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PURPOSE: To clinically evaluate oral implant restorations placed by undergraduate students in the dental clinical curriculum at KU Leuven (Belgium) in terms of function and esthetics. MATERIALS AND METHODS: A retrospective observational cohort study was designed. The esthetic and functional evaluations of implant-supported restorations placed in the framework of the undergraduate implant dentistry clinical training program using White/Pink Esthetic Score (WES/PES) and visual analog scale (VAS) scoring was performed. Furthermore, complications were registered based retrospectively on the patient's medical file. The following research questions were stipulated: (1) How well do implant-supported restorations placed by undergraduate students perform esthetically? and (2) Which complications occurred and how were these managed? RESULTS: Between August 2008 and July 2014 (6 academic terms), 251 implants (Brånemark System Mk III, Nobel Biocare) were placed in 113 patients by 155 students (> 40% of all students enrolled in the training program). Of these implants, 228 were restored in 101 patients by 118 students with varying restoration types. Esthetic scoring of the restorations in 83 of these patients revealed a satisfying mean WES of 8.14 ± 2.09 (out of 10) and PES of 9.56 ± 3.14 (out of 14). Complications were registered in 18.9% of the cases. DISCUSSION: Clinical training in implant dentistry for undergraduates contributes to the development of advanced skills in the dental student's Master education. Overall, patients were satisfied with their implant-supported restorations. Implant and restoration success rates and complication incidence were confirmed by long-term data in the oral implant literature. ispartof: INTERNATIONAL JOURNAL OF PROSTHODONTICS vol:34 issue:4 pages:433-440 ispartof: location:United States status: published

Objectives: New strategies for implant surface functionalization in the prevention of peri-implantitis while not compromising osseointegration are currently explored. The aim of this in vivo study was to assess the osseointegration of a titanium-silica composite implant, previously shown to enable controlled release of therapeutic concentrations of chlorhexidine, in the Göttingen mini-pig oral model. Material and methods: Three implant groups were designed: macroporous titanium implants (Ti-Porous); macroporous titanium implants infiltrated with mesoporous silica (Ti-Porous + SiO2 ); and conventional titanium implants (Ti-control). Mandibular last premolar and first molar teeth were extracted bilaterally and implants were installed. After 1 month healing, the bone in contact with the implant and the bone regeneration in the peri-implant gap was evaluated histomorphometrically. Results: Bone-to-implant contact and peri-implant bone volume for Ti-Porous versus Ti-Porous + SiO2 implants did not differ significantly, but were significantly higher in the Ti-Control group compared with Ti-Porous + SiO2 implants. Functionalization of titanium implants via infiltration of a SiO2 phase into the titanium macropores does not seem to inhibit implant osseointegration. Yet, the importance of the implant macro-design, in particular the screw thread design in a marginal gap implant surgery set-up, was emphasized by the outstanding results of the Ti-Control implant. Conclusions: Next-generation implants made of macroporous Ti infiltrated with mesoporous SiO2 do not seem to compromise the osseointegration process. Such implant functionalization may be promising for the prevention and treatment of peri-implantitis given the evidenced potential of mesoporous SiO2 for controlled drug release. ispartof: Clinical and Experimental Dental Research vol:7 issue:4 ispartof: location:United States status: published

Obesity is the main cause of type 2 diabetes mellitus (T2DM). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for this obesity-related health problem. However, the adverse effects of T2DM on bone tissue persist or even aggravate after this surgical procedure. As studies on the mandibular condyle bone are scarce, the aim of the present study was to assess its compositional characteristics in T2DM and RYGB conditions. Thirty-two male C57BL/6 mice at 8 weeks of age were randomly assigned to receive either a high-fat or low-fat diet. After 14 weeks of high-fat diet intake, seven obese mice were subjected to RYGB surgery. All animals were euthanized at the age of 30 weeks. Mandibular bones were removed and the trabecular condyle region was assessed using Raman spectroscopy. A decreased mineralization was observed for both T2DM and RYGB condyle bones when compared to controls, with elevated carbonate substitutions for the RYGB group. No compositional differences in crystallinity and presence of advanced glycation end products were found between the groups, with the exception of an increased presence of N-carboxymethyl-lysine in RYGB bone compared to their T2DM counterpart. Site-specific measurements revealed a non-uniform bone composition, with increasing mineralization and carbonate substitutions towards the centre of the mandibular condyle. T2DM and RYGB surgery affect the mandibular condyle bone quality, as investigated at compositional level. Assessment of bone structural properties and remodelling should be carried out to further explore the effects of T2DM and RYGB surgery on this skeleton area. Electronic supplementary material The online version of this article (10.1007/s00223-020-00732-0) contains supplementary material, which is available to authorized users.

Introduction The biomedical sciences (BMS) are a central part of the dental curriculum that underpins teaching and clinical practice in all areas of dentistry. Although some specialist groups have proposed curricula in their particular topic areas, there is currently no over-arching view of what should be included in a BMS curriculum for undergraduate dental programmes. To address this, the Association for Dental Education in Europe (ADEE) convened a Special Interest Group (SIG) with representatives from across Europe to develop a consensus BMS curriculum for dental programmes. Curriculum This paper summarises the outcome of the deliberations of this SIG, and details a consensus view from the SIG of what a BMS curriculum should include. Conclusions Given the broad nature of BMS applied to dentistry, this curriculum framework is advisory and seeks to provide programme planners with an indicative list of topics which can be mapped to specific learning objectives within their own curricula. As dentistry becomes increasingly specialised these will change, or some elements of the undergraduate curriculum may move to the postgraduate setting. So, this document should be seen as a beginning and it will need regular review as BMS curricula in dentistry evolve.

Introduction The aim of this nonrandomized, multicenter controlled clinical trial was to evaluate the impact of leukocyte–platelet-rich fibrin (LPRF) on regenerative endodontic procedures (REPs) of immature permanent teeth in terms of periapical bone healing (PBH) and further root development (RD). Methods Healthy patients between 6–25 years with an inflamed or necrotic immature permanent tooth were included and divided between the test (= REP + LPRF) and control (= REP-LPRF) group depending on their compliance and the clinical setting (university hospital or private practice). After receiving REP ± LPRF, the patients were recalled after 3, 6, 12, 24, and 36 months. At each recall session, the teeth were clinically and radiographically (by means of a periapical radiograph [PR]) evaluated. A cone-beam computed tomographic (CBCT) imaging was taken preoperatively and 2 and 3 years postoperatively. PBH and RD were quantitatively and qualitatively assessed. Results Twenty-nine teeth with a necrotic pulp were included, from which 23 (9 test and 14 control) were analyzed. Three teeth in the test group had a flare-up reaction in the first year after REP. Except for 2 no shows, all the analyzed teeth survived up to 3 years after REP, and, in case of failure, apexification preserved them. Complete PBH was obtained in 91.3% and 87% of the cases based on PR qualitative and quantitative evaluation, respectively, with no significant difference between the groups with respect to the baseline. The PR quantitative change in RD at the last recall session with respect to the baseline was not significant (all P values > .05) in both groups. The qualitative assessment of the type of REP root healing was nonuniform. In the test group, 55.6% of the teeth presented no RD and no apical closure. Only 50% of the 14 teeth assessed with CBCT imaging presented complete PBH. Regarding volumetric measurements on RD 3 years after REP for the change with respect to the baseline in root hard tissue volume, mean root hard tissue thickness, and apical area, the control group performed significantly in favor of RD than the test group (P = .03, .003, and 0.05 respectively). For the volumetric change 3 years after REP with respect to the baseline in root length and maximum root hard tissue thickness, no significant difference (P = .72 and .4, respectively) was found between the groups. The correlation between the PR and CBCT variables assessing RD was weak (root lengthening) to very weak (root thickening). Conclusions REP-LPRF seems to be a viable treatment option to obtain PBH and aid further RD of necrotic immature permanent teeth. Caution is needed when evaluating REP with PR.

Aim This systematic review investigates the effectiveness of implant-supported fixed partial denture (IS-FPD) in patients with history of periodontitis (HP) vs. patients with no history of periodontitis (NHP). Methods A literature search was performed on different databases on May 2020. Prospective and retrospective studies assessing survival (primary outcome), success and biological/mechanical complications of IS-FPDs in HP vs. NHP patients at ≥1 year after implant loading were evaluated. Meta-analyses were conducted by estimating hazard ratio (HR), risk ratio (RR) and standardized mean differences (SMD) with 95% confidence intervals (CI) using random effect models. Results Of the initially identified 4096 articles, 349 underwent a full-text evaluation. Finally, 17 were included. Pooled data analyses showed that overall implant survival was significantly higher in the NHP than the HP group (HR = 2.06; 95% CI = 1.37-3.09; I2 = 0%). This difference was noted when follow-up ≥5 years. The risk of peri-implantitis was higher in HP than NHP patients (RR = 3.3; 95% CI = 1.31-8.3; I2 = 0%), whereas the mean marginal bone level change over time was not different between the groups (SMD = -0.16 mm; 95% CI = -1.04-0.73; I2 = 98%). Conclusions In partially edentulous patients receiving IS-FPDs, a history of periodontitis is associated with poorer survival rate and higher risk of peri-implantitis during a 5-10 years period after implant loading.

To clinically evaluate oral implant restorations placed by undergraduate students in the dental clinical curriculum at KU Leuven (Belgium) in terms of function and esthetics.A retrospective observational cohort study was designed. The esthetic and functional evaluations of implant-supported restorations placed in the framework of the undergraduate implant dentistry clinical training program using White/Pink Esthetic Score (WES/PES) and visual analog scale (VAS) scoring was performed. Furthermore, complications were registered based retrospectively on the patient's medical file. The following research questions were stipulated: (1) How well do implant-supported restorations placed by undergraduate students perform esthetically? and (2) Which complications occurred and how were these managed?Between August 2008 and July 2014 (6 academic terms), 251 implants (Brånemark System Mk III, Nobel Biocare) were placed in 113 patients by 155 students (40% of all students enrolled in the training program). Of these implants, 228 were restored in 101 patients by 118 students with varying restoration types. Esthetic scoring of the restorations in 83 of these patients revealed a satisfying mean WES of 8.14 ± 2.09 (out of 10) and PES of 9.56 ± 3.14 (out of 14). Complications were registered in 18.9% of the cases.Clinical training in implant dentistry for undergraduates contributes to the development of advanced skills in the dental student's Master education. Overall, patients were satisfied with their implant-supported restorations. Implant and restoration success rates and complication incidence were confirmed by long-term data in the oral implant literature.

Biological tissues have a complex and heterogeneous 3D structure, which is only partially revealed by standard histomorphometry in 2D. We here present a novel chemical compound for contrast-enhanced microfocus computed tomography (CE-CT), a Hafnium-based Wells-Dawson polyoxometalate (Hf-POM), which allows simultaneous 3D visualization of mineralized and non-mineralized skeletal tissues, such as mineralized bone and bone marrow vasculature and adipocytes . We validated the novel contrast agent, which has a neutral pH in solution, by detailed comparison with (immuno)histology on murine long bones as blueprint , and showed that Hf-POM-based CE-CT can be used for virtual 3D histology. Furthermore, we quantified the 3D structure of the different skeletal tissues, as well as their spatial relation to each other, during aging and diet-induced obesity. We discovered, based on a single CE-CT dataset per sample, clear differences between the groups in bone structure, vascular network organization, characteristics of the adipose tissue and proximity of the different tissues to each other. These findings highlight the complementarity and added value of Hf-POM-based CE-CT compared to standard histomorphometry. As this novel technology provides a detailed 3D simultaneous representation of the structural organization of mineralized bone and bone marrow vasculature and adipose tissue, it will enable to improve insight in the interactions between these three tissues in several bone pathologies and to evaluate the in vivo performance of biomaterials for skeletal regeneration.

The impact of diabetes mellitus on bone fracture healing is clinically relevant as the patients experience delayed fracture healing. Even though efforts have been made to understand the detrimental effects of type 2 diabetes mellitus (T2DM) on the fracture healing process, the exact mechanisms causing the pathophysiological outcomes remain unclear. The aim of this study was to assess alterations in bone fracture healing (tibial fracture surgery, intramedullary pinning) of diet-induced obese (DIO) mice, and to investigate the in vitro properties of osteochondroprogenitors derived from the diabetic micro-environment. High-resolution contrast-enhanced microfocus X-ray computed tomography (CE-CT) enabled a simultaneous 3D assessment of the amount and spatial distribution of the regenerated soft and hard tissues during fracture healing and revealed that osteogenesis as well as chondrogenesis are altered in DIO mice. Compared to age-matched lean controls, DIO mice presented a decreased bone volume fraction and increased callus volume and adiposity at day 14 post-fracture. Of note, bone turnover was found altered in DIO mice relative to controls, evidenced by decreased blood serum osteocalcin and increased serum CTX levels. The in vitro data revealed that not only the osteogenic and adipogenic differentiation of periosteum-derived cells (PDCs) were altered by hyperglycemic (HG) conditions, but also the chondrogenic differentiation. Elevated PPARγ expression in HG conditions confirmed the observed increase in differentiated adipocytes in vitro. Finally, chondrogenesis-related genes COL2 and COL10 were downregulated for PDCs treated with HG medium, confirming that chondrogenic differentiation is compromised in vitro and suggesting that this may affect callus formation and maturation during the fracture healing process in vivo. Altogether, these results provide novel insights into the alterations of long bone fracture repair and suggest a link between HG-induced dysfunctionality of osteochondroprogenitor differentiation and fracture healing impairment under T2DM conditions.

Aim Osseointegration of titanium implants is predictable, but can be improved via surface functionalization. Materials and Methods One hundred and twenty implants were installed in parietal bone of 12 domestic pigs and left to heal for 1 or 3 months. Five groups were defined according surface treatments: immersion in water (H2O), 10% polyphosphoric acid (PPA10), 1% phosphorylated pullulan (PPL1), 10% phosphorylated pullulan (PPL10) or 10% phosphorylated pullulan + 1 μg bone morphogenetic protein-2 (PPL10 BMP). As primary outcome, implant osseointegration was evaluated by quantitative histology, namely peri-implant bone formation (B/T in %) and bone-to-implant contact (BIC in %) for each healing period. The Wilcoxon signed-rank test and Mann–Whitney U-test with α = 0.05 were performed. Results PPL10 and PPA10 groups showed significantly higher B/T and BIC results than the control (H2O) group at 1-month (p .05). After 3 months, no experimental group showed a significant difference compared to the control group (H2O) for both investigated parameters (B/T and BIC; p > .05). Conclusion Functionalizing titanium implants with inorganic or organic phosphate-containing polymers at 10 wt% concentration may stimulate peri-implant bone formation and implant osseointegration at early healing times.

Micro-computed tomography can be applied for the assessment of the micro-architectural characteristics of the cortical and trabecular bones in either physiological or disease conditions. However, reports often lack a detailed description of the methodological steps used to analyse these images, such as the volumes of interest, the algorithms used for image filtration, the approach used for image segmentation, and the bone parameters quantified, thereby making it difficult to compare or reproduce the studies. This study addresses this critical need and aims to provide standardized assessment and consistent parameter reporting related to quantitative jawbone image analysis. Various regions of the rat jawbones were screened for their potential for standardized micro-computed tomography analysis. Furthermore, the volumes of interest that were anticipated to be most susceptible to bone structural changes in response to experimental interventions were defined. In the mandible, two volumes of interest were selected, namely, the condyle and the trabecular bone surrounding the three molars. In the maxilla, the maxillary tuberosity region and the inter-radicular septum of the second molar were considered as volumes of interest. The presented protocol provides a standardized and reproducible methodology for the analysis of relevant jawbone volumes of interest and is intended to ensure global, accurate, and consistent reporting of its morphometry. Furthermore, the proposed methodology has potential, as a variety of rodent animal models would benefit from its implementation. ispartof: International Journal of Oral Science vol:9 issue:2 pages:87-94 ispartof: location:India status: published

Purpose: To investigate the effect of coating a titanium implant surface with a phosphorylated exopolysaccharide, pullulan, on the peri-implant bone formation and implant osseointegration. Materials and Methods: Implants were placed in the skull bone of 12 domestic pigs and healed for 1 or 3 months. Osseointegration of (un)coated implants was evaluated by quantitative histology (peri-implant bone fraction [BF] and bone-to-implant-contact [BIC]). The Wilcoxon-Mann-Whitney test with α = .05 was used to statistically compare BF and BIC of the coated and uncoated implants. Results: Significantly more BF was observed surrounding pullulan-coated implants compared with uncoated implants (P < .05) and for both healing periods (P < .05). BIC was positively affected by the exopolysaccharide coating, with significantly more BIC after the 3-month healing period compared with the uncoated implant (P < .05). Furthermore, BIC remained stable over time for the coated implants, while it significantly decreased for the uncoated ones (P < .05). Conclusion: These findings reveal the capacity of functionalizing the titanium implant surface with phosphorylated pullulan to improve the mineralization of the implant-bone interface.

Roughened surfaces are increasingly being used for dental implant applications as the enlarged contact area improves bone cell anchorage, thereby facilitating osseointegration. However, the additional surface area also entails a higher risk for the development of biofilm associated infections, an etiologic factor for many dental ailments, including peri-implantitis. To overcome this problem, we designed a dental implant composed of a porous titaniumsilica (Ti/SiO2 ) composite material and containing an internal reservoir that can be loaded with antimicrobial compounds. The composite material consists of a sol-gel derived mesoporous SiO2 diffusion barrier integrated in a macroporous Ti load-bearing structure obtained by powder metallurgical processing. The antimicrobial compounds can diffuse through the porous implant walls, thereby reducing microbial biofilm formation on the implant surface. A continuous release of µM concentrations of chlorhexidine through the Ti/SiO2 composite material was measured, without initial burst effect, over at least 10 days and using a 5 mM chlorhexidine solution in the implant reservoir. Metabolic staining, CFU counting and visualisation by scanning electron microscopy confirmed that Streptococcus mutans biofilm formation on the implant surface was almost completely prevented due to chlorhexidine release (preventive setup). Moreover, we demonstrated efficacy of released chlorhexidine against mature Streptococcus mutans biofilms (curative setup). In conclusion, we provide a proof of concept of the sustained release of chlorhexidine, one of the most widely used oral antiseptics, through the Ti/SiO2 material thereby preventing and eradicating biofilm formation on the surface of the dental implant. In principle, our flexible design allows for the use of any bioactive compound, as discussed. ispartof: European Cells & Materials vol:33 pages:13-27 ispartof: location:Switzerland status: published

Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with obesity and hyperglycemia. Roux-en-Y gastric bypass (RYGB) surgery is a common treatment for severely obese patients and T2DM. Both RYGB and T2DM are linked to increased skeletal fragility, though the exact mechanisms are poorly understood. Our aim was to characterize the structural, mechanical and compositional properties of bones from diet-induced obese and RYGB-treated obese (bypass) mice to elucidate which the exact factors are contributing to the increased skeletal fragility. To achieve this, a combinatory approach including microfocus X-ray computed tomography, 3-point bending, finite element modeling and Raman spectroscopy, was used. Compared to aged-matched lean controls, the obese mice displayed decreased cortical thickness, trabecular bone loss, decreased stiffness and increased Young’s modulus. For the bypass mice, these alterations were even more pronounced, and additionally they showed low mineral-to-matrix ratio in the cortical endosteal area. Accumulation of the advanced glycation end-product (AGE) pentosidine was found in the cortex of obese and bypass groups and this accumulation was correlated with an increased Young’s modulus. In conclusion, we found that the increased fracture risk in T2DM- and post-RYGB bones is mainly driven by accumulation of AGEs and macro-structural alterations, generating biomechanical dysfunctionality. ispartof: Scientific Reports vol:8 issue:1 pages:5881-1 ispartof: location:England status: published

Objectives To overcome shortcomings of hydraulic calcium-silicate cements (hCSCs), an experimental tricalcium silicate (TCS) cement, named ‘TCS 50’, was developed. In vitro research showed that TCS 50 played no negative effect on the viability and proliferation of human dental pulp cells, and it induced cell odontogenic differentiation. The objective was to evaluate the pulpal repair potential of TCS 50 applied onto exposed minipig pulps. Methods Twenty permanent teeth from three minipigs were mechanically exposed and capped using TCS 50; half of the teeth were scheduled for 7-day and the other half for 70-day examination (n = 10). Commercial hCSCs ProRoot MTA and TheraCal LC were tested as references (n = 8). Tooth discoloration was examined visually. After animal sacrifice, the teeth were scanned using micro-computed tomography; inflammatory response at day 7 and day 70, mineralized tissue formation at day 70 were assessed histologically. Results Up to 70 days, TCS 50 induced no discoloration, ProRoot MTA generated gray/black discoloration in all teeth. For TCS 50, 40.0% pulps exhibited a mild/moderate inflammation at day 7. No inflammation was detected and complete reparative dentin with tubular structures was formed in all pulps after 70 days. ProRoot MTA induced a similar response, TheraCal LC generated a less favorable response in terms of initial inflammation and reparative dentin formation; however, these differences were not significant (Chi-square test of independence: p > 0.05). Significance TCS 50 induced reparative dentinogenesis in minipig pulps. It can be considered as a promising pulp-capping agent, also for aesthetic areas.

The objective of this study is to examine the effect of low-magnitude, high-frequency (LMHF) loading, and anti-osteoporosis medications such as parathyroid hormone (PTH) and bisphosphonates on peri-implant bone healing in an osteoporosis model, and to assess their combined effects on these processes. Thirteen-week-old ovariectomized rats (n = 44) were divided into three groups: PTH, alendronate, and saline. After 3 weeks of drug administration, titanium implants were inserted into the tibiae. Each group was subdivided into two groups: with or without LMHF loading via whole-body vibration (50 Hz at 0.5 g, 15 min per day, 5 days per week). Rats were killed 4 weeks following implantation. Removal torque test, micro-CT analyses (relative gray (RG) value, water = 0, and implant = 100), and histomorphometric analyses (bone-to-implant contact (BIC) and peri-implant bone formation (bone volume/tissue volume (BV/TV))) were performed. Removal torque values and BIC were significantly differed by loading and drug administration (ANOVA). Post hoc analysis showed that PTH-treated groups were significantly higher than the other drug-treated groups. BV/TV was significantly enhanced by PTH administration. In cortical bone, RG values were significantly increased by loading. In trabecular bone, however, RG values were significantly increased by PTH administration. These findings suggest that LMHF loading and PTH can act locally and additively on the bone healing process, improving the condition of implant osseointegration. Whole-body vibration and administration of a hormone used to treat osteoporosis can enhance bone healing at the site of a titanium implant. Toru Ogawa of Tohoku University Graduate School of Dentistry in Sendai, Japan, and colleagues gave anti-osteoporosis medications, either parathyroid hormone or the bisphosphonate drug alendronate, to female rat models of osteoporosis. After three weeks of drug administration or a saline control, the researchers inserted titanium implants into the rats’ leg bones. Half the rats were then exposed to whole-body vibration, which applies low-magnitude, high-frequency mechanical forces. A multitude of tests showed that parathyroid hormone improved bone healing at the implant more than alendronate or saline did. The vibrational stimulus further increased the healing. The findings suggest that these treatments could aid in oral bone healing for patients receiving dental implants.

Introduction Knowledge about macro- and micro-structural characteristics may improve in vivo estimation of the quality and quantity of regenerated bone tissue. For this reason, micro-CT imaging has been applied to evaluate alveolar bone remodelling, alterations of periodontal ligament thickness and cortical and trabecular bone changes in rodent jaw bones. In this paper, we provide a systematic review on the available micro-CT literature on jaw bone micro-architecture. Methodology A detailed search through the PubMed database was performed. Articles published up to December 2013 and related to maxilla, mandible and condyle with quantitatively analysed bone micro-architectural parameters were considered eligible for inclusion. Two reviewers assessed the search results according to inclusion criteria designed to identify animal studies quantifying the bone micro-architecture of the jaw rodent bones in physiological or drug-induced disease status, or in response to interventions such as mechanical loading, hormonal treatment and other metabolic alterations. Finally, the reporting quality of the included publications was evaluated using the tailored ARRIVE guidelines outlined by Vignoletti and Abrahamsson (2012). Results Database search, additional manual searching and assessment of the inclusion and exclusion criteria retrieved 127 potentially relevant articles. Eventually, 14 maxilla, 20 mandible and 12 condyle articles with focus on bone healing were retained, and were analysed together with 3 methodological papers. Each study was described systematically in terms of subject, experimental intervention, follow-up period, selected region of interest used in the micro-CT analysis, parameters quantified, micro-CT scanner device and software. The evidence level evaluated by the ARRIVE guidelines showed high mean scores (between 18 and 25; range: 0–25), indicating that most of the selected studies are well-reported. The major obstacles identified were related to sample size calculation, absence of adverse event descriptions, randomization or blinding procedures. Conclusions The evaluated studies are highly heterogeneous in terms of research topic and the different regions of interest. These results illustrate the need for a standardized methodology in micro-CT analysis. While the analysed studies do well according to the ARRIVE guidelines, the micro-CT procedure is often insufficiently described. Therefore we recommend to extend the ARRIVE guidelines for micro-CT studies., Highlights • This review investigates discrepancies between reports using micro-CT imaging of rodent jaw bone, the applied methodology and reported results. • Knowledge about the bone micro-architecture of the rodent jaw is scarce. • Jaw bone micro-architecture varies according to ROI selections and the methodology applied to define a specific region are insufficient.

More insight into the biological fundamentals of leukocyte platelet-rich fibrin (L-PRF) guided healing is necessary to recommend its application, in particular in deficient bone sites that need to support implants. This study investigated the short-term bone healing effect of L-PRF treatment in cylindrical non-critical sized bone defects with 3 mm diameter and 6 mm depth in tibiae of 18 adult male New Zealand White rabbits. After a randomization process, 96 bone defects were prepared and half of them were filled with a L-PRF membrane, while untreated defects in the opposite tibia served as control group. The rabbits were euthanized after 7, 14 or 28 days of healing. The bone healing of the cortical and medullary areas was investigated by micro-CT, while the expression of molecular markers (RUNX2, VEGFA, COL1A2 and BMP2) was assessed by qRT-PCR. Treatment with L-PRF did not affect the micro-structural bone characteristics of the repaired bone tissue, except for a decrease in the trabecular connectivity at the cortical level after 14 days of healing. At this time, RUNX2 and VEGFA mRNA levels were significantly lower in the treated defects. L-PRF membranes thus had a temporary negative influence on the bone microarchitecture (Tb.Pf) and on the RUNX2 and VEGFA expression during early bone healing. Overall, L-PRF treatment did not enhance bone regeneration in these non-critical size defects after 28 days. ispartof: Scientific Reports vol:7 ispartof: location:England status: published

The spread of antibiotic resistance and the challenges associated with antiseptics such as chlorhexidine have necessitated a search for new antibacterial agents against oral bacterial pathogens. As a result of failing traditional approaches, drug repurposing has emerged as a novel paradigm to find new antibacterial agents. In this study, we examined the effects of the FDA-approved anticancer agent toremifene against the oral bacteria Porphyromonas gingivalis and Streptococcus mutans . We found that the drug was able to inhibit the growth of both pathogens, as well as prevent biofilm formation, at concentrations ranging from 12.5 to 25 μM. Moreover, toremifene was shown to eradicate preformed biofilms at concentrations ranging from 25 to 50 μM. In addition, we found that toremifene prevents P. gingivalis and S. mutans biofilm formation on titanium surfaces. A time-kill study indicated that toremifene is bactericidal against S. mutans . Macromolecular synthesis assays revealed that treatment with toremifene does not cause preferential inhibition of DNA, RNA, or protein synthesis pathways, indicating membrane-damaging activity. Biophysical studies using fluorescent probes and fluorescence microscopy further confirmed the membrane-damaging mode of action. Taken together, our results suggest that the anticancer agent toremifene is a suitable candidate for further investigation for the development of new treatment strategies for oral bacterial infections.

Oral infections are among the most common diseases worldwide. Many protocols for the prevention and treatment of oral infections have been described, yet no golden standard has been developed so far. The antiseptic chlorhexidine and antibiotics are often used in these treatment procedures. However, long-term use of chlorhexidine can lead to side effects and extensive use of antibiotics can promote the development of antibiotic-resistant bacteria, which in turn can compromise the effectiveness of the treatment. Consequently, it remains important to search for new antibacterial agents for the treatment of oral infections. In this study, we report on the antibacterial activity of the anti-asthma drug zafirlukast against oral pathogens Porphyromonas gingivalis and Streptococcus mutans. Furthermore, its activity against oral biofilms grown on titanium surfaces was confirmed. In addition, we demonstrated that zafirlukast displays no cytotoxicity against human osteoblasts. Combined, this study paves the way for further research to determine the potential of zafirlukast to be used as a new antibiotic against oral pathogens. ispartof: FEMS Microbiology Letters vol:364 issue:2 ispartof: location:England status: published

Structured Abstract Objectives To determine the role of Msx2 in craniofacial morphology and growth, we used a mouse model and performed a quantitative morphological characterization of the Msx2 −/− and the Msx2 +/− phenotype using a 2D cephalometric analysis applied on micrographs. Materials and Methods Forty-four three-and-a-half-month-old female CD1 mice were divided into the following three groups: Msx2 +/+ (n = 16), Msx2 +/− (n = 16), and Msx2 −/− (n = 12). Profile radiographs were scanned. Modified cephalometric analysis was performed to compare the three groups. Results Compared with the wild-type mice, the Msx2 −/− mutant mice presented an overall craniofacial size decrease and modifications of the shape of the different parts of the craniofacial skeleton, namely the neurocranium, the viscerocranium, the mandible, and the teeth. In particular, dysmorphologies were seen in the cochlear apparatus and the teeth (taurodontism, reduced incisor curvature). Finally contrary to previous published results, we were able to record a specific phenotype of the Msx2 +/− mice with this methodology. This Msx2 +/− mouse phenotype was not intermediate between the Msx2 −/− and the wild-type animals. Conclusion Msx2 plays an important role in craniofacial morphogenesis and growth because almost all craniofacial structures were affected in the Msx2−/− mice including both intramembranous and endochondral bones, the cochlear apparatus, and the teeth. In addition, Msx2 haploinsufficiency involves a specific phenotype with subtle craniofacial structures modifications compared with human mutations.

Dynamic loading can affect the bone surrounding implants. For ultrastructural exploration of the peri-implant tissue response to dynamic loading, titanium implants were installed in rat tibiae, in which one implant was loaded while the contralateral served as the unloaded control. The loaded implants received stimulation either within 24 hrs after implantation (immediate loading) or after a 28-day healing period (delayed loading) for 4, 7, 14, 21, or 28 days. The samples were processed for histology and gene expression quantification. Compared with the unloaded control, bone-to-implant contact increased significantly by immediate loading for 28 days (p < .05), but not in case of delayed loading. No effect of loading was observed on the bone formation in the implant thread areas, on the blood vessel area, and on endosteal callus formation. Loading during healing (immediate) for 7 days induced, relative to the unloaded control, a 2.3-fold increase of Runx2 in peri-implant cortical bone (p < .01) without a change in the RANKL/Opg ratio. Loading after healing (delayed) for 7 days up-regulated Runx2 (4.3-fold, p < .01) as well as Opg (22.3-fold, p < .05) compared with the unloaded control, resulting in a significantly decreased RANKL/Opg ratio. These results indicate a stimulating effect of dynamic loading on implant osseointegration when applied during the healing phase. In addition, gene expression analyses revealed molecular adaptations favoring bone formation and, at the same time, affecting bone remodeling. ispartof: Journal of Dental Research vol:93 issue:3 pages:313-318 ispartof: location:United States status: published

Osteoporosis could potentially complicate oral implant treatment because of disease-specific characteristics such as the abnormal bone condition, poor healing ability caused by bisphosphonates (BPs), and bisphosphonate-related osteonecrosis of the jaw (BRONJ). These problems must be resolved to ensure that oral implant treatment is successful in osteoporotic patients.

Purpose The purpose of this study was to compare the clinical performance of two dental implant types possessing a different macro-design in the in vivo pig model. Materials and methods Titanium Aadva(TM) implants (GC, Tokyo, Japan) were compared with OsseoSpeed(TM) implants (Astra, Molndal, Sweden), with the Aadva implant displaying significant larger inter-thread dimensions than the OsseoSpeed implant. Implants were installed in the parietal bone of 12 domestic pigs and left for healing for either 1 or 3 months. Implant osseointegration was evaluated by quantitative histology (bone volume relative to the tissue volume [BV/TV]; bone-to-implant contact [BIC]) for distinct implant regions (collar, body, total implant length) with specific implant thread features. The Wilcoxon-Mann-Whitney nonparametric test with α = 0.05 was performed. Results An inferior amount of bone enveloping the Aadva implant compared with the OsseoSpeed implant was observed, in particular at the implant body part with its considerable inter-thread gaps (p Conclusion Although the Aadva implant displayed a clinically acceptable level of osseointegration, the findings demonstrate that implant macro-design features can impact the dynamics of implant osseointegration. Consideration of specific implant macro-design features should be made relative to the biological and mechanical microenvironment.

Porphyromonas gingivalis is a major pathogen involved in oral diseases such as periodontitis and peri‐implantitis. Management of these diseases typically includes mechanical debridement of the colonized surfaces followed by application of antiseptics or antibiotics. Disadvantages associated with the use of antiseptics and the growing worldwide problem of antibiotic resistance have necessitated the search for alternative agents. In this study, the antibacterial and antibiofilm properties of AM404, an active metabolite of paracetamol, were tested against P. gingivalis and other bacterial pathogens. The activity of AM404 was tested against 10 bacteria, including both oral and nonoral human pathogens. The minimal inhibitory concentration (MIC) of AM404 was determined by measuring optical density (OD) values. The minimum biofilm inhibitory concentration (MBIC) was detected by crystal violet staining. The activity of structural analogs of AM404 was tested by MIC determinations. The effect of AM404 on P. gingivalis biofilms formed on titanium disks as a model for dental implants was evaluated by colony forming unit counting. Potential cytotoxicity of AM404 towards HEK‐293 (human embryonic kidney cells), HepG2 (human hepatoma cells), IEC‐6 (rat intestinal cells), and Panc‐1 cells (pancreatic cancer cells) was assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays. To get more insight in the mode of action of AM404, we used the fluorescent dyes N‐phenyl‐1‐napthylamine and SYTOX green to investigate outer and inner membrane damage of P. gingivalis induced by AM404, respectively. Of all tested pathogens, AM404 only inhibited growth and biofilm formation of P. gingivalis. Moreover, it showed potent activity against P. gingivalis biofilms formed on titanium surfaces. A structure–activity analysis demonstrated that the unsaturated carbon chain is essential for its antibacterial activity. Importantly, AM404 was not toxic towards the tested mammalian cells up to concentrations approaching 4× the MIC. Membrane damage assays using fluorescent probes N‐phenyl‐1‐napthylamine and SYTOX green revealed that membrane permeabilization presumably is the primary antibacterial mode of action of AM404. Collectively, our results suggest that AM404 has the potential to be used for the development of new drugs specifically targeting P. gingivalis‐related infections.

High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging. ispartof: Scientific Reports vol:6 issue:1 ispartof: location:England status: published

Alendronate therapy has been associated with serious side effects. Altering the alendronate concentration and combining with high-frequency loading as mechanical intervention was explored in this animal study as a treatment for osteoporosis. The bone anabolic potency of high-frequency loading was overruled by the different alendronate dosages applied in the present study. Further exploration of reduced hormonal therapy associated with mechanical interventions in osteoporosis treatment should be sought. The aim of the present study was to investigate the effect of alendronate (ALN) administration at two different dosages, associated or not with high-frequency (HF) loading, on the bone microstructural response. Sixty-four female Wistar rats were used, of which 48 were ovariectomized (OVX) and 16 were sham-operated (shOVX). The OVX animals were divided into three groups: two groups were treated with alendronate, at a dosage of 2 mg/kg (ALN(2)) or at a reduced dosage of 1 mg/kg (ALN(1)) three times per week. A third OVX group did not receive pharmaceutical treatment. All four groups were mechanically stimulated via whole body vibration (WBV) at HF (up to 150 Hz) or left untreated (shWBV). ALN and HF were administered for 6 weeks, starting at 10-week post-(sh)OVX. Tibia bone structural parameters were analyzed using ex vivo microcomputed tomography. Trabecular bone loss and structural deterioration resulting from ovariectomy were partially restored by ALN administration, demonstrated by the improvement of trabecular patter factor (Tb.Pf), trabecular separation (Tb.Sp), and structure model index (SMI) of the ALN groups compared to that of the OVX group, regardless of the applied dosage [ALN(2) or ALN(1)] or mechanical loading regime (shWBV or WBV). However, a significant positive effect of the ALN(1) administration on trabecular (decrease of Tb.Sp and SMI) and cortical bone (increase of cortical thickness) microarchitecture compared to that of the OVX status group was observed for both loading regimes was not seen for ALN(2). Furthermore, HF loading resulted in cortical bone changes, with an increased trabeculary area and endocortical perimeter. Finally, the benefits of a combined therapy of ALN with HF loading could not be discerned in the present experimental conditions. The bone anabolic potency of HF loading was overruled by the ALN dosages applied in the present study. Further altering the ALN dosage combined with robust mechanical stimuli needs to be considered in osteoporosis research and eventually therapy.

BACKGROUND: Appropriate oral hygiene is required to maintain oral health in denture wearers. This study aims to compare the role of denture cleaning methods in combination with overnight storage conditions on biofilm mass and composition on acrylic removable dentures. METHODS: In a cross-over randomized controlled trial in 13 older people, 4 conditions with 2 different mechanical cleaning methods and 2 overnight storage conditions were considered: (i) brushing and immersion in water without a cleansing tablet, (ii) brushing and immersion in water with a cleansing tablet, (iii) ultrasonic cleaning and immersion in water without a cleansing tablet, and (iv) ultrasonic cleaning and immersion in water with a cleansing tablet. Each test condition was performed for 5 consecutive days, preceded by a 2-days wash-out period. Biofilm samples were taken at baseline (control) and at the end of each test period from a standardized region. Total and individual levels of selected oral bacteria (n = 20), and of Candida albicans were identified using the Polymerase Chain Reaction (PCR) technique. Denture biofilm coverage was scored using an analogue denture plaque score. Paired t-tests and Wilcoxon-signed rank tests were used to compare the test conditions. The level of significance was set at α< 5%. RESULTS: Overnight denture storage in water with a cleansing tablet significantly reduced the total bacterial count (p

Objectives: Biofilm-associated implant infections represent a serious public health problem. Covalent immobilization of antimicrobial agents on titanium (Ti), thereby inhibiting biofilm formation of microbial pathogens, is a solution to this problem. Methods: Vancomycin (VAN) and caspofungin (CAS) were covalently bound on Ti substrates using an improved processing technique adapted to large-scale coating of implants. Resistance of the VAN-coated Ti (VAN-Ti) and CAS-coated Ti (CAS-Ti) substrates against in vitro biofilm formation of the bacterium Staphylococcus aureus and the fungal pathogen Candida albicans was determined by plate counting and visualized by confocal laser scanning microscopy. The efficacy of the coated Ti substrates was also tested in vivo using an adapted biomaterial-associated murine infection model in which control-Ti, VAN-Ti or CAS-Ti substrates were implanted subcutaneously and subsequently challenged with the respective pathogens. The osseointegration potential of VAN-Ti and CAS-Ti was examined in vitro using human bone marrow-derived stromal cells, and for VAN-Ti also in a rat osseointegration model. Results: In vitro biofilm formation of S. aureus and C. albicans on VAN-Ti and CAS-Ti substrates, respectively, was significantly reduced compared with biofilm formation on control-Ti. In vivo, we observed over 99.9% reduction in biofilm formation of S. aureus on VAN-Ti substrates and 89% reduction in biofilm formation of C. albicans on CAS-Ti substrates, compared with control-Ti substrates. The coated substrates supported osseointegration in vitro and in vivo. Conclusions: These data demonstrate the clinical potential of covalently bound VAN and CAS on Ti to reduce microbial biofilm formation without jeopardizing osseointegration. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Aim The aim of this search was to assess the biological consequences that overload might have on already osseointegrated oral implants through a systematic screening of the scientific literature. Method Detailed searches through PUBMED, OVID, EMBASE and LILACS databases were made. Articles published up to December 2011 and those reported on the clinical, radiographic and/or histological outcome of oral implants subjected to so-called overload were considered eligible for inclusion. Identified studies were assessed by one non-blinded reviewer according to well-defined inclusion and exclusion criteria. When doubt arose, the co-authors were counselled until final agreement was obtained. The PICO questions formulated was:“what is the effect of overload vs. no overload on bone/implant loss in clinically stable implants?” Results The database searches as well as additional hand searching, resulted in 726 potentially relevant titles. Eventually, 16 clinical and 25 animal studies were considered relevant to the topic. After inclusion/exclusion criteria assessment, all clinical studies and all but three animal studies and one systematic review were considered at high risk of bias and excluded. The included animal studies did not reveal an association between overload and peri-implant bone loss in the absence of peri-implant inflammation, whereas in its presence, overload seemed to aggravate the peri-implant tissue breakdown. Conclusions The effect of implant overload on bone/implant loss in clinically well-integrated implants is poorly reported and provides little unbiased evidence to support a cause-and-effect relationship. The PICO question remained unanswered. At the animal level, “overload”, mimicked by supra-occlusal contacts acting in an uninflamed peri-implant environment, did not negatively affect osseointegration and even was anabolic. In contrast, supra-occlusal contacts in the presence of inflammation significantly increased the plaque-induced bone resorption.

Resume Les limites imposees par l’autogreffe osseuse ont pousse au developpement de nouvelles strategies pour le traitement des grandes pertes de substances osseuses. L’ingenierie tissulaire osseuse consiste a associer des cellules osteocompetentes telles que les cellules stromales mesenchymateuses (CSM) a des matrices, telles les ceramiques, dans le but de regenerer le tissu lese. Cependant, le benefice therapeutique de ces « materiaux cellularises » n’atteint pas encore celui de l’autogreffe; ce resultat est notamment du a la mort prematuree des cellules (chargees dans le materiau) apres leur implantation dans le site lese. Dans le but d’ameliorer le potentiel therapeutique de ces materiaux cellularises, differentes strategies peuvent etre mises en place. Dans ce cadre, le projet Glassbone vise a optimiser les conditions de preparation des produits d’ingenierie tissulaire en s’articulant autour de trois axes: la recherche d’une matrice en ceramique optimale pour la formation osseuse; la survie post-implantation des cellules constituant les materiaux cellularises, et enfin le preconditionnement pour promouvoir la viabilite cellulaire in vivo. L’ensemble du projet ouvre la voie vers l’elaboration de nouveaux materiaux « pro-survie » permettant une meilleure regeneration tissulaire.

The aim of this study was to investigate the effect of controlled high- (HF) and low-frequency (LF) mechanical loading on peri-implant bone healing. Custom-made titanium implants were inserted in both tibiae of 69 adult Wistar rats. For every animal, one implant was loaded by compression through the axis of tibia (test), whereas the other one was unloaded (control). The test implants were randomly distributed among four groups receiving different loading regimes, which were determined by ex vivo calibration. Within the HF (40 Hz) or LF (2 Hz) loading category, the magnitudes were chosen as low- (LM) and high-magnitude (HM), respectively, leading to constant strain rate amplitudes for the two frequency groups. This resulted in the four loading regimes: (i) HF-LM (40 Hz–0.5 N); (ii) HF-HM (40 Hz–1 N); (iii) LF-LM (2 Hz–10 N); and (iv) LF-HM (2 Hz–20 N) loading. Loading was performed five times per week and lasted for one or four weeks. Tissue samples were processed for histology and histomorphometry (bone-to-implant contact, BIC; and peri-implant bone fraction, BF) at the cortical and medullar level. Data were analysed statistically with ANOVA and paired t -tests with the significance level set at 0.05. For the one-week experiments, an increased BF adjacent to the implant surface at the cortical level was exclusively induced by the LF-HM loading regime (2 Hz–20 N). Four weeks of loading resulted in a significant effect on BIC (and not on BF) in case of HF-LM loading (40 Hz–0.5 N) and LF-HM loading (2 Hz–20 N): BIC at the cortical level significantly increased under both loading regimes, whereas BIC at the medullar level was positively influenced only in case of HF-LM loading. Mechanical loading at both HF and LF affects osseointegration and peri-implant BF. Higher loading magnitudes (and accompanying elevated tissue strains) are required under LF loading to provoke a positive peri-implant bone response, compared with HF loading. A sustained period of loading at HF is needed to result in an overall enhanced osseointegration.

Bioengineered bone scaffolds are intended for use in large bone defects. Successful bone constructs should stimulate and support both the onset and the continuance of bone ingrowth. In an attempt to improve their performance and to compete with the one of autologous bone grafts, a growing symbiosis at the biological and material level is required. Recent advances have been made to further exploit the osteogenic potential of MSCs in scaffold development. Current research encompasses new strategies for reducing cell death after implantation and the manufacturing of tailored, instructive scaffolds.

Shortening of the healing time before loading risks impeding successful titanium implant anchorage into compromised bone. A thorough understanding at the genetic scale of the early phases of bone regeneration at the implant interface is required before the development of strategies to enhance implant osseointegration. In this study a new in vivo implant model to explore the mechanism by which titanium implant osseointegration is affected by the host bone properties is presented. An implant was conceptualized enabling standardized harvesting of peri-implant tissue for quantitative molecular analysis while preserving the mimicking of the clinical setting. The implant is partly indented to provide a well-defined healing compartment from where tissue differentiation and de novo bone formation can be investigated and partly screw-threaded to provide a good implant anchorage into the bone. The feasibility of the implant design was assessed in osteopenic bone conditions, evoked by simulated weightlessness. Wistar rats were either hindlimb unloaded by tail suspension (HU) for 9 days or acted as controls (CTL). The status of compromised bone tissue through 9-days HU was confirmed by micro-X-ray computed tomography. The implant was installed in the proximal tibial bone 7 days after the onset of HU or CTL. Two days postimplantation, the peri-implant regenerating tissue responses were recorded by measuring expression of inflammatory, angiogenic, and bone resorption parameters (hypoxia-inducible factor 1, alpha subunit; vascular endothelial growth factor A; angiopoietin 1; endothelial PAS domain protein 1; fibroblast growth factor 2; tumor necrosis factor; interleukin 11; acid phosphatase 5, tartrate resistant; tumor necrosis factor (ligand) superfamily, member 11/RANKL). We successfully demonstrated that HU-associated bone conditions evoked a significant alteration of expression of the angiogenic markers in the peri-implant regenerative tissue during initial implant osseointegration, whereas the expression levels of the inflammatory and bone resorption parameters remained unchanged. We concluded that this in vivo implant model provides a well-designed and controlled method to examine molecular responses in implant osseointegration to impaired bone conditions. This model may serve to explore the application of anabolic strategies in peri-implant osteogenesis.

Despite a myriad of studies confirming the interaction between biology and mechanics, the exact nature of the main mechanical stimuli and their influence on the bone regeneration processes are still unclear. The hypothesis of this study was that the outcome of peri-implant healing under different implant loading regimens can be explained by the influence of fluid flow on the combination of angiogenesis and osteogenesis through its influence on cell proliferation and differentiation. To investigate this hypothesis a mathematical model of bone regeneration was applied to simulate the peri-implant healing in an in vivo repeated sampling bone chamber for different axial micromechanical implant loading regimes. When mechanical loading was modeled to influence both osteogenic and angiogenic processes, a good agreement was observed between simulations and experiments concerning the amount of bone in the bone chamber, its radial and longitudinal distribution, and the bone-implant contact for different implant displacement magnitudes.

While mathematical models are able to capture essential aspects of biological processes like fracture healing and distraction osteogenesis, their predictive capacity in peri-implant osteogenesis remains uninvestigated. We tested the hypothesis that a mechano-regulatory model has the potential to predict bone regeneration around implants. In an in vivo bone chamber set-up allowing for controlled implant loading (up to 90 μ m axial displacement), bone tissue formation was simulated and compared qualitatively and quantitatively with histology. Furthermore, the model was applied to simulate excessive loading conditions. Corresponding to literature data, implant displacement magnitudes larger than 90 μ m predicted the formation of fibrous tissue encapsulation of the implant. In contradiction to findings in orthopedic implant osseointegration, implant displacement frequencies higher than 1 Hz did not favor the formation of peri-implant bone in the chamber. Additional bone chamber experiments are needed to test these numerical predictions.

Several mechanoregulatory tissue differentiation models have been proposed over the last decade. Corroboration of these models by comparison with experimental data is necessary to determine their predictive power. So far, models have been applied with various success rates to different experimental set-ups investigating mainly secondary fracture healing. In this study, the mechanoregulatory models are applied to simulate the implant osseointegration process in a repeated sampling in vivo bone chamber, placed in a rabbit tibia. This bone chamber provides a mechanically isolated environment to study tissue differentiation around titanium implants loaded in a controlled manner. For the purpose of this study, bone formation around loaded cylindrical and screw-shaped implants was investigated. Histologically, no differences were found between the two implant geometries for the global amount of bone formation in the entire chamber. However, a significantly larger amount of bone-to-implant contact was observed for the screw-shaped implant compared to the cylindrical implant. In the simulations, a larger amount of bone was also predicted to be in contact with the screw-shaped implant. However, other experimental observations could not be predicted. The simulation results showed a distribution of cartilage, fibrous tissue and (im)mature bone, depending on the mechanoregulatory model that was applied. In reality, no cartilage was observed. Adaptations to the differentiation models did not lead to a better correlation between experimentally observed and numerically predicted tissue distribution patterns. The hypothesis that the existing mechanoregulatory models were able to predict the patterns of tissue formation in the in vivo bone chamber could not be fully sustained.

Critical factors for the establishment of osseointegration are the implant surface microtopography and the local mechanical environment. The present study evaluated the bone response around a turned (T) and a roughened (R) implant for either an unloaded or a well-controlled loaded situation.Bone chambers were installed in the tibia of 20 rabbits. In each of the chambers, two identical displacement-controlled loading experiments were performed: 30 microm for 400 cycles at 1 Hz, three times a week for 9 weeks versus 0-microm implant displacement. A linear mixed model and a logistic mixed model with alpha = 5% were set to study the significant effect of the surface texture on the peri-implant bone response in the unloaded (T-0 microm versus R-0 microm) and the loaded (T-30 microm versus R-30 microm) mode.Results indicated no microtopographic dependence of the bone response further away from the implant in unloaded and loaded conditions. For a load-free implant, osseointegration seemed to occur with a higher incidence at a roughened compared to a turned implant surface. In the presence of loading, the topographic dependency of the osteogenic activity at the interface was overruled by the loading-related bone response, revealing no significant differences in osseointegration incidence between T and R.A predominant effect of the interfacial mechanical environment over the implant surface characteristics on the differentiating cell population is suggested.

Both implant surface characteristics and mechanical loading are known to affect implant osseointegration. Their interaction and the underlying mechanisms by which they affect peri-implant healing processes are still unknown. The aim of this study is therefore to investigate the influence of a turned versus a rough (Plus®, Dentsply Friadent) implant surface on peri-implant bone formation in case of unloaded or loaded implant healing. Material and Methods: Bone formation was evaluated around screw-shaped implants under four experimental conditions using a repeated sampling bone chamber methodology: (1) unloaded turned implant (CU), (2) unloaded implant with a rough surface (TU), (3) loaded turned implant (CL), and (4) loaded implant with a rough surface (TL). Peri-implant tissue samples were paraffin embedded after implant removal and examined histologically and histomorphometrically. A mixed model was used for statistical analysis. Results: The surface of bone tissue relative to the total tissue area (bone area fraction) was not affected by the experimental conditions. The areas of bone trabeculae relative to the bone area (bone fraction) were significantly higher for TL compared with CU and TU. The bone fraction in the vicinity (100 μm zone) of the implant (BFZ) was significantly the highest around the loaded roughened implants (TL). Conclusion: Implant loading did not affect bone formation in the absence of surface roughness, and implant surface roughness had no effect in the absence of loading. However, a bone-stimulating effect in the implant's vicinity was assigned to the rough surface when the implant was loaded.

Initial osteogenesis at the implant interface is, to a great extent, determined by the implant surface characteristics and the interfacial loading conditions. The present study investigated the effect of various degrees of relative movement on the tissue differentiation around a roughened screw-shaped immediately loaded implant. Repeated-sampling bone chambers were installed in the tibia of 10 rabbits. In each of the chambers, three experiments were performed by inducing 0 (control), 30, and 90 microm implant displacement for 9 wk. A linear mixed model and a logistic mixed model with alpha = 5% determined statistical significance. Tissue filling of the bone chamber was similar for the three test conditions. The bone area fraction was significantly higher for 90 microm implant displacement compared with no displacement. A significantly higher fraction of bone trabeculae was found for 30 and 90 microm implant displacement compared with the unloaded situation. The incidence of osteoid-to-implant and bone-to-implant contact was significantly higher for 90 microm implant displacement compared with 30 and 0 microm implant displacement. Significantly more osteoid in contact with the implant was found for the loaded conditions compared with no loading. Well-controlled micro-motion positively influenced bone formation at the interface of a roughened implant. An improved bone reaction was detected with increasing micro-motion.

Summary Mechanical loading at high frequency affects bone. Whether this also applies to osteoporotic bone, combined or not with bisphosphonate therapy, was investigated in this animal study through imaging. An anabolic effect of high-frequency loading on osteoporotic bone, however non-synergistic with bisphosphonates, was found, thereby revealing its potential for treatment of osteoporosis. Introduction In an effort to elucidate the effect of high-frequency (HF) loading on bone and to optimize its potential for treatment osteoporosis, this study aimed to investigate the effect of HF loading via whole body vibration (WBV), alone or in association with bisphosphonate treatment (alendronate—ALN), on the micro-architecture of ovariectomy (OVX)-induced compromised bone. Methods Eighty-four female Wistar rats were ovariectomized (OVX) or sham-operated (shOVX). OVX animals were treated either with ALN (3 days/week at a dose of 2 mg/kg) or with saline solution. Each group (shOVX, OVX, ALN) was further divided into subgroups relative to the loading status (sham-WBV versus WBV) and the duration of experimental period (4 days versus 14 days). (Sham)WBV loading was applied for 10 min/day using 10 consecutive steps of HF loading (130, 135, 140, 145, 150, 130, 135, 140, 145, 150 Hz). Tibial bone structural responses to WBV and/or ALN treatment were analyzed using ex vivo micro-computed tomography. Results The animal’s hormonal status displayed a major impact on the trabecular and cortical bone structural parameters. Furthermore, mechanical treatment with HF WBV increased the cortical thickness and reduced the medullar area in OVX rats. However, OVX trabecular bone was not affected by HF stimuli. Finally, ALN prevented OVX-associated bone loss, but the association of ALN with WBV did not lead to a synergistic bone response in OVX bone. Conclusions HF WBV mechanical stimulation displayed an anabolic effect on osteoporotic cortical bone, confirming its therapeutic properties for enhancing compromised bone. Additionally, its association with bisphosphonates’ administration did not produce any additive effect on the bone micro-architecture in the present study. ispartof: Osteoporosis International vol:26 issue:1 pages:303-313 ispartof: location:England status: published

Loading, early after implant placement, has gained rapid interest in dentistry. Primary implant stability, as e.g. defined by resonance frequency instrumentation, has been isolated as a predicator when immediate and early implant loading is applied. The aim of this study was to investigate the effect of early (after 7 days) mechanical loading on the establishment of osseointegration by means of resonance frequency analysis (RFA). Percutaneous titanium implants were installed in both tibiae of 10 guinea-pigs. One week after implant installation, one implant (test) was loaded daily for 6 weeks, while the contra-lateral served as the unloaded one (control). A sinusoidally varying bending moment was applied at a frequency of 3 Hz and a force amplitude of 5 N, for 1800 cycli. Resonance frequency was measured at implant installation and from then on weekly using the RFA-device (Osstell). Contrary to control implants, that showed a decrease in stability 1 week after installation, reaching a minimum at 3 weeks (-200 Hz), test implants showed a progressive increase in stability over time. After 6 weeks, the mean resonance frequency of test and control implants reached the same values. As confirmed by recent literature, early loading does not have to endanger the establishment of osseointegration of titanium implants. On the contrary, controlled loading is beneficial to maintain the implant stability during the early critical healing period as determined by RFA-measurements.