Platelet-derived extracellular vesicles formulated with hyaluronic acid gels for application at the bone-implant interface: An animal study.

Background/Objective: Platelet derived extracellular vesicles (pEV) are promising therapeutical tools for bone healing applications. In fact, several in vitro studies have already demonstrated the efficacy of Extracellular Vesicles (EV) in promoting bone regeneration and repair in various orthopedic models. Therefore, to evaluate the translational potential in this field, an in vivo study was performed. Methods: Here, we used hyaluronic acid (HA) gels formulated with pEVs, as a way to directly apply pEVs and retain them at the bone defect. In this study, pEVs were isolated from Platelet Lysate (PL) through size exclusion chromatography and used to formulate 2% HA gels. Then, the gels were locally applied on the tibia cortical bone defect of New Zeland White rabbits before the surgical implantation of coin-shaped titanium implants. After eight weeks, the bone healing process was analyzed through biomechanical, micro-CT, histological and biochemical analysis. Results: Although no biomechanical differences were observed between pEV formulated gels and non-formulated gels, biochemical markers of the wound fluid at the interface presented a decrease in Lactate dehydrogenase (LDH) activity and alkaline phosphatase (ALP) activity for pEV HA treated implants. Moreover, histological analyses showed that none of the treatments induced an irritative effect and, a decrease in the fibrotic response surrounding the implant for pEV HA treated implants was described. Conclusion: In conclusion, pEVs improve titanium implants biocompatibility at the bone-implant interface, decreasing the necrotic effects of the surgery and diminishing the fibrotic layer associated to the implant encapsulation that can lead to implant failure.

Impact of simultaneous placement of implant and block bone graft substitute: an in vivo peri-implant defect model.

BACKGROUND: Insufficient bone volume around an implant is a common obstacle when dental implant treatment is considered. Limited vertical or horizontal bone dimensions may lead to exposed implant threads following placement or a gap between the bone and implant. This is often addressed by bone augmentation procedures prior to or at the time of implant placement. This study evaluated bone healing when a synthetic TiO2 block scaffold was placed in circumferential peri-implant defects with buccal fenestrations. METHODS: The mandibular premolars were extracted and the alveolar bone left to heal for 4 weeks prior to implant placement in six minipigs. Two cylindrical defects were created in each hemi-mandible and were subsequent to implant placement allocated to treatment with either TiO2 scaffold or sham in a split mouth design. After 12 weeks of healing time, the samples were harvested. Microcomputed tomography (MicroCT) was used to investigate defect fill and integrity of the block scaffold. Distances from implant to bone in vertical and horizontal directions, percentage of bone to implant contact and defect fill were analysed by histology. RESULTS: MicroCT analysis demonstrated no differences between the groups for defect fill. Three of twelve scaffolds were partly fractured. At the buccal sites, histomorphometric analysis demonstrated higher bone fraction, higher percentage bone to implant contact and shorter distance from implant top to bone 0.5 mm lateral to implant surface in sham group as compared to the TiO2 group. CONCLUSIONS: This study demonstrated less bone formation with the use of TiO2 scaffold block in combination with implant placement in cylindrical defects with buccal bone fenestrations, as compared to sham sites.

Pre-cementation procedures' effect on dental zirconias with different yttria content.

OBJECTVE: Several pre-cementation procedures have been advocated to enhance adhesion between zirconia and resin-based cement. There is, however, limited documentation on how these pre-treatments affect the strength of zirconia crowns as most tests are performed on discs or bars. The aim was to assess the effect of pre-cementation procedures on fracture mode, fracture strength and cement retention on zirconia. METHODS: Two dental zirconia materials with different yttria content were assessed (<4 and>5 mol%). Both discs (n = 45) and crown-shaped specimens (n = 30) of the two materials were pretreated with either air-abrasion or hot-etching with KHF2 and compared with untreated controls with regards to surface roughness, crystallography, wettability, cement adhesion and fracture strength. RESULTS AND SIGNIFICANCE: Air-abrasion improves adhesion and strength of zirconia with moderate yttria content (<4 mol%). Acid etching with heated KHF2 showed the best effect on strength and cement retention on zirconia with higher yttria content (>5 mol%). Application of KHF2 was, however, complicated on crown-shaped specimens. Pre-treatment and cementation protocols should be optimized for different dental zirconias to improve both strength and retention.

The influence of the resin-based cement layer on ceramic-dentin bond strength.

The purpose of the study was to measure the cement thickness obtained when ceramic rods were luted to dentin and to analyze the relation between cement thickness and the previously published tensile bond strength of similar test specimens. In addition, the ISO standard 4049:2019 method was used to determine the film thickness of the used cements. Zirconia (n = 100) and lithium disilicate (n = 50) rods were cemented to bovine dentin using one of five different resin-based cements. The ceramic-dentin test specimens were cut into two slices and the cement thickness was measured using a scanning electron microscope and compared to the bond strength values of similar specimens already published. The mean cement thickness recorded for ceramic rods cemented to dentin was in the range 20-40 µm, which was larger than the cement film thickness found by the ISO method. The cement film thickness determined according to ISO standard methods did not concur with the results obtained when cementing ceramic rods to dentin. For cementing ceramic restorations, a cement thickness in the range 25-35 µm seems to be favorable for the bond strength.

Discrepancy in alloy composition of imported and non-imported porcelain-fused-to-metal (PFM) crowns produced by Norwegian dental laboratories.

Purpose: Even though the use of full ceramic crowns have become a well-established practice in dental clinics compare to the last decade, the use of imported casted porcelain-fused-to-metal (PFMs) crowns is still prevalent. The use of imported PFMs is often economically driven; however, when dentists order PFMs, they do not have capabilities to examine its true alloy content. Therefore, we raise the questions whether cheaper imported PFMs have more discrepancies in alloy content compared to domestically produced PFMs? Materials and Methods: This study included 62 porcelain-fused-to-metal crowns: 41 produced in Norway and 21 imported. Their alloy-composition was determined non-destructively by EDX and SEM. Results and Conclusions: Imported PFMs demonstrated larger deviations compared with non-imported PFMs. Significant deviation was found in key metallic elements in the different alloys (W, In, Pd, Ag). The detected deviations in key element such as Wolfram and Indium could influence the PFMs service time. These finding may be of international concern.

Comparison of postoperative intraoral scan versus cone beam computerised tomography to measure accuracy of guided implant placement-A prospective clinical study.

OBJECTIVE: To evaluate the accuracy of implant placement with a digitally planned guided implant procedure. Two methods for identifying the actual postoperative positioning of the implants were compared: CBCT and IO scanning. MATERIAL AND METHODS: Twenty-eight implants with a sandblasted and acid-etched surface were placed in thirteen patients using tooth-supported surgical guides following a digital planning procedure. The implants were submerged for 12-15 weeks. New CBCT images were taken for identification of the implant position. After second stage surgery, scan bodies were mounted on the implants and scanned with an IO digital scanner. The recordings from the CBCT images and the IO scans were compared with respect to the identified positions of the implants. RESULTS: The study did not resolve any significant differences of the identified positioning of the implants as measured by CBCT or IO, except for the apical deviations at the coronal and apical points. The angular difference between CBCT and IO scanning at the coronal point was -0.011 (±0.6) degrees, whereas the 3D deviation was 0.03(±0.17) mm. The distal deviation between CBCT and IO scanning was 0.01(± 0.16) mm, and the vestibular deviation 0.033(± 0.16) mm and the apical deviation difference was 0.09(± 0.16) mm. The 3D deviation at the apical point was 0.04(± 0.22) mm. The distal deviation between CBCT and IO scanning was 0.06(± 0.19) mm, and the vestibular deviation 0.032(± 0.23) mm and the apical deviation difference was 0.09(± 0. 16) mm. CONCLUSION: The study demonstrated that accuracy measurements using IO scanning yields comparable results to those obtained by CBCT.

Debonding mechanism of zirconia and lithium disilicate resin cemented to dentin.

To evaluate debonding mechanism of zirconia and lithium disilicate cemented to dentin mimicking what could occur in a clinical setting. A null hypothesis of no difference in tensile bond strength between groups of zirconia and lithium disilicate cemented with resin cements was also tested. Zirconia rods (n = 100) were randomly assigned to two different surface treatment groups; air borne particle abrasion and hot etching by potassium hydrogen difluoride (KHF2). Lithium disilicate rods (n = 50) were surface etched by hydrofluoric acid (HF). Five different dual cure resin cements were used for cementing rods to bovine dentin. Ten rods of each test group were cemented with each cement. Test specimens were thermocycled before tensile bond strength testing. Fracture morphology was visualized by light microscope. Mean surface roughness (Sa value) was calculated for randomly selected rods. Cohesive fracture in cement was the most frequent observed fracture morphology. Combination of adhesive and cohesive fractures were second most common. Fracture characterized as an adhesive between rod and cement was not observed for KHF2 etched zirconia. Highest mean tensile bond strength was observed when cementing air borne particle abraded zirconia with Variolink Esthetic (Ivoclar Vivadent). All surface treatments resulted in Sa values that were significant different from each other. The number of cohesive cement fractures observed suggested that the cement was the weakest link in bonding of zirconia and lithium disilicate.

Titanium implants coated with UV-irradiated vitamin D precursor and vitamin E: in vivo performance and coating stability.

OBJECTIVES: This study aimed at evaluating the biological response of titanium implants coated with UV-irradiated 7-dehydrocholesterol (7-DHC) and vitamin E (VitE) in vivo and analyzing the effects of aging on their stability and bioactivity in vitro. MATERIAL AND METHODS: Titanium surfaces were coated with 7-DHC and VitE, UV-irradiated and incubated for 48 h at 23°C to allow cholecalciferol synthesis. The in vivo biological response was tested using a rabbit tibia model after 8 weeks of healing by analyzing the wound fluid and the mRNA levels of several markers at the bone-implant interface (N = 8). The stability of the coating after storage up to 12 weeks was determined using HPLC analysis, and the bioactivity of the stored modified implants was studied by an in vitro study with MC3T3-E1 cells (N = 6). RESULTS: A significant increase in gene expression levels of osteocalcin was found in the bone tissue attached to implants coated with the low dose of 7-DHC and VitE, together with a higher ALP activity in the wound fluid. Implants treated with the high dose of 7-DHC and VitE showed increased tissue necrosis and inflammation. Regarding the aging effects, coated implants were stable and bioactive up to 12 weeks when stored at 4°C and avoiding oxygen, light and moisture. CONCLUSION: This study demonstrates that Ti implants coated with UV-irradiated 7-DHC and VitE promote in vivo gene expression of bone formation markers and ALP activity, while they keep their osteopromotive potential in vitro and composition when stored up to 12 weeks at 4°C.

Internal fit of single crowns produced by CAD-CAM and lost-wax metal casting technique assessed by the triple-scan protocol.

STATEMENT OF PROBLEM: Whether single crowns produced by computer-aided design and computer-aided manufacturing (CAD-CAM) have an internal fit comparable to crowns made by lost-wax metal casting technique is unknown. PURPOSE: The purpose of this in vitro study was to compare the internal fit of single crowns produced with the lost-wax and metal casting technique with that of single crowns produced with the CAD-CAM technique. MATERIAL AND METHODS: The internal fit of 5 groups of single crowns produced with the CAD-CAM technique was compared with that of single crowns produced in cobalt-chromium with the conventional lost-wax and metal casting technique. Comparison was performed using the triple-scan protocol; scans of the master model, the crown on the master model, and the intaglio of the crown were superimposed and analyzed with computer software. The 5 groups were milled presintered zirconia, milled hot isostatic pressed zirconia, milled lithium disilicate, milled cobalt-chromium, and laser-sintered cobalt-chromium. RESULTS: The cement space in both the mesiodistal and buccopalatal directions was statistically smaller (P<.05) for crowns made by the conventional lost-wax and metal casting technique compared with that of crowns produced by the CAD-CAM technique. CONCLUSIONS: Single crowns made using the conventional lost-wax and metal casting technique have better internal fit than crowns produced using the CAD-CAM technique.

Clinical evaluation of CAD/CAM metal-ceramic posterior crowns fabricated from intraoral digital impressions.

PURPOSE: The aim of this in vivo study was to evaluate the accuracy of metal-ceramic crowns fabricated using computer-aided design/computer-assisted manufacturing (CAD/CAM) in conjunction with intraoral digital impressions. MATERIALS AND METHODS: Fifty patients in a general practice participated in the study. Patients were provided with crowns fabricated from digital impressions taken with an intraoral chairside scanner. Prior to crown insertion, the marginal integrity, esthetics, and occlusal and articulation contacts were evaluated using California Dental Association (CDA) criteria. The precementation space of the crowns was evaluated with the replica technique. RESULTS: No adjustments were needed for any of the interproximal contact points. Adjustments of occlusion and articulation contacts were needed in 20% of the restorations. Clinical evaluation of the marginal integrity showed satisfactory results according to the CDA criteria. The 50 silicone replicas showed a median precementation space of 46 µm at the marginal measurement location, 94 µm at the midaxial location, and 185 µm at the centro-occlusal location. CONCLUSIONS: The precementation spaces of the crowns were within the acceptable range for CAD/CAM restorations.

Porous ceramic titanium dioxide scaffolds promote bone formation in rabbit peri-implant cortical defect model.

Titanium oxide (TiO2) scaffolds have previously been reported to exhibit very low mechanical strength. However, we have been able to produce a scaffold that features a high interconnectivity, a porosity of 91% and a compressive strength above 1.2 MPa. This study analyzed the in vivo performance of the porous TiO2 scaffolds in a peri-implant cortical defect model in the rabbit. After 8 weeks of healing, morphological microcomputed tomography analyses of the defects treated with the TiO2 scaffolds had significantly higher bone volume, bone surface and bone surface-to-volume ratio when compared to sham, both in the cortical and bone marrow compartment. No adverse effects, i.e. tissue necrosis or inflammation as measured by lactate dehydrogenase activity and real-time reverse transcription polymerase chain reaction analysis, were observed. Moreover, the scaffold did not hinder bone growth onto the adjacent cortical titanium implant. Histology clearly demonstrated new bone formation in the cortical sections of the defects and the presence of newly formed bone in close proximity to the scaffold surface and the surface of the adjacent Ti implant. Bone-to-material contact between the newly formed bone and the scaffold was observed in the histological sections. Islets of new bone were also present in the marrow compartment albeit in small amounts. In conclusion, the present investigation demonstrates that TiO2 scaffolds osseointegrate well and are a suitable scaffold for peri-implant bone healing and growth.

Porous titanium granules in the surgical treatment of peri-implant osseous defects: a randomized clinical trial.

PURPOSE: Porous titanium granules (PTG) may have potential as an osteoconductive bone graft substitute to treat peri-implant osseous defects. The aim of this study was to analyze clinical and radiographic outcomes of peri-implant osseous defects after treatment with PTG. MATERIALS AND METHODS: This prospective, randomized, case-control, clinical 12-month study compared open-flap debridement and surface decontamination with titanium curettes and 24% ethylenediaminetetraacetic acid gel (n = 16) to the same protocol but with the addition of PTG (n = 16). One-, two-, and three-wall infrabony defects were included. Patients were given amoxicillin and metronidazole 3 days before surgery and for 7 days afterwards. Implants were submerged and allowed to heal for 6 months. Probing pocket depths, bleeding on probing, implant stability using resonance frequency analysis, and radiographic evaluation were performed at baseline and at 12 months. The threshold for significance was set at .05. RESULTS: Change in radiographic defect height and percent fill of the peri-implant osseous defect significantly favored patients treated with PTG. Both treatment modalities demonstrated significant improvements in probing pocket depth, but significant differences between groups were not observed. The PTG-treated implants showed an increase in implant stability quotient (ISQ) of 1.6 units, compared with a decrease of 0.7 ISQ for the control group. No adverse effects were associated with PTG treatment. CONCLUSIONS: Reconstruction with PTG resulted in significantly better radiographic peri-implant defect fill compared with controls; however, the results do not necessarily imply reosseointegration or osseointegration of PTG particles. Improvements in clinical parameters were seen in both groups, but no differences between groups were demonstrated.

Micro CT and human histological analysis of a peri-implant osseous defect grafted with porous titanium granules: a case report.

Treatment of peri-implant osseous defects represents a significant challenge for clinicians, and the need to evolve within predictable surgical procedures is important. This case report describes the surgical treatment and grafting with porous titanium granules (PTG) of one patient with a peri-implant osseous defect. The suggested thrombogenic properties of titanium are intriguing from the perspective of osseous reconstructive surgery. In an ongoing randomized clinical trial using PTG for treatment of peri-implant osseous defects, one patient with one test implant was excluded and scheduled for implant removal. The surgical therapy included open flap debridement with surface decontamination with 24% EDTA gel, grafting with PTG, and resubmersion of the implant. After 12 months of healing, the implant with surrounding tissues was excised en bloc and micro CT and histological analyses were performed. Analyses showed PTG in close contact with new bone and with bone growing both into the porosities of the graft material and onto the adjacent implant surface. Element analysis demonstrated calcium and phosphorus in the new tissue embedding the PTG and the implant. Int J Oral Maxillofac Implants 2011;26:e9-e14.

Porous titanium granules promote bone healing and growth in rabbit tibia peri-implant osseous defects.

OBJECTIVES: The aim of this study was to investigate the osteoconductive properties and biological performance of porous titanium granules used in osseous defects adjacent to titanium implants. MATERIAL AND METHODS: In this animal experimental study, calibrated defects were prepared in the tibias of 24 New Zealand rabbits. The defects were randomized into two tests and one control group. The test defects were grafted with either metallic or oxidized porous titanium granules (PTG or WPTG, respectively), whereas control defects were left empty (sham). The defects were closed with a submerged coin shaped titanium implant. Defects were left for healing for 4 weeks. After healing, the implants were removed and the new bone tissue formed onto the implant surface was analyzed for run x 2, osteocalcin, collagen-I, tartrate-resistant acid phosphatase, H(+)-ATPase, tumor necrosis factor-alpha, interleukin (IL)-6 and IL-10 gene expression using reverse transcriptase polymerase chain reaction. Wound fluid from the healed defects was analyzed for lactate dehydrogenase and alkaline phosphatase activity. Finally osteoconductivity was analyzed by micro-computed tomography and histology. RESULTS: Significantly more new bone formed in PTG and WPTG grafted defects compared with sham. The new bone grew both through the porosities of the granules and onto the implant surfaces. The WPTG group showed significantly less expression of key inflammation markers, but with no significant difference in a marker for necrosis. The WPTG also showed a significant increase in collagen-I mRNA expression compared with PTG. CONCLUSION: The results suggest that PTG and WPTG are both osteoconductive materials that can be used to promote bone formation in osseous defects adjacent to titanium implants without hampering implant osseointegration.

In vivo performance of absorbable collagen sponges with rosuvastatin in critical-size cortical bone defects.

Rosuvastatin (RSV) is a synthetic statin with favourable pharmacologic properties, but its local effect in bone has yet to be investigated. The aim of this study was to evaluate the potential of absorbable collagen sponge (ACS) as a carrier for RSV to enhance bone formation in critical-size cortical bone defects adjacent to titanium implants. ACS, treated with different concentrations of RSV (R1 = 8.7 + or - 1.8 microg; R2 = 52.0 + or - 4.4 microg; R3 = 259.1 + or - 8.8 microg) or phosphate-buffered saline alone, were placed into the bone marrow through a defect made in the proximal tibial cortical bone of New Zealand White rabbits. One empty defect (SHAM) served as an internal control in each animal. After a healing time of 4 weeks, a concentration-dependent increase of alkaline phosphatase activity in ACS treated with RSV was detected in the bone fluid after removing the implants. In addition, a significant concentration-dependent increase in BMP-2 mRNA levels was found in the cortical bone tissue adjacent to the RSV-treated ACS. The cortical architecture of bone defects analysed by micro-computed tomography showed a trend towards higher bone volume in the ACS+R1 group compared with SHAM, which was accompanied by an increase in the bone mineral density. Evaluation of histological sections showed new bone formation in ACS treated with RSV but not in untreated ACS. These results indicate that RSV, when administered locally in bone, may have a potential effect in stimulating bone formation.

A study on the effect of dual blasting with TiO2 on titanium implant surfaces on functional attachment in bone.

In the present study, the effect of a dual treatment of titanium implants and the subsequent bone response after implantation were investigated. Coin-shaped c.p. titanium implants were placed into the tibias of 12 rabbits. The implant, which was dually blasted with TiO2 particles of two different sizes, was compared with implants that were blasted with only one of these particle sizes. Implants in group 1 were grit blasted with small particles, 22-28 microm in size, and group 2 with coarser particles, 180-220 microm size. These two treatments gave different surface micro textures. To test the effect of a combination of two different treatments, group 3 implants were blasted first with the 180- to 220-microm and subsequently with the 22- to 28-microm particles. The surface topography of the implant specimens was examined by scanning electron microscopy and by a confocal laser scanner and a numeric evaluation of S(a), S(t), and S(dr) was recorded. Group 2 implants, which were blasted with only the coarse particles, showed a significantly better functional attachment (p < 0.001) than the other two groups. Group 1, which was blasted with only small particles, showed the lowest retention in bone. There was a positive correlation between the topographical and mechanical evaluation of the surfaces.

Tensile force testing of optimized coin-shaped titanium implant attachment kinetics in the rabbit tibiae.

In the present study, the bone response of titanium implants at early bone healing stages, was evaluated using a tensile test. Test surface of coin-shaped cp. titanium implants were standardized by grit blasting with TiO(2), grain size 180-220 microm. The surface topography of the implant specimens was examined by SEM, and by a confocal laser scanner for evaluation of S(a), S(t) and S(dr). The implants were placed onto the leveled site on the tibia of 12 New Zealand White rabbits, 4 implants in each animal. The rabbits were divided into three groups with different observation times i.e. 2, 4 and 6 weeks. The retention of 12 implants were tested by measuring the pull-out force needed to detach the implant from the bone. There was a significant increase in implant retention from 2 to 4 and to 6 weeks healing time (p<0.05). Four implants from each time point were randomly chosen for histological evaluation. The histological appearance of the implant-bone interface at the different healing times showed noticeable differences in the degree of bone healing and maturation, suggesting that, in rabbits, 6 weeks healing time is a suitable observation point for tensile testing of surface optimized osseointegrating implants.

Effect of micro-roughness produced by TiO2 blasting--tensile testing of bone attachment by using coin-shaped implants.

The aim of the present study was to examine bone response to micro-rough titanium implants. Forty coin-shaped implants were divided into eight groups according to their surface roughness. The first group had electropolished surfaces. The surfaces of implant groups 2-8 were blasted with TiO2 particles with incremental grain sizes ranging from 7.5-12.5 to 270-330 microns. Five implants from each group were placed into the cortical bone of the proximal tibia in New Zealand Black rabbits. To avoid bone overgrowth during the retention phase the implants were fitted into tight polytetrafluoroethylene (PTFE) caps leaving only the flat test surface exposed to bone. The healing period was set to 10 weeks, and implants with attached bone were evaluated using a tensile testing machine. In groups 1-7 a significant correlation between the micro-roughness of the implant surfaces and retention strength was observed. Maximum bone bonding was observed with implants blasted with 180-220 microns grain size (group 7). Blasting with larger TiO2 particles appeared to decrease the effect. The findings suggest that the best grain size of TiO2 particles for optimising retention of titanium implants in cortical bone should be in the 180-220 microns range.

The use of a coin shaped implant for direct in situ measurement of attachment strength for osseointegrating biomaterial surfaces.

Most animal models currently used to study the retention of implants in bone are influenced by shear forces introduced during the retention test. This is mainly due to the implant design, which most often are cylindrical, conical or threaded. In these models interlocking between bone and implant surface will increase the effect of genuine bone bonding and thus give a false positive outcome. The purpose of the present study was to establish a model for testing functional attachment of implants in situ, with minimal influence of interlocking and shear forces. The model involves the use of flat coin shaped implant placed onto the cortical bone of rabbit tibia without mechanical fixation to the bone. The implant is passively retained on the cortical bone by a titanium band retainer. During the healing period, the contact between the coin shaped implants and the bone is restricted to the flat test surfaces. To prevent interlocking effects from lateral bone attachments a polytetrafluoroethylene (PTFE) cap covering the vertical and the upper faces of the implants were used. The tensile test was performed with a gradual, calibrated pull, perpendicular to the bone-implant interface. This pullout model makes it possible to study the kinetics and strength of bone bonding with negligible influence of shear forces or mechanical interlocking.