Early osteogenic response of osteoprogenitor cells on modified titanium implant surfaces leads to improved osteogenesis

Background: Implant surface micro-roughness and hydrophilicity are known to improve the osteogenic differentiation potential of osteoprogenitor cells. This study was aimed to determine whether topographically and chemically modified titanium implant surfaces stimulate an initial osteogenic response in osteoprogenitor cells, which leads to their improved osteogenesis. ----- ----- Methods: Statistical analysis of microarray gene expression profiling data available from studies (at 72 hours) on sand-blasted, large grit acid etched (SLA) titanium surfaces was performed. Subsequently, human osteoprogenitor cells were cultured on SLActive (hydrophilic SLA), SLA and polished titanium surfaces for 24 hours, 3 days and 7 days. The expression of BMP2, BMP6, BMP2K, SP1, ACVR1, FZD6, WNT5A, PDLIM7, ITGB1, ITGA2, OCN, OPN, ALP and RUNX2 were studied using qPCR. ----- ----- Results: Several functional clusters related to osteogenesis were highlighted when genes showing statistically significant differences (from microarray data at 72 hours) in expression on SLA surface (compared with control surface) were analysed using DAVID (online tool). This indicates that differentiation begins very early in response to modified titanium surfaces. At 24 hours, ACVR1 (BMP pathway), FZD6 (Wnt pathway) and SP1 (TGF-β pathway) were significantly up-regulated in cultures on the SLActive surface compared to the other surfaces. WNT5A and ITGB1 also showed higher expression on the modified surfaces. Gene expression patterns on Day 3 and Day 7 did not reveal any significant differences.----- ----- Conclusion: These results suggest that the initial molecular response of osteoprogenitor cells to modified titanium surfaces may be responsible for an improved osteogenic response via the BMP and Wnt signalling pathways.

The microRNA expression signature on modified titanium implant surfaces influences genetic mechanisms leading to osteogenic differentiation

Topographically and chemically modified titanium implants are recognized to have improved osteogenic properties; however, the molecular regulation of this process remains unknown. This study aimed to determine the microRNA profile and the potential regulation of osteogenic differentiation following early exposure of osteoprogenitor cells to sand-blasted, large-grit acid-etched (SLA) and hydrophilic SLA (modSLA) surfaces. Firstly, the osteogenic characteristics of the primary osteoprogenitor cells were confirmed using ALP activity and Alizarin Red S staining. The effect of smooth (SMO), SLA and modSLA surfaces on the TGF-β/BMP (BMP2, BMP6, ACVR1) and non-canonical WNT/Ca2+ (WNT5A, FZD6) pathways, as well as the integrins ITGB1 and ITGA2, was determined. It was revealed that the modified titanium surfaces could induce the activation of TGF-β/BMP and non-canonical WNT/Ca2+ signaling genes. The expression pattern of microRNAs (miRNAs) related to cell differentiation was evaluated. Statistical analysis of the differentially regulated miRNAs indicated that 35 and 32 miRNAs were down-regulated on the modSLA and SLA surfaces respectively, when compared with the smooth surface (SMO). Thirty-one miRNAs that were down-regulated were common to both modSLA and SLA. There were 10 miRNAs up-regulated on modSLA and nine on SLA surfaces, amongst which eight were the same as observed on modSLA. TargetScan predictions for the down-regulated miRNAs revealed genes of the TGF-β/BMP and non-canonical Ca2+ pathways as targets. This study demonstrated that modified titanium implant surfaces induce differential regulation of miRNAs, which potentially regulate the TGF-β/BMP and WNT/Ca2+ pathways during osteogenic differentiation on modified titanium implant surfaces.

Is flapless implant surgery a viable option in posterior maxilla? : a review

This article reviews the literature on the outcome of flapless surgery for dental implants in the posterior maxilla. The literature search was carried out in using the keywords: flapless, dental implants and maxilla. A hand search and Medline search were carried out on studies published between 1971 and 2011. The authors included research involving a minimum of 15 dental implants with a followup period of 1 year, an outcome measurement of implant survival, but excluded studies involving multiple simultaneous interventions, and studies with missing data. The Cochrane approach for cohort studies and Oxford Centre for Evidence- Based Medicine were applied. Of the 56 published papers selected, 14 papers on the flapless technique showed high overall implant survival rates. The prospective studies yielded 97.01% (95% CI: 90.72–99.0) while retrospective studies or case series illustrated 95.08% (95% CI: 91.0–97.93) survival. The average of intraoperative complications was 6.55% using the flapless procedure. The limited data obtained showed that flapless surgery in posterior maxilla areas could be a viable and predictable treatment method for implant placement. Flapless surgery tends to be more applicable in this area of the mouth. Further long-term clinical controlled studies are needed.

Shortening cemented femoral implants. An in vitro investigation to quantify exeter femoral implant rotational stability vs simulated implant length

The Exeter stems vary in length from 90 to 150 mm. The shorter stems generally have lower offsets. The purpose of this study was to determine if length of stem, with fixed offset, affected rotational stability. Mechanical testing was carried out on 10 implant-cement constructs with 2 loading profiles, rising from chair and stair climbing, at different simulated implant lengths using purpose-built apparatus. This paper presents a mechanism for clinically observed rotational stability and explains the mechanical characteristics required for rotational stability in Exeter femoral stems. © 2012.

How important is length? : mechanical testing and measurement of a cemented, polished, tapered femoral implant

Total hip arthroplasty (THA) has a proven clinical record for providing pain relief and return of function to patients with disabling arthritis. There are many successful options for femoral implant design and fixation. Cemented, polished, tapered femoral implants have been shown to have excellent results in national joint registries and long-term clinical series. These implants are usually 150mm long at their lateral aspect. Due to their length, these implants cannot always be offered to patients due to variations in femoral anatomy. Polished, tapered implants as short as 95mm exist, however their small proximal geometry (neck offset and body size) limit their use to smaller stature patients. There is a group of patients in which a shorter implant with a maintained proximal body size would be advantageous. There are also potential benefits to a shorter implant in standard patient populations such as reduced bone removal due to reduced reaming, favourable loading of the proximal femur, and the ability to revise into good proximal bone stock if required. These factors potentially make a shorter implant an option for all patient populations. The role of implant length in determining the stability of a cemented, polished, tapered femoral implant is not well defined by the literature. Before changes in implant design can be made, a better understanding of the role of each region in determining performance is required. The aim of the thesis was to describe how implant length affects the stability of a cemented, polished, tapered femoral implant. This has been determined through an extensive body of laboratory testing. The major findings are that for a given proximal body size, a reduction in implant length has no effect on the torsional stability of a polished, tapered design, while a small reduction in axial stability should be expected. These findings are important because the literature suggests that torsional stability is the major determinant of long-term clinical performance of a THA system. Furthermore, a polished, tapered design is known to be forgiving of cement-implant interface micromotion due to the favourable wear characteristics. Together these findings suggest that a shorter polished, tapered implant may be well tolerated. The effect of a change in implant length on the geometric characteristics of polished, tapered design were also determined and applied to the mechanical testing. Importantly, interface area does play a role in stability of the system; however it is the distribution of the interface and not the magnitude of the area that defines stability. Taper angle (at least in the range of angles seen in this work) was shown not to be a determinant of axial or torsional stability. A range of implants were tested, comparing variations in length, neck offset and indication (primary versus cement-in-cement revision). At their manufactured length, the 125mm implants were similar to their longer 150mm counterparts suggesting that they may be similarly well tolerated in the clinical environment. However, the slimmer cement-in-cement revision implant was shown to have a poorer mechanical performance, suggesting their use in higher demand patients may be hazardous. An implant length of 125mm has been shown to be quite stable and the results suggest that a further reduction to 100mm may be tolerated. However, further work is required. A shorter implant with maintained proximal body size would be useful for the group of patients who are unable to access the current standard length implants due to variations in femoral anatomy. Extending the findings further, the similar function with potential benefits of a shorter implant make their application to all patients appealing.

The effects of lane-changing on the immediate follower : anticipation, relaxation, and change in driver characteristics

This paper investigates the effects of lane-changing in driver behavior by measuring (i) the induced transient behavior and (ii) the change in driver characteristics, i.e., changes in driver response time and minimum spacing. We find that the transition largely consists of a pre-insertion transition and a relaxation process. These two processes are different but can be reasonably captured with a single model. The findings also suggest that lane-changing induces a regressive effect on driver characteristics: a timid driver (characterized by larger response time and minimum spacing) tends to become less timid and an aggressive driver less aggressive. We offer an extension to Newell’s car-following model to describe this regressive effect and verify it using vehicle trajectory data.

Comparison of self-reported driving behaviours and experiences of immediate-uptake and delayed-uptake licence holders

The objective of this paper was to explore experiences of ‘immediate-uptake’ (intermediate licensure at age 17-18 years, n = 928) and ‘delayed-uptake’ (intermediate licensure at age 19-20 years, n = 158) driver’s licence holders in the Australian state of Queensland. In Queensland, the graduated driver licence program applies to all novices irrespective of age. Drivers who obtained a Provisional 1 (intermediate) (P1) licence completed a survey exploring pre-Licence and Learner experiences, including the Behaviour of Young Novice Drivers Scale (BYNDS). Six months later, 351 drivers from this sample (n = 300 immediate-uptake) completed a survey exploring P1 driving. Delayed-uptake Learners reported significantly more difficulty gaining driving practice, which appeared to be associated with significantly greater engagement in unsupervised driving during the Learner period. Whilst a larger proportion of delayed-uptake novices, particularly males, reported the use of more active punishment avoidance strategies (avoiding Police, talking themselves out of a ticket) in the P1 phase, there was no significant difference in the BYNDS scores in the Learner and P1 phases according to licence-uptake category. Delayed-uptake novices report more difficulty meeting GDL requirements and place themselves at increased risk by driving unsupervised during the Learner licence phase. Additional efforts such as mentoring programs which can support the delayed-uptake Learner in meeting their GDL obligations merit further consideration to allow this novice group to gain the full benefits of the GDL program and to reduce their risk of harm in the short-term.

Dosimetric effects of a high-density spinal implant

In this study, a treatment plan for a spinal lesion, with all beams transmitted though a titanium vertebral reconstruction implant, was used to investigate the potential effect of a high-density implant on a three-dimensional dose distribution for a radiotherapy treatment. The BEAMnrc/DOSXYZnrc and MCDTK Monte Carlo codes were used to simulate the treatment using both a simplified, recltilinear model and a detailed model incorporating the full complexity of the patient anatomy and treatment plan. The resulting Monte Carlo dose distributions showed that the commercial treatment planning system failed to accurately predict both the depletion of dose downstream of the implant and the increase in scattered dose adjacent to the implant. Overall, the dosimetric effect of the implant was underestimated by the commercial treatment planning system and overestimated by the simplified Monte Carlo model. The value of performing detailed Monte Carlo calculations, using the full patient and treatment geometry, was demonstrated.

Mechanical testing and modelling of a bone-implant construct

Finite Element modelling of bone fracture fixation systems allows computational investigation of the deformation response of the bone to load. Once validated, these models can be easily adapted to explore changes in design or configuration of a fixator. The deformation of the tissue within the fracture gap determines its healing and is often summarised as the stiffness of the construct. FE models capable of reproducing this behaviour would provide valuable insight into the healing potential of different fixation systems. Current model validation techniques lack depth in 6D load and deformation measurements. Other aspects of the FE model creation such as the definition of interfaces between components have also not been explored. This project investigated the mechanical testing and FE modelling of a bone– plate construct for the determination of stiffness. In depth 6D measurement and analysis of the generated forces, moments and movements showed large out of plane behaviours which had not previously been characterised. Stiffness calculated from the interfragmentary movement was found to be an unsuitable summary parameter as the error propagation is too large. Current FE modelling techniques were applied in compression and torsion mimicking the experimental setup. Compressive stiffness was well replicated, though torsional stiffness was not. The out of plane behaviours prevalent in the experimental work were not replicated in the model. The interfaces between the components were investigated experimentally and through modification to the FE model. Incorporation of the interface modelling techniques into the full construct models had no effect in compression but did act to reduce torsional stiffness bringing it closer to that of the experiment. The interface definitions had no effect on out of plane behaviours, which were still not replicated. Neither current nor novel FE modelling techniques were able to replicate the out of plane behaviours evident in the experimental work. New techniques for modelling loads and boundary conditions need to be developed to mimic the effects of the entire experimental system.

Flapless dental implant surgery : a retrospective study of 1,241 consecutive implants

Purpose: The purpose of this study was to identify retrospectively the predictors of implant survival when the flapless protocol was used in two private dental practices. Materials and Methods: The collected data were initially computer searched to identify the patients; later, a hand search of patient records was carried out to identify all flapless implants consecutively inserted over the last 10 years. The demographic information gathered on statistical predictors included age, sex, periodontal and peri-implantitis status, smoking, details of implants inserted, implant locations, placement time after extraction, use of simultaneous guided hard and soft tissue regeneration procedures, loading protocols, type of prosthesis, and treatment outcomes (implant survival and complications). Excluded were any implants that required flaps or simultaneous guided hard and soft tissue regeneration procedures, and implants narrower than 3.25 mm. Results: A total of 1,241 implants had been placed in 472 patients. Life table analysis indicated cumulative 5-year and 10-year implant survival rates of 97.9% and 96.5%, respectively. Most of the failed implants occurred in the posterior maxilla (54%) in type 4 bone (74.0%), and 55.0% of failed implants had been placed in smokers. Conclusion: Flapless dental implant surgery can yield an implant survival rate comparable to that reported in other studies using traditional flap techniques.