Microstructure and magnetic susceptibility of as-cast Zr–Mo alloys

The microstructures and magnetic susceptibilities of Zr–Mo alloys were investigated to develop a Zr alloy with a low magnetic susceptibility for magnetic resonance imaging (MRI). The microstructure was evaluated with an X-ray diffractometer (XRD), an optical microscope (OM) and a transmission electron microscope (TEM), and the magnetic susceptibility was measured with a magnetic susceptibility balance. The α′ phase with acicular structure was dominant in Zr–1Mo alloys, while the ω and β phases with the equiaxed and relatively flat (no acicular) microstructure was dominant in Zr–3Mo. The mixed microstructural features of Zr–1Mo and Zr–3Mo were observed in Zr–2Mo, which consists of the α′, ω and β phases. The β phase is stabilized when the Mo content exceeds over 3 mass% Mo. As-cast Zr–Mo alloys showed a minimum value of magnetic susceptibility at 3 mass% Mo, and the value abruptly increased up to 10% Mo before remaining stable up to 15 mass% Mo. XRD, OM and TEM revealed that the minimum value of the susceptibility was closely related to the appearance of the athermal ω phase in the β phase. As the Mo content decreases from 3 mass%, the α′ phase appears with the ω and β phases. On the other hand, as the Mo content increases from 3 mass%, the β phase increases and the ω phase decreases. Thus the appearance of the α′ and β phase leads to an increase in magnetic susceptibility. The magnetic susceptibility of as-cast Zr–3Mo alloy was almost one-third that of Ti–6Al–4V, which is commonly used for medical implant devices. Zr–Mo alloys are useful for medical devices used under MRI.     

Microstructure,mechanical and corrosion properties of Mg–Dy–Gd–Zr alloys for medical applications

In previous investigations, a Mg–10Dy (wt.%) alloy with a good combination of corrosion resistance and cytocompatibility showed great potential for use as a biodegradable implant material. However, the mechanical properties of Mg–10Dy alloy are not satisfactory. In order to allow the tailoring of mechanical properties required for various medical applications, four Mg–10(Dy + Gd)–0.2Zr (wt.%) alloys were investigated with respect to microstructure, mechanical and corrosion properties. With the increase in Gd content, the number of second-phase particles increased in the as-cast alloys, and the age-hardening response increased at 200 °C. The yield strength increased, while the ductility reduced, especially for peak-aged alloys with the addition of Gd. Additionally, with increasing Gd content, the corrosion rate increased in the as-cast condition owing to the galvanic effect, but all the alloys had a similar corrosion rate (～0.5 mm year^?1) in solution-treated and aged condition.     

Genetically engineered silk–collagen-like copolymer for biomedical applications: Production,characterization and evaluation of cellular response

Genetically engineered protein polymers (GEPP) are a class of multifunctional materials with precisely controlled molecular structure and property profile. Representing a promising alternative for currently used materials in biomedical applications, GEPP offer multiple benefits over natural and chemically synthesized polymers. However, producing them in sufficient quantities for preclinical research remains challenging. Here, we present results from an in vitro cellular response study of a recombinant protein polymer that is soluble at low pH but self-organizes into supramolecular fibers and physical hydrogels at neutral pH. It has a triblock structure denoted as C₂S^H₄₈C₂, which consists of hydrophilic collagen-inspired and histidine-rich silk-inspired blocks. The protein was successfully produced by the yeast Pichia pastoris in laboratory-scale bioreactors, and it was purified by selective precipitation. This efficient and inexpensive production method provided material of sufficient quantities, purity and sterility for cell culture study. Rheology and erosion studies showed that it forms hydrogels exhibiting long-term stability, self-healing behavior and tunable mechanical properties. Primary rat bone marrow cells cultured in direct contact with these hydrogels remained fully viable; however, proliferation and mineralization were relatively low compared to collagen hydrogel controls, probably because of the absence of cell-adhesive motifs. As biofunctional factors can be readily incorporated to improve material performance, our approach provides a promising route towards biomedical applications.     

An electrochemical study on self-ordered nanoporous and nanotubular oxide on Ti–35Nb–5Ta–7Zr alloy for biomedical applications

Highly ordered nanoporous and nanotubular oxide layers were developed on low-rigidity β Ti–35Nb–5Ta–7Zr alloy by controlled DC anodization in electrolyte containing 1 M H₃PO₄ and 0.5 wt.% NaF at room temperature. The as-formed and crystallized nanotubes were characterized by electron microscopy, energy-dispersive X-ray spectrometry and X-ray diffraction. The electrochemical passivation behavior of the nanoporous and nanotubular oxide surfaces were investigated in Ringer’s solution at 37 ± 1 °C employing a potentiodynamic polarization technique and impedance spectroscopy. The diameters of the as-formed nanotubes were in the range of 30–80 nm. The nanotubular surface exhibited passivation behavior similar to that of the nanoporous surface. However, the corrosion current density was considerably higher for the nanotubular alloy. The surface after nanotube formation seemed to favor an immediate and effective passivation. Electrochemical impedance spectra were simulated by equivalent circuits and the results were discussed with regard to biomedical applications.     

α-Tricalcium phosphate: synthesis, properties and biomedical applications

Nowadays, α-tricalcium phosphate (α-TCP, α-Ca₃(PO₄)₂) is receiving growing attention as a raw material for several injectable hydraulic bone cements, biodegradable bioceramics and composites for bone repair. In the phase equilibrium diagram of the CaO–P₂O₅ system, three polymorphs corresponding to the composition Ca₃(PO₄)₂ are recognized: β-TCP, α-TCP and α′-TCP. α-TCP is formed by heating the low-temperature polymorph β-TCP or by thermal crystallization of amorphous precursors with the proper composition above the transformation temperature. The α-TCP phase may be retained at room temperature in a metastable state, and its range of stability is strongly influenced by ionic substitutions. It is as biocompatible as β-TCP, but more soluble, and hydrolyses rapidly to calcium-deficient hydroxyapatite, which makes α-TCP a useful component for preparing self-setting osteotransductive bone cements and biodegradable bioceramics and composites for bone repairing. The literature published on the synthesis and properties of α-TCP is sometimes contradictory, and therefore this article focuses on reviewing and critically discussing the synthetic methods and physicochemical and biological properties of α-TCP-based biomaterials (excluding α-TCP-based bone cements).     

Cardiovascular applications of biomaterials and implants–an overview

This paper was originally commissioned by the UK Department of Health as a contribution to the work of its Biomaterials and Implants Research Advisory Group. This group was set up under the Chairmanship of Professor Sir Colin Berry with the following terms of reference: (i) to identify recent advances in the field of biomaterials; (ii) to consider the future contribution of biomaterials in improving human health; (Hi) to advise the Standing Group on Health Technology in areas where developments and assessment are needed; and (iv) to report to the Director of Research and Development (Professor Sir Michael Peckham) by October 1995. The cardiovascular field was one of several areas in biomaterials/implants considered by the Advisory Group. Amongst other areas considered were orthopaedics, dentistry, urology, wound repair and ophthalmology. Additionally, consideration was also given to such topics as chemical and biochemical sensors, drug release, hydrogels, membranes and artificial organs. The final report of the Advisory Group will be published at the end of this year. However, the Department has agreed that individual working papers such as the present one can be published independently in appropriate scientific journals.     

New magnetic-resonance-imaging-visible poly(ε-caprolactone)-based polyester for biomedical applications

A great deal of effort has been made since the 1990s to enlarge the field of magnetic resonance imaging. Better tissue contrast, more biocompatible contrast agents and the absence of any radiation for the patient are some of the many advantages of using magnetic resonance imaging (MRI) rather than X-ray technology. But implantable medical devices cannot be visualized by conventional MRI and a tool therefore needs to be developed to rectify this. The synthesis of a new MRI-visible degradable polymer is described by grafting an MR contrast agent (DTPA-Gd) to a non-water-soluble, biocompatible and degradable poly(ε-caprolactone) (PCL). The substitution degree, calculated by (1)H nuclear magnetic resonance and inductively coupled plasma-mass spectrometry, is close to 0.5% and proves to be sufficient to provide a strong and clear T1 contrast enhancement. This new MRI-visible polymer was coated onto a commercial mesh for tissue reinforcement using an airbrush system and enabled in vitro MR visualization of the mesh for at least 1 year. A stability study of the DTPA-Gd-PCL chelate in phosphate-buffered saline showed that a very low amount of gadolinium was released into the medium over 52 weeks, guaranteeing the safety of the device. This study shows that this new MRI-visible polymer has great potential for the MR visualization of implantable medical devices and therefore the post-operative management of patients.     

Magnesium alloys as implant materials – Principles of property design for Mg–RE alloys

Magnesium alloys have attracted increasing interest in the past years due to their potential as implant materials. This interest is based on the fact that magnesium and its alloys are degradable during their time of service in the human body. Moreover magnesium alloys offer a property profile that is very close or even similar to that of human bone. The chemical composition triggers the resulting microstructure and features of degradation. In addition, the entire manufacturing route has an influence on the morphology of the microstructure after processing. Therefore the composition and the manufacturing route have to be chosen carefully with regard to the requirements of an application. This paper discusses the influence of composition and heat treatments on the microstructure, mechanical properties and corrosion behaviour of cast Mg–Gd alloys. Recommendations are given for the design of future degradable magnesium based implant materials.     

Development of wear resistant NFSS–HA novel biocomposites and study of their tribological properties for orthopaedic applications

Implants made of nickel free austenitic stainless steel can reduce the toxic effect of released nickel ion and compounds from the conventional stainless steels. On the other hand, hydroxyapatite is a ceramic which has been used in orthopaedic applications due to its good osteoconductivity, biocompatibility and bioactivity. However, there is no evidence in the literature up to now on producing composites based on nickel free stainless steel and hydroxyapatite and study of their tribology. The aim of this work was to produce novel biocomposites made up of nickel free stainless steel with hydroxyapatite (prepared by heat treating bone ash) and studying their tribology under various loads in air and in Ringer’s physiological solution. Different amounts of hydroxyapatite powder (10, 20, 30 and 40% Vol.) were added to this nickel free stainless steel powder to get the biocomposites. Variation of their density, hardness, wear resistance and friction with the ceramic (hydroxyapatite) content and wear load were investigated in air and in Ringer’s solution. The density of the composites was decreased by increasing the volume percentage of the hydroxyapatite, while wear resistance of the composites was increased. The wear mechanism of these composites was changed by increasing the wear load and consequently the volume loss was enhanced dramatically. Furthermore, by increasing the sliding distance, the rate of volume loss was decreased slightly. The friction coefficient of the composites was also decreased by increasing the weight percentage of hydroxyapatite. Effect of the physiological Ringer’s solution on wear resistance and friction coefficient of the composites was nearly negligible. The wear mechanisms of the samples were identified by studying the SEM images of the worn surfaces of the tested samples in different wear loads and HA contents.     

Microstructure,mechanical properties and bio-corrosion properties of Mg–Si(–Ca,Zn) alloy for biomedical application

Mg–Si alloy was investigated for biomedical application due to the biological function of Si in the human body. However, Mg–Si alloy showed a low ductility due to the presence of coarse Mg₂Si. Ca and Zn elements were used to refine and modify the morphology of Mg₂Si in order to improve the corrosion resistance and the mechanical properties. The cell toxicity of Mg, Zn and Ca metals was assessed by an MTT test. The test results indicated that increasing the concentrations of Mg, Zn and Ca ions did not cause cell toxicity, which showed that the release of these three elements would not lead to cell toxicity. Then, microstructure, mechanical properties and bio-corrosion properties of as-cast Mg–Si(–Ca, Zn) alloys were investigated by optical microscopy, scanning electronic microscopy, mechanical properties testing and electrochemical measurement. Ca element can slightly refine the grain size and the morphology Mg₂Si phase in Mg–Si alloy. The bio-corrosion resistance of Mg–Si alloys was improved by the addition of Ca due to the reduction and refinement of Mg₂Si phase; however, no improvement was observed in the strength and elongation. The addition of 1.6% Zn to Mg–0.6Si can modify obviously the morphology of Mg₂Si phase from course eutectic structure to a small dot or short bar shape. As a result, tensile strength, elongation and bio-corrosion resistance were all improved significantly; especially, the elongation improved by 115.7%. It was concluded that Zn element was one of the best alloying elements of Mg–Si alloy for biomedical application.     

Development and characterization of novel electrically conductive PANI–PGS composites for cardiac tissue engineering applications

Cardiovascular diseases, especially myocardial infarction, are the leading cause of morbidity and mortality in the world, also resulting in huge economic burdens on national economies. A cardiac patch strategy aims at regenerating an infarcted heart by providing healthy functional cells to the injured region via a carrier substrate, and providing mechanical support, thereby preventing deleterious ventricular remodeling. In the present work, polyaniline (PANI) was doped with camphorsulfonic acid and blended with poly(glycerol-sebacate) at ratios of 10, 20 and 30 vol.% PANI content to produce electrically conductive composite cardiac patches via the solvent casting method. The composites were characterized in terms of their electrical, mechanical and physicochemical properties. The in vitro biodegradability of the composites was also evaluated. Electrical conductivity increased from 0 S cm⁻¹ for pure PGS to 0.018 S cm⁻¹ for 30 vol.% PANI–PGS samples. Moreover, the conductivities were preserved for at least 100 h post fabrication. Tensile tests revealed an improvement in the elastic modulus, tensile strength and elasticity with increasing PANI content. The degradation products caused a local drop in pH, which was higher in all composite samples compared with pure PGS, hinting at a buffering effect due to the presence of PANI. Finally, the cytocompatibility of the composites was confirmed when C2C12 cells attached and proliferated on samples with varying PANI content. Furthermore, leaching of acid dopants from the developed composites did not have any deleterious effect on the viability of C2C12 cells. Taken together, these results confirm the potential of PANI–PGS composites for use as substrates to modulate cellular behavior via electrical stimulation, and as biocompatible scaffolds for cardiac tissue engineering applications.     

Synthesis and characterisation of a new superelastic Ti–25Ta–25Nb biomedical alloy

In this study, a new Ti–25Ta–25Nb (mass%) beta alloy was synthesised by cold crucible semi-levitation melting. This technique made it possible to obtain homogeneous ingots although the elements used have very different melting points. After melting, a thermo-mechanical treatment was applied in order to obtain a perfectly recrystallised beta microstructure. For this alloy composition, the tensile tests showed a very low Young’s modulus associated with an important super-elastic behaviour, which contributes to decrease the elastic modulus under stress and to increase the recoverable strain. On the other hand, the corrosion tests, which were carried out in a neutral Ringer solution, indicated a corrosion resistance higher than that of the commercially pure CP Ti alloy. These results show that this new alloy possesses all the characteristics necessary for its long-term use in medical implants.     

Optimization of Cr content of metastable β-type Ti-Cr alloys with changeable Young's modulus for spinal fixation applications

Metallic implant rods used in spinal fixtures should have a Young's modulus that is sufficiently low to prevent stress shielding for the patient and sufficiently high to suppress springback for the surgeon. Therefore, we propose a new concept: novel biomedical titanium alloys with a changeable Young's modulus via deformation-induced ω phase transformation. In this study, the Cr content in the range of 10-14 mass% was optimized to produce deformation-induced ω phase transformation, resulting in a large increase in the Young's modulus of binary Ti-Cr alloys. The springback and cytotoxicity of the optimized alloys were also examined. Ti-(10-12)Cr alloys exhibit an increase in Young's modulus owing to deformation-induced ω phase transformation. In this case, such deformation-induced ω phase transformation occurs along with {332}(β) mechanical twinning, resulting in the maintenance of acceptable ductility with relatively high strength. Among the examined alloys, the lowest Young's modulus and largest increase in Young's modulus are obtained from the Ti-12Cr alloy. This alloy exhibits smaller springback than and comparable cytocompatibility to the biomedical Ti alloy Ti-29Nb-13Ta-4.6Zr.     

Penicillin susceptibility breakpoints for Streptococcus pneumoniae and their effect on susceptibility categorisation in Germany (1997–2013)

Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. From July 1, 1997, to June 30, 2013, data on penicillin susceptibility were available for 20,437 isolates. 2,790 of these isolates (13.7 %) originate from patients with meningitis and 17,647 isolates (86.3 %) are from non-meningitis cases. A slight decline in isolates susceptible at 0.06 and 0.12 μg/ml can be noticed over the years. Overall, 89.1 % of the isolates had minimum inhibitory concentrations (MICs) of ≤0.015 μg/ml. In 2012/2013, the first three isolates of Streptococcus pneumoniae with MICs of 8 μg/ml were found. The application of different guidelines with other MIC breakpoints for the interpretation of penicillin resistance leads to differences in susceptibility categorisation. According to the pre-2008 Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, 5.3 % of isolates overall were intermediate and 1.4 % were resistant to penicillin. Application of the 2008–2014 CLSI interpretive criteria resulted in 7.6 % resistance among meningitis cases and 0.5 % intermediate resistance in non-meningitis cases. Referring to the 2009–2014 European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 7.6 % of the isolates in the meningitis group were resistant to penicillin. In the non-meningitis group, 6.1 % of the isolates were intermediate and 0.5 % were resistant. These differences should be kept in mind when surveillance studies on pneumococcal penicillin resistance are compared.     

Random co-polymers based on the poloxamer Bayfit® 10WF15 for biomedical applications

Random co-polymers were prepared from the poloxamer Bayfit(?) 10WF15 and their thermal and biological properties analyzed. The poloxamer was characterized, functionalized with methacrylate groups (Bayfit-MA) and further co-polymerized with 2-hydroxyethyl methacrylate (HEMA) with Bayfit-MA feed contents of 1, 5 and 10 wt%. Co-polymers were partially soluble in organic solvents and exhibited a single glass transition temperature indicative of a random monomer distribution in the macromolecular chains. In thermogravimetric studies the co-polymers showed two degradation stages, around 210 and 350 °C, respectively. The thermosensitive behaviour of the poloxamer was studied by turbidimetry. Cloud point temperatures of aqueous solutions of Bayfit(?) 10WF15 (0.5-5 wt%) ranged from 15 to 18 °C and for Bayfit(?) 10WF15 methacrylate (0.5-1 wt%) from 6 to 7 °C. DSC thermograms of hydrated co-polymers showed the typical endothermic peaks with phase transition temperatures close to that of physiological medium. The biocompatibility of initial poloxamer and derivatives was analyzed with human fibroblasts cultures. The IC(50) value of Bayfit(?) 10WF15 was 1.4 mg/ml. Cellular extracts of the co-polymers were not cytotoxic and cellular proliferation and DNA content depended on co-polymer composition.     

Poly(γ-glutamic acid) modulates the properties of poly(ethylene glycol) hydrogel for biomedical applications

In this paper, a series of copolymer hydrogels were fabricated from methacrylated poly(γ-glutamic acid) (mPGA) and poly(ethylene glycol) diacrylate (PEGDA). The effect of ionic strength and pH on the swelling behavior and mechanical properties of these hydrogels were studied in detail. Release of Rhodamine B as a model drug from the hydrogel was evaluated under varied pH. In vitro photoencapsulation of bovine cartilage chondrocytes was performed to assess the cytotoxicity of this copolymer hydrogel. The results revealed that the copolymer hydrogel is ionic- and pH-sensitive, and does not exhibit acute cytotoxicity; this copolymer hydrogel may have promising application as matrix for controlled drug release and scaffolding material in tissue engineering.     

Biocompatibility and biodegradability of Mg–Sr alloys: The formation of Sr-substituted hydroxyapatite

Magnesium is an attractive material for use in biodegradable implants due to its low density, non-toxicity and mechanical properties similar to those of human tissue such as bone. Its biocompatibility makes it amenable for use in a wide range of applications from bone to cardiovascular implants. Here we investigated the corrosion rate in simulated body fluid (SBF) of a series of Mg–Sr alloys, with Sr in the range of 0.3–2.5%, and found that the Mg–0.5 Sr alloy showed the slowest corrosion rate. The degradation rate from this alloy indicated that the daily Sr intake from a typical stent would be 0.01–0.02 mg day^?1, which is well below the maximum daily Sr intake levels of 4 mg day^?1. Indirect cytotoxicity assays using human umbilical vascular endothelial cells indicated that Mg–0.5 Sr extraction medium did not cause any toxicity or detrimental effect on the viability of the cells. Finally, a tubular Mg–0.5 Sr stent sample, along with a WE43 control stent, was implanted into the right and left dog femoral artery. No thrombosis effect was observed in the Mg–0.5 Sr stent after 3 weeks of implantation while the WE43 stent thrombosed. X-ray diffraction demonstrated the formation of hydroxyapatite and Mg(OH)₂ as a result of the degradation of Mg–0.5 Sr alloy after 3 days in SBF. X-ray photoelectron spectroscopy further showed the possibility of the formation of a hydroxyapatite Sr-substituted layer that presents as a thin layer at the interface between the Mg–0.5 Sr alloy and the corrosion products. We believe that this interfacial layer stabilizes the surface of the Mg–0.5 Sr alloy, and slows down its degradation rate over time.