Purpose: To evaluate the controlled release effect of Clarithromycin loaded in PLGA microspheres in a rabbit calvaria defect model. Methods: Clarithromycin-loaded PLGA microspheres (MSPs) were formulated by modified O/W single emulsion/solvent evaporation method. After characterization, in vivo animal experiment was conducted. Four critical size bone defects were created in the calvaria of New Zealand White rabbits (n=21, n=7/time point). The bone defects were randomly designated to 4 groups: Group 1: No augmentation (sham), Group 2: beta-Tricalcium phosphate (β-TCP), Group 3: beta-Tricalcium phosphate (β-TCP) with 0.12 µg clarithromycin, and Group 4: beta-Tricalcium phosphate (β-TCP) with 6.12 µg PLGA microspheres (loaded with 0.12 µg clarithromycin). After 2, 4 and 12 weeks of healing, the levels of bone regeneration were evaluated using micro- computed tomography and histology. Results: The average size of the PLGA microspheres was 26.38 μm that showed 94% encapsulation efficacy with clarithromycin. Clarithromycin release from PLGA microspheres revealed sustained release for around 4 weeks with approximately 50% release of clarithromycin during the first week. In the histological analysis, new bone formation was evident at 2 and 4 weeks of healing in all groups and bone formation increased as a function of healing time in vivo. At 12 weeks, Group 4 showed significantly higher amount of newly formed bone compared to Group 1 (p=0,002). Moreover, during the micro CT exam, Group 4 expressed significantly higher bone formation compared to Group 1 at all time points tested (p=0.00, 0.014, and 0.002 in 2, 4, and 12 weeks, respectively). Conclusions: PLGA microspheres demonstrated initial burst release of clarithromycin followed by a sustained release profile. The in vivo findings showed that β-TCP with clarithromycin-loaded microspheres can enhance bone formation in bone defects.

PURPOSE: There is no clinical consensus to determine the right balance between underpreparation and marginal bone level changes. The purpose of this systematic review and meta-regression was to investigate the influence of the type of drilling preparation of the implant site in relation to the bone mineral density on the clinical success, expressed in terms of the MBL and implant failure rate.

STUDY SELECTION: A thorough search was performed using the digital databases MEDLINE PubMed, EMBASE, and Cochrane Central Register of Controlled Trials by entering research lines or various combinations of free words. The main keywords used were "dental implants", "bone density", and "torque".

RESULTS: The mean bone resorption in the conventional preparation group was -0.43 (± 0.28) mm, whereas it was -0.80 (± 0.37) mm in the underprepared group. For the D1/D2/D3 bone group, the slope was significantly different from zero and linearity; the D4 bone group slope was not significantly different from zero and was almost parallel, although it was significantly different from linearity. The box and whiskers plot shows that the MBL in underprepared sites tended to be significantly higher with a higher variation than that in conventionally prepared sites.

CONCLUSION: Within its limits, our meta-regression analysis showed that MBL is influenced by the type of drilling preparation and bone mineral density. In particular, a lower MBL was observed in the D1 bone with conventional preparation than with underpreparation. Moreover, a greater implant-to-osteotomy site mismatch was positively associated with greater MBLs in the bone densities of D1/D2/D3.

We previously reported that CaCl2 hydrothermal-treated (Ca-HT) titanium (Ti) implants induced a tight sealing at the interface between the implant and peri-implant epithelium (PIE) after implantation. However, it is not clear how long this improved epithelium sealing can be maintained. We subsequently investigated whether the positive effect of Ca-HT to promote sealing between the PIE and implant was sustained longer term. Maxillary molars were extracted from rats and replaced with either Ca-HT implants (Ca-HT group), distilled water-HT implants (DW-HT group) or non-treated implants (control group). After 16 weeks, the majority of implants in the Ca-HT group remained at the maxillary with no apical extension of the PIE. Conversely, half the number of control implants was lost following down-growth of the PIE. The effect of Ca-HT on migration and proliferation of rat oral epithelial cells (OECs) was also investigated. In OECs cultured on Ca-HT Ti plates, protein expression in relation to cell migration decreased, and proliferation was higher than other groups. Surface analysis indicated HT enhanced the formation of surface TiO2 layer without altering surface topography. Consequently, Ca-HT of Ti reduced PIE down-growth via tight epithelial attachment to the surface, which may enhance implant capability for a longer time post-implantation.

The aim of this study was to evaluate the amount of bone formation beneath a defect area after treatment with titanium mesh membranes with different thicknesses and pore sizes alone or in combination with bone graft to induce bone formation during the early stage of healing time. The mandibular premolars were extracted bilaterally from three adult beagle dogs, and 8-mm-diameter bone defects were created on the buccal site of the premolar regions. Hydroxyapatite bone graft substitute was applied in the defect site unilaterally, and other site was left empty. Then, a novel micro-porous mesh (50 μm in pore diameter) or commercially available macro-porous titanium mesh (1700 μm in pore diameter) was placed on the defect and secured with screws. After 4 weeks, the mandibles were harvested, imaged using micro-computed tomography, and prepared for histological and morphometric evaluation. Higher new bone volumes (mm3), percentage of new bone volumes in the total defect volumes (bone ratio: %), and new bone area (mm2) through morphometric evaluation were found on the novel membranes with 50-μm-diameter pores compared to the commercial titanium mesh. Moreover, experiment sites without bone graft were observed with higher new bone volume and bone ratio compared with sites with bone graft. However, bone mineral density of novel mesh was observed to be lower compared with other experimental sites. Under the experimental condition, the result of this study suggests that titanium meshes with 50-μm-diameter pores were effective for guided bone regeneration in the early stage of healing.

Objectives: The release of magnesium ions (Mg21) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improve- ment in osseointegration would influence the bone remodel- ing also during the maturation stage of bone healing. Methods: Titanium implants were coated with mesoporous titania layers and either loaded with Mg21 (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical test- ing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR. Results: Mg21 releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), colla- gen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups. Significance: The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation.

Objectives: When implants are inserted, the initial implant stability is dependent on the mechanical stability. To increase the initial stability, it was hypothesized that bone condensation implants will enhance the mechanical stability initially and that the moderately rough surface will further contribute to the secondary stability by enhanced osseointegration. It was further hypothesized that as the healing progresses the difference in removal torque will diminish. In addition, a 3D model was developed to simulate the interfacial shear strength. This was converted to a theoretical removal torque that was compared to the removal torque obtained in vivo. Material and methods: Condensation implants, inducing bone strains of 0.015, were installed into the left tibia of 24 rabbits. Non-condensation implants were installed into the right tibia. All implants had a moderately rough surface. The implants had an implantation time of 7, 28, or 84 days before the removal torque was measured. The interfacial shear strength at different healing time was estimated by the means of finite element method. Results: At 7 days of healing, the condensation implant had an increased removal torque compared to the non-bone-condensation implant. At 28 and 84 days of healing, there was no difference in removal torque. The simulated interfacial shear strength ratios of bone condensation implants at different implantation time were in line with the in vivo data. Conclusions: Moderately rough implants that initially induce bone strain during installation have increased stability during the early healing period. In addition, the finite element method may be used to evaluate differences in interlocking capacity.

Objectives The objective of this study is to develop a Ti fibre knit block without sintering, and to evaluate its deformability and new bone formation in vivo. Material and Methods A Ti fibre with a diameter of 150 μm was knitted to fabricate a Ti mesh tube. The mesh tube was compressed in a metal mould to fabricate porous Ti fibre knit blocks with three different porosities of 88%, 69%, and 50%. The elastic modulus and deformability were evaluated using a compression test. The knit block was implanted into bone defects of a rabbit’s hind limb, and new bone formation was evaluated using micro computed tomography (micro-CT) analysis and histological analysis. Results The knit blocks with 88% porosity showed excellent deformability, indicating potential appropriateness for bone defect filling. Although the porosities of the knit block were different, they indicated similar elastic modulus smaller than 1 GPa. The elastic modulus after deformation increased linearly as the applied compression stress increased. The micro-CT analysis indicated that in the block with 50% porosity new bone filled nearly all of the pore volume four weeks after implantation. In contrast, in the block with 88% porosity, new bone filled less than half of the pore volume even 12 weeks after implantation. The histological analysis also indicated new bone formation in the block. Conclusions The titanium fibre knit block with high porosity is potentially appropriate for bone defect filling, indicating good bone ingrowth after porosity reduction with applied compression.

Our aim was to try and find out whether contamination with saliva during insertion of dental implants affects osseointegration in bone that has been augmented with different grafts. Six bony defects were created in each of the calvaria of six sheep, and then augmented with three different materials (autogenous bone, bovine bone, and resorbable biphasic ceramic bone substitute) After five weeks of healing, three implants contaminated with saliva (contaminated group) and three not contaminated (uncontaminated group) were placed in the centre of the augmented areas. For histomorphometric analysis, bone implant contact, bone area fraction occupancy, bone and material area, and bony area were measured after a healing period of five weeks. There was a significant difference between the contaminated and uncontaminated groups (p=0.036) for bone implant contact only in the augmented areas, but there were no significant differences in bone area fraction occupancy, bone and material area, and bony area. We conclude that contamination with saliva during placement of dental implants can significantly compromise bone implant contact in augmented areas, but had no significant effect on the formation of bone in areas more distant from the surface of the implant. We suggest that salivary contamination should be avoided during placement of dental implants in augmented areas.

Purpose: The purpose of this study was to examine the volumetric alterations and osseointegration properties in the augmented area of the ring technique using different types of bone graft material in sheep mandible bone. Materials and Methods: Three different materials (columnar forms, 7-mm diameter, 3-mm height) were stabilized using dental implants with a turned surface in the mandible bone of Finnish Dorset cross-bred sheep: group A, autogenous bone; group B, bovine bone; group C, biphasic bone substitute. Animals were euthanized after 5 weeks (N = 6). Three-dimensional image data by digital oral scanner were taken at the surgery and sacrifice, and the volume alteration of the material was calculated. The bone samples were fixed in formalin and dehydrated in ethanol. Resin-embedded samples were subjected to non-decalcified ground sectioning, and histologic and histomorphometric analysis (bone and material area alteration, bone-to-implant contact [BIC]) were done. Results: In three-dimensional (3D) image analysis, group A showed a statistically higher percentage of remaining materials compared with groups B and C. The histologic observation showed no new bone formations around the implants in all groups, especially at the maxillary site of the implant in the augmented area. In histomorphometric analysis, group A showed a statistically higher percentage of bone area (BA) compared with groups B and C; however, in all groups, bone-to-implant contact (BIC) showed low values, and there were no statistical differences between groups. Conclusion: The results of this study suggested that the autogenous bone maintained bone volume around the dental implant using the ring technique, and the impact of surface properties was of some importance; osseointegration with the turned surface in the augmented area showed low BIC values in all groups.

PURPOSE: Based on the current evidence, the effect of implant macrogeometry has a significant influence on osseointegration. Thus, this study evaluated histomorphometrically and histologically the bone response to acid-etched in comparison to grit-blasted/acid-etched (GB) and machined control (C) surfaced implants possessing identical macrogeometry placed in high-density bone. MATERIALS AND METHODS: Implant surface topography of the 3 different surfaced implants has previously been characterized. The macrogeometry of the implants were conical, and healing chambers were created in the cortical regions. The 3 groups were placed in the external mandibular body of adult male sheep (n = 5). After 6 weeks in vivo, all samples were retrieved for histologic observation and histomorphometry (eg, bone-to-implant contact [BIC] and bone area fraction occupancy [BAFO]). RESULTS: No statistical difference was observed for BIC and for BAFO, although there was a tendency that the mean values for BAFO was higher for the textured surface groups. CONCLUSIONS: It is suggested that the effect of surface topography is minimal in high-density bone and osseointegration seemed to be macrogeometry dependent.

Our aim was to investigate the possible impact of contamination with saliva on osseointegration during placement of implants with simultaneous bone augmentation. Six hemispheric shape bone defects (8mm in diameter×4mm deep) were prepared in each iliac bone of six sheep. A dental implant (2.9mm in diameter×10mm long) was placed in the centre of each defect, and then pairs of defects were filled with one of the following bone augmentation materials: autogenous bone, autogenous bone plus bovine bone, or resorbable biphasic ceramic bone substitute. One site in each augmentation group was impregnated with saliva (contaminated group), while the other was not (non-contaminated group). Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within implant threads were measured after a healing period of five weeks, both in respect of the implant inserted in the augmented bone and in that inserted in the residual bone. Overall results showed that there was a significant difference between the contaminated and non-contaminated group for BIC in the augmented implant (p=0.028), while there were no significant differences in the implant in residual bone (p=0.722). For BAFO, there were no significant differences between the contaminated and non-contaminated groups among the different augmentation materials. The results showed that contamination with saliva during placement of an implant with simultaneous bone augmentation had a serious deleterious effect on osseointegration of the aspect of the implant within the augmented defect. Contamination with saliva during placement of an implant with simultaneous bone augmentation should therefore be avoided.

This study aimed to evaluate the effect of surface hydrophilicity on the biomechanical aspects of osseointegration of dental implants in the tibia and femur of rabbits. Forty-eight mature female New Zealand White rabbits were included, and 96 commercially pure, Grade 4, titanium dental implants (control group), and 96 implants of same macro geometry with the hydrophilic surface (test group) were used in this study. One osteotomy was performed in each tibia and femur on both sides of the rabbit, and four implants were placed in each rabbit. Control and test groups were randomly allocated on the left and right sides. During surgery, insertion torque (ITQ) value of the complete implant placement was recorded. After healing periods of 0, 2, 4, and 8 weeks after surgery, Implant Stability Quotient (ISQ) value, and removal torque (RTQ) values were measured. No statistical difference was observed for ITQ, for ISQ and for RTQ between the control group and test group in tibia/femur for all time periods. The effect of hydrophilic properties on moderately roughened surfaces has no impact in terms of biomechanical outcomes (ISQ values and RTQ values) after a healing period of 2 to 8 weeks in rabbit tibias /femurs.

OBJECTIVES: The aim of this study was to evaluate whether salivary contamination during placement of implants with different surface characteristics affects osseointegration in native and in augmented bone areas.

MATERIALS AND METHODS: Forty eight implants with machined surface (MS) and 48 implants with moderately rough surface (RS) were tested in the calvaria of 12 sheep. At the first surgery, 64 bony critical defects were randomly created and were subsequently augmented with two materials (autogenous or bovine bone). After 5 weeks of graft healing, 8 implants were placed per sheep, in native bone and in the centre of the augmented defects. Forty eight implants were soaked with saliva before placement (contaminated group [CG]), while 48 implants were not (non-contaminated group [NCG]). Five weeks after implant placement, bone-to-implant contact (BIC) and bone material area fraction occupancy (BMAFO) were calculated histomorphometrically.

RESULTS: Saliva contamination showed a significant negative effect (p = .000) on BIC, especially in augmented areas. RS showed significant positive effect on BIC, compared to MS (p = .000), while there were no significant differences for different bone conditions (p = .103). For BMAFO, the contamination showed a significantly negative affect (p = .000), while there were no significant differences for surface characteristics (p = .322) and for bone condition (p = .538).

CONCLUSION: Saliva contamination during dental implant placement has a negative effect on osseointegration in augmented areas. Moderately rough surface has a possible advantage in the aspect of initial bone to implant contact. However, it seems to be advisable to avoid saliva contamination especially for implants placed in augmented bone areas.

This study investigated the level of magnetic energy around implants possessing a static magnetic field (SMF) and assessed the in vivo influence of SMF on bone regeneration. Implants possessing a sintered neodymium magnet internally were placed in a rabbit femur. An implant without SMF was placed as control. After 12 weeks of healing in vivo, the bone samples were subjected to histologic/histomorphometric evaluation. The bone-to-implant contact for the test group and the control group were 32.4 +/- 13.6% and 17.1 +/- 4.5%, respectively, and the differences were statistically significant (P < .05). The results suggested that the SMF promoted new bone apposition.

Purpose: The aim of this study was to evaluate the effectiveness of a novel bone substitute material fabricated using a biodegradable polymer-calcium phosphate nanoparticle composite. Methods: Porous structured poly-L-lactic acid (PLLA) and hydroxyapatite (HA) nanoparticle composite, which was fabricated using solid-liquid phase separation and freeze-drying methods, was grafted into bone defects created in rat calvarium or tibia. Rats were killed 4 weeks after surgery, and histological analyses were performed to evaluate new bone formation. Results: Scanning electron microscopic observation showed the interconnecting pores within the material and the pore diameter was approximately 100 to 300 mm. HA nanoparticles were observed to be embedded into the PLLA beams. In the calvarial implantation model, abundant blood vessels and fibroblastic cells were observed penetrating into pores, and in the tibia model, newly formed bone was present around and within the composite. Conclusions: The PLLA-HA nanoparticle composite bone substitute developed in this study showed biocompatibility, elasticity, and operability and thus has potential as a novel bone substitute.

BACKGROUND: The intraosseous temperature during implant installation has never been evaluated in an in vivo controlled setup. The aims were to investigate the influence of a drilling protocol and implant surface on the intraosseous temperature during implant installation, to evaluate the influence of temperature increase on osseointegration and to calculate the heat distribution in cortical bone. METHODS: Forty Branemark implants were installed into the metatarsal bone of Finnish Dorset crossbred sheep according to two different drilling protocols (undersized/non-undersized) and two surfaces (moderately rough/turned). The intraosseous temperature was recorded, and Finite Element Model (FEM) was generated to understand the thermal behavior. Non-decalcified histology was carried out after five weeks of healing. The following osseointegration parameters were calculated: Bone-to-implant contact (BIC), Bone Area Fraction Occupancy (BAFO), and Bone Area Fraction Occupancy up to 1.5 mm (BA1.5). A multiple regression model was used to identify the influencing variables on the histomorphometric parameters. RESULTS: The temperature was affected by the drilling protocol, while no influence was demonstrated by the implant surface. BIC was positively influenced by the undersized drilling protocol and rough surface, BAFO was negatively influenced by the temperature rise, and BA1.5 was negatively influenced by the undersized drilling protocol. FEM showed that the temperature at the implant interface might exceed the limit for bone necrosis. CONCLUSION: The intraosseous temperature is greatly increased by an undersized drilling protocol but not from the implant surface. The temperature increase negatively affects the bone healing in the proximity of the implant. The undersized drilling protocol for Branemark implant systems increases the amount of bone at the interface, but it negatively impacts the bone far from the implant.

PURPOSE: The aim of this multi-scale in silico study was to evaluate the influence of resorption cavities on the mechanical properties and load distribution in cortical bone after implant placement with two different drilling protocols.

MATERIAL AND METHODS: Two different micro-scale bone structures were assessed: cortical bone models with cavities (test) and without cavities (control) were designed from μCT data. In a macro-scale model, representing a mandibular ridge, oblique load of 150 N was applied on the implant-abutment. Maximum principal stress/strain, and shear stress/strain were calculated in the macro- and micro-scale models.

RESULTS: Test presented anisotropic material properties. In tests, significantly greater maximum values of Maximum principal stress/strain were calculated in micro-scale model. These values were located at the implant neck area in the macro-scale model and in the proximity of cavities in the micro-scale model respectively. Greater values of shear stress/strain were found in the test along the mandibular horizontal plane.

CONCLUSIONS: Cortical bone with resorption cavities following undersized drilling showed an impaired load distribution compared with bone without cavities. Subsequently, stress/strain distribution suggests that this bone model is more prone to microdamage, thus delaying the healing process.

ObjectiveThe aim of this study was to investigate the extent of cortical bone remodeling between two different drilling protocols by means of histomorphometric, mu-CT, and biomechanical analyses. Material and methodsA total of 48 implants were inserted into the mandible of six sheep following two drilling protocols: Group A (Test, n=24), undersized preparation; Group B (Control, n=24), non-undersized preparation. The animals were euthanatized to obtain 5 and 10weeks of implantation time. Removal torque (RTQ) was measured on 12 implants of each group and the peri-implant bone was mu-CT scanned. Bone volume density (BV/TV) was calculated in pre-determined cylindrical volumes, up to 1.5mm from implant surface. Non-decalcified histology was prepared on the remaining 12 implants from each group, where total bone-to-implant contact (totBIC) and newly-formed BIC (newBIC) was measured. Bone Area Fraction Occupancy (BAFO) was determined in pre-determined areas up to 1.5mm from implant surface. Paired sample t test or Wilcoxon signed-rank test was used to investigate differences between the groups. ResultsGroup A presented significantly increased RTQ value at 5weeks, while no difference was observed at 10weeks. Group B presented increased BV/TV value at 5weeks. Both groups showed comparable values for totBIC at both time-points. However, Group A presented significantly lower newBIC at 5weeks. Higher BAFO was observed in Group B at 5weeks. ConclusionsImplants inserted into undersized sites has an increased biomechanical performance, but provoked major remodeling of the cortical bone during the early healing period compared to non-undersized preparations. After 10weeks, no difference was observed.

Purpose: To investigate the causes for internal implant fractures, which is suggested to be one of the reasons for marginal bone loss. Materials and Methods: From a 14-year database of 6051 implants, 10 single implant vertical fractures were identified and the abutments were all castable abutments. The abutments presented contamination and irregularities at the internal connecting areas. The hypothesis was that perfect fit was disturbed by laboratory polishing procedures, and finite element analysis (FEA) using overcorrected and undercorrected castable abutment models were created and tested against a perfect fit model Results: The results from the FEA presented that both overcorrected and undercorrected models presented nonuniform excessive plastic strain distribution in the neck portion of the implants where clinically an implant fracture was noted Conclusions: The results suggested that laboratory procedures could induce plastic strain of the implant-abutment complex, which increases the risk of fracture

Purpose: To evaluate the effect of misfit at implant-level fixed partial dentures (ILFPDs) and marginal bone support on the generation of implant cracks. Materials and Methods: This in vitro study included a mechanical fatigue test and finite element analysis. A mechanical cycling loading test was performed using 16 experimental models, each consisting of two parallel implants subdivided into four groups based on the misfit and the supporting bone condition. The framework, firmly seated at implants, was dynamically loaded vertically with a force of 1,600/160 N and 15 Hz for 1 × 106 cycles. Optical microscope, scanning electron microscope (SEM), and computed tomography three-dimensional (CT-3D) analyses were performed to detect impairments. Finite element models, representing the setups in the mechanical fatigue test, were used to represent the fatigue life. Results: None of the mechanical components presented distortion or fracture at the macroscopic level during the test. In a microscopy evaluation, the fatigue test revealed scratches visible in the inner part of the conical portion of the implants regardless of the groups. SEM and CT-3D analysis revealed one implant from the misfit/no bone loss group with a microfracture in the inner part of the conical interface. The simulated effective stress levels in the coronal body were higher in the misfit groups compared with the no misfit groups. The misfit groups presented effective stress levels, above 375 MPa, that penetrated the entire wall thickness. The no bone loss group presented an effective stress level above 375 MPa along its axial direction. In the no misfit group, the area presenting effective stress levels above 375 MPa in the conical connection was larger for the bone loss group compared with the no bone loss group. Conclusion: This study confirmed that implant fracture is an unlikely adverse event. A clear pattern of effective distribution greater than fatigue limit stresses could be noticed when the misfit was present. The dynamic load simulation demonstrated that the crack is more likely to occur when implants are fully supported by marginal bone compared with a bone loss scenario. Within the limitations of this study, it is speculated that marginal bone loss might follow the appearance of an undetected crack. Further research is needed to develop safe clinical protocols with regard to ILFPD.