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Numerous advanced surface modification techniques exist to improve bone integration and antibacterial properties of titanium based implants and prostheses. A simple and straightforward method of obtaining uniform and controlled TiO(2) coatings of devices with complex shapes is H(2)O(2)-oxidation and hot water aging. Based on the photoactivated bactericidal properties of TiO(2), this study was aimed at optimizing the treatment to achieve high photocatalytic activity. Ti-6Al-4V samples were H(2)O(2)-oxidized and hot water aged for up to 24 and 72 h, respectively. Degradation measurements of rhodamine B during UV-A illumination of samples showed a near linear relationship between photocatalytic activity and total treatment time, and a nanoporous coating was observed by scanning electron microscopy. Grazing incidence X-ray diffraction showed a gradual decrease in crystallinity of the surface layer, suggesting that the increase in surface area rather than anatase formation was responsible for the increase in photocatalytic activity.

Seawater dimethyl sulfide (DMS) and distribution of phytoplankton biomass were investigated in relation to sea ice conditions, hydrography and nutrients, onboard the Swedish icebreaker Oden as a part of the International Arctic Ocean Expedition, 1991. The expedition lasted from the beginning of August until the middle of October and covered sampling between 75° to 90° N in the open waters and along the ice edge zone in the Greenland Sea-Fram Strait area as well as in the pack ice of the western part of the Nansen and Amundsen basins and in the Makarov basin. Surface seawater DMS concentrations showed a clear seasonal progression related to biological activity, ranging from 0.04 to 12 nmol dm −3 . The highest values were found in open waters along the ice edge in the beginning of August, while the lowest concentrations were measured beneath heavy pack ice in late September. On average DMS fell about 30% per week in the open waters south of and within the ice edge zone whereas a significant higher seasonal decline, about 45% per week, was observed in the pack ice during freeze-up. The importance of the phytoplankton bloom and zooplankton abundance both at the ice edge zone and in the pack ice during summer ice-melt to DMS concentrations in seawater has been demonstrated. We also demonstrated a potential for intense DMS production in the open waters in the wake of the receding ice. The extremely low surface concentrations of DMS during the freeze-up of the pack ice were probably primarily controlled by removal processes within the water column. The turnover time of DMS in the pack ice water column was calculated to be of the order of 13 days with the most effective sink seemingly of micro-biological origin. Although, our limited set of data indicated the likelyhood of a relationship between DMS and degraded phytoplankton material (phaeopigments), seawater DMS showed no simple correlation with phytoplankton standing stock over the large areas and different seasons covered. The area weighed summer and winter fluxes of DMS from the Arctic Polar Ocean to the atmosphere were estimated to be 2.0 and 0.03 μ mol m −2 day −1 , respectively. On an annual basis, winter biogenic sulfur emissions are negligible compared to the summer emissions in the region. The total emissions of marine biogenic sulfur from the Northern Hemispheric high latitudes was estimated to be approximately 4 Gmol yr −1 . DOI: 10.1034/j.1600-0889.1996.t01-1-00003.x

Currently available treatments for the degenerated intervertebral disc present disadvantages, such as surgical invasiveness and inadequate load distribution results. Load-bearing, injectable materials may be interesting for future therapies, but have not been studied in depth. In this study, the existing literature was screened for studies on injectable materials for the intervertebral disc and a rationale for load-bearing, injectable materials was formulated. Requirements for such a material were discussed, partly based on the experience of materials used for similar applications. Important properties were discussed and found to include biocompatibility, bioactivity, porosity, handling, injectability, working time, setting time, radiopacity, containment and mechanical properties, where several of these properties are linked to one another. In conclusion, there is a need for consensus on the properties of new materials developed for use in minimally invasive procedures in the spine. A substantial amount of attention may need to be given to non-toxic setting reactions.

While recent studies have demonstrated the importance of the initial mechanical insult in the severity of spinal cord injury, there is a lack of information on the detailed cord-column interaction during such events. In vitro models have demonstrated the protective properties of the cerebrospinal fluid, but visualization of the impact is difficult. In this study a computational model was developed in order to clarify the role of the cerebrospinal fluid and provide a more detailed picture of the cord-column interaction. The study was validated against a parallel in vitro study on bovine tissue. Previous assumptions about complete subdural collapse before any cord deformation were found to be incorrect. Both the presence of the dura mater and the cerebrospinal fluid led to a reduction in the longitudinal strains within the cord. The division of the spinal cord into white and grey matter perturbed the bone fragment trajectory only marginally. In conclusion, the cerebrospinal fluid had a significant effect on the deformation pattern of the cord during impact and should be included in future models. The type of material models used for the spinal cord and the dura mater were found to be important to the stress and strain values within the components, but less important to the fragment trajectory.

Degeneration of the intervertebral disk constitutes one of the major causes of low back pain in adults aged 2050 years old. In this study, injectable, in situ setting, degradable composites aimed for intervertebral disk replacement were prepared. beta-TCP and calcium carbonate particles were mixed into acrylic-terminated oligo[D,L-lactide-co-(epsilon-caprolactone)], which were crosslinked at room temperature. The structure of the oligomers was confirmed by H-1-NMR spectroscopy. The composites were examined via SEM, and the mechanical properties of the crosslinked networks were determined. The porous beta-TCP particles showed good mechanical anchorage to the matrix due to polymer penetration into the pores. In vitro degradation tests showed that the composites containing beta-TCP slowly degraded, whereas the composites containing CaCO3 exhibited apatite formation capacity. It was concluded that the surface area, morphology, and solubility of the fillers might be used to control the degradation properties. The incorporation of fillers also increased both the elastic modulus and the maximum compression strength of the composites, properties that were similar to those of the physiological disk. These materials have potential for long-term intervertebral disk replacement and regenerative scaffolds because of their low degradation rates, bioactivity, and mechanical properties.

An engineered protein prevents aggregation of the Aβ peptide and facilitates clearance of Aβ from the brain in a fruit fly model of Alzheimer's disease., Protein aggregation, arising from the failure of the cell to regulate the synthesis or degradation of aggregation-prone proteins, underlies many neurodegenerative disorders. However, the balance between the synthesis, clearance, and assembly of misfolded proteins into neurotoxic aggregates remains poorly understood. Here we study the effects of modulating this balance for the amyloid-beta (Aβ) peptide by using a small engineered binding protein (ZAβ3) that binds with nanomolar affinity to Aβ, completely sequestering the aggregation-prone regions of the peptide and preventing its aggregation. Co-expression of ZAβ3 in the brains of Drosophila melanogaster expressing either Aβ42 or the aggressive familial associated E22G variant of Aβ42 abolishes their neurotoxic effects. Biochemical analysis indicates that monomer Aβ binding results in degradation of the peptide in vivo. Complementary biophysical studies emphasize the dynamic nature of Aβ aggregation and reveal that ZAβ3 not only inhibits the initial association of Aβ monomers into oligomers or fibrils, but also dissociates pre-formed oligomeric aggregates and, although very slowly, amyloid fibrils. Toxic effects of peptide aggregation in vivo can therefore be eliminated by sequestration of hydrophobic regions in monomeric peptides, even when these are extremely aggregation prone. Our studies also underline how a combination of in vivo and in vitro experiments provide mechanistic insight with regard to the relationship between protein aggregation and clearance and show that engineered binding proteins may provide powerful tools with which to address the physiological and pathological consequences of protein aggregation., Author Summary Alzheimer's disease is thought to be a result of neuronal damage caused by toxic aggregated forms of the Aβ peptide in the brain. There is no cure and existing treatments are ineffective in reversing or preventing disease progression. Here we describe a novel strategy that makes use of an engineered “Affibody” protein to study the disease and potentially combat its underlying causes. The Affibody occludes the aggregation-prone regions of Aβ peptides, preventing their aggregation into toxic forms, and it also acts to dissolve pre-formed Aβ aggregates. It is functional in vivo, as its co-expression with Aβ peptides in transgenic fruit flies prevents the neuronal damage and premature death that result from expression of Aβ peptides alone. Moreover, we show that the origin of this protection is the enhanced clearance of Aβ peptides from the brain. These findings open up new opportunities for using engineered binding proteins to probe the origins of Alzheimer's disease and potentially to develop a new class of therapeutic agents.

In vivo testing of spinal cord biomechanics is surrounded with difficulties. This is due to methodological issues such as reproducibility and visualization problems as well as ethical concerns and the possible lack of correlation between animal models and the human tissue response. Therefore, a number of in vitro and computational studies have been performed in order to increase the understanding of the spinal cord’s mechanical behaviour during trauma. Due to its well defined nature, the burst fracture and its effect on the spinal cord have been frequently studied, but investigations on other injuries such as distraction and dislocation are also cited in the literature. In vitro models have utilised a variety of materials including polymers and biological tissue from different animals. Similarly a variety of models have been used in computational studies to represent the cord which range in terms of both geometric complexity and material models. This chapter aims to provide a review of the methods and materials used in vitro and computational models of the spinal cord injury.

The purpose of the study was to assess the effect of CSF and the size of the impacting bone fragment area on spinal cord deformation during trauma.A transverse impact rig was used to produce repeated impacts on bovine and surrogate cord models. Tests were recorded with high-speed video and performed on specimens with and without CSF and/or dura mater and with 3 different impactor areas.The CSF layer was found to reduce the maximum cord deformation significantly. A 50% reduction in impact area significantly increased the maximum cord deformation by 20-30%. The surrogate model showed similar trends to the bovine model but with lower absolute deformation values.Cerebrospinal fluid protects the cord during impact by reducing its deformation. A smaller bone fragment impact area increases the deformation of the cord, in agreement with clinical results, where a higher impact energy-possibly giving rise to smaller fragments-results in a worse neurological deficit.

Background The objective was to identify separate cognitive domains in the standard assessment tools (MMSE, ADAS-Cog) and analyze the process of decline within domains during three years in Alzheimer's disease (AD) patients with donepezil treatment. Method AD patients (n = 421) were recruited from a clinical multi-centre study program in Sweden. Patients were assessed every six months during three years. All patients received donepezil starting directly after study entry. After dropouts, 158 patients remained for analyses over three years. Data for the other patients were analysed until they dropped out (4 groups based on length in study). Results Factor analyses of all items suggested that there were three intercorrelated factors: a General, a Memory and a Spatial factor for which we constructed corresponding domains. Overall there was a cognitive improvement at six months followed by a linear drop over time for the three domains. Some group and domain differences were identified. Patients who remained longer in the study had better initial performance and a slower deterioration rate. The early dropouts showed no improvement at six months and many dropped out due to side effects. The other groups displayed a performance improvement at six months that was less pronounced in the Memory domain. Before dropping out, deterioration accelerated, particularly in the Spatial domain. Conclusion The course of illness in the three domains was heterogeneous among the patients. We were not able to identify any clinically relevant correlates of this heterogeneity. As an aid we constructed three algorithms corresponding to the cognitive domains, which can be used to characterize patients initially, identify rapid decliners and follow the course of the disease.

Background: Memory disturbance, deficient concentration, and fatigue are symptoms seen in amnestic mild cognitive impairment (MCI) as well as in mild traumatic brain injury (TBI). The aim of this study was to assess if an established rehabilitation program commonly used in TBI can aid MCI patients to develop compensatory memory strategies that can improve their cognition, occupational performance, and quality of life (QoL). Methods: Fifteen patients with MCI participated in the program 2 days per week for 8 weeks. Cognitive function, occupational performance, and self-perceived QoL were assessed at baseline, at the end of the intervention, and at follow-up after 6 months. Results: Significant improvements were seen in cognitive processing speed, occupational performance, and in some of the QoL domains. Conclusion: As this goal-oriented rehabilitation program in MCI resulted in some improvements in cognition, occupational performance, and QoL, further randomized controlled studies are warranted.

The increasing resistance of certain bacteria to antibiotics commonly used in bone cements has led to a demand for alternative antibacterial agents. The antibiotics added to bone cements may, however, have detrimental effects on the mechanical properties of the cement.We evaluated the mechanical effects of adding vancomycin and meropenem to bone cement by compression, bending and fatigue tests.Addition of vancomycin at a concentration of up to 2.5% (w/w) had no effect on the compressive strength. Bending and fatigue strength were negatively affected by vancomycin but not by meropenem.A cement containing 1.25% vancomycin and 1.25% meropenem might be an interesting compromise between the introduction of antibacterial properties and preservation of the mechanical properties. With this concentration of additives the compressive strength and the fatigue strength remain unchanged, while the bending strength (-14%) and the bending modulus (-9%) are only slightly reduced and remain above the limits set by the ISO5833 standard.

Antibiotic-loaded bone cement is extensively used in joint arthroplasty, but increasing bacteria resistance against common antibiotics has lead to a demand for alternative drugs. However, bone cement containing new additives must be characterized both biologically and mechanically. This study evaluated elution kinetics, antibacterial activity, and mechanical properties for cement loaded with vancomycin and/or meropenem. The presence of meropenem broadened the antibacterial spectrum and enhanced the elution of vancomycin. The mechanical properties were negatively affected by 1.0 g of vancomycin, but these detrimental effects were acceptable when only 0.5 g of vancomycin were added to a cement containing 0.5 g of meropenem. Further investigations on this formulation with adjusted antibiotic amounts are, however, necessary to reach the optimal compromise between the antibacterial and the mechanical properties of the bone cement.

© 2016 The Authors. Calcium phosphate cements (CPCs) are widely used in bone repair. Currently there are two main types of CPCs, brushite and apatite. The aim of this project was to evaluate the mechanical properties of particularly promising experimental brushite and apatite formulations in comparison to commercially available brushite- and apatite-based cements (chronOS™ Inject and Norian® SRS®, respectively), and in particular evaluate the diametral tensile strength and biaxial flexural strength of these cements in both wet and dry conditions for the first time. The cements' porosity and their compressive, diametral tensile and biaxial flexural strength were tested in wet (or moist) and dry conditions. The surface morphology was characterized by scanning electron microscopy. Phase composition was assessed with X-ray diffraction. It was found that the novel experimental cements showed better mechanical properties than the commercially available cements, in all loading scenarios. The highest compressive strength (57.2±6.5 MPa before drying and 69.5±6.0 MPa after drying) was found for the experimental brushite cement. This cement also showed the highest wet diametral tensile strength (10.0±0.8 MPa) and wet biaxial flexural strength (30.7±1.8 MPa). It was also the cement that presented the lowest porosity (approx. 12%). The influence of water content was found to depend on cement type, with some cements showing higher mechanical properties after drying and some no difference after drying.

The mechanical fixation of endosseous implants, such as screws, in trabecular bone is challenging because of the complex porous microstructure. Development of new screw designs to improve fracture fixation, especially in high-porosity osteoporotic bone, requires a profound understanding of how the structural system implant/trabeculae interacts when it is subjected to mechanical load. In this study, pull-out tests of screw implants were performed. Screws were first inserted into the trabecular bone of rabbit femurs and then pulled out from the bone inside a computational tomography scanner. The tests were interrupted at certain load steps to acquire 3D images. The images were then analysed with a digital volume correlation technique to estimate deformation and strain fields inside the bone during the tests. The results indicate that the highest shear strains are concentrated between the inner and outer thread diameter, whereas compressive strains are found at larger distances from the screw. Tensile strains were somewhat smaller. Strain concentrations and the location of trabecular failures provide experimental information that could be used in the development of new screw designs and/or to validate numerical simulations. Electronic supplementary material The online version of this article (doi:10.1007/s10237-017-0891-9) contains supplementary material, which is available to authorized users.

There is a plethora of calcium phosphate (CaP) scaffolds used as synthetic substitutes to bone grafts. The scaffold performance is often evaluated from the quantity of bone formed within or in direct contact with the scaffold. Micro-computed tomography (µCT) allows three-dimensional evaluation of bone formation inside scaffolds. However, the almost identical x-ray attenuation of CaP and bone obtrude the separation of these phases in µCT images. Commonly, segmentation of bone in µCT images is based on gray scale intensity, with manually determined global thresholds. However, image analysis methods, and methods for manual thresholding in particular, lack standardization and may consequently suffer from subjectivity. The aim of the present study was to provide a methodological framework for addressing these issues. Bone formation in two types of CaP scaffold architectures (foamed and robocast), obtained from a larger animal study (a 12 week canine animal model) was evaluated by µCT. In addition, cross-sectional scanning electron microscopy (SEM) images were acquired as references to determine thresholds and to validate the result. µCT datasets were registered to the corresponding SEM reference. Global thresholds were then determined by quantitatively correlating the different area fractions in the µCT image, towards the area fractions in the corresponding SEM image. For comparison, area fractions were also quantified using global thresholds determined manually by two different approaches. In the validation the manually determined thresholds resulted in large average errors in area fraction (up to 17%), whereas for the evaluation using SEM references, the errors were estimated to be less than 3%. Furthermore, it was found that basing the thresholds on one single SEM reference gave lower errors than determining them manually. This study provides an objective, robust and less error prone method to determine global thresholds for the evaluation of bone formation in CaP scaffolds.

The porosity of a calcium phosphate cement is a key parameter as it affects several important properties of the cement. However, a successful, non-destructive porosity measurement method that does not include drying has not yet been reported for calcium phosphate cements. The aim of this study was to evaluate isopropanol solvent exchange as such a method. Two different types of calcium phosphate cements were used, one basic (hydroxyapatite) and one acidic (brushite). The cements were allowed to set in an aqueous environment and then immersed in isopropanol and stored under three different conditions: at room temperature, at room temperature under vacuum (300 mbar) or at 37℃. The specimen mass was monitored regularly. Solvent exchange took much longer time to reach steady state in hydroxyapatite cements compared to brushite cements, 350 and 18 h, respectively. Furthermore, the immersion affected the quasi-static compressive strength of the hydroxyapatite cements. However, the strength and phase composition of the brushite cements were not affected by isopropanol immersion, suggesting that isopropanol solvent exchange can be used for brushite calcium phosphate cements. The main advantages with this method are that it is non-destructive, fast, easy and the porosity can be evaluated while the cements remain wet, allowing for further analysis on the same specimen.

Many of the failures of total joint replacements are related to tribology, i.e., wear of the cup, head and liner. Accumulation of wear particles at the implants can be linked to osteolysis which leads to bone loss and in the end aseptic implant loosening. Therefore it is highly desirable to reduce the generation of wear particles from the implant surfaces. Silicon nitride (Si(3)N(4)) has shown to be biocompatible and have a low wear rate when sliding against itself and is therefore a good candidate as a hip joint material. Furthermore, wear particles of Si(3)N(4) are predicted to slowly dissolve in polar liquids and they therefore have the potential to be resorbed in vivo, potentially reducing the risk for aseptic loosening. In this study, it was shown that α-Si(3)N(4)-powder dissolves in PBS. Adsorption of blood plasma indicated a good acceptance of Si(3)N(4) in the body with relatively low immune response. Si(3)N(4) sliding against Si(3)N(4) showed low wear rates both in bovine serum and PBS compared with the other tested wear couples. Tribofilms were built up on the Si(3)N(4) surfaces both in PBS and in bovine serum, controlling the friction and wear characteristics.