Biocompatibility and degradation of the open-pored magnesium scaffolds LAE442 and La2.

Porous magnesium implants are of particular interest for application as resorbable bone substitutes, due to their mechanical strength and a Young's modulus similar to bone. The objective of the present study was to compare the biocompatibility, bone and tissue ingrowth, and the degradation behaviour of scaffolds made from the magnesium alloys LAE442 (n= 40) and Mg-La2 (n= 40)in vivo. For this purpose, cylindrical magnesium scaffolds (diameter 4 mm, length 5 mm) with defined, interconnecting pores were produced by investment casting and coated with MgF2. The scaffolds were inserted into the cancellous part of the greater trochanter ossis femoris of rabbits. After implantation periods of 6, 12, 24 and 36 weeks, the bone-scaffold compounds were evaluated usingex vivo µCT80 images, histological examinations and energy dispersive x-ray spectroscopy analysis. The La2 scaffolds showed inhomogeneous and rapid degradation, with inferior osseointegration as compared to LAE442. For the early observation times, no bone and tissue could be observed in the pores of La2. Furthermore, the excessive amount of foreign body cells and fibrous capsule formation indicates insufficient biocompatibility of the La2 scaffolds. In contrast, the LAE442 scaffolds showed slow degradation and better osseointegration. Good vascularization, a moderate cellular response, bone and osteoid-like bone matrix at all implantation periods were observed in the pores of LAE442. In summary, porous LAE442 showed promise as a degradable scaffold for bone defect repair, based on its degradation behaviour and biocompatibility. However, further studies are needed to show it would have the necessary mechanical properties required over time for weight-bearing bone defects.

The effects of severe plastic deformation on the mechanical and corrosion characteristics of a bioresorbable Mg-ZKQX6000 alloy.

In this work, a bioresorbable Mg-ZKQX6000 (Mg-6Zn-0.6Zr-0.4Ag-0.2Ca (wt%)) alloy was severely plastically deformed via equal channel angular pressing (ECAP) according to three unique hybrid routes at low temperatures (200 °C to 125 °C). The roles of ECAP processing on microstructure, and ensuing mechanical properties and corrosion rates, are assessed. Microstructurally, ECAP induces a complex plethora of features, especially variations in grain sizes and precipitates' sizes, distributions, and morphologies for individual cases. Mechanically, ECAP generally refined grain size, resulting in ultra-high strength levels of about 400 MPa in ultimate tensile strength for several cases; however, deformation via ECAP of precipitates induced embrittlement and low elongation to failure levels. Corrosion testing, conducted in simulated bodily fluid at bodily pH levels to mimic conditions in the human body, revealed consistent corrosion rates across several techniques (mass loss, hydrogen evolution, and electrochemical impedance spectroscopy (EIS)), showing that severe plastic deformation deteriorates corrosion resistance for this material. In-situ corrosion monitoring explained that corrosion accelerated after ECAP due to the creation of heterogeneous, anodic shear zones, which exhibited dense regions of refined grains and fine precipitates. Suggestions for future design and thermomechanical processing of Mg alloys for bioresorbable orthopedic implants are provided.

An exploration of plastic deformation dependence of cell viability and adhesion in metallic implant materials.

The relationship between cell viability and adhesion behavior, and micro-deformation mechanisms was investigated on austenitic 316L stainless steel samples, which were subjected to different amounts of plastic strains (5%, 15%, 25%, 35% and 60%) to promote a variety in the slip and twin activities in the microstructure. Confocal laser scanning microscopy (CLSM) and field emission scanning electron microscopy (FESEM) revealed that cells most favored the samples with the largest plastic deformation, such that they spread more and formed significant filopodial extensions. Specifically, brain tumor cells seeded on the 35% deformed samples exhibited the best adhesion performance, where a significant slip activity was prevalent, accompanied by considerable slip-twin interactions. Furthermore, maximum viability was exhibited by the cells seeded on the 60% deformed samples, which were particularly designed in a specific geometry that could endure greater strain values. Overall, the current findings open a new venue for the production of metallic implants with enhanced biocompatibility, such that the adhesion and viability of the cells surrounding an implant can be optimized by tailoring the surface relief of the material, which is dictated by the micro-deformation mechanism activities facilitated by plastic deformation imposed by machining.

A novel biodegradable frontal sinus stent (MgNd2): a long-term animal study.

The frontal sinus recess consists of anatomically narrow passages that are prone to stenosis in endonasal frontal sinus surgery for chronic sinus disease. Over the past 100 years, diverse frontal sinus stents have been developed and evaluated in clinical and animal studies. However, superinfection, formation of granulations tissue, stent dislocation and late stenosis of the duct have remained challenges and subject of debate in the literature. Currently developed biodegradable materials, including rare earth-containing magnesium alloys are promising candidates for application as temporary implant materials. The Mg 2 % wt Nd alloy (MgNd2) was used to design a nasal stent that fit the porcine anatomy. In the current study, we evaluate biocompatibility, biodegradation and functionality of a frontal sinus stent in 16 minipigs over 6 months. Intraoperative endoscopy revealed free stent lumen in all cases. Blood examination and clinical examinations indicated no systematic or local inflammation signs. The histopathology and elements analysis showed a very good biocompatibility. The µ-computed tomography-based volumetric analysis showed substantial stent degradation within 6 months. Our MgNd2 based stent appears to be a promising, solid basis for the development of a frontal sinus stent for clinical use.

MgNd2 alloy in contact with nasal mucosa: an in vivo and in vitro approach.

Biodegradable and biocompatible magnesium alloys appear to be very promising not only for temporary clinical application but also for developing deformable and degradable medical implants. This study analyzes the in vivo degradation behavior and the impact on the paranasal sinuses of the highly ductile Mg-2 wt%Nd alloy (MgNd2) in order to provide a basis for a satisfying stent system for the therapy of a chronic sinusitis. Moreover, in vitro tests were carried out on primary porcine nasal epithelial cells (PNEC). For the in vivo tests, cylindrical MgNd2 specimens were implanted into the sinus' mucosa of minipigs. During and after a total period of 180 days the long-term biodegradation and biocompatibility properties after direct contact with the physiological tissue were analyzed. Biodegradation was investigated by measuring the mass and volume losses of the MgNd2 specimens as well as by performing element analyses to obtain information about the degradation layer. The influence on the surrounding tissue of paranasal sinuses was evaluated by endoscopic and histopathological examinations of the mucosa. Here, only a locally unspecific chronic infection was found. The degradation rate showed a maximum after 45 days postsurgery and was determined to decrease subsequently. In vitro experiments using PNEC showed adequate biocompatibility of MgNd2. This study demonstrates a good in vivo biocompatibility for MgNd2 in the system of paranasal sinuses and underlines the promising properties of alloy MgNd2 for biodegradable nasal stent applications.

Protection of yttria-stabilized zirconia for dental applications by oxidic PVD coating.

In this study, the application of transparent physical vapor deposition (PVD) coatings on zirconia ceramics was examined as an approach to retard the low-temperature degradation of zirconia for dental applications. Transparent monolayers of titanium oxide (TixOy) and multilayers consisting of titanium oxide-alumina-titanium oxide (TixOy-AlxOy-TixOy) were deposited onto standardized discs of 3Y-TZP using magnetron sputtering. Using X-ray photospectroscopy and time-of-flight secondary-ion mass spectrometry, the compositions of the coatings were verified, and an approximate thickness of 50 nm for each type of coating was ascertained. After aging the coated and uncoated samples in water vapor at 134°C and 3 bar for 4, 8, 16, 32, 64 and 128 h, the monoclinic phase content was determined using X-ray diffraction, and its impact on mechanical properties was assessed in biaxial flexural strength tests. In addition, the depth of the transformation zone was measured from scanning electron microscopy images of the fracture surfaces of hydrothermally aged samples. The results revealed that the tetragonal-to-monoclinic phase transformation of the zirconia ceramic was retarded by the application of PVD coatings. During the first stages of aging, the coated samples exhibited a significantly lower monoclinic phase content than the uncoated samples and, after 128 h of aging, showed a transformation zone which was only ∼12-15 µm thick compared to ∼30 µm in the control group. Biaxial flexural strength decreased by ∼10% during aging and was not influenced by the application of a PVD coating.

In vivo degradation effects of alloy MgNd2 in contact with mucous tissue.

Magnesium alloys are currently being investigated for use as resorbable biomaterials. Various applications for magnesium based implant materials have already been presented. Currently, stents and structures that sustain diseased or narrowed vessels seem to be the most promising areas. This study focuses on the use of a magnesium fluoride (MgF2 ) coated magnesium neodymium based alloy (MgNd2 ) and its use as a postsurgery stent material to avoid proliferation in the sinus region. Simple cylindrical shaped specimens were sown to the sinus' mucosa of pigs and left in place for different periods of time to investigate the long-term corrosion resistance of the alloy and its coating during direct contact with physiological tissue. Investigations made within this study explicitly focused on the corrosive behavior of the alloy in the region of a physiological sinus. Thus, losses in mass and volume, and element analyses were considered to obtain information about the specimens' corrosion performance over time. Furthermore, micrographs support the alloy specific corrosion type analyses which focus on grain boundary effects. This study demonstrates the general in vivo applicability of fluoride coated MgNd2 . The progress of corrosion was determined to be adequate and homogeneous over a total period of 180 days.

Evaluation of passive oxide layer formation-biocompatibility relationship in NiTi shape memory alloys: geometry and body location dependency.

A systematic set of ex-situ experiments were carried out on Nickel-Titanium (NiTi) shape memory alloy (SMA) in order to identify the dependence of its biocompatibility on sample geometry and body location. NiTi samples with three different geometries were immersed into three different fluids simulating different body parts. The changes observed in alloy surface and chemical content of fluids upon immersion experiments designed for four different time periods were analyzed in terms of ion release, oxide layer formation, and chemical composition of the surface layer. The results indicate that both sample geometry and immersion fluid significantly affect the alloy biocompatibility, as evidenced by the passive oxide layer formation on the alloy surface and ion release from the samples. Upon a 30 day immersion period, all three types of NiTi samples exhibited lower ion release than the critical value for clinic applications. However; a significant amount of ion release was detected in the case of gastric fluid, warranting a thorough investigation prior to utility of NiTi in gastrointestinal treatments involving long-time contact with tissue. Furthermore, certain geometries appear to be safer than the others for each fluid, providing a new set of guidelines to follow while designing implants making use of NiTi SMAs to be employed in treatments targeting specific body parts.

Magnesium degradation products: effects on tissue and human metabolism.

Owing to their mechanical properties, metallic materials present a promising solution in the field of resorbable implants. The magnesium metabolism in humans differs depending on its introduction. The natural, oral administration of magnesium via, for example, food, essentially leads to an intracellular enrichment of Mg(2+) . In contrast, introducing magnesium-rich substances or implants into the tissue results in a different decomposition behavior. Here, exposing magnesium to artificial body electrolytes resulted in the formation of the following products: magnesium hydroxide, magnesium oxide, and magnesium chloride, as well as calcium and magnesium apatites. Moreover, it can be assumed that Mg(2+) , OH(-) ions, and gaseous hydrogen are also present and result from the reaction for magnesium in an aqueous environment. With the aid of physiological metabolic processes, the organism succeeds in either excreting the above mentioned products or integrating them into the natural metabolic process. Only a burst release of these products is to be considered a problem. A multitude of general tissue effects and responses from the Mg's degradation products is considered within this review, which is not targeting specific implant classes. Furthermore, common alloying elements of magnesium and their hazardous potential in vivo are taken into account.

Requirement of NEMO/IKKγ for effective expansion of KRAS-induced precancerous lesions in the pancreas.

Pancreatic carcinoma, a leading cause of cancer death, is thought to develop out of pancreatic intraepithelial neoplasia (PanIN). PanIN lesions have not yet attained the fully malignant phenotype, but show increased proliferation and dysplasia, and frequently bear an oncogenic KRAS mutation. Pancreatic cancer development is associated with increased activity of the transcription factor NF-κB. NEMO (IKKγ) is a subunit of the IKK complex essential for the activation of canonical NF-κB signaling and has been ascribed both oncogenic and tumor-suppressive roles in gastrointestinal tumors. Here, we wanted to address the function of NEMO in pancreatic tumorigenesis. We therefore conditionally ablated NEMO in a mouse model for pancreatic carcinoma based on the expression of oncogenic KRAS in pancreatic precursor cells. Mice were analyzed for PanIN lesions and for the activation of associated signaling pathways. NEMO ablation in the pancreas, while in itself not causing any overt pathology, led to a drastic (>93%) decrease in the prevalence of both low-grade and high-grade PanIN in 10-month-old mice expressing oncogenic KRAS. Also, the inflammatory and fibrotic response associated with KRAS action in the pancreas was virtually abolished, including expression of inflammatory cytokines and activation of the interleukin-6/STAT3 axis. Moreover, the activation of MAPK signaling, Notch and KLF4 signaling normally observed in KRAS-induced PanIN was strongly reduced or absent when NEMO was ablated. Our study suggests that NEMO, an IKK subunit necessary for canonical NF-κB activation, is dispensable for normal pancreatic development and function, but essential for the propagation of KRAS-induced PanIN lesions.

Corrosion fatigue behavior of a biocompatible ultrafine-grained niobium alloy in simulated body fluid.

The present study reports on the corrosion fatigue behavior of ultrafine-grained (UFG) Niobium 2 wt-% Zirconium (NbZr) alloy in simulated body fluid (SBF). The alloy was processed using multipass equal channel angular processing at room temperature, resulting in a favorable combination of high strength and ductility along with superior biocompatibility and excellent corrosion resistance. Electrochemical measurements revealed stable passive behavior in SBF saline solutions, similar to conventional Ti-6Al-4V alloy. High-cycle fatigue tests showed no alteration in the crack initiation behavior due to the SBF environment, and an absence of pitting and corrosion products. More severe test conditions were obtained in the fatigue crack growth experiments in saline environments. Crack growth rates in UFG NbZr were marginally increased in SBF as compared to laboratory air at a constant test frequency of 20 Hz. Upon a 100 fold decrease in the test frequency, slightly higher crack growth rates were observed only in the near-threshold region. Such excellent corrosion and corrosion fatigue properties of UFG NbZr recommend it as an attractive new material for biomedical implants.

(41)Ca in tooth enamel. Part I: a biological signature of neutron exposure in atomic bomb survivors.

The detection of (41)Ca atoms in tooth enamel using accelerator mass spectrometry is suggested as a method capable of reconstructing thermal neutron exposures from atomic bomb survivors in Hiroshima and Nagasaki. In general, (41)Ca atoms are produced via thermal neutron capture by stable (40)Ca. Thus any (41)Ca atoms present in the tooth enamel of the survivors would be due to neutron exposure from both natural sources and radiation from the bomb. Tooth samples from five survivors in a control group with negligible neutron exposure were used to investigate the natural (41)Ca content in tooth enamel, and 16 tooth samples from 13 survivors were used to estimate bomb-related neutron exposure. The results showed that the mean (41)Ca/Ca isotope ratio was (0.17 +/- 0.05) x 10(-14) in the control samples and increased to 2 x 10(-14) for survivors who were proximally exposed to the bomb. The (41)Ca/Ca ratios showed an inverse correlation with distance from the hypocenter at the time of the bombing, similar to values that have been derived from theoretical free-in-air thermal-neutron transport calculations. Given that gamma-ray doses were determined earlier for the same tooth samples by means of electron spin resonance (ESR, or electron paramagnetic resonance, EPR), these results can serve to validate neutron exposures that were calculated individually for the survivors but that had to incorporate a number of assumptions (e.g. shielding conditions for the survivors).

Defect formation in thin polyelectrolyte films on polycrystalline NiTi substrates.

This paper reports on the mechanical properties of ultrathin PAA/PAH (polyacrylic acid/polyallylamine hydrochloride) polyelectrolyte films deposited by a layer-by-layer technique on a polycrystalline Nickel-Titanium (NiTi) substrate. Since thin polyelectrolyte films are potentially suitable coatings to reduce the Ni release in biomedical applications, the mechanical properties of the thin films were determined by applying monotonic and cyclic tensile strains of 5% and 3%, respectively. While single tensile strains up to 5% revealed the amazing strain to failure of the applied coating, cyclic strains resulted in defect formation within the polyelectrolytes. To provide a better understanding of the mechanisms that are determining the defect formation, macroscopic and microscopic defect localizations were determined by digital image correlation-and EBSD (electron back-scattered diffraction)-techniques. Defects emerged particularly within areas of elevated local strain differences and were predominantly observed in the vicinity of grain boundaries. To relate these findings to the transformation behavior of polycrystalline NiTi considering strain localizations and intergranular constraints, crystallographic data obtained from the EBSD measurements were correlated with the defect distribution. EBSD data revealed a distinct dependence of defect formation on misorientation of neighboring grains.

Fatigue damage in cancellous bone: an experimental approach from continuum to micro scale.

Repeated loadings may cause fatigue fractures in bony structures. Even if these failure types are known, data for trabecular bone exposed to cyclic loading are still insufficient as the majority of fatigue analyses on bone concentrate on cortical structures. Despite its highly anisotropic and inhomogeneous structure, trabecular bone is treated with continuum approaches in fatigue analyses. The underlying deformation and damage mechanism within trabecular specimens are not yet sufficiently investigated. In the present study different types of trabecular bone were loaded in monotonic and cyclic compression. In addition to the measurement of integral specimen deformations, optical deformation analysis was employed in order to obtain strain distributions at different scale levels, from the specimens' surface to the trabeculae level. These measurements allowed for the possibility of linking the macroscopic and microscopic mechanical behaviour of cancellous bone. Deformations were found to be highly inhomogeneous across the specimen. Furthermore strains were found to already localise at very low load levels and after few load cycles. Microcracks in individual trabeculae were induced in the very early stage of cyclic testing. The results provide evidence of the capability of the method to supply essential data on the failure behaviour of individual trabeculae in future studies.

Design and application of a mechanical load frame for in situ investigation of ferromagnetic shape memory alloys by magnetic force microscopy.

An in situ mechanical load frame has been developed for a commercially available atomic force microscope. This frame allows examining changes in topography and magnetic domain configuration under a given constant load or strain. First results obtained on Ni-Mn-Ga ferromagnetic shape memory alloy single crystals are presented. The magnetic force microscopy (MFM) measurements under different strain levels confirm the one-to-one correspondence, i.e., the magnetomicrostructural coupling between the martensite twins and the magnetic domains. Additionally, the growth of the twin variant with favorable orientation to the compression axis during martensite detwinning was observed. It will be shown that this load frame can be used for the investigation of the relationship between the microstructure and the magnetic domain structure in ferromagnetic shape memory alloys by MFM.

Anisotropy of the fatigue behaviour of cancellous bone.

The fatigue behaviour of materials is of particular interest for the failure prediction of materials and structures exposed to cyclic loading. For trabecular bone structures only a few sets of lifetime data have been reported in the literature and structural measures are commonly not considered. The influence of load contributions which are not aligned with the main physiological axis remains unclear. Furthermore site and species dependent relationships are not well described. In this study five different groups of trabecular bone, defined in terms of orientation, species and site were exposed to cyclic compression. In total, 108 fatigue tests were analysed. The lifetimes were found to decrease drastically when off-axis loads were applied. Additionally, species and site strongly affect fatigue lifetimes. Strains at failure were also found to be a function of orientation.

Deformation behaviour of bovine cancellous bone.

Repetitive cyclic loading from daily activities is reported to induce fatigue damage and microcracking in bone structures. In terms of osteoporotic structures or in cases of serious damage of skeleton segments and the replacement by metallic implants the degree of damage due to cyclic loading will be even more pronounced. It is generally assumed that fatigue induced cracking and crack propagation essentially act as driving forces for complex physiological phenomena such as remodelling processes of bones and the adaptation to applied loads. In cases where the crack propagation rate exceeds the remodelling velocity, sudden and unexpected fracture of the bone is observed. Especially for implant reinforced structures the deviation in stiffness to the bone material can induce high peak stresses and accelerate crack propagation. Whereas, for cortical bone the mechanical behaviour under cyclic loading is sufficiently described, only rough data are available for trabaecular structures. In this study the deformation behaviour of bovine vertebra trabecular bone specimens is investigated under cyclic compressive loading. A powerlaw relationship was found between the applied load ratio and cycles to failure. A linear decrease of maximum, integral strains at failure with increasing applied load ratio was observed. Optical deformation measurement of the surface strains revealed that low strains (0-1 increasing applied load ratio whereby the higher strains behave directly opposite. This indicates that different failure mechanisms are acting at low cycle and high cycle fatigue, respectively.