at the office

41 (10.0%)

111 (27.1%)

 Prior to sedation

31 (7.6%)

72 (17.6%)

 During operation

1 (0.2%)

1 (0.2%)

 Completion of operation

3 (0.7%)

9 (2.2%)

Hypertensive group without preoperative oral nifedipine (N = 62)

 On arrival at the office

22 (35.5%)**

34 (54.8%)**

 Prior to sedation

13 (21.0%)**

27 (43.5%)**

 During operation

2 (3.2%)*

5 (8.1%)**

 Completion of operation

5 (8.1%)**

6 (9.7%)**

Hypertensive group with preoperative oral nifedipine (N = 44)

 On arrival at the office

44 (100%)**

40 (90.9%)**

 Prior to sedation

8 (18.2%)*

24 (54.5%)**

 During operation

1 (2.2%)

4 (9.1%)**

 Completion of operation

3 (6.8%)*

8 (18.2%)**

*p <0.05, **p <0.01 vs normotensive group (Fisher’s exact test). SBP, systolic blood pressure; RPP, rate pressure product.

Table 3

Changes in values of hemodynamic parameters

SBP (mmHg)

DBP (mmHg)

PR (bpm)

RPP (bpm × mmHg)

Normotensive patients (N = 410)

 On arrival at the office

133.0 ± 18.4

76.4 ± 12.5

79.2 ± 13.4

10,603 ± 2,623

 Prior to sedation

128.5 ± 18.3*

70.5 ± 11.9*

76.8 ± 13.0*

9,927 ± 2,485*

 During operation

109.7 ± 11.9*

62.7 ± 10.0*

70.6 ± 10.2*

7,768 ± 1,555*

 Completion of operation

115.9 ± 14.2*

66.1 ± 11.3*

70.4 ± 10.7*

8,196 ± 1,796*

Hypertensive patients without preoperative oral nifedipine (N = 62)

 On arrival at the office

152.5 ± 17.6

88.3 ± 11.8

84.6 ± 14.3

12,972 ± 3,055

 Prior to sedation

143.2 ± 18.1*

77.4 ± 9.6*

82.7 ± 13.4

11,874 ± 2,540*

 During operation

118.9 ± 15.5*

67.2 ± 10.0*

75.2 ± 12.8*

8,977 ± 2,164*

 Completion of operation

125.4 ± 19.1*

68.8 ± 12.6*

74.7 ± 10.9*

9,360 ± 1,977*

Hypertensive patients with preoperative oral nifedipine (N = 44)

 On arrival at the office

182.1 ± 13.8

102.8 ± 12.5

87.2 ± 17.1

15,901 ± 3,623

 Prior to sedation

144.7 ± 23.1*

77.3 ± 15.9*

89.3 ± 16.1

12,986 ± 3,437*

 During operation

119.8 ± 16.5*

65.8 ± 10.0*

78.0 ± 12.3*

9,413 ± 2,265*

 Completion of operation

130.1 ± 18.8*

71.4 ± 13.2*

78.4 ± 13.6*

10,294 ± 2,728*

*p <0.01 vs value on arrival at the office (Dunnett’s multiple comparison test). SBP, systolic blood pressure; DBP, diastolic blood pressure; PR, pulse rate; RPP, rate pressure product.

Although the mean SBP in the hypertensive group was significantly higher than that in the normotensive group during operation, SBP <160 mmHg was maintained in all patients except three in the hypertensive group (2.8%) and one in the normotensive group (0.2%). The values of DBP in patients in the hypertensive group were higher than those in the normotensive group throughout the observation course, and changes in DBP in each group were similar to those in SBP. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

On arrival at the office, RPP ≥12,000 bpm × mmHg was found in 74 patients (70%) in the hypertensive group and 111 patients (27%) in the normotensive group. More than 90% of the patients with preoperative nifedipine showed high RPP on arrival at the office. Among patients with high RPP, all patients in the normotensive group, 10% of the patients without nifedipine in the hypertensive group and 35% of patients with nifedipine in the hypertensive group had RPP <12,000 bpm × mmHg until initiation of intravenous sedation. The values of RPP during operation under intravenous sedation were maintained at a normal range except in nine patients (8.5%) in the hypertensive group and one patient (0.2%) in the normotensive group. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

In patients with oral nifedipine in the hypertensive group, the PR value slightly increased prior to initiation of intravenous sedation (p = 0.224) and then significantly decreased until completion of the operation (p < 0.001).

All patients stated a pleasant feeling and amnesia during surgery. No complication occurred during surgery, and no cognitive and motor dysfunctions were observed 1 h after surgery. The patients revealed SBP of >160 mmHg during and at completion of operation showed maximum SBP of 180 mmHg in the normotensive group, 190 mmHg on the hypertensive group without preoperative oral nifedipine, and 180 mmHg in the hypertensive group with preoperative oral nifedipine. They did not complaint any symptom such as headache, confusion, and chest pain. Upon leaving the office, high SBP of the patients decreased to the level on arrival without any antihypertensive treatment.

Discussion

In 44 (8.5%) of the 516 implant surgery cases, oral nifedipine had to be administered, since preoperative SBP was higher than 160 mmHg in these patients. Within 30 min of administration of nifedipine, SBP of hypertensive patients decreased to a similar range as that of hypertensive patients who did not need administration of oral nifedipine. Intravenous sedation after nifedipine administration to hypertensive patients resulted in stable hemodynamics during implant surgery. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [6] classified hypertensive patients into five categories based on systolic or diastolic blood pressure. Patients with normal blood pressure (<120/80 mmHg), prehypertension (120 to 139/80 to 89 mmHg), or stage I hypertension (140 to 159/90 to 99 mmHg) can receive regular dental care, though a stress reduction protocol is necessary for stage I hypertension [2,7]. In accordance with the guidelines during oral surgery, the blood pressure of hypertensive patients should be maintained at a normal or prehypertension level. RPP is a reliable predictor of myocardial oxygen consumption [8], and RPP >12,000 bpm × mmHg is associated with myocardial ischemia [9,10]. In this study, although blood pressure was managed by a physician, hypertensive patients showed SBP >160 mmHg when they visited the dental office for dental implant surgery, and 50% of hypertensive patients showed high RPP after 30 min of rest. In patients presenting with high blood pressure and high RPP, anxiety and fear must be reduced by conscious sedation and antihypertensives to prevent cardiovascular complications during dental implant surgery. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Increases in SBP due to psychological stress are proportional to age and baseline blood pressure [4]. Intravenous sedation stabilizes measurable changes in blood pressure and pulse rate due to fear and anxiety about dental treatment and has been used to manage patients with ischemic heart disease and hypertension [11]. In this study, the effect of intravenous sedation was as follows: SBP and RPP, compared with those prior to intravenous sedation, were decreased by 15% and 20% in patients with normal blood pressure, 15% and 25% in hypertensive patients without oral nifedipine, and 15% to 20% and 20% to 30% in hypertensive patients with administered nifedipine, respectively. That is, SBP and myocardial oxygen consumption of prehypertension and stage I hypertension can be reduced to the levels recommended for dental treatment before surgery by intravenous sedation.

For patients with stage 2 hypertension before operation, it is difficult to maintain the recommended blood pressure during surgery using only intravenous sedation, and it is necessary to decrease blood pressure by antihypertensive drugs. In this study, the blood pressure of patients with sustained hypertension was reduced to stage I hypertension about 30 min after administration of oral nifedipine. On the other hand, the decrease in RPP after oral nifedipine administration was not less than 12,000 bpm × mmHg, which could be due to the fact that an increase in pulse rate with nifedipine by reflex tachycardia. Thereafter, blood pressure and RPP during surgery under intravenous sedation has remained at levels similar to those of hypertensive patients with well-controlled blood pressure. Maximum effect (21.4% decreases in SBP) appears in 30 to 60 min and lasts about 3 h on oral administration of nifedipine [12]. The half-lives of oral nifedipine, diltiazem and verapamil, and calcium antagonists are 0.2 to 1 h, 6 to 8 h, and 6 to 8 h, respectively [13]. Since oral nifedipine has the properties of fast onset (30 to 45 min) [14] and relatively short duration, it is suitable for outpatient dental implant surgery and is useful in perioperative management of patients with hypertension. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

The overdose of vasoconstrictor that is added to the local anesthetic in order to prolong the anesthetic effect and hemostatic action may cause increased blood pressure and arrhythmias. Elevation of blood pressure in hypertensive patients is greater than that in normotensive patients during dental surgery [15]. Although there is an increase in blood pressure and tachycardia when using three cartridges of local anesthetic containing epinephrine 1:10,000 (5.4 ml), there are no adverse symptoms in patients with normal blood pressure [16]. Little recommended that the amount of local anesthetic solution administered should be less than two cartridges (3.6 ml) for patients with hypertension [1]. Nakamura et al. reported that patients with essential hypertension who have been administered nifedipine can receive less than 3.6 cartridges of local anesthetic containing epinephrine 1:80,000 (6.4 ml) [17]. The administration of exogenous epinephrine with local anesthesia produces the highest plasma concentration in 3 to 6 min and lasts for 20 min [18]. It has been reported that the anesthetic rate of 2% lidocaine containing 1:10,000 epinephrine is 47% 45 min after administration and 27% 60 min after administration [19]. During dental implant surgery which requires a relatively long duration and a wide field in patients with hypertension, administration of conduction anesthesia including inferior alveolar block and posterior superior alveolar nerve block is desirable. When the patient complains of pain, it is important to add local anesthesia while monitoring blood pressure to prevent increased blood pressure caused by pain.

Implant surgery is performed in patients with a wide age range, including elderly patients with hypertension. Dentists or oral surgeons often encounter hypertensive patients who are undiagnosed or noncompliant. Among Japanese over the age of 30, 60% of men and 44.6% of women suffer from high blood pressure, and 33.8% of men and 25.6% of women with a history of hypertension have not been managed medically [20]. In this study, though 13 of the patients did not have a history of hypertension, they were diagnosed with essential hypertension by a physician because they had high blood pressure before surgery. Among patients with a history of high blood pressure, 31 patients (29%) showed high blood pressure before surgery. Because there are many of dental patients with undiagnosed or noncompliant hypertension, blood pressure measurement before treatment, particularly invasive surgery, is indispensable. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

For dental implant surgery in hypertensive patients who are not adequately controlled, the application of intravenous sedation and preoperative antihypertensive medication would be useful in order to prevent perioperative hypertension crisis including hypertension emergency with end-organ damage or hypertension urgency without end-organ damage. Since sublingual administration of immediate-release (IR) nifedipine may cause side effects such as significant decrease in blood pressure, reflex tachycardia, and acute myocardial infarction [21], the sublingual administration of IR nifedipine to hypertension crisis has not been approved by the Food and Drug Administration (1985) and Japanese Society of Hypertension Guidelines for the Management of Hypertension (2000). Since we could manage patients with high blood pressure without any cerebrovascular complications by oral administration of nifedipine under closely monitoring, it may be concluded that preoperative administration of oral nifedipine to patients with high blood pressure may be effective to prevent hypertensive crisis due to sudden rise in blood pressure during surgery. Further studies are necessary to evaluate the usefulness of captopril, clonidine, and labetalol, which have been reported as alternatives to nifedipine in emergency hypertension [2224] in patients with high blood pressure. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Conclusions

In this study, we showed that the stable hemodynamic was obtained by performing intravenous sedation and oral administration of nifedipine for patients with hypertension. It is important not only to understand the systemic management of the patient but also to obtain stabled hemodynamic by performing intravenous sedation and oral administration of nifedipine for patients with hypertension in order to perform the implant surgery safely, and it could be possible to prevent the medical sequelae.

Abbreviations

SBP: 

Systolic blood pressure

DBP: 

Diastolic blood pressure

PR: 

Pulse rate

RPP: 

Rate pressure product

ECG: 

Electrocardiogram

SpO2 : 

Percutaneous oxygen saturation

ANOVA: 

Analysis of variance

IR: 

Immediate-release

Declarations

References

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Genomic analyses of early peri-implant bone healing in humans: a systematic review — International Journal of Implant Dentistry 2015 1:5

Genomic analyses of early peri-implant bone healing in humans: a systematic review

  • Siddharth Shanbhag,
  • Vivek Shanbhag and
  • Andreas Stavropoulos
International Journal of Implant Dentistry 2015 1:5

Received: 14 November 2014

Accepted: 27 January 2015

Published: 1 March 2015


Abstract

Objective

The objective of the study was to systematically review the literature for studies reporting gene expression analyses (GEA) of the biological processes involved in early human peri-implant bone healing.

Methods

Electronic databases (MEDLINE, EMBASE) were searched in duplicate. Controlled and uncontrolled studies reporting GEA of human peri-implant tissues – including ≥5 patients and ≥2 time points – during the first 4 weeks of healing were eligible for inclusion. Methodological quality and risk of bias were also assessed.

Results

Four exploratory studies were included in reporting GEA of either tissues attached to SLA or SLActive implants after 4 to 14 days or cells attached to TiOBlast or Osseospeed implants after 3 to 7 days. A total of 111 implants from 43 patients were analyzed using validated array methods; however, considerable heterogeneity and risk of bias were detected. A consistent overall pattern of gene expression was observed; genes representing an immuno-inflammatory response were overexpressed at days 3 to 4, followed by genes representing osteogenic processes at day 7. Genes representing bone remodeling, angiogenesis, and neurogenesis were expressed concomitantly with osteogenesis. Several regulators of these processes, such as cytokines, growth factors, transcription factors, and signaling pathways, were identified. Implant surface properties seemed to influence the healing processes at various stages via differential gene expression. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Conclusion

Limited evidence from gene expression studies in humans indicates that osteogenic processes commence within the first post-operative week and they appear influenced at various stages by implant surface properties.

Keywords

Dental implantOsseointegrationGene expressionMolecular assessment

Review

Introduction

Osseointegrated oral implants are an integral part of modern reconstructive dentistry and are associated with favorable long-term therapeutic outcomes [1]. Osseointegration was originally defined as the direct contact between vital bone and a load-bearing implant observed at the light microscopic, i.e., histological, level [2]. Morphogenesis of implant osseointegration has been assessed in several preclinical in vivo and clinical histological studies [36], providing the basis for understanding the biological process. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

The biological events during the early phase of osseointegration are directly influenced by the osseous microenvironment (i.e., cells, signaling molecules, and matrix) into which the implant is placed and have many similarities with general wound healing mechanisms [7]. Implant surgery induces trauma, resulting in bleeding and fibrin clot formation and an inflammatory reaction that dominate the events of the first post-operative week. The deposition of vital new bone on the implant surface by osteoblasts (osteogenesis), a fundamental requirement for osseointegration, occurs via secretion of a complex extracellular matrix (ECM) of proteins, which subsequently undergoes mineralization to form bone [8,9]. Primary (woven) bone lined by osteoblasts can indeed be observed on the implant surface already after 1 week [3,5]. In parallel, removal of the created bone debris and remodeling of necrotized bone (due to the pressure exerted by the implant) is underway. Replacement of woven bone by organized and mechanically superior lamellar bone can be observed from the second to fourth week (depending on the species) and progressively increases until woven bone is almost entirely replaced (8 to 12 weeks). These events, including the nutrition of the newly formed tissue, are sustained through concomitantly occurring angiogenesis, i.e., formation of new blood vessels from existing ones [10,11]. Thus, osseointegration is a dynamic process whereby bone formation and remodeling occur in parallel around the implant [4,6]. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Morphogenesis of osseointegration and assessment of the degree of bone-to-implant contact is usually performed by means of histological evaluation [12], while the underlying molecular processes may be more precisely evaluated at genetic level [13,14]. Data from gene expression analyses of fracture healing provide the basis for understanding these processes [15]. These studies have identified the cells, signals, and interactions governing the key processes of bone regeneration. Bone-forming osteoblasts are primarily derived from marrow-resident multipotent progenitor cells (mesenchymal stem cells (MSCs)), which are recruited to the regeneration site. This process of MSC recruitment and differentiation along the osteogenic lineage is termed as osteoinduction and is controlled primarily by various pro/anti-inflammatory cytokines (CKs) and by growth factors (GFs) secreted by inflammatory cells and/or osteoblasts or by GF resident within the extracellular matrix (e.g., bone morphogenetic proteins (BMPs)) in response to injury [1618]. Moreover, CKs and GFs act as signaling molecules via specific signaling pathways and guide the process of cell differentiation in the proper temporal sequence [19,20]. Intermediaries in this process are various bone-specific transcription factors (TFs), which act as ‘molecular switches’ during cell differentiation and are targets of CKs and GFs [21]. TFs facilitate bone-specific gene transcription and ultimately gene expression by which MSCs undergo differentiation and acquire the osteoblastic phenotype [22]. While GFs regulate mainly osteoinduction and osteogenesis, pro-inflammatory CKs regulate the antagonist process of bone resorption by inducing the differentiation of hematopoietic stem cells (HSCs) into osteoclasts and macrophages [23], contributing to the dynamic nature of bone regeneration and remodeling. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Recent in vitro [24] and preclinical in vivo [25] studies have focused on the early molecular biological responses to various titanium implant surfaces. Understanding these early responses is essential for efforts aiming to accelerate and enhance the process of osseointegration [26]. Upregulation or downregulation of specific genes in peri-implant tissues identified by analyses of genetic material (DNA, RNA) reflects the nature and timing of the various healing processes, which in turn could be potential ‘molecular targets’ for enhancing osseointegration [27,28]. The aim of the present study was to systematically review the available literature on gene expression analyses of the biological processes involved in early human peri-implant bone healing.

Methods

Study design

A study protocol for a systematic qualitative literature review was developed based on recommended methods [29]. The focused question was ‘what biological processes are reflected by gene expression analyses in peri-implant tissues of humans during the early stages (up to 4 weeks) of healing?’

Inclusion and exclusion criteria

All studies, controlled (using different implants) or uncontrolled, reporting gene expression analyses of peri-implant tissues harvested from ≥5 human patients at ≥2 time points during the first 4 weeks of healing, were eligible for inclusion. Studies reporting the use of either ‘experimental’ (micro) or standard implants with clear description of implant surface properties, placed in the maxilla or mandible and retrieved at a later time point, were eligible for inclusion. Studies reporting (1) analyses of peri-implant mucosa or sulcular fluid or peri-implant tissues of failing or infected implants (peri-implantitis), (2) only histological or immunohistochemical analyses without gene expression of harvested tissues, and (3) in vitroand preclinical in vivo studies were excluded. Primary outcome of interest was the biological process (or processes) reflected by gene expression at a particular time point of peri-implant tissue healing. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Search strategy

Electronic databases of MEDLINE (via PubMed) and EMBASE were searched by one author (SS) for relevant English-language literature up to and including June 2014. The search strategy used for MEDLINE was (((((“gene expression” OR transcriptome OR transcriptional OR molecular OR microarray))) AND ((osseointegration OR healing OR “peri implant”))) AND implants) AND ((human OR humans OR patients OR subjects)). Unpublished literature was searched via the Google and Google Scholar search engines. Additionally, the bibliographies of all relevant studies and review articles were searched.

Study selection

Titles and abstracts of the search identified studies were screened by two authors (SS and VS) based on the inclusion criteria, and full texts of all eligible studies were obtained. Differences in assessment of eligibility were resolved by discussion with the third author (AS). Full texts were independently reviewed by both reviewers, and final inclusion was based on the aforementioned inclusion criteria. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Data extraction

Both reviewers independently extracted data from the full texts of included articles using specially designed forms. Data on author(s), study design, implant type/surface, any additional procedures performed, number of patients (in each group), presence of a control group, procedure and time of implant retrieval, methods of gene expression analysis, and main results, were extracted. Descriptive summaries of the studies were entered into tables, and a qualitative synthesis of evidence was planned. Any disagreement between the reviewers regarding data extraction was resolved by discussion. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Assessment of methodology and risk of bias

Assessment of the methodological validity of the included studies was performed using criteria adapted from previous reports [30,31]. Aspects of study design, genotyping methods, and data analyses were considered using nine criteria (Table 1). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Table 1

Assessment of the genotyping methodology in the included studies

Methodology

Ivanovski et al. [ 34 ]

Donos et al. [35 ]

Bryington et al. [36 ]

Thalji et al. [ 37 ]

Tissue harvesting

Tissue attached to implant carefully removed with a curette, preexisting hard tissue discarded

Tissue attached to implant carefully removed with a curette and homogenized

Implants removed by reverse threading and homogenized; cell lysates isolated

Implants removed by reverse threading and homogenized; cell lysates isolated

Sample preparation

Total RNA isolation, purification, quantity/quality analysis and biotin-labeling

Total RNA isolation, purification, quantity/quality analysis and biotin-labeling

Total RNA isolation, quantification

Total RNA isolation, purification, quantity/quality analysis and biotin-labeling

Array technique

Microarray hybridization (Human WG-6 V3)

Microarray hybridization (Human WG-6 V3)

RT-PCR (custom RT-PCR array for osteogenesis genes; human inflammatory cytokines and receptors PCR array)

Microarray hybridization (Affymetrix Human Gene 1.1 ST)

Scanning, data preparation

Bead Station 500/Bead Studio v3 software, raw probe expression values extracted

Bead Station 500/ Bead Studio v3 software, raw probe expression values extracted

RT2 SYBR Green qPCR Master Mix/7500 Real-Time PCR system

Affymetrix Gene Chip Scanner

Processing

Noisy data discarded

Noisy data discarded

Normalization of osteogenesis and cytokine array

Unclear

Clustering

GO categories (DAVID tool)

GO categories (DAVID tool)

Osteogenesis genes; cytokine-related genes

GO categories (Gene Spring)

Statistical analysis

Gene Spring software

Gene Spring software

RT2 Profiler software

Gene Spring software

Comparisons

Pair-wise comparisons between three time points (4 vs. 7 days, 7 vs. 14 days, and 4 vs. 14 days)

Pair-wise comparisons at each time point (4, 7, and 14 days) between SLA and SLActive surfaces

T-test to evaluate differences between each implant surface per time point

Two-way ANOVAs to determine differences between implant surface type and time points; pair-wise comparisons of each implant surface independently at different time points (day 7 vs. day 3)

GO, gene ontology; DAVID, Database for Annotation, Visualization and Integrated Discovery.

The risk of bias in the included studies was assessed using an adaptation of published guidelines for reporting systematic reviews of periodontal genetic association studies [32]. Mainly, aspects of study design and methodological validity were assessed using 15 criteria and scored as ‘yes,’ ‘no,’ or ‘unclear’ based on the information provided in the study manuscript (Table 2). Moreover, published guidance [33] regarding the qualitative and quantitative syntheses of results from genetic association studies was consulted, and heterogeneity across the included studies was assessed to explore the possibility of a meta-analysis.

Table 2

Assessment of risk of bias and heterogeneity within and across the included studies

Category

Ivanovski et al. [ 34 ]

Donos et al. 2011 [ 35 ]

Bryington et al. [ 36 ]

Thalji et al. [ 37 ]

Study design

  Comparison

None (only SLActive)

SLA vs. SLActive

TiOBlast vs. Osseospeed

TiOBlast vs. Osseospeed

  Setting

University

University

University

University

  Population, inclusion criteria

9 healthy volunteers with no mandibular third molars, no contraindications for oral surgery; age 21 to 48, median 29 years

9 healthy volunteers with no mandibular third molars; age 21 to 48, median 29 years

6 women, 4 men; implant patients, systemically healthy (no HTN, diabetes, CVD); age 25 to 58, mean 36.2 years

9 women, 2 men; implant patients, systemically healthy; age 47 to 69, mean 60.2 years

  Exclusion criteria

Smokers

Smokers

Smokers, pregnancy, periodontal/periapical disease, subjects taking bisphosphonates, hormone replacement therapy, corticosteroids

Smokers, uncontrolled diabetes, history of head/neck radiotherapy, taking corticosteroids, bisphosphonates

  Comparability of groups

Unclear

Unclear

Unclear

Unclear

  Potential confounders, e.g., post-op medication

Unclear

Unclear

Unclear

Unclear

  Power calculation

No

No

No

No

  Statistical correction

For multiple sampling

For multiple sampling

Unclear

For multiple sampling

Methods

  Tissue analyzed

Peri-implant tissue

Peri-implant tissue

Implant-adherent cells

Implant-adherent cells

  Genetic material analyzed

Total RNA

Total RNA

Total RNA

Total RNA

  Success rate

Unclear

16/18 samples (88.8%)

7/10 subject samples (70%)

Unclear

  Genotyping method

Microarray

Microarray

RT-PCR

Whole-genome microarray

  Genotype counts

Yes

Yes

Yes

Yes

  Blinding

Unclear

Unclear

Yes

Unclear

  Reproducibility, validated genotyping accuracy

No

No

No

No

All studies were judged to be at a high risk of bias with substantial heterogeneity across studies.

Results and discussion

The included studies basically report on commercially available implants from two major manufacturers and involve comparisons of different implant surface technologies in regard with topography and/or chemistry modifications within each implant system. Various analyses were performed in the included studies; however, an attempt has been made to synthesize the various findings and discuss them herein irrespective of the specific implant systems, based on the assumption that basic biological mechanisms of peri-implant bone wound healing are largely implant system independent. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Search results and study characteristics

Of the 242 search identified studies, only four studies were finally included in the review, all focusing on the impact of implant surface on early human peri-implant bone healing (Figure 1; Table 3). Genetic analyses of total RNA isolated from either newly formed peri-implant bone harvested by trephination [34,35] or from cells adherent to implants retrieved by reverse threading [36,37] were performed. In total, 111 implants from 43 patients were analyzed. All four studies reported the use of commercially existing implant surfaces, i.e., either a chemically modified, hydrophilic, sand-blasted, acid-etched surface (SLActive®, Institute Straumann AG, Basel, Switzerland); or a hydrophilic (SLActive®) versus a hydrophobic unmodified SLA® (Institute Straumann AG, Basel, Switzerland) surface; or a micro-topographic titanium-oxide grit-blasted surface (TiOBlast®, AstraTech, Molndal, Sweden) versus a chemically modified nano-topographic grit-blasted surface (Osseospeed®, AstraTech, Molndal, Sweden). Implant retrieval times were at 3 or 4 days and 7 days in all studies and additionally at 14 days in two studies [34,35].

Figure 1

Flowchart for study selection ( n  = number of studies).

Table 3

Summary of findings from the included studies ( n  = 4)

Study

Ivanovski et al. [ 34]

Donos et al. [ 35 ]

Bryington et al. [ 36 ]

Thalji et al. [ 37 ]

Design

9 patients; 9 implants placed

18 patients; 18 implants placed

10 patients; 60 implants placed

11 patients; 44 implants placed

Total RNA extracted from peri-implant tissue (trephine)

16 samples analyzed

42 samples analyzed

Total RNA extracted from implant adherent cells (reverse thread)

Total RNA extracted from peri-implant tissue (trephine)

Total RNA extracted from implant adherent cells (reverse thread)

Surface

SLActive

SLA vs. SLActive

TiOBlast vs. Osseospeed

TiOBlast vs. Osseospeed

GE day 3/4

Upregulated

Upregulated on SLA

Upregulated on both surfaces

No significant differences between surfaces at any time point (P > 0.05)

 CKs (TNF-a, IL-6, IL-2)

 Neurogenesis

 Osteogenesis (Runx2, Osx, BMP6, OPN)

Results presented as GE at day 7 vs. day 3 for each surface

 Immune-inflammatory cells (LC, MP)

 Collagen organization

 Inflammatory CKs (IL-1A,B, TNF)

 Inflammatory NF-kB p/w

Upregulated on SLActive

 MP activity

 Ras protein p/w

Upregulated on Osseospeed

 Collagen organization

 Chemotaxis (CCL18, CXCL10, CXCL14)

 CK response

 Anti-inflammatory CKs (TOLLIP, IL9, IL22)

GE day 7

Upregulated

Upregulated on both surfaces

Upregulated on both surfaces

Upregulated on both surfaces

 MSC genes (HOX, Sp3)

 Inflammatory CKs (IL1, IL2, IL6, TNFS)

 Osteogenesis (Runx2, Osx*, OCN*, OPN, BMP6, BSP)

 ECM (Coll, GPs, PGs)

 GF (TGF-B receptor)

 Neurogenesis

 [* Osseo > TiOB; P < 0.05]

 Collagen organization (PLODs, LOX, PCOLCE)

 VEGF sig. (vs. day 14)

 Upregulated on SLActive

 Angiogenesis/VEGF sig. (ANXA, EPAS1)

 Wnt p/w

 Neurogenesis (BDNF, NTF3)

 Ossification

Downregulated

 ECM (OPN)

 Remodeling (MMPs, TIMPs)

 Inflammatory NF-kB p/w (vs. day 4)

 BMP p/w (BMP4, BMP2K)

 Osteoclastic (CTSK, ACP5)

 MAPK sig.

 Chemotaxis (CKs, MP activity)

 Mineralization

 Anti-inflammatory CKs (CCL22, CCL18)

 Focal adhesion (integrins)

Downregulated on both surfaces

 Angiogenesis (VEGF sig., P13-Akt p/w)

 Inflammatory CKs (IL1A, IL1B)

Downregulated on SLActive

 Inflammatory cells (LC)

GE day 14

Upregulated

Upregulated on both surfaces

 ECM (Coll, OC, ON, ALP)

 BMP p/w (BMP4, BMP2K)

 TFs (Osx, Dlx5, Twist1, Smad6)

Downregulated on both surfaces

 Remodeling (MMP, CTSK)

 Inflammatory cells (LC)

 GFs (BMP, GDF)

 Angiogenesis (VEGF sig.)

 Neurogenesis

 TGF-b/BMP, Notch p/w

 Ras protein p/w

 Wnt-receptor genes

 Notch genes (up/down)

Downregulated

 Inflammatory response (vs. day 7)

GE, gene expression; CKs, cytokines; p/w, pathway; MSC, mesenchymal stem cells; GF, growth factors; sig., signaling; ECM, extracellular matrix; TFs, transcription factors; MP, macrophage; LC, lymphocytes; GPs, glycoproteins; PGs, proteoglycans.

Assessment of methodology and risk of bias

All studies used validated methods for gene expression analysis; genetic data was analyzed using microarray (three studies) or real-time PCR (RT-PCR) (one study) methods (Table 1). Total RNA was isolated from lysates of either trephined peri-implant tissues or implant-adherent cells, and subjected to microarray processing or RT-PCR. Although moderate-to-good agreement has been reported between the two methods, validation of DNA microarray results by the more sensitive PCR array is generally recommended [38]. None of the microarray studies identified have validated their results using RT-PCR. Genotyping data (gene lists) were imported and analyzed using computer software and further condensed into functionally and biologically relevant categories. Nevertheless, differential gene expression in relation to a particular cell type or region of tissue analyzed was not performed [35]. Gene ‘upregulation’ was reported when genes were expressed at a higher level on one implant surface in comparison to another; in context, differentiation between gene expression and over-expression may be difficult to define. Statistical methods were used to compare differences in gene expression between different time points and/or implant surfaces (P < 0.05 significance level), while correcting for possible errors, i.e., false gene discovery rate due to multiple sampling [39]. There was considerable heterogeneity across the included studies in terms of study design, population, implant surface technology, genotyping methods, and data analyses (Table 2). Therefore, no meta-analysis of association between gene expression and implant surface properties was relevant.

Thus, high risk of bias should be considered when interpreting the results, due to the above methodological limitations and the overall limited information (four studies) available.

Biological processes identified through gene expression in peri-implant tissues

Conventional implant surgery involves osteotomy preparation and insertion of the implant into the alveolar bone. The immediate local effects of this procedure, functionally relevant to subsequent healing processes, are (1) bone trauma, (2) formation of bone debris, (3) hemostasis and clot formation, and (4) hypoxia. These effects involve the release of specific CKs and GFs within the local environment [7], resulting in recruitment of two primary cell types to the site, inflammatory cells and progenitor cells (MSCs and HSCs) [19], which in turn regulate the subsequent healing processes. A summary of differentially regulated genes relating to the involved biological processes is presented in Table 4, while Figure 2 represents an evidence-based illustrative model summarizing these processes.

Table 4

Summary of biological processes and associated genes reported in the included studies

Process

Upregulated genes

Category (gene code)

Inflammation/immune response

  Pro-inflammatory cytokines

Tumor necrosis factor (TNF-a, TNFSF9)

Interleukin (IL-6, IL-2, IL-1 F9, IL-23A, IL-6ST)

Interferon (IFNA2)

Nuclear factor-kB (I-kB kinase/NF-kB)

  Anti-inflammatory cytokines

Interleukin (IL-22, IL-9)

Toll interacting protein (TOLLIP)

  Cells

Lymphocyte, macrophage negative proliferation (BTLA, LST1)

Macrophage scavenger receptor (MSR1)

  Chemotaxis

Chemokines (CCR8, CCL18, CCL22, CXCL10, CXCL14)

Osteoinduction/osteogenesis

Growth factors (GF)/signaling pathways

Insulin-like GF (IGF1)

Transforming GF (TGF-b, TGF-b receptor 1, 2 and 3, TGF-a)

Platelet-derived GF (PDGF receptor)

Bone morphogenetic proteins (BMP4, BMP6, BMP receptor 1A, BMP2-K)

Growth and differentiation factor (GDF10)

Wnt frizzled receptor (FZD3, FZD8, FRZB)

Notch (NOTCH2)

Ras-protein signal transduction (RAP1B, RAP1A, RASGRP4)

Mitogen activated protein kinase (MAP3K7IP2, MAPK9, MAP2K3, MAP3K2)

  Transcription factors

‘Master switches’ [RUNX2, SP7 (OSX)]

Homeobox (DLX1, DLX5, HOXD12, MSX1, HOXA5, HOXB1, HOXB6, HOXC6)

SP [SP1, SP3, SP7 (Osx)]

Twist (TWIST 1-receptor)

  ECM deposition/organization

Collagen (Col1A1, Col12A1, Col6A3, Col3A1, Col6A1, Col11A1, Col11A2, Col13A1, Col5A2)

Non-collagen proteins [BGLAP (OC), SPARC (ON), SPP1 (OP), BSP, IBSP, POSTN, ECM1]

Small leucine-rich proteoglycans (SLRP) (DCN, BGN, LUM)

Heat-shock protein 47 (HSP47)

Alkaline phosphatase (ALPL)

Cadherin (CDH11)

Integrin (ITGB4, ITGB5)

Laminin (LAMA2, LAMA3)

Pro-collagen lysyl-hydroxylase (PLOD1, PLOD2, PLOD3)

Pro-collagen C-endopeptidase enhancer (PCOLCE)

Lysyl-oxidase (LOX)

Osteoclast activity/remodeling

Cathepsin K (CTSK, CTSK-receptor)

Tartarate-resistant acid phosphatase (TRAP/ACP5)

Matrix metallopeptidase (MMP2, MMP12, MMP9, MMP7, MMP13)

Tissue inhibitor metallopeptidase (TIMP2, TIMP3)

Angiogenesis

Vascular endothelial GF-signaling (EPAS1, ANXA2, EGR1-binding protein)

Phosphatidyl-inositol 3-kinase (PI3K)-Akt signaling

Neurogenesis

Brain-derived neurotrophic factor (BDNF)

Neurotrophin 3 (NTF3)

NK2 homeobox 2(NKX2-2)

Tubby-like protein 3 (TULP3)

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Figure 2

Summary of biological processes identified via gene expression during early peri-implant bone healing. CKs, cytokines; GFs, growth factors; EPC, endothelial progenitor cells; EC, endothelial cells; MSC, mesenchymal stem cells; OB, osteoblasts; ECM, extracellular matrix; HSC, haematopoietic stem cells; MP, macrophages; OC, osteoclasts. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Inflammation

All studies reported a significant upregulation of genes associated with inflammation during the first time point of observation (day 3 or 4) regardless of the implant surface. Specifically, upregulation regarded pro-inflammatory cytokines of the interleukin (IL), tumor necrosis factor (TNF), and interferon (IFN) families, as well as genes associated with proliferation of lymphocytes and macrophages (MPs). Previous in vitro [40,41] and animal [42] studies have reported the significance of MPs at the bone-implant interface and identified favorable MP activity in relation to modified rough surfaces as demonstrated by in vitro gene expression that was associated with increased in vivo bone formation. Also, the nuclear factor-kB (NF-kB) inflammatory pathway was upregulated at day 4 [34], while macrophage activity and chemokines of the CCL and CXL families in the peri-implant tissues continued to remain prominent at day 7. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

However, this inflammatory response was generally downregulated at later time points (day 7 or 14). For example, in one study, genes associated with pro-inflammatory cytokines (IL-1B, IL-1A, IL-1R2) and chemokines (CCL22, CCL18) were downregulated and upregulated, respectively, on day 7, at both implant surface technologies examined (Osseospeed and TiOBlast) [37]. Moreover, the anti-inflammatory response seemed to be modulated by surface properties. In one study, genes related to anti-inflammatory cytokines such as IL-9, IL-22, toll-like receptor inhibitor protein (TOLLIP), and several key chemokines (CCL18, CXCL10, CXCL18) were significantly upregulated on Osseospeed surfaces but not TiOBlast, at day 3 [36]. In another study, genes associated with inflammatory cell proliferation were significantly downregulated earlier on SLActive surfaces compared to the SLA, i.e., at day 7 instead of day 14 [35]. Therefore, the initial inflammatory response seems to be important for the recruitment of cells that govern subsequent healing processes and is regulated by a natural biological immune response which may be further modified by implant surface properties. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Osteogenic differentiation

Cells along the osteogenic differentiation pathway may be artificially categorized as (1) undifferentiated MSCs, (2) osteo-chondro-progenitor cells, (3) pre-osteoblasts, and (4) osteoblasts; although in reality, a developmental continuum without distinct boundaries may exist [43]. While pre-differentiated osteoblasts in the marrow compartment only play a minor role in bone wound healing, a more prominent role is that of undifferentiated MSCs which are recruited to the regeneration site where they differentiate into osteoblasts [16]. The recruitment and differentiation of MSCs is regulated by CKs and GFs [17,19]. The GFs most commonly implicated in bone wound healing are BMPs, members of the TGF-β family, PDGF, and IGF-1 [19,20]. Moreover, the bone debris created during implant surgery, the peri-implant blood clot (i.e., platelets) and the differentiating MSCs themselves further contribute to release of GFs at the site [44,45].

All studies reported some evidence of osteogenic differentiation at an early time point (day 3 or 4) via expression of genes associated with key growth factors (bone morphogenetic proteins (BMP4, BMP6, BMP2-kinase), growth and differentiation factor-10 (GDF10), transforming growth factors (TGF-α, TGF-β), platelet-derived growth factor (PDGF), and insulin-like growth factor-1 (IGF1)), transcription factors (Runx2, Osx, Dlx3, Dlx5, Msx1, HOX genes, Sp1, Sp3), and/or osteogenic signaling pathways (TGF-β/BMP signaling, Wnt-receptors, Ras-protein/mitogen-activated protein kinase (Ras/MAPK) signal transduction). In all studies, these genes were further upregulated at day 7. Upregulation of osteogenic factors seemed regulated by implant surface. The key transcription factor osterix (Osx) was upregulated on the Osseospeed surface, but not TiOBlast at day 7 [36], while tissues adjacent to SLActive surfaces demonstrated comparatively greater BMP and Ras/MAPK expression compared to SLA surfaces at day 7 [35]. Previous in vivo animal studies have reported correlations between upregulated osteogenic gene expression in peri-implant tissues and enhanced histological and biomechanical measures of osseointegration during early (1- to 4-week) healing times [27,46]; nevertheless, it is unclear whether upregulation and/or overexpression of genes at a specific time point directly correlates to increased protein production in vivo.

The key signaling pathways, via which GFs guide osteogenic cell differentiation, are the TGF-β/BMP- and Wnt-mediated pathways [19,47]. While the BMP pathway ensures differentiation of MSCs into osteo-chondro-progenitors (OCPs), the Wnt pathway is essential for subsequent osteoblastic commitment, i.e., Wnt acts ‘downstream’ of BMP to ensure that OCPs differentiate into osteoblasts and not chondroblasts [47]. Genes associated with both TGF-β/BMP and Wnt pathway (Wnt receptors) were upregulated at day 7 [34,35] and day 14 [34] on SLA and SLActive surfaces, suggesting the occurrence of osteogenic differentiation at these time points.

GF-regulated signaling pathways exert their effects on differentiating cells via activation of TFs. The TFs Runx2 and Osx are considered as ‘master switches’ and absolute requirements for osteoblast differentiation [21] – while Runx2 is essential for MSC differentiation, Osx acting ‘downstream’ of Runx2 controls osteoblastic fate determination [48,49]. An upregulation of these genes was observed in relation to the TiOBlast, Osseospeed, and SLActive surfaces in the present review. However, at day 7, expression of Osx was significantly greater on Osseospeed than TiOBlast surfaces. This finding is consistent with previous animal [50,51] and human studies [52] where superior in vivo osseointegration (i.e., larger amount of bone-to-implant contact occurring earlier) of Osseospeed versus TiOBlast implants was reported. Thus, it appears that implant surface topography and/or chemistry influence peri-implant bone healing in humans both at the signaling pathway and transcription factor level.

ECM production

Deposition of new bone on the implant surface involves the secretion of a complex ECM (scaffold) of proteins by osteoblasts, which subsequently undergoes mineralization [9]. Expression of ECM proteins is a reliable indicator of early osteogenic activity [19] and was identified in all four studies at days 7 and 14. All studies reported some evidence of ECM production and/or organization at days 7 and 14. Upregulated genes associated with ECM deposition included various collagens (Col 1 to 11), non-collagen proteins (osteopontin (OPN), osteonectin (ON), osteocalcin (OCN), bone sialoprotein (IBSP), periostin (POSTN), and ECM protein-1), alkaline phosphatase (ALP), and bone-specific adhesion proteins (integrins (ITGB4, ITGB5), laminins (LAMA2, LAMA3), and cadherins (CDH11)). Osteocalcin, the most bone-specific ECM protein and a late marker of osteogenic differentiation [19], was significantly upregulated on Osseospeed (versus TiOBlast) surfaces at day 7 [36]. Osteopontin, an ECM protein essential for mineralization [53], was significantly upregulated on SLActive comparing to SLA surfaces at day 7 [35]. The possibility that implant surface features enhance osteogenic differentiation of MSCs via upregulation of specific genes (e.g., SLActive versus SLA in regard with BMP and Wnt signaling) has been demonstrated in vitro [54].

Furthermore, genes associated with collagen fibril formation/organization (heat-shock protein-47 (HSP-47), pro-collagen C-endopeptidase enhancer (PCOLCE), small leucine-rich proteoglycans (SLRP)) and post-translational modification (pro-collagen lysyl-hydroxylases (PLOD1, PLOD2, PLOD3) and lysyl-oxidase (LOX)) were upregulated on Osseospeed and TiOBlast surfaces [37]. Collagen comprises approximately 90% of the ECM and collagen fibrillogenesis and organization directly determine the biomechanical properties of bone [55,56]. Genes associated with collagen fibril formation, maturation, and post-translational modification expressed by osteoblasts [57,58] were upregulated on TiOBlast and Osseospeed implants, representing early ECM organization at the bone-implant interface. These modifications determine the pattern of collagen cross-linking which in turn influences tissue organization, mineralization, and ultimately mechanical bone strength [56], and in the case of osseointegration, the integrity of the bone-implant interface [37]. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Osteoclastic activity and remodeling

While GFs regulate osteogenesis, pro-inflammatory CKs (e.g., IL-1, IL-6, TNF-α) simultaneously regulate the antagonist process of bone resorption via osteoclasts [23]. Moreover, osteoblasts themselves stimulate osteoclastogenesis via macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL) genes but also closely regulate this process via osteoprotegerin (OPG), an inhibitor of RANKL [59].

Two studies reported expression of genes associated with osteoclastic activity and ECM degradation (cathepsin-K (CTSK), tartarate-resistant acid phosphatase (ACP5), and/or matrix metalloproteinases (MMPs)), on Osseospeed and TiOBlast surfaces at day 7 [37], and SLActive surfaces at day 14. However, upregulation of MMP inhibitors (TIMP-2, -3) was also reported on TiOBlast and Osseospeed surfaces suggesting a control of the resorption process. Although no studies reported differential RANKL/OPG expression, a previous in vitro study [60] reported significant downregulation of osteoclastogenic genes on SLActive surfaces. Collectively, these data reaffirm the dynamic nature of bone formation and resorption at the implant-bone interface, even in early healing stages, and suggest the possibility for implant surface technology modulation of bone remodeling. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Angiogenesis

Angiogenesis is closely related to osteogenesis and occurs simultaneously during bone regeneration [11]. Physiological oxygen tensions in bone are about 12.5% O2 but fall to 1% O2 in regeneration sites due to disruption of the local vasculature as a result of injury and/or surgery [61,62]. A key event that stimulates angiogenesis (and osteogenesis) at regeneration sites is hypoxia, via the hypoxia inducible (transcription) factor-1 (HIF-1) that regulates expression of angiogenic genes [63]. The key cells involved in angiogenesis are macrophages, which in response to hypoxia and inflammation release chemotactic and angiogenic growth factors (e.g., VEGF) [40,64], and endothelial progenitor cells (EPCs) which differentiate into endothelial cell lining blood vessels [65]. VEGF is the single most important regulator of EPC differentiation and vessel formation [66]. Moreover, a role for VEGF in osteogenic differentiation has also been suggested mainly via interaction with the BMP signaling pathway [67].

In the present review, a significant simultaneous upregulation of several angiogenesis-related genes was identified at day 7 in all included studies. Pro-angiogenic factors (ANXA2, EPAS-1) were upregulated at TiOBlast and Osseospeed surfaces at day 7 [37]. Genes associated with VEGF and P13K-AKT signaling pathways were upregulated at SLActive (but not SLA) surfaces on day 7 and continued to be upregulated on day 14 [35]. The P13K-AKT pathway is reported to be important for endothelial cell survival, migration, and vessel formation, in addition to aiding VEGF-mediated angiogenesis [68]. Previous in vitro studies have reported the pro-angiogenic effects of SLActive surfaces by promoting VEGF expression in EPCs and osteoblasts [65,69], while enhanced histological osseointegration of SLActive implants has been directly correlated with increased angiogenesis in a dog model [70,71]. Thus, implant surface technology appears to have the possibility to also influence angiogenesis at early stages of wound healing. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Neurogenesis

Bone innervation includes both myelinated and unmyelinated nerve fibers located in the periosteum, bone cortex, Haversian systems, Volkmann’s canals, and the marrow spaces [72]. An interesting finding in the present review was the significant upregulation of genes associated with neurogenesis, more than any other biological process, on SLActive and SLA surfaces at all time points [34,35]. Specific processes represented were axon formation, growth and differentiation, and the neural signaling pathway. This is consistent with previous in vivoreports of murine fracture healing [73] and calvarial defect regeneration in relation to SLA surfaces [74,75]. Key neurotrophic factors (brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NTF3)), essential for neuronal survival and differentiation during development [76], were significantly upregulated on SLActive versus SLA surfaces at day 7 suggesting an effect of surface modulation. The P13K-AKT pathway, upregulated on SLActive surfaces (in relation to angiogenesis), has also been implicated in neuronal survival and subsequent neural development [77,78] and could have contributed to upregulation of neurogenic genes at these surfaces. Indeed, previous histologic reports have described changes in bone innervation after implant placement (and loading) and the presence of nerve fibers within the peri-implant bone, in animals and humans [7981]. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

It can be hypothesized that peri-implant neurogenesis is one of the underlying mechanisms governing the phenomenon of osseoperception, defined as the tactile sensibility of osseointegrated implants to occlusal forces induced via activation of nerve endings and/or receptors in the peri-implant environment [82,83]. Moreover, recent evidence suggests that implant surface properties may influence the degree of osseoperception in humans [84], which can be correlated with the genomic evidence for implant surface modulation of neurogenesis during osseointegration. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Finally, the present review findings are consistent with a recent gene expression study of healing extraction sockets in humans [85]. This study reported an initial upregulation of pro-inflammatory cytokines (IL-1, IL-6) at day 1, but by day 7, genes suggestive of immune response (IL-10), osteogenesis (TGF, BMP4, BMP7, OCN and ALP), and angiogenesis (VEGF) were upregulated, continuing until day 14, suggesting that the basic biological processes governing alveolar wound healing and osseointegration are the same.

Conclusions

Based on limited evidence of gene expression data from four studies involving 43 patients, the following remarks can be made:

  1. 1.

    Early peri-implant healing (2 weeks) involves a sequence of biological events which are similar to those observed in other bone wound healing scenarios (fractures, extraction-sockets).

  2. 2.

    Osseointegration depends on osteogenesis at the implant interface, but other simultaneously occurring processes such as inflammation, bone resorption, angiogenesis and neurogenesis also play an important role, as evidenced by consistent and concomitant gene expression.

  3. 3.

    Several genes associated with key regulators of biological processes, such as cells, cytokines, growth factors, transcription factors, signaling pathways, and secretory products, were shown to be differentially regulated during peri-implant healing in a manner that was largely consistent – in terms of nature and timing – with previous in vitro and preclinical in vivo histological studies of osseointegration.

  4. 4.

    Implant surface technology can influence osseointegration, at every step of the early wound healing process, i.e., anti-inflammatory response, progenitor cell recruitment, osteoinduction, growth factor/transcription factor expression, signaling pathway regulation, and extracellular matrix production. However, the relevance of those observations is questionable; no distinct differences have been demonstrated in terms of histological outcomes at later time points or short- and long-term clinical performance among the various implant surface technologies discussed herein.

Declarations

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Current status of implant prosthetics in Japan: a survey among certified dental lab technicians — International Journal of Implant Dentistry 2015 1:4

Current status of implant prosthetics in Japan: a survey among certified dental lab technicians

  • Yoshiyuki Hagiwara
  • Tatsuya Narita,
  • Yohei Shioda,
  • Keisuke Iwasaki,
  • Takayuki Ikeda,
  • Shunsuke Namaki and
  • Thomas J Salinas
International Journal of Implant Dentistry 2015 1:4

Received: 13 October 2014

Accepted: 22 January 2015

Published: 17 February 2015


Abstract

Background

There are many implant cases in which dental technicians take initiative with regard to the design of implant prostheses, and to a certain extent, this area of care is one in which dentists do not necessarily play the leading role. Moreover, inadequate communication between dental technicians and dentists and insufficient instructions for technicians has been highlighted as issues in the past. The purpose of this questionnaire is to improve the quality of implant prostheses and thereby contribute to patient service by clarifying, among other aspects of treatment, problem areas and considerations in the fabrication of implant prostheses, conceptual-level knowledge, and awareness of prosthodontics on the part of the dentists in charge of treatment and methods for preventing prosthetic complications. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Methods

A cross-sectional survey was given to 120 certified dental technicians. To facilitate coverage of a broad range of topics, we classified the survey content into the following four categories and included detailed questions for (1) the conditions under which implant technicians work, (2) implant fixed prostheses, (3) implant overdentures, and (4) prosthetic complications. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Results

Out of 120 surveys sent, 74 technicians responded resulting in a response rate of 61.6%.

Conclusions

This survey served to clarify the current state of implant prosthodontics, issues, and considerations in the fabrication of implant prostheses, and the state of prosthetic complications and preventive initiatives, all from a laboratory perspective. The results of this survey suggested that, to fabricate prostheses with a high level of predictability, functional utility, and aesthetic satisfaction, it is necessary to reaffirm the importance for dentists to increase their prosthetic knowledge and work together with dental technicians to develop comprehensive treatment plans, implement an organized approach to prosthesis design, and accomplish occlusal reconstruction.

Keywords

QuestionnaireSurveyImplant prosthesisCertified dental techniciansProsthetic complications

Background

Currently, dental implant treatment is evaluated on the basis not only of restoring masticatory function, but also a variety of other factors, including the implant and superstructure survival rate and psychological impacts [13]. Numerous factors must be taken into account, to offer highly predictable implant treatment, and there is no doubt that prosthetic-related factors such as the type and compatibility of the prosthesis, as well as occlusion, make a major contribution to that goal [49]. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Recently, a restoration-driven approach to implant treatment has gained recognition and is being put into practice on a broad basis [10,11]. However, an increasingly diverse range of patient cases has led to a situation in which it is impossible to ascertain such aspects of actual practice as prosthesis type and design, making it necessary to reaffirm the importance of treatment carried out from a prosthetic perspective [12]. Many surveys querying dentists or patients with regard to implant treatment have been reported in the literature, addressing such topics as the state of implant treatment in particular countries and regions [13,14], quality of life and patient satisfaction [1517], peri-implantitis and mucositis [18], and implant education [19,20]. However, very few surveys have queried dental technicians, whose job it is to fabricate implant prostheses [21,22].

Dental technicians play a major role in current implant treatment because of increases in both the importance of their participation as part of the treatment team from the treatment planning stage [21] and the frequency of prosthesis repairs, refabrication, and related procedures in the event of prosthetic complications. In particular, the types of prosthetic complications being experienced and associated trends are becoming clear thanks to numerous systematic reviews undertaken recently to investigate the implant complications. Fixed prostheses are prone to issues such as screw loosening, crown detachment, and fracturing of the veneering material on a frequent basis [2327]. Similarly, implant overdentures are frequently affected by progressive loosening of attachments, denture base fractures, and a sequential need for relining [28,29]. However, because understanding the status of these complications is based on the results of surveys targeting dentists, information is needed on the situation as seen from the standpoint of implant technicians, to clarify the causes of these complications and the techniques for dealing with them. Issues including inadequate communication between dental technicians and dentists and insufficient instructions for technicians have been pointed out in the past [21,30,31]. These reports derive from surveys targeting older fixed or removable prosthesis designs, leaving it unclear not only whether those issues have been rectified in the face of expanding use of implant prostheses in recent years, but also to what degree the opinions and wishes of dental technicians are being reflected in implant treatment.

This survey consists of a questionnaire targeting the certified dental technicians of the Japanese Society of Oral Implantology (JSOI) [32] who are primarily involved in fabricating dental implant restorations. It was formulated to clarify the current status of implant prostheses from a prosthetic and technician-oriented standpoint through questions addressing current trends among dental implant technicians, fixed prostheses, implant overdentures, and prosthetic complications and measures. The certified dental technicians of JSOI queried by the survey are involved in implant-related laboratory work on a comparatively frequent basis, and the responses they provided can be expected to accurately reflect the current state of implant laboratory practice in Japan. Our goal through this questionnaire is ultimately to improve the quality of implant prostheses and thereby contribute to patient service. We aim to do this by clarifying, among other aspects of treatment, problem areas, and considerations in the fabrication of implant prostheses, the conceptual-level knowledge base and awareness of prosthodontics on the part of the dentists in charge of treatment and methods for preventing prosthetic complications.

Methods

This cross-sectional questionnaire survey was performed among the certified dental technicians of JSOI from September to December in 2011. Selected were 120 out of 285 certified dental technicians of JSOI using a random number table and mailing each questionnaire directly to the participant. To facilitate coverage of a broad range of topics, the survey classified content into the following four categories and included detailed questions for each: (1) the conditions under which implant technicians work (questions 1 and 2); (2) implant fixed prostheses (methods of retention, abutment, and prosthesis types; questions 3–6); (3) implant overdentures (questions 7 and 8); and (4) prosthetic complications (complication types, methods of treatment and prevention; questions 9–14). Details of the questions and results are provided in Tables 123, and 4. Given that no previous survey regarding implant dental technician data had been developed, an original form for this purpose was constructed following suggested guidelines [33,34]. Important to the construction validity, both the questionnaire authors and their audience were clinical specialists and were aware of the topic content. The content sought in the questionnaire was a measure of responder demographics, clinical experiences, and subjective perceptions. Additionally, interpretation errors were minimized because of content familiarity and standardization, which improved reliability, and no pretest measures were obtained given the mail-based assessment method. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Table 1

Conditions characterizing implant laboratories

Question

Values

Q1. The years of experience working as a dental technician, and the number of dentists from whom job orders are received.

Mean (SD)

17.0 (6.8) years

36.5(12.4)/Lab.

Q2. Who takes the leading role in treatment planning and prosthetic design (initiative with regard to prostheses)?

Dentists mainly exercise initiative

39.3%

Technicians mainly exercise initiative

15.0%

Technicians are often consulted when it comes to specific cases and parts

16.8%

Decisions are made in collaboration with each other

28.9%

Table 2

Implant fixed prostheses

Question

Values

Q3. The percentages of implant fixed prostheses:

Cement-retained

61.4%

Screw-retained

38.6%

Q4. What are the proportions of abutments used with cement-retained prostheses?

CAD/CAM (titanium)

19.7%

CAD/CAM (zirconia)

12.1%

Custom abutments (UCLA-type abutment + gold alloy)

33.2%

Two-piece-type titanium (prepable type)

28.3%

Other

6.5%

Q5. What types of materials (i.e. veneer, coping) are used to make implant prostheses in the anterior region?

Porcelain fused to metal crown

43.4%

All ceramic crown (zirconia)

27.1%

All ceramic crown (other materials)

6.6%

Indirect composites (facing crown)

21.3%

Indirect composites (jacket crown)

2.4%

Q6. What types of implant fixed prostheses are used in the posterior region?

Porcelain fused to metal crown (full bake)

31.4%

Porcelain fused to metal crown (metal occlusal)

9.1%

All ceramic crown (zirconia)

14.3%

Indirect composite veneer crown (full bake)

22.3%

Indirect composite veneer crown (metal occlusal)

12.6%

Metal crown

10.3%

Table 3

Implant overdentures (IODs)

Question

Values

Q7. The design of the implant overdenture:

Decision made according to instructions of dentist

43.2%

Work is left to technicians

19.3%

Decided upon through consultation with each other

37.5%

Q8. What are the proportions of attachment types used with IODs?

Bar and clip

35.6%

Magnet

30.2%

Ball and socket

19.0%

Locator

5.2%

ERA

2.3%

Other

7.7%

Table 4

Prosthetic complications

Question

Values

Q9. What are the main issues generally encountered?

Compatibility precision issues

29.6%

Aesthetic issues

33.2%

Occlusal issues

37.2%

Q10. What are the main fabrication challenges faced?

Poor implant location and orientation

42.4%

Inadequate consideration of occlusion

17.0%

Defects and inaccuracies in impression and bite registration

29.0%

Defective or unreasonable prosthesis design

10.6%

Other

1.0%

Q11. What are the frequently received repair requests involving implant fixed prostheses?

Facing damage and chipping

54.5%

Facing discoloration and wear (indirect composite veneer crowns)

17.0%

Bridge connector fracture

10.0%

Design changes and modification associated with additional implants

13.9%

Other

4.6%

Q12. What kind of creative steps do you take in order to prevent veneer fracture and chipping in the molar region?

Use of metal occlusal designs

15.1%

Use of indirect composite resin material

15.7%

Devise metal coping designs

36.3%

Cover the distal-most part with metal

24.0%

Nothing in particular

8.9%

Q13. What are the frequently received repair requests for IODs?

Fracturing of the denture base or denture tooth detachment/fracture

53.8%

Mesostructure (attachment) damage

8.4%

Occlusal reconstruction due to denture wear or attrition

24.1%

Replacement of the attachment system (transition to another system)

8.1%

Other

5.6%

Q14. Do you have any requests for dentists who practice implant treatment?

To consult technicians or allow technicians to participate from the treatment planning stage

28.3%

To use suitable implant location and orientation

31.8%

To improve treatment and condition of soft tissue

21.8%

To study more about prostheses and occlusion

14.5%

Other

3.6%

Results and discussion

Out of 120 surveys sent, 74 technicians responded, resulting in a response rate of 61.6%. A summary of the responses is provided in Tables 123, and 4 and Figures 12345678, and 9.

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Figure 1

Q4. What are the proportions of abutments used with cement-retained prostheses?

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Figure 2

Q5. What types of materials (i.e. veneer, coping) are used to make implant prostheses in the anterior region?

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Figure 3

Q6. What types of implant fixed prostheses are used in the posterior region?

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Figure 4

Q8. What are the proportions of attachment types used with IODs?

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Figure 5

Q10. What are the main fabrication challenges faced?

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Figure 6

Q11. What are the frequently received repair requests involving implant fixed prostheses?

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Figure 7

Q12. What kind of creative steps do you take in order to prevent veneer fracture and chipping in the molar region?

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Figure 8

Q13. What are the frequently received repair requests for IODs?

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Figure 9

Q14. Do you have any requests for dentists who practice implant treatment?

Because implant treatment (implant prostheses) requires a significant amount of specialized, high-precision laboratory procedures, this area of dental care exhibits slightly different trends than prosthetic treatment as it was practiced in the past, and this work is concentrated at specialized fabrication labs. Moreover, there are many cases in which dental technicians take initiative with regard to the design of implant prostheses, and to a certain extent, this area of care is one in which dentists do not necessarily play the leading role. In light of these circumstances, it was intended for this questionnaire to verify trends in implant treatment from a different perspective than has been used in the past, by investigating the current state of practice in the field from the dental technician perspective. By evaluating implant treatment from the standpoint of dental technology/prosthodontics and identifying current trends and problem areas, it was expected to gain information that enables highly predictable implant treatment.

  1. 1.

    Conditions characterizing implant laboratories (Table 1)

    The dental technicians who responded to this questionnaire have an average of about 17 years of experience in the field, indicating that they possess an adequate level of fabrication experience. In light of the reality that dental implant treatment is a comparatively new field, these personnel can be proficient with digital techniques as they differ from past generations of technicians who practiced the craft. On average, each dental technician serves about 36.5 customers, although that number varies depending on the scale of the fabrication lab at which they work. While implant laboratory work consists of complex processes, the fees are high, and labs generate a stable flow of revenue given a constant stream of work requests (Q1).

    Dentists play a leading role in 39.3% of the time in implant treatment planning and prosthetic design, and dental technicians are consulted concerning cases and part usage 34.7% of the time, suggesting the approach to implants is driven by prosthetic considerations (by dentists) to some degree. However, because dental technicians indicated that they take the initiative 15% of the time, it is impossible to ignore issues involving the care, skill, and judgment of dentists offering implant treatment. This is distinct from the question of whether communication or information transmission between dentists and dental technicians is adequate, but rather relates to implant treatment knowledge, especially decisions about which prostheses and other treatment tools to use. The repercussions of this problem extend to the rate of incidence of prosthetic complications occurring after the start of functional use, their prevention, and the measures that are undertaken to address them (Q2). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

    Education of dental technicians varies by country, and there are a variety of means by which personnel master fabrication knowledge and skills. For example, a survey of dental technicians in the UK conducted by Bower et al. [35] reveals that while subjects read commercial magazines published for dental technicians, they rarely subscribed to academic journals in the field of prosthodontics, and two thirds of the survey’s respondents had never attended a training course on fabrication practices. By contrast, certified dental technicians of JSOI are required to belong to an academic society and to participate in society meetings and certification courses to maintain their credentials. Subscription to JSOI’s journal is an example of the advantages of membership for continuing education. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

  2. 2.

    Implant fixed prostheses (Table 2)

    Implant fixed prostheses employ either cement or screw retention. While there are a variety of reports comparing the two methods in terms of such metrics as their respective prognoses, success rates, and advantages and disadvantages [7,3638], no reports have been published concerning their relative frequency of use. Our questionnaire indicated a distribution of 61.4% cement-retained versus 38.6% screw-retained prostheses (Q3), suggesting that cement retention is used more frequently in Japan. Unfortunately, the fabrication-oriented focus of this survey prevented clarification of the types of cement used for cement retention and the breakdown between provisional and definitive cement.

    Next, concerning the types of abutments used with cement-retained prostheses (Q4) (Figure 1), CAD/CAM abutments accounted for about one third of the total (titanium, 19.7%; zirconia, 12.1%), and custom UCLA-type abutments made from cast gold alloy accounted for about the same proportion. It is likely that this breakdown is because, in many cases, implant systems using fabricated crowns are not supported by CAD/CAM abutments. CAD/CAM system use is also subject to numerous limitations because of the licensing process imposed by the Ministry of Health, Labour and Welfare (MHLW) in Japan, which is strict when compared with its constituents in other countries. The questionnaire also indicated that titanium two-piece abutments (preparable type) are used in about the same proportion; 28% of the time. This reflects such factors as efforts to keep laboratory costs down and to shorten delivery time frames, in addition to the above reasons. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

    Concerning the types of prostheses used in the anterior region (i.e., veneering materials), the questionnaire indicated a trend toward selection of roughly the same materials for both single crowns and bridges (Q5) (Figure 2). As a rule, porcelain fused to metal (PFM) crowns accounted for 43.7% of the total, but selection of metal-free restorations using zirconia has been increasing in recent years, reaching approximately 27.1%. Incidentally, veneering porcelain was also used as the veneer material for zirconia copings. The questionnaire also indicated that while highly filled indirect composites such as Estenia (Kuraray, Osaka, Japan) were used 21.3% of the time, primarily for facing crowns, these materials were used infrequently for jacket crowns (2.4%). There is a low risk of facing damage and chipping for prostheses in the anterior region. Nonetheless, the questionnaire revealed the unexpected result that indirect composite facing crowns accounted for 21.3% of the total. This may be because there are many indirect composite resins (Estenia, Ceramage, etc.) available in Japan, and crowns and bridges in the anterior region (natural abutment teeth) are covered by certain types of insurance in the country (National Health Insurance and Social Insurance), with the result that Japanese dentists are familiar with these materials and use them frequently. Consequently, it can be surmised that using these materials in implant prostheses is more common than in Europe and the USA. However, no survey of prosthesis selection has yet been carried out, and future research on that subject is expected.

    Concerning the types of prostheses used in the posterior region (Q6) (Figure 3), PFM design accounts for about 40% of the total, although the questionnaire also revealed a trend (in 9.1% of all cases) toward metal occlusal designs to avoid fracture and chipping of the veneer material. The same trend is evident in indirect composite facing crowns, where metal occlusal designs are used in about 35% of all cases that this type of prosthesis represents. In the past, the PFM crown was frequently used in implant crowns and bridges. However, a trend is seen toward increasing indirect composite resin use as a veneer material for implant superstructures. In addition to improvements in the physical properties (strength, wear resistance, and discoloration resistance) of indirect composites in recent years, their selection as veneer materials that chemically bond to titanium against the backdrop of increasing CAD/CAM-designed titanium frameworks, because of the low reliability of veneering porcelain, in terms of bonding strength, when used with titanium frames. There is also a greater possibility of direct (in-mouth) repair of failed veneering materials and greater shock-absorbing potential relative to occlusal force in comparison with porcelain [39]. The trend to adhere resin materials instead of porcelain, from Brånemark and colleagues’ recommendations for acrylic resin as an occlusal surface material in the early 1980s, also cannot be ignored [40]. All metal crowns were used about 10.3% of the time in molar regions because of a lack of strong aesthetic requirements. Zirconia, however, accounted for 14.3%; only about half of its use in the anterior region. Possible reasons include this region not being an aesthetic area and veneer material fracture and chipping problems that have yet to be completely resolved [23,41,42]. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

  3. 3.

    Implant overdentures (IODs) (Table 3)

    Some 19% of IOD design work is left to technicians, while 80% is performed according to the instructions of, or in consultation with, dentists (Q7). As was the case with the question concerning overall prosthesis design described above, these results indicate that a team approach is being put into practice.

    Bar and clip attachments were most commonly used for IODs, followed by magnet, ball, and socket, and Locator attachments (Q8) (Figure 4). It is noteworthy among the questionnaire results that magnetic attachment use is highest in Asian countries, including Japan [43]. Additionally, it is thought that the low use of Locators (5.2%) is strongly influenced by Japan’s strict pharmaceutical regulations and because the MHLW in Japan had not yet licensed the device at the time the questionnaire was administered. Conversely, ball and socket attachments have been standardized by major implant manufacturers, and the freedom with which prefabricated parts can be used has led to their comparatively broad use. IOD use in Japan is by no means widespread; a survey of IOD use in ten countries by Carlsson et al. [44] revealed that the adoption rate of these devices in Japan was just 7% for individuals with mandibular edentulism. This number was lower than in any of the other nine countries, and future changes in IOD use in Japan are a topic that remains interesting.

  4. 4.

    Prosthetic complications (Table 4)

    According to Papaspyridakos et al. [2], indicators such as implant level (the relationship between the implant and bone) and the state of soft tissue around the implant are the most frequently used indices of implant success, followed by the presence and status of any implant prosthetic complication. Implant prosthetic complications include materials science-related factors, biomechanical and occlusion-related factors, and aesthetic factors. A systematic review of numerous complications that have been reported recently reveals the prostheses, restoration methods, materials, and areas most susceptible to complications [2,2329]. Additionally, the frequency of prosthesis repairs, and repair costs cannot be ignored from a medical economic standpoint [2]. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

    Of the problems and issues generally encountered on the laboratory side, compatibility precision, aesthetic issues, and occlusal issues each accounted for about one third of the total (Q9). When these results are examined in connection with laboratory challenges (Q10) (Figure 5), it becomes clear that technicians regard poor implant location and orientation (42.4%) as obstacles to success. Many other issues derived from factors such as dentists’ skill level and treatment planning knowledge are directly related to quality implant treatment, such as defects and inaccuracies in impression-taking and bite registration (29%), inadequate establishment of appropriate occlusal schemes (17%), and deficient or unreasonable prosthesis design (10.6%). These issues can easily give rise to a variety of prosthetic complications after initiating functional use (and may also lead to biological complications), and dentists who offer dental implant treatment should reflect on improving their techniques. In particular, unsuitable implant locations, positions, and orientations can be prevented through appropriate preoperative examination and planning based on diagnostic wax-ups and surgical templates.

    Looking at repair requests (i.e., complications) involving the superstructures of fixed implant prostheses (Q11) (Figure 6), facing damage and chipping accounted for more than half of all requests (54.5%). Generally speaking, there are many reports that indicate a high incidence of complications related to fixed prostheses involving abutment screw loosening, detachment of cement-retained crowns, and veneer (porcelain/composite resin) fracturing and damage. Because this question addressed repair of implant prostheses, we did not obtain information about complications that can be resolved in a chair-side setting. However, the high rate of requests for facing repairs makes it clear that veneer material chipping and similar issues are occurring at a high frequency [2527]. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

    Although the literature includes reports indicating a greater incidence of chipping and fractures for veneering porcelain than hardened resin [45,46] and for bridges than single crowns [26,27], this questionnaire does not shed light on the relative repair rates for porcelain and composite resin, nor the types of prostheses most likely to experience these issues. In the future, it would be worthwhile to conduct follow-up surveys on the differences among veneering materials and prostheses as well as veneer material failure trends.

    Other cases requiring repair seen by technicians include facing discoloration (veneering composite resin) (17%) (Figure 7) and design changes and modification requests associated with additional implants (13.9%). Studies have pointed to issues related to degradation of materials science characteristics for veneering composites that are distinct from those associated with porcelain, including loss of glossiness because of the deterioration of the surface and discoloration, wear, and attrition due to long-term use [47]. It is interesting to note how relatively frequently repairs are performed to address these issues. It has become clear that no small number of laboratory work requests deal with these issues experienced by patients undergoing implant treatment because of changes over time in the area surrounding existing implant treatments that occasionally necessitate additional implants and superstructure design changes or modifications.

    The questionnaire revealed several creative steps, based on laboratory considerations, being taken to prevent veneer chipping and fractures, a frequent and problematic prosthetic complication (Q12) (Figure 7). Technicians were taking into account metal (including zirconia) coping designs (36.3%), covering only the distal-most part of the molar region with metal (24%), using veneering composite resin (15.7%), and using metal occlusal designs (15.1%). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

    The type of coping is important in preventing veneer fractures, and it is necessary to secure adequate veneering material thickness and to consider the dispersion of stress [48]. Particularly as zirconia becomes more common, there has been a move to improve coping designs using CAD/CAM and to exercise care concerning the prevention of veneering porcelain fracture [49,50]. Responses to this survey support the idea that this concept has been gaining popularity among technicians in recent years.

    Conversely, it was not expected that 15.7% of respondents would indicate that they use composite resin to prevent veneering material fractures. Moreover, there is no evidence that veneering composites are more resistant to fracture than porcelain (as they are more prone to chipping) [45,46]. As noted above, veneering composites are often used in Japan, and one theory is that this trend is driven by a conceptual assumption that veneering composites are softer than porcelain and less likely to fracture from a materials science standpoint. It can be concluded that the ability to repair prostheses directly in the mouth is also a deciding factor. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

    More than half of all repair requests for IODs (i.e., complications) (Q13) (Figure 8) involve fracturing of the denture base or denture tooth detachment (53.8% of all repair requests). The questionnaire also revealed that reconstruction of occlusion because of wear or attrition of denture teeth (24.1%) is a frequent issue leading to laboratory orders. While the literature includes reports of frequent IOD-related prosthetic complications such as attachment-related compromised retention, detachment or fracturing of denture teeth, relining, and attachment damage [25,28,29], this survey showed a somewhat different trend. It can be inferred that these results differ from actual complication trends because they constitute responses to cases sent to labs as repair requests, and because the survey targeted dental technicians. The causes of this phenomenon can be found in responses to other questions as described above. In short, the questionnaire suggested the possibility that inadequate awareness of prosthetics is making IOD complications in Japan more complex, with issues including the comparatively frequent use of resin bases, problems with implant location and orientation, and inadequate consideration of occlusion by dentists.

    Finally, technicians gave voice to the several requests for dentists, who are their customers, as a result of their daily experiences accomplishing implant laboratory procedures (Q14) (Figure 9). These included asking dentists to use suitable implant location and orientation (31.8%), to allow technicians to participate and consult with technicians from the treatment planning stage (28.3%), to improve consideration of soft tissue as well as its condition (21.8%), and to add more in-depth knowledge of prosthesis and occlusal design (14.5%). As observed, implant location and orientation issues in particular not only complicate technical work, but may also cause a variety of complications after the initiation of loading. For cases involving a broad range of implant prostheses and occlusal reconstruction, if not all cases, the dental technicians should be a part of the team from the treatment planning stage to enable restoration-driven implant treatment in the true sense of the term. At the same time, a dentist with an extensive understanding of prosthodontics should play the leading role in treatment of such cases. This survey succeeded in identifying prosthetic problems by examining implant prosthetic complications from the dental technician’s perspective. As stated in the description of the survey’s purpose, it is hoped that dentists make use of this report to reaffirm prosthetic concepts and awareness so that there is achievement of predictable implant prosthetic treatment.

Conclusions

This survey served to clarify the current status of implant prosthodontics, issues, and considerations in their fabrication, and the status of prosthetic complications and preventive initiatives, all from a laboratory perspective.

  1. 1.

    Concerning implant treatment, it was concluded that dentists either play the leading role or work in collaboration with technicians, including in the formulation of treatment direction and that a team approach has been achieved to a certain extent. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

  2. 2.

    This survey identified the problems that technicians address on a frequent basis in the fabrication of prostheses (these should be noted by dentists), including implant location and angulation, impression and bite registration precision, and occlusal considerations. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

  3. 3.

    Concerning prevention of veneer fractures, it was also concluded that the best approach consists of metal occlusal (including a metal backing for the distal-most area) and coping designs.

  4. 4.

    The results of this survey suggest that, to fabricate prostheses with a high level of predictability, functional utility, and aesthetic satisfaction, it is necessary to reaffirm the importance of dentists increasing their prosthetic knowledge and working together with dental technicians to develop comprehensive treatment plans, design prostheses, and accomplish occlusal reconstruction.

Declarations

Acknowledgements

This paper was partially supported by a Grant-in-Aid for Scientific Research (C) (No. 24592935) from the Japan Society for the Promotion of Science.

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The relationship between the bone characters obtained by CBCT and primary stability of the implants

The relationship between the bone characters obtained by CBCT and primary stability of the implants

  • Masahiro Wada
  • Yasutane Tsuiki,
  • Tohru Suganami,
  • Kazunori Ikebe,
  • Motofumi Sogo,
  • Ikuhisa Okuno and
  • Yoshinobu Maeda
International Journal of Implant Dentistry 2015 1:3

Received: 18 September 2014

Accepted: 20 November 2014

Published: 12 February 2015


Abstract

Background

The aim of this study is to investigate the correlation between the thickness of the cortical bone or the voxel values that are obtained by cone beam CT (CBCT) and the insertion torque values (ITVs) or the implant stability quotient (ISQ) values. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Methods

A pig’s ilium was used as the implant placement site. The implants used in this study were two kinds of diameters (3.8 mm, 5.0 mm) and two kinds of lengths (7.0 mm, 12.0 mm) having a general threadlike shape with a mechanically polished surface. To measure the bone density and the cortical thickness around the implants accurately, the CBCT scanning was performed immediately just after the formation of the implant cavity. The initial stabilities were evaluated by the ITVs and the ISQ values. The bone density and cortical thickness around the implants were measured by an implant simulation software (Landmarker ver. 5.0 with special specifications for this study). The relationships of the thickness of the cortical bone and the voxel values with the ITVs and the ISQ values were analyzed using Pearson’s correlation coefficient. To evaluate the influence on the ITVs and the ISQ values among multiple factors, multiple regression analysis was performed. P < 0.05 was considered statistically significant.

Results

A significant positive correlation was found between the thickness of the cortical bone and the ITVs or the ISQ values in all kinds of implants. In addition, a significant positive correlation was also found between the voxel values and the ITVs. From the multiple regression analysis, the thickness of the cortical bone and the voxel values had a positive influence on the ITVs and the ISQ values. In addition, the length of the implant had a positive influence on the ISQ values at the 3.8-mm-diameter implant. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Conclusions

In this limited study, there were correlations between the thickness of the cortical bone or the voxel values obtained from the CBCT scanning and the implant stabilities. Besides, it was confirmed that the thickness of the cortical bone, the voxel value, and the implant length had positive correlations with the ITVs and the ISQ values.

Keywords

Primary stabilityCBCTVoxel value

Background

The primary stability of an implant at the time of placement is considered as one of the key factors for clinical success of implant treatment [16]. Orenstein et al. reported that implants that were appropriately stabilized without any mobility at the time of placement had a significantly high survival rate compared with those that were not [7].

The evaluation of the primary implant stability is usually performed after placement. Some of the main methods include mobility test, resonance frequency analysis, and the measurements of the removal torque values and the insertion torque values (ITVs). In particular, the measurement of the removal torque values is an objective evaluation method, but its clinical application is difficult because it is an irreversible and invasive method. Mobility test is useful for the evaluation of an implant whose osseointegration was surely obtained, but there is a possibility that the primary stability could decrease by the impact of the tapping head. On the other hand, the measurement of ITVs and the measurement of implant stability quotient (ISQ) values by using a resonance frequency analyzer are non-invasive, convenient, and objective evaluation methods. Therefore, these methods are used for evaluation in various researches investigating the primary stability including immediate loading implants [811].

The primary stability is significantly affected by bone quality. Herrmann conducted a study of the prognosis for as long as more than 5 years and reported that poor bone quality and quantity had a major impact on the long-term failure rate of implants [12]. Jaffin observed the prognosis of implants for 5 years after providing the final restoration [13]. As a result, the failure rate of the implants was 3% when the implant was placed in the alveolar bone having a thick cortical bone or otherwise a dense spongy bone even if the cortical bone was thin, whereas it was 35% when the implant was placed in the alveolar bone having both a thin cortical bone and a sparse spongy bone. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Some of the methods to evaluate the bone quality that influences the primary implant stability have already been applied in a clinical practice. Lekholm and Zarb classified bone density into four types in terms of radiography, with the thickness of the cortical bone and the density of the spongy bone as the indexes [14]. This classification method is accepted most commonly at present but is problematic with accuracy and reproducibility because it is a subjective evaluation. On the other hand, Misch classified CT values (Hounsfield unit) into five steps (D1: >1,250 HU; D2: 850 to 1,250 HU; D3: 350 to 850 HU; D4: 150 to 350 HU; D5: <150 HU) to evaluate the bone quality [15]. The CT value is the value obtained by multi-detector CT (MDCT) and is defined as the relative value of the X-ray attenuation coefficient of the object for water, with the X-ray attenuation by water defined as zero. Today, this classification has been used for the evaluation of the bone quality because it is an objective method compared with that of Lekholm and Zarb. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Turkyilmaz et al. placed 24 implants in human dry bones and calculated CT values using MDCT images before surgery to examine correlations with the ITVs and the ISQ values [16]. They reported that there were significant correlations of CT values with both ITVs and ISQ values and that bone density (CT value) was one of the factors that had an influence on the primary implant stability. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

In recent years, cone beam CT (CBCT) has been used for preoperative diagnosis in implant treatment. CBCT is superior for its high definition, reduction of the exposure dose, low cost, and usability compared with MDCT [1721]. However, CBCT does not have a linear relationship compared with the CT values obtained by MDCT, and therefore, it is considered difficult to evaluate bone density quantitatively [2224]. The major causes arise from the lack of calibration of X-rays, the localized imaging area that allows various external anatomical structures, and too many scattered radiations. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

It is therefore considered that MDCT is appropriate for the precise evaluation of bone density. However, since the use of CBCT is spreading rapidly among general practitioners, it is clinically of great significance to predict the primary stability after implant placement using the information obtained by CBCT. In addition, in late years, CBCT or the calibration software which can convert the voxel values into CT values is developed.

We therefore investigated in this study the correlation between the thickness of the cortical bone or the voxel values that are obtained by CBCT and the ITVs or the ISQ values.

Methods

Bone models

A flat part of a pig’s ilium was used as the implant placement site to secure as vertical implant placement and an equal depth of insertion to the bone surface as possible (Figure 1).

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Figure 1

The bone model in this study (a pig’s ilium). (a) The whole picture of the ilium. (b) The flat part of the posterior margin of the ilium. (c) The CT image of the ilium.

CBCT scan

GXCB-500® (GENDEX, Des Plaines, IL, USA) was used as the CBCT device to obtain almost identical voxel values to the CT values that could be obtained from MDCT. Scanning conditions were as follows: the tube current, 5 mA; the tube voltage, 120 kV; the field of view (FOV), 85-mm diameter to secure a complete size for scanning; and the voxel size, 0.1 mm3. In addition, the scanning was performed by immersing the samples in a polypropylene container with water in it to create as similar scanning environment as possible to the one that had soft tissues around the bone model. Of note, the scanning was performed immediately just after the formation of the implant cavity to accurately measure the voxel values around the inserted implants.

Implants

External Hex Implants for laboratory use (SETiO®, GC Company, Tokyo, Japan) having a general threadlike shape with a mechanically polished surface were used. They were two kinds of diameters (3.8 mm, 5.0 mm) and two kinds of lengths (7.0 mm, 12.0 mm) consisting a total of four groups, and 25 pieces of implants were used in each group (Figure 2).

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Figure 2

The implants in this study. Two kinds of diameters (3.8 mm, 5.0 mm) and two kinds of lengths (7.0 mm, 12.0 mm) having a general threadlike shape with a mechanically polished surface.

Formation of the implant cavities

When forming an implant cavity, it is necessary to move the drill back and forth along the insertion direction. This process is usually done by an operator with freehand, but it is likely to cause unevenness in the diameter of the implant cavity. Therefore, an implant cavity-forming device was used to prevent this in our experiment (Figure 3). This device is able to adjust the up-and-down movement speed and the rotation speed of the drill. In this study, the implant cavity was constructed at a moving speed of 5 mm/s that was close to the actual up-and-down movement speed obtained from the preliminary experiment and at 800 rpm according to the manufacturer’s protocol. It was also confirmed in the preliminary experiment that using this device would significantly reduce the unevenness of the diameter of the implant cavity.

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Figure 3

The special implant cavity-forming device. This device is able to adjust the up-and-down movement speed and the rotation speed of the drill.

All the procedures of forming an implant cavity were unified as follows according to protocols. Firstly, the implant cavity was constructed by using a 2.0-mm-depth drill after marking the implant site using a guide drill. Secondly, a 3.1-mm pilot drill and a 3.1-mm twist drill were used to form a cavity for an implant with 3.8-mm diameter, and a 4.3-mm pilot drill and a 4.3-mm twist drill were used to form a cavity for an implant with 5.0-mm diameter. Of note, this experiment was performed under a non-irrigation environment because the rise of temperature would not be problematic. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Placement of an implant and the measurement of the implant stabilities

Handy Type Torque Meter (HTG2-200NC, IMADA-SS Corp, Aichi, Japan) was used for the placement of an implant, and the maximum torque values were measured. The specifications of the Handy Type Torque Meter were as follows: the measurement unit, Ncm; the accuracy, within ±0.5% FS; the measurement maximum torque, 200 Ncm; and the minimum resolution function, 0.1 Ncm. Thus, the device had enough coverage of the torque measurement in this study (96.0 Ncm at maximum). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Osstell Mentor® (Integration Diagnostics AB, Gôteborg, Sweden) was used as a resonance frequency analysis device to measure the ISQ values. The accompanying smart peg (type 1) was attached to the implant for the measurement at every 90°, and the average value was calculated.

Measurement of the voxel values and the thickness of the cortical bone around implants

An implant simulation software (Landmarker ver. 5.0 with special specifications for study purposes, iCAT, Osaka, Japan) was used for analysis. The evaluation site was selected on the smallest area that was as adjacent to the implant as possible so as not to include the area that was immune to the primary stability. Specifically, the width of the measurement site was defined as 0.50 mm, i.e., from 0.25 mm inside (the to-be-compressed area at the time of placement) to 0.25 mm outside of the virtual implant. The area adjacent to the bottom of the implant was excluded from the measurement site because the maximum torque value and the ISQ value were both subject to the lateral force a great deal (Figures 4 and 5). Then, the voxel values of the measurement site were extracted into the comma-separated values (CSV) files. Subsequently, the average of the voxel values of the measurement site was calculated and defined as the voxel value of the whole bone around the implant. Additionally, the average of the voxel values was calculated at every 0.1-mm depth from the surface of the bone to determine the thickness of the cortical bone from the voxel values. The threshold of the voxel value for the border of the cortical bone and the spongy bone was decided to be 350, which had a strong correlation (Pearson’s correlation coefficient, 0.897) with the actual measurement in the preliminary examination.

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Figure 4

Setting the evaluation site. An implant placement simulation software (Osaka Landmarker ver. 5.0 with special specifications for study purposes, iCAT, Osaka, Japan) was used as the image analysis software. The virtual implant was placed in the implant cavity by simulation.

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Figure 5

Measurement site of the voxel values. The width of the measurement site was defined as 0.50 mm, i.e., from 0.25 mm inside (the to-be-compressed area at the time of placement) to 0.25 mm outside (the same width of the aforementioned) of the virtual implant.

Statistical analysis

The relationships of the thickness of the cortical bone and the voxel values with the ITVs and the ISQ values were analyzed using Pearson’s correlation coefficient. Then, multiple regression analysis was performed using the ITVs or the ISQ values as the dependent variable and using the thickness of the cortical bone, the voxel value, and the length of the implant as the independent variables to evaluate the influence on the ITVs and the ISQ values among multiple factors. The statistical analyses were performed using the SPSS ver. 22 software (SPSS Co., Chicago, IL, USA). P < 0.05 was considered statistically significant. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Results

Relationship between the thickness of the cortical bone and voxel values with implant stabilities

A significant positive correlation was found between the thickness of the cortical bone and ITVs or ISQ values in all kinds of implants. In addition, a significant positive correlation was also found between the voxel values and ITVs. On the other hand, in the relationship between the voxel values and ISQ values, we cannot confirm a correlation of the implant of 5.0 mm in width and 12.0 mm in length (Table 1).

Table 1

Correlation between bone factors and stability factors

Bone factors/stability factors

Diameter (mm)

Length (mm)

r

P

n

Thickness of the cortical bone/ITVs

3.8

7

0.744**

<0.001

24

12

0.560**

0.005

23

5

7

0.815**

<0.001

25

12

0.760**

<0.001

24

Thickness of the cortical bone/ISQ

3.8

7

0.831**

<0.001

24

12

0.409

0.052

23

5

7

0.707**

<0.001

25

12

0.426*

0.038

24

Voxel values/ITVs

3.8

7

0.601**

0.002

24

12

0.745**

<0.001

23

5

7

0.850**

<0.001

25

12

0.667**

<0.001

24

Voxel values/ISQ

3.8

7

0.684**

<0.001

24

12

0.447*

0.032

23

5

7

0.695**

<0.001

25

12

0.270

0.202

24

ITVs, insertion torque values. **P < 0.01; *P < 0.05.

Influence of the implant of 3.8 mm in width on the ITVs and the ISQ values of each factor

Multiple regression analysis was performed using the ITVs or the ISQ values as the dependent variable and using the thickness of the cortical bone, the voxel value, and the length of the implant as the independent variables. The standardized partial regression coefficients of the thickness of the cortical bone and the voxel value were 0.400 and 0.459, respectively, which turned out to be significant explanatory variables. However, that of the length of the implant did not become an explanatory variable. When using the ISQ values as the independent variable, the standardized partial regression coefficients of the thickness of the cortical bone, the voxel value, and the length of the implant were 0.326, 0.304, and 0.420, respectively, all of which became significant explanatory variables. From these results, it was confirmed that the thickness of the cortical bone and the voxel values had a positive influence on ITVs, while the thickness of the cortical bone, the voxel value, and the length of the implant had a positive influence on the ISQ values (Table 2). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Table 2

Statistical analysis of the results of the multiple regression analysis of the 3.8-mm-width implant

Dependent variable = ITVs

(n = 47)

Independent variables

Standardized partial regression coefficient (P value)

 Thickness of the cortical bone

0.400 (=0.02)

 Voxel value

0.459 (<0.01)

 Length of the implant

0.005 (=0.97)

R 2 = 0.633

Dependent variable = ISQ values

(n = 47)

Independent variables

Standardized partial regression coefficient (P value)

 Thickness of the cortical bone

0.326 (=0.04)

 Voxel value

0.304 (<0.01)

 Length of the implant

0.420 (<0.01)

R 2 = 0.593

Influence of each factor of the implant of 5.0 mm in width on ITVs and the ISQ values

The standardized partial regression coefficients of ITVs for the thickness of the cortical bone and the length of the implant were 0.408 and 0.526, respectively, which became significant explanatory variables. In addition, those of the ISQ values for the thickness of the cortical bone and the length of the implant were 0.440 and 0.750, respectively, which also became significant explanatory variables. From these results, it was confirmed that the thickness of the cortical bone and the length of the implant had a positive influence on ITVs and the ISQ values. However, the voxel value of ITVs and that of the ISQ values failed to become explanatory variables (Table 3).

Table 3

Statistical analysis of the results of the multiple regression analysis of the 5.0-mm-width implant

Dependent variable = ITVs

(n = 49)

Independent variables

Standardized partial regression coefficient (P value)

 Thickness of the cortical bone

0.408 (=0.04)

 Voxel value

0.365 (=0.10)

 Length of the implant

0.526 (<0.01)

R 2 = 0.638

Dependent variable = ISQ values

(n = 49)

Independent variables

Standardized partial regression coefficient (P value)

 Thickness of the cortical bone

0.440 (=0.02)

 Voxel value

−0.060 (=0.98)

 Length of the implant

0.750 (<0.01)

R 2 = 0.836

Discussion

Measurement of the cortical bone thickness and the voxel values

Ikumi used a MDCT scan for actual patients to calculate the CT values of the 1-mm surrounding area of the planned implant placement site using implant simulation software [25]. However, it is likely that the precise measurement cannot be performed in the case where the actual implant cavity was formed off the planned implant site because the density of the bone around the planned implant site was evaluated by preoperative simulation.

Therefore, we evaluated the bone quality 0.5 mm surrounding the implant, which was thought to have a strong effect on the primary stabilities, by CBCT scanning after forming the implant cavities.

Nkenke used an axial image to define the thickness of the cortical bone from the average thickness of the cortical bone around the implant measured by eye estimation and then evaluated its relationship with ITVs [26]. Whereas in this study, we measured the thickness of the cortical bone by setting the threshold for the voxel values around the implant for the purpose of securing reproducibility of the measurement of the thickness of the cortical bone. The threshold that we set was determined in the preliminary experiment so that it would highly correlate with the measurement values of the thickness of the cortical bone measured by eye estimation. Conversely, the limitation of this study is that the CBCT device is lacking some precision for estimation of bone density compared to quantitative computed tomography. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Relationship between the thickness of the cortical bone and the voxel values measured by CBCT and the primary stability of the implant

To date, there are several studies that investigated the relationship between the thickness of the cortical bone and the primary stability of the implant. Motoyoshi placed a total of 87 mini-implants, which were used as anchors for orthodontic treatment, in the buccal alveolar bone in the molar region of actual patients [27]. As a result, they reported that they found a positive significant correlation between the thickness of the cortical bone measured by using medical CT images and the torque value at the time of placement. Roze measured the thickness of the cortical bone of the jawbones in three human bodies using μCT and placed a total of 22 implants [28]. According to this report, there was a significant correlation between the thickness of the cortical bone and the ISQ values measured immediately after the implant placement. Furthermore, Isoda reported a significant correlation between the bone quality around the implants and the implant stabilities. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Although this study is different from the previous studies in that the thickness of the cortical bone and bone density were determined from the voxel values calculated by CBCT, a significantly positive correlation of the thickness of the cortical bone and the voxel values with ITVs and ISQ values was confirmed as in the previous studies. Furthermore, the multiple regression analysis with the ITVs and the ISQ values as the dependent variables showed that the thickness of the cortical bone as well as the voxel values had a positive influence.

Based on these results, it was revealed that the thickness of the cortical bone obtained from CBCT had a correlation with the ITVs and the ISQ values which are the indexes of the primary stability of the implant. It was also revealed that the voxel values correlated with ITVs and ISQ values. It is desirable to be able to infer the primary stability at the time of implant placement not only from the thickness of the cortical bone but also from the voxel values, if the cortical bone cannot be observed on the CT images of the extraction socket immediately after or at a certain period of time after the tooth extraction (until the maturation of the bone). Conversely, there was no statistical correlation between the voxel values and ISQ values among 5-mm-diameter, 12-mm-length implants. These ISQ values were high enough regardless of bone densities, and this caused that the correlation did not confirm between voxel values and ISQ values. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

In addition, these results were confirmed by using mechanically polished surface implants. Therefore, it is thought that primary stability becomes more stable by using rough-surface implants.

Conclusions

In this limited study, there was a correlation between the thickness of the cortical bone or the voxel values obtained from the CBCT scanning images prior to the implant placement and the implant stabilities. Besides, it was confirmed that the thickness of the cortical bone, the voxel value, and the length of the implant had positive correlations with the ITVs and that the thickness and length had positive correlations with the ISQ values.

Declarations

Acknowledgements

This study was partially supported by GC Company.

References

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Evaluation of implant-materials as cell carriers for dental stem cells under in vitro conditions — International Journal of Implant Dentistry 2015 1:2

Evaluation of implant-materials as cell carriers for dental stem cells under in vitro conditions

  • Martin Gosau,
  • Sandra Viale-Bouroncle,
  • Hannah Eickhoff,
  • Esthera Prateeptongkum,
  • Anja Reck,
  • W Götz,
  • Christoph Klingelhöffer,
  • Steffen Müller and
  • Christian Morsczeck
International Journal of Implant Dentistry 2015 1:2

Received: 17 September 2014

Accepted: 20 November 2014

Published: 12 February 2015


Abstract

Background

Dental stem cells in combination with implant materials may become an alternative to autologous bone transplants. For tissue engineering different types of soft and rigid implant materials are available, but little is known about the viability and the osteogenic differentiation of dental stem cells on these different types of materials. According to previous studies we proposed that rigid bone substitute materials are superior to soft materials for dental tissue engineering. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Methods

We evaluated the proliferation, the induction of apoptosis and the osteogenic differentiation of dental stem/progenitor cells on a synthetic bone-like material and on an allograft product. The soft materials silicone and polyacrylamide (PA) were used for comparison. Precursor cells from the dental follicle (DFCs) and progenitor cells from the dental apical papilla of retained third molar tooth (dNC-PCs) were applied as dental stem cells in our study.

Results

Both dental cell types attached and grew on rigid bone substitute materials, but they did not grow on soft materials. Moreover, rigid bone substitute materials only sustained the osteogenic differentiation of dental stem cells, although the allograft product induced apoptosis in both dental cell types. Remarkably, PA, silicone and the synthetic bone substitute material did not induce the apoptosis in dental cells. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Conclusions

Our work supports the hypothesis that bone substitute materials are suitable for dental stem cell tissue engineering. Furthermore, we also suggest that the induction of apoptosis by bone substitute materials may not impair the proliferation and the differentiation of dental stem cells. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Keywords

Dental stem cellsHydroxyapatiteAllograft productOsteogenic differentiationSilicone

Background

While bone substitute materials are routinely used, especially vertical bone, augmentation of the jaws is still a problematic step. Dental stem cells in combination with bone substitute materials may accelerate the augmentation of alveolar bone and perhaps, stem cell-based therapies can become an alternative to autologous, allogenic, or synthetic bone transplants and substitutes [1,2]. However, scaffolds are required for cell delivery, and here, commercially available bone substitute materials could be an excellent source for dental tissue engineering.

For more than 10 years, human dental stem cell research has focused on the identification and characterization of human stem/progenitor cell populations, which can be isolated, for example, from retained third molars of juvenile patients [3]. One example for such type of dental stem cells are undifferentiated cells from the dental follicle (DFCs) [4,5]. These highly proliferative cells can be differentiated in vitro into periodontal ligament (PDL) cells, cementoblasts and osteoblasts, and into PDL-like cells in vivo [4]. Preliminary results from animal studies suggested that DFCs have also a good osteogenic differentiation potential and could be an excellent source for the regeneration of craniofacial bone [6]. Another excellent source for cellular therapies of mineralized tissues is progenitor cells from the dental apical papilla of retained third molar tooth (dNC-PCs) [7]. These dental cells differentiate into osteoblast-like cells after the induction with osteogenic differentiation medium under in vitroconditions and under in vivo conditions in immunocompromised mice [8].

For the osteogenic differentiation under in vivo conditions, stem cells are combined actually with hydroxyl-apatite (HAP) or β tricalcium phosphate (TCP) scaffolds [4,9]. Although this is routinely applied, we know only little about the adherence and the viability of dental progenitor cells on these implant materials. Conversely, an optimal bone substitute material has not been identified so far for different dental stem cell types. In a recent study, we investigated, therefore, cell survival/proliferation and cell differentiation of DFCs in combination with a commercially available TCP [10]. Here, DFCs attached on TCP and cell numbers increased after 6 days of cultivation. We showed that DFCs had a typical flattened-shaped morphology with close contacts to the bone substitute material [10]. Interestingly, the gene expression of osteogenic markers such as osteopontin or RUNX2 was increased, and the alkaline phosphatase (ALP) activity was induced on TCP in differentiated DFCs [10]. All these data support the assumption that TCP could be the optimal scaffold for a successful differentiation protocol of DFC.

Unfortunately, an additional study showed that TCP induced apoptosis in DFCs [11]. However, the induction of apoptosis exposed a risk for cellular therapies. We decided therefore to evaluate additional implant materials for the identification of a suitable scaffold for dental stem cells. Soft materials such as silicone are successfully used in regenerative medicine, and they are suitable for tissue engineering, but, however, we propose that rigid and bone-like materials are superior for dental tissue engineering than soft implant materials. Therefore, this study evaluated and compared solid bone substitute materials with elastic materials such as silicone or polyacrylamide (PA). This study investigated the proliferation, the induction of apoptosis, and the osteogenic differentiation of DFCs and dNC-PCs after the attachment on implant-materials. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Methods

Cell culture

The isolation and characterization of DFCs and dNC-PCs were described in previous studies [4,7,12]. DFCs were routinely cultivated in DMEM (Sigma-Aldrich, St. Louis, MO, USA) supplemented with 10% fetal bovine serum (Sigma-Aldrich, St. Louis, MO, USA) and 100 μg/ml penicillin/streptomycin (standard cell culture medium). dNC-PCs were cultivated in DMEM (Sigma-Aldrich) supplemented with 15% fetal bovine serum (Sigma-Aldrich) and 100 μg/ml penicillin/streptomycin (standard cell culture medium). For experiments, both cell types were used after passage 6. DFCs and dNC-PCs expressed typical markers for dental stem cells such as CD105, Nestin, and STRO-1 (Additional file 1: Figure S1). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Preparation of polyacrylamide materials

Five milliliter of PA gel solution with the concentration of 8% acrylamide and 0.06% bis-acrylamide (Bio-Rad, Hercules, CA, USA) were mixed and degas under vacuum for at least 20 min to remove oxygen. Then, 30 μl of 0.1 mg/mL ammonium persulfate (Sigma-Aldrich, St. Louis, MO, USA) and 20 μl TEMED (Applichem, Omaha, NE, USA) were added and placed into the mini protean casting strand and frame (Bio-Rad) to form 1-mm thickness of substrate. After letting the gel to polymerize for 30 to 45 min, gently remove and rinse gel with 50-mM HEPES, pH 8.5 (Applichem, Omaha, NE, USA). PA gel was then cut into circular shape with 14 mm diameters and placed in 24 well plates for the experiment. Sulfo-SANPAH (Pierce Biotechnologies, Rockford, IL USA) 0.5 mg/mL in 50-mM HEPES, pH 8.5 was pipetted onto the surface and exposed to the UV light for photoactivation procedure. After photoactivation, the substrate was washed several times in 50-mM HEPES. A 0.2 mg/mL of type I collagen (Sigma-Aldrich, St. Louis, MO, USA) was then layered onto the surface of gel and incubated 4 h at room temperature or overnight at 4°C on a shaker. After washing with PBS, the gels were stored in PBS at 4°C. Before platting the cells, the gel was exposed to UV for 15 min for the sterilization and replace PBS with complete culture medium for 1 h at 37°C. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Implant materials

The bone substitutes Maxgraft® (AP) and Maxresorb® (SB) were obtained from the company Botiss (botiss dental GmbH, Berlin, Germany). Maxgraft® is a sterile, high-safety allograft product (AP), derived from human donor bone. It is processed by an audited and certified bone bank (Cells+ Tissue Bank Austria, Berlin, Germany). In contrast, Maxresorb® is a fully synthetic bone graft substitute (SB) with controlled resorption properties. It is a homogenous composition of 60% hydroxyapatite and 40% beta-tri-calcium phosphate. SB maintains the volume and mechanical stability over a long time period. The osteoconductivity of SB is achieved by a matrix of interconnecting pores and a very high porosity of approximately 80%, as well as pore sizes from 200 to 800 μm (www.botiss.com). Experiments with AP and SB were done with solid blocks (10 × 10 × 20 mm cancellous block). PA was produced in our lab (see above), and silicone-based implant materials were obtained from Vivomed (Downpatrick, UK) as tubes. Silicone tubes were cut in pieces with a size which is similar to that of AP and SB.

Implant materials were washed with PBS or cell culture medium before use. DFCs and dNC-PCs were seeded onto materials for indicated periods of time. For the isolation of total RNA and the estimation of vital cell numbers, implant materials with cells were transferred to a fresh well with cell culture medium.

For the evaluation of apoptosis induction, cell culture eluates were produced by incubating 0.1 mL of bone substitutes or soft materials in 1-mL standard medium at 37°C for 24 h. This incubation step with the implant material was repeated twice with fresh cell culture media. Three eluates were pooled for cell culture experiments. DFCs were seeded onto cell culture plates and cultivated in standard cell culture media. After cell seeding (12 to 24 h), cell culture media were changed, and cells were cultivated in cell culture media with material eluates. After 24 h of cultivation, cells were harvested for flow cytometry analyses or protein isolation for Western blots (see below). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Cell counting kit 8 assay

Numbers of vital cells were evaluated after days 1, 2, 3, and 6. For cell counting, cell cultures were incubated with the cell counting kit 8 (CCK8) ready to use solution according to manufactures instructions (Dojindo, Rockville, MD, USA). The optical density (O.D.) was measured at a wavelength of 450 nm. For the evaluation of the cell adherence (normalized to standard cell culture dishes), cell proliferation (normalized to cell number at day 1 of cell culture) relative cell numbers were calculated. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Flow cytometry analysis

The induction of apoptosis in DFCs and dNC-PCs was evaluated by measuring the Cell Event® Caspase3/7 Green Flow cytometry assay (Life Technologies, Carlsbad, CA, USA). For the Caspase3/7assay, cells were cultivated in eluates as described above. After 24 h, cells were harvested by trypsin-EDTA treatment, washed with PBS, and stained first with Caspase3/7 Green Detection Reagent (25 min, 37°C). After this step 1-mM SYTOX® AADvanced dead cell stain solution was added to the sample (5 min, 37°C). Cell fluorescence was analyzed at 488-nm excitation and applied to standard fluorescence compensation. Emission of fluorescence was measured with 530/30 BP (Caspase3/7 Green Detection Reagent) and with 690/50 BP (SYTOX® AADvanced dead cell stain) filters. Cells positive for Caspase3/7 Green Detection Reagent were identified as apoptotic cells, while dead cells were positive for SYTOX® AADvanced dead cell stain. However, vital cells were negatively stained for both staining solutions.

Western blotting

For protein isolation, cells were treated with lysis buffer (250 μl phosphatase, 100 mM Na3VO4, 137 mM NaCl, 200 mM Tris, 480 mM NaF, 1% NP-40, 10% Glycerol) on ice for 2 min. A protease-inhibitor (1 Protease Inhibitor Cocktail tablet from Roche) was included to minimize protein degradation. Cell lysates were placed on ice for 10 min. Protein samples were separated by SDS-polyacrylamide gel electrophoresis in pre-casted 12% Tris-glycine gels (Invitrogen, Waltham, MA, USA) and blotted to nitrocellulose membranes. Membranes were blocked with skimmed milk for 1 h and incubated with primary antibodies that were specific for proteins BAX (pro apoptotic protein), BCL2 (anti apoptotic protein), and β-Actin (housekeeper protein). Washed membranes were then incubated with a horseradish peroxidase-labeled secondary antibody. The detection of the secondary antibody was performed via chemiluminescence and X-ray films (GE Healthcare, Pewaukee, WI, USA).

Osteogenic differentiation

DFCs were cultivated until sub-confluence (>80%) in standard cell culture medium before the differentiation starts with the osteogenic differentiation medium (ODM) comprised DMEM (PAA) supplemented with 10% fetal bovine serum (Sigma-Aldrich), 100 μmol/L ascorbic acid 2-phosphate, 10 mmol/L KH2PO4, 1 × 10−8 mol/L dexamethasone sodium phosphate (Sigma-Aldrich, St. Louis, MO, USA), HEPES (20 mmol/L) and 100 μg/ml penicillin/streptomycin. The differentiation was evaluated by qRT-PCR and ALP activity detection.

ALP activity detection

Cells were washed with PBS buffer and lysed by shock freezing (−80°C). Diluted 1:1 in 1 × PBS, 100 mM p-nitrophenyl phosphate (Sigma) was added to each sample. After incubation at 37°C for 60 min, the reaction was stopped by adding 300 μL of 0.3 M NaOH and the liberated p-nitrophenol was measured at 405 nm. ALP activity values were normalized to total DNA concentration, which were determined by the Quant-iT PicoGreen dsDNA Assay (Invitrogen). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Prime PCR arrays

For the evaluation of osteogenic marker expression, the Biorad PrimePCR array (Development – Hedgehog and PTH signaling pathways in bone and cartilage development) was used, which consists of the most important markers for the osteogenic differentiation. Total RNAs, which were isolated from differentiated dental cells at day 7, were reverse-transcripted with the iScript™ Advanced cDNA Synthesis Kit for RT-qPCR (Biorad) according to the manufacturers protocol. PCRs were made with SsoAdvanced™ Universal SYBR® Green Supermix (Biorad) on the StepOne real-time PCR machine (Life Technologies, Carlsbad, CA, USA). Results were analyzed with the PrimePCR™ Analysis Software (Biorad), and the output is presented as Clustergrams. While red tiles signify a high gene expression, black/gray and green tiles show a middle gene expression and a low gene expression, respectively. Black tiles with a cross designate no gene expression. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Histology

Combinations of SB with dNC-PCs and AP with dental cells yielded from cell cultures after 7 days of osteogenic differentiation were fixed in 4% formaldehyde/0.1 M PBS at 4°C for at least 24 h. Tissues were decalcified with EDTA and subsequently dehydrated in an ascending series of ethanol and embedded in paraffin. Serial sections of 5 μm were cut in different planes for orientation and stained with hematoxylin-eosin (HE).

Results

Cell viability

Dental cells were cultivated in standard cell culture media until passage 6. Cell adherence and cell proliferation/growth were measured for the estimation of cell viability on tested rigid and soft materials. In Figure 1, the cell adherence of dNC-PCs on bone substitute materials was better than that of DFCs. However, both dental cells types adhered very well on silicone. Unluckily, dental cells did not adhere on PA; only single cells survived for longer than 48 h (Figure 1B). For the evaluation of cell proliferation, relative cell numbers on implant materials were measured (Figure 2). While cell proliferation of dNC-PCs was moderate (Figure 2A), relative cell numbers of DFCs increased dramatically on bone substitute materials (Figure 2B). However, these results proved the viability of dNC-PCs and DFCs on SB and AP. Interestingly, dental cells formed large spheroid cell clusters on silicone, but cells lost their adherence to this material (Figure 2C), so numbers of silicone adherent cells decreased until day 6 of cell culture (data not shown). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

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Figure 1

Cell attachment on tested materials. (A) Relative cell adherence of DFCs and dNC-PCs; (B) dental cells did little adhere on PA; representative pictures of DFCs.

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Figure 2

C ell proliferation of dNC-PCs and DFCs on tested materials. (A) and (B) Relative cell numbers; (C)spheroid cell clusters on silicone (representative pictures for DFCs); Silicone (24 and 48 h).

The induction of apoptosis and/or cell death was estimated by flow cytometry and western-blot analyses (Figure 3). While eluates of SB, PA, and silicone did neither induce cell death nor apoptosis, AP induced both cell death and apoptosis in DFCs and dNC-PCs. Both dental cell types expressed the pro-apoptotic marker BAX and the anti-apoptosis marker BCL2 under standard cell culture conditions (Figure 3B). However, BCL2 was not expressed on AP. Interestingly, BCL2 was also not expressed in DFCs after cultivation on SB. The low expression of BCL2 in DFCs may explain the low cell adherence on SB and AP (Figure 1). مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

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Figure 3

Evaluation of programmed cell death (apoptosis) in dental stem cells. (A) Flow cytometry analyses (for details materials and methods) show percentage of vital cells (black number), apoptotic cells (blue number), and dead cells (red number). (B) Western blot analyses show the expression of the pro-apoptotic marker BAX and the anti-apoptotic marker BCL2.

Osteogenic differentiation

We measured the normalized ALP activity in dNC-PCs and DFCs after cultivation on tested materials (Figure 4). While ALP activities in dental cells on bone substitutes were increased or comparable to that of differentiated cells in standard cell culture dishes (control), the specific ALP activity was decreased on silicone (Figure 4B). A PCR array analysis showed that AP induced the expression of osteogenic differentiation markers (Figure 5A). Moreover, differentiated cells formed thick connective tissue like matrices on bone substitute materials (Figure 5B). These results reminded on the differentiation of osteogenic progenitor cells.

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Figure 4

Osteogenic differentiation of dental stem cells. Normalized ALP activity of dNC-PCs and DFCs on AP and SB (A) and on silicone (B). Cells were differentiated on standard cell culture dishes for control.

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Figure 5

Evaluation of osteogenic differentiation. (A) Clustergram of PCR-array results; (B-C) histology of differentiated dental cells on AP (B) and SB (C). Representative results are shown for dNC-PCs.

PA after collagen I modification

The soft material PA was also treated with the extracellular matrix protein collagen to improve cell adherence. We tested representatively DFCs with collagen I modified PA. DFCs adhered and proliferated on modified PA, but, however, the specific ALP activity was reduced in comparison to that of DFCs on standard cell culture dishes (Figure 6). This reduction of the specific ALP activity was similar to that of silicone.

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Figure 6

Cultivation and osteogenic differentiation of DFCs on PA after modification with collagen I. (Left) Relative cell number and (Right) normalized ALP activity.

Discussion

Scaffolds play an important role in tissue engineering. However, little is known about the proliferation and differentiation of DFCs and dNC-PCs on different types of materials. As we have learned from previous studies mechanical properties such as surface stiffness are decisive for a successful osteogenic differentiation of dental stem cells [13,14]. Moreover, we showed that bone substitute materials such as β-tricalcium phosphate (TCP) supports the osteogenic differentiation [10]. Our study proposed therefore that bone-like materials such as commercially available bone substitutes are superior for dental tissue engineering. Therefore, bone substitute materials SB and AP were compared with soft or connective tissue like materials. SB is synthetic and consists of 60% HAP and 40% TCP. In contrast, AP is an allograft product, which was derived from human donor bone. For comparison, two different soft materials silicone or PA were used in our study. Whereas silicone is routinely applied in regenerative medicine, the self-made PA scaffold has been very often used in cell biology studies [15].

dNC-PCs and DFCs attached on SB, AP, and silicone, but not on PA unless it was untreated. A modification with the extracellular matrix protein collagen permitted the attachment of dental cells. Interestingly, cell proliferation on silicone was hampered, because dental cells grew in non-attached spheroid cell clusters. This formation of spheroid cell clusters reminds on the neurogenic differentiation of DFCs [1618]. The proliferation of DFCs on SB and AP was better than that of dNC-PCs, because the attachment of DFCs on these materials was lower than that of dNC-PCs. However, we conclude that bone substitute materials are suitable for dental cell attachment and proliferation. Our results for bone substitute materials are comparable to that of previous studies with different dental cell types. Kasaj and co-workers showed that cell adherence and cell proliferation of PDL cells on nanostructured HAP bone replacement grafts in vitro [19]. In another study, PDL cells adhere and proliferate on chitosan or on a combination of chitosan and nanostructured HAP [20]. In this setting, the combination of chitosan and nanostructured HAP was even favored by PDL cells. The adhesion and proliferation of dental pulp derived cells on HAP was demonstrated by Abe et al. [21]. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

In a previous study, we showed that TCP induced the programmed cell death (apoptosis) in DFCs [11]. Our new study investigated therefore the induction of apoptosis in dental cells. While SB and soft materials did not induce apoptosis or cell death, AP induced obviously cell death and apoptosis in dental cells. Here, the results for dNC-PCs and DFCs were almost the same. Interestingly, neither silicone nor PA induced the apoptosis in dental cells but did not also sustain the osteogenic differentiation of dental cells. Here, the ALP activity was strongly inhibited. Although no explanation for the induction of apoptosis by AP is available, the induction of apoptosis by AP does not correlate with the induction of the osteogenic differentiation. Both bone substitute materials sustained the differentiation, but only AP induced the expression of typical osteogenic differentiation markers. The induction of both osteogenic markers and apoptosis is very similar to that of our previous studies with TCP [10,11]. Interestingly, a study with pre-differentiated human cord blood stem cells showed also very similar effects on TCP [22]. They discovered a reduced number of pre-differentiated stem cells after long term cultures on TCP [22]. But although cell numbers decreased between days 1 and 7, the gene expression of osteogenic cell differentiation markers was increased [22]. In contrast, Marino et al. demonstrated that TCP scaffolds promoted both cell proliferation and osteogenic differentiation of human adipose stem cells [23]. However, additional studies are required to disclose the molecular relationship between apoptosis and the osteogenic differentiation. مقالات دندانپزشکی رایگان با متن کامل مقاله فقط در سایت تخصصی ستاتیرا

Finally, we could show that surface modifications are important for the attachment and cell proliferation of dental cells (Figure 6). Our results are in accordance to the results obtained in previous studies. For example, modifications such as fibronectin coating of TCP or composites with a combination of polymer of poly glycolic-lactic acid (PGLA) with TCP may also influence cell attachment and proliferation of seeded cells [24,25]. Moreover, Seebach et al. showed that TCP products from different suppliers differ substantially in their morphology and that surface or porous structure seems to be of importance for the cell seeding and proliferation [25]. Unfortunately, a modification of PA with collagen did not improve the osteogenic differentiation of dental stem cells.

Conclusions

In conclusion, our work supports our hypothesis that soft implant materials are not suitable for dental tissue engineering. Moreover, our study also supports the results of our previous studies with DFCs and TCP that induction of apoptosis did not impair the proliferation and the differentiation in dental stem cells.

Declarations

Acknowledgement

This study was supported by a grant from the Deutschen Gesellschaft für Implantologie (DGI) e.V.

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