High-quantum yield alloy-typed core/shell CdSeZnS/ZnS quantum dots for bio-applications.

BACKGROUND: Quantum dots (QDs) have been used as fluorophores in various imaging fields owing to their strong fluorescent intensity, high quantum yield (QY), and narrow emission bandwidth. However, the application of QDs to bio-imaging is limited because the QY of QDs decreases substantially during the surface modification step for bio-application. RESULTS: In this study, we fabricated alloy-typed core/shell CdSeZnS/ZnS quantum dots (alloy QDs) that showed higher quantum yield and stability during the surface modification for hydrophilization compared with conventional CdSe/CdS/ZnS multilayer quantum dots (MQDs). The structure of the alloy QDs was confirmed using time-of-flight medium-energy ion scattering spectroscopy. The alloy QDs exhibited strong fluorescence and a high QY of 98.0%. After hydrophilic surface modification, the alloy QDs exhibited a QY of 84.7%, which is 1.5 times higher than that of MQDs. The QY was 77.8% after the alloy QDs were conjugated with folic acid (FA). Alloy QDs and MQDs, after conjugation with FA, were successfully used for targeting human KB cells. The alloy QDs exhibited a stronger fluorescence signal than MQD; these signals were retained in the popliteal lymph node area for 24 h. CONCLUSION: The alloy QDs maintained a higher QY in hydrophilization for biological applications than MQDs. And also, alloy QDs showed the potential as nanoprobes for highly sensitive bioimaging analysis.

A Complex Evaluation of the In-Vivo Biocompatibility and Degradation of an Extruded ZnMgSr Absorbable Alloy Implanted into Rabbit Bones for 360 Days.

The increasing incidence of trauma in medicine brings with it new demands on the materials used for the surgical treatment of bone fractures. Titanium, its alloys, and steel are used worldwide in the treatment of skeletal injuries. These metallic materials, although inert, are often removed after the injured bone has healed. The second-stage procedure-the removal of the plates and screws-can overwhelm patients and overload healthcare systems. The development of suitable absorbable metallic materials would help us to overcome these issues. In this experimental study, we analyzed an extruded Zn-0.8Mg-0.2Sr (wt.%) alloy on a rabbit model. From this alloy we developed screws which were implanted into the rabbit tibia. After 120, 240, and 360 days, we tested the toxicity at the site of implantation and also within the vital organs: the liver, kidneys, and brain. The results were compared with a control group, implanted with a Ti-based screw and sacrificed after 360 days. The samples were analyzed using X-ray, micro-CT, and a scanning electron microscope. Chemical analysis revealed only small concentrations of zinc, strontium, and magnesium in the liver, kidneys, and brain. Histologically, the alloy was verified to possess very good biocompatibility after 360 days, without any signs of toxicity at the site of implantation. We did not observe raised levels of Sr, Zn, or Mg in any of the vital organs when compared with the Ti group at 360 days. The material was found to slowly degrade in vivo, forming solid corrosion products on its surface.

Temperature dependence of nickel ion release from nitinol medical devices.

Nitinol exhibits unique (thermo)mechanical properties that make it central to the design of many medical devices. However, nitinol nominally contains 50 atomic percent nickel, which if released in sufficient quantities, can lead to adverse health effects. While nickel release from nitinol devices is typically characterized using in vitro immersion tests, these evaluations require lengthy time periods. We have explored elevated temperature as a potential method to expedite this testing. Nickel release was characterized in nitinol materials with surface oxide thickness ranging from 12 to 1564 nm at four different temperatures from 310 to 360 K. We found that for three of the materials with relatively thin oxide layers, ≤ 87 nm nickel release exhibited Arrhenius behavior over the entire temperature range with activation energies of 80 to 85 kJ/mol. Conversely, the fourth ''black-oxide'' material, with a much thicker, complex oxide layer, was not well characterized by an Arrhenius relationship. Power law release profiles were observed in all four materials; however, the exponent from the thin oxide materials was approximately 1/4 compared with 3/4 for the black-oxide material. To illustrate the potential benefit of using elevated temperature to abbreviate nickel release testing, we demonstrated that a > 50 day 310 K release profile could be accurately recovered by testing for less than 1 week at 340 K. However, because the materials explored in this study were limited, additional testing and mechanistic insight are needed to establish a protective temperature scaling that can be applied to all nitinol medical device components.

Mechanical properties and biodegradability of Mg-Zn-Ca alloys: homogenization heat treatment and hot rolling.

In this study, Mg was alloyed with Zn and Ca to produce six different Mg-Zn-Ca alloys (designated as ZX alloys) by the gravity die casting method. Zn contents of the alloys were 1 wt., 3 wt., and 5 wt.% and Ca contents of the alloys were 0.2 wt. and 1.8 wt.%. Homogenization heat treatment was applied to all cast alloys. After that, a part of each homogenization heat-treated alloys was hot-rolled. Microstructure, mechanical properties, electrochemical and immersion corrosion behaviors at simulated physiological conditions of the heat-treated and hot-rolled alloys were compared. Increasing the amount of alloying elements (Zn and Ca) in Mg reduces grain size and improves the hardness. It was seen that the microstructure consisted of α-Mg as a matrix phase and intermetallic phases: Mg2Ca phase for the alloy having Zn/Ca = 0.37 (ZX12) and Ca2Mg6Zn3 phase for the other alloys. When the mechanical properties and corrosion rates of homogenized and hot-rolled alloys were compared, it was seen that hot-rolled ZX10-h (Mg-0.94Zn-0.16Ca) alloy can be considered as a fracture bone fixation plate material with its acceptable properties: 121 ± 2.1 MPa yield strength, 226 ± 3.7 MPa tensile strength, % 4.1 ± 0.2 elongation, and 0.062 mm/year immersion corrosion rate.

Optimizing an Osteosarcoma-Fibroblast Coculture Model to Study Antitumoral Activity of Magnesium-Based Biomaterials.

Osteosarcoma is among the most common cancers in young patients and is responsible for one-tenth of all cancer-related deaths in children. Surgery often leads to bone defects in excised tissue, while residual cancer cells may remain. Degradable magnesium alloys get increasing attention as orthopedic implants, and some studies have reported potential antitumor activity. However, most of the studies do not take the complex interaction between malignant cells and their surrounding stroma into account. Here, we applied a coculture model consisting of green fluorescent osteosarcoma cells and red fluorescent fibroblasts on extruded Mg and Mg-6Ag with a tailored degradation rate. In contrast to non-degrading Ti-based material, both Mg-based materials reduced relative tumor cell numbers. Comparing the influence of the material on a sparse and dense coculture, relative cell numbers were found to be statistically different, thus relevant, while magnesium alloy degradations were observed as cell density-independent. We concluded that the sparse coculture model is a suitable mechanistic system to further study the antitumor effects of Mg-based material.

Bioaccessibility of nickel and cobalt in synthetic gastric and lung fluids and its potential use in alloy classification.

This study investigated nickel and cobalt ion release from the metals and several alloys in synthetic gastric, as well as interstitial and lysosomal lung fluids. Results were used to calculate the relative bioaccessible concentrations (RBCs) of the metals. Nickel release from SS 316L powder in gastric fluid was >300-fold lower than from a simple mixture of powders of the same bulk composition. Gastric bioaccessibility data showed 50-fold higher metal releases per gram of sample from powder than massive forms. RBCs of nickel and cobalt in the alloy powders were lower, equal, or higher in all fluids tested than their bulk concentrations. This illustrates the fact that matrix effects can increase or decrease the metal ion release, depending on the metal ingredients, alloy type, and fluid, consistent with research by others. Acute inhalation toxicity studies with cobalt-containing alloy powders showed that the RBC of cobalt in interstitial lung fluid predicted acute toxicity better than bulk concentration. This example indicates that the RBC of a metal in an alloy may estimate the concentration of bioavailable metals better than the bulk concentration, and the approach may provide a means to refine the classification of alloys for several human health endpoints.

Upshift of the d Band Center toward the Fermi Level for Promoting Silver Ion Release, Bacteria Inactivation, and Wound Healing of Alloy Silver Nanoparticles.

Silver (Ag)-based nanoparticles (NPs) with a high potential of Ag+ release have been known to be capable of promoting bacteria inactivation and the wound healing process; however, keeping a steady flux of high levels of Ag+ in Ag-based NPs is still challenging. Herein, a novel strategy in terms of altering the intrinsic electronic structure of Ag NPs was attempted to facilitate Ag oxidation and boost the Ag+ flux, as results of improved antibacterial and wound healing performance of Ag NPs. Gold (Au), platinum (Pt), and palladium (Pd) were doped into Ag NPs to tune their d band centers to upshift toward the Fermi level, and the formed Pd-Ag alloy NPs showed the largest shift, followed by Pt-Ag and Au-Ag NPs, as determined by density function theory calculation and ultraviolet photoemission spectroscopy measurement. Further X-ray photoelectron spectroscopy analysis indicates that a larger upshift could induce less electron filling in the antibonding orbital and a higher Ag oxidation level, leading to the more remarkable Ag+ release as determined by inductively coupled plasma optical emission spectrometry. All these alloy Ag NPs could more efficiently inhibit bacterial growth and accelerate the wound healing process than pure Ag NPs, and their antibacterial activity and wound healing performance were progressively proportional to the upshift values of the d band center. Taken together, tuning the d band center to upshift toward the Fermi level becomes a feasible strategy for designing therapeutic Ag-based NPs with a promising antibacterial and wound healing performance.

Mechanical Strength, Biodegradation, and in Vitro and in Vivo Biocompatibility of Zn Biomaterials.

Zn-based biomaterials have emerged as promising new types of bioresorbable metallics applicable to orthopedic devices, cardiovascular stents, and other medical applications recently. Compared to other degradable metallic biomaterials (i.e., Mg- or Fe-based), Zn biomaterials have a more appropriate corrosion rate without hydrogen gas evolution. Here, we evaluated the potential of Zn-based metallics as medical implants, both in vitro and in vivo, alongside a standard benchmark Mg alloy, AZ31. The mechanical properties of the pure Zn were not strong enough but were significantly enhanced (microhardness > 70 kg/mm2, strength > 220 MPa, elongation > 15%) after alloying with Sr or Mg (1.5 at. %), surpassing the minimal design criteria for load-bearing device applications. The corrosion rate of Zn-based biomaterials was about 0.4 mm/year, significantly slower than that of AZ31. The measured cell viability and proliferation of three different human primary cells fared better for Zn-based biomaterials than AZ31 using both direct and indirect culture methods. Platelet adhesion and activation on Zn-based materials were minimal, significantly less than on AZ31. The hemolysis ratio of red cells (<0.5%) after incubation with Zn-based materials was also well below the ISO standard of 5%. Moreover, Zn-based biomaterials promoted stem cell differentiation to induce the extracellular matrix mineralization process. In addition, in vivo animal testing using subcutaneous, bone, and vascular implantations revealed that the acute toxicity and immune response of Zn-based biomaterials were minimal/moderate, comparable to that of AZ31. No extensive cell death and foreign body reactions were observed. Taken together, Zn-based biomaterials may have a great potential as promising candidates for medical implants.

The influence of alloying and fabrication techniques on the mechanical properties, biodegradability and biocompatibility of zinc: A comprehensive review.

Zinc has been identified as one of the most promising biodegradable metals along with magnesium and iron. Zinc appears to address some of the core engineering problems associated with magnesium and iron when applied to biomedical implant applications; hence the increase in the amount of research investigations on the metal in the last few years. In this review, the current state-of-the-art on biodegradable Zn, including recent developments, current opportunities and future directions of research are discussed. The discussions are presented with a specific focus on reviewing the relationships that exist between mechanical properties, biodegradability, and biocompatibility of zinc with alloying and fabrication techniques. This work hopes to guide future studies on biodegradable Zn that will help in advancing this field of research. STATEMENT OF SIGNIFICANCE: (i) The review offers an up-to-date and comprehensive review of the influence of alloying and fabrication technique on mechanical properties, biodegradability and biocompatibility of Zn; (ii) the work cites the most relevant biodegradable Zn fabrication processes including additive manufacturing techniques; (iii) the review includes a listing of research gap and future research directions for the field of biodegradable Zn.

Microstructure, mechanical properties, biocompatibility, and in vitro corrosion and degradation behavior of a new Zn-5Ge alloy for biodegradable implant materials.

Zinc (Zn)-based alloys are considered a new class of biodegradable implant materials due to their superior chemical stability and processability compared to biodegradable magnesium (Mg) alloys. In this study, we report a new biodegradable Zn-5Ge alloy with highly desirable mechanical, corrosion, and biological properties. Microstructural characterization revealed the effective grain-refining effect of germanium (Ge) on the Zn alloy. Tensile test results indicated that the hot-rolled Zn-5Ge alloy showed an ultimate tensile strength of 237.0 MPa, a yield strength of 175.1 MPa, and an elongation of 21.6%; while as-cast pure Zn showed an ultimate tensile strength of 33.6 MPa, a yield strength of 29.3 MPa, and an elongation of 1.2%. The corrosion rates measured by potentiodynamic polarization tests in Hank's solution in ascending order are: as-cast Zn-5Ge (0.1272 mm/y) < as-cast pure Zn (0.1567 mm/y) < hot-rolled Zn-5Ge (0.2255 mm/y) < hot-rolled pure Zn (0.3057 mm/y). Immersion tests revealed that the degradation rate of as-cast Zn-5Ge is 0.042 mm/y, less than half of that of hot-rolled pure Zn and ∼62% of that of as-cast pure Zn. Moreover, the Zn-5Ge alloy showed excellent in vitro hemocompatibility and the addition of 5% Ge effectively enhanced the hemocompatibility of pure Zn. CCK-8 assay using murine preosteoblast MC3T3-E1 cells indicated that the diluted extracts at a concentration <12.5% of both the as-cast Zn-5Ge alloy and pure Zn showed grade 0 cytotoxicity; the diluted extracts at the concentrations of 50% and 25% of Zn-5Ge alloy showed a significantly higher cell viability than those of pure Zn. STATEMENT OF SIGNIFICANCE: Zinc (Zn)-based alloys are currently considered a new class of biodegradable implant materials due to their excellent processability. Here, we report a novel Zn-5Ge alloy with highly desirable mechanical, corrosion and biological properties. The tensile test results indicated that the hot-rolled Zn-5Ge alloy showed an ultimate tensile strength of 237.0 MPa, a yield strength of 175.1 MPa and an elongation of 21.6%; while as-cast pure Zn showed an ultimate tensile strength of 33.6 MPa, a yield strength of 29.3 MPa and an elongation of 1.2%. The corrosion rate measured by potentiodynamic polarization tests in Hank's solution in the ascending order is: as-cast Zn-5Ge (0.1272 mm/y) < as-cast pure Zn (0.1567 mm/y) < hot-rolled Zn-5Ge (0.2255 mm/y) < hot-rolled pure Zn (0.3057 mm/y). Immersion tests revealed that the degradation rate of the as-cast Zn-5Ge is 0.042 mm/y, less than half of that of the hot-rolled pure Zn, ∼62% of that of as-cast pure Zn. Moreover, the Zn-5Ge alloy showed excellent in vitro biocompatibility.

Recovery of low volumes of wear debris from rat stifle joint tissues using a novel particle isolation method.

Less than optimal particle isolation techniques have impeded analysis of orthopaedic wear debris in vivo. The purpose of this research was to develop and test an improved method for particle isolation from tissue. A volume of 0.018 mm3 of clinically relevant CoCrMo, Ti-6Al-4V or Si3N4 particles was injected into rat stifle joints for seven days of in vivo exposure. Following sacrifice, particles were located within tissues using histology. The particles were recovered by enzymatic digestion of periarticular tissue with papain and proteinase K, followed by ultracentrifugation using a sodium polytungstate density gradient. Particles were recovered from all samples, observed using SEM and the particle composition was verified using EDX, which demonstrated that all isolated particles were free from contamination. Particle size, aspect ratio and circularity were measured using image analysis software. There were no significant changes to the measured parameters of CoCrMo or Si3N4 particles before and after the recovery process (KS tests, p > 0.05). Titanium particles were too few before and after isolation to analyse statistically, though size and morphologies were similar. Overall the method demonstrated a significant improvement to current particle isolation methods from tissue in terms of sensitivity and efficacy at removal of protein, and has the potential to be used for the isolation of ultra-low wearing total joint replacement materials from periprosthetic tissues. STATEMENT OF SIGNIFICANCE: This research presents a novel method for the isolation of wear particles from tissue. Methodology outlined in this work would be a valuable resource for future researchers wishing to isolate particles from tissues, either as part of preclinical testing, or from explants from patients for diagnostic purposes. It is increasingly recognised that analysis of wear particles is critical to evaluating the safety of an orthopaedic device.

Impact of nitinol stent surface processing on in-vivo nickel release and biological response.

Although nitinol is widely used in percutaneous cardiovascular interventions, a causal relationship between nickel released from implanted cardiovascular devices and adverse systemic or local biological responses has not been established. The objective of this study was to investigate the relationship between nitinol surface processing, in-vivo nickel release, and biocompatibility. Nitinol stents manufactured using select surface treatments were implanted into the iliac arteries of minipigs for 6 months. Clinical chemistry profile, complete blood count, serum and urine nickel analyses were performed periodically during the implantation period. After explant, stented arteries were either digested and analyzed for local nickel concentration or fixed and sectioned for histopathological analysis of stenosis and inflammation within the artery. The results indicated that markers for liver and kidney function were not different than baseline values throughout 180 days of implantation regardless of surface finish. In addition, white blood cell, red blood cell, and platelet counts were similar to baseline values for all surface finishes. Systemic nickel concentrations in serum and urine were not significantly different between processing groups and comparable to baseline values during 180 days of implantation. However, stents with non-optimized surface finishing had significantly greater nickel levels in the surrounding artery compared to polished stents. These stents had increased stenosis with potential for local inflammation compared to polished stents. These findings demonstrate that proper polishing of nitinol surfaces can reduce in-vivo nickel release locally, which may aid in minimizing adverse inflammatory reactions and restenosis. STATEMENT OF SIGNIFICANCE: Nitinol is a commonly used material in cardiovascular medical devices. However, relationships between nitinol surface finishing, in-vivo metal ion release, and adverse biological responses have yet to be established. We addressed this knowledge gap by implanting single and overlapped nitinol stents with different surface finishes to assess systemic impact on minipigs (i.e. serum and urine nickel levels, liver and kidney function, immune and blood count) over the 6 month implantation period. In addition, nickel levels and histopathology in stented arteries were analyzed on explant to determine relationships between surface processing and local adverse tissue reactions. The findings presented here highlight the importance of surface processing on in-vivo nickel release and subsequent impact on local biological response for nitinol implants.

Zinc-based alloys for degradable vascular stent applications.

The search for biodegradable metals with mechanical properties equal or higher to those of currently used permanent biomaterials, such as stainless steels, cobalt chromium and titanium alloys, desirable in vivo degradation rate and uniform corrosion is still an open challenge. Magnesium (Mg), iron (Fe) and zinc (Zn)-based alloys have been proposed as biodegradable metals for medical applications. Over the last two decades, extensive research has been done on Mg and Fe. Fe-based alloys show appropriate mechanical properties, but their degradation rate is an order of magnitude below the benchmark value. In comparison, alongside the insufficient mechanical performance of most of its alloys, Mg degradation rate has proven to be too high in a physiological environment and corrosion is rarely uniform. During the last few years, Zn alloys have been explored by the biomedical community as potential materials for bioabsorbable vascular stents due to their tolerable corrosion rates and tunable mechanical properties. This review summarizes recent progress made in developing Zn alloys for vascular stenting application. Novel Zn alloys are discussed regarding their microstructural characteristics, mechanical properties, corrosion behavior and in vivo performance. STATEMENT OF SIGNIFICANCE: Numerous studies on magnesium and iron materials have been reported to date, in an effort to formulate bioabsorbable stents with tailorable mechanical characteristics and corrosion behavior. Crucial concerns regarding poor ductility and remarkably rapid corrosion of magnesium, and very slow degradation of iron, seem to be still not desirably fulfilled. Zinc was introduced as a potential implant material in 2013 due to its promising biodegradability and biocompatibility. Since then, extensive investigations have been made toward development of zinc alloys that meet clinical benchmarks for vascular scaffolding. This review critically surveys the zinc alloys developed since 2013 from metallurgical and biodegradation points of view. Microstructural features, mechanical, corrosion and in vivo performances of these new alloys are thoroughly reviewed and evaluated.

Predicting patient exposure to nickel released from cardiovascular devices using multi-scale modeling.

Many cardiovascular device alloys contain nickel, which if released in sufficient quantities, can lead to adverse health effects. However, in-vivo nickel release from implanted devices and subsequent biodistribution of nickel ions to local tissues and systemic circulation are not well understood. To address this uncertainty, we have developed a multi-scale (material, tissue, and system) biokinetic model. The model links nickel release from an implanted cardiovascular device to concentrations in peri-implant tissue, as well as in serum and urine, which can be readily monitored. The model was parameterized for a specific cardiovascular implant, nitinol septal occluders, using in-vitro nickel release test results, studies of ex-vivo uptake into heart tissue, and in-vivo and clinical measurements from the literature. Our results show that the model accurately predicts nickel concentrations in peri-implant tissue in an animal model and in serum and urine of septal occluder patients. The congruity of the model with these data suggests it may provide useful insight to establish nickel exposure limits and interpret biomonitoring data. Finally, we use the model to predict local and systemic nickel exposure due to passive release from nitinol devices produced using a wide range of manufacturing processes, as well as general relationships between release rate and exposure. These relationships suggest that peri-implant tissue and serum levels of nickel will remain below 5 µg/g and 10 µg/l, respectively, in patients who have received implanted nitinol cardiovascular devices provided the rate of nickel release per device surface area does not exceed 0.074 µg/(cm2 d) and is less than 32 µg/d in total. STATEMENT OF SIGNIFICANCE: The uncertainty in whether in-vitro tests used to evaluate metal ion release from medical products are representative of clinical environments is one of the largest roadblocks to establishing the associated patient risk. We have developed and validated a multi-scale biokinetic model linking nickel release from cardiovascular devices in-vivo to both peri-implant and systemic levels. By providing clinically relevant exposure estimates, the model vastly improves the evaluation of risk posed to patients by the nickel contained within these devices. Our model is the first to address the potential for local and systemic metal ion exposure due to a medical device and can serve as a basis for future efforts aimed at other metal ions and biomedical products.

The degradation and transport mechanism of a Mg-Nd-Zn-Zr stent in rabbit common carotid artery: A 20-month study.

Mg-based stent is a promising candidate of the next generation fully degradable vascular stents. The latest progress includes the CE approval of the Magmaris ® WE43 based drug eluting stent. However, so far, the long term (more than 1 year implantation) in vivo degradation and the physiological effects caused by the degradation products were still unclear. In this study, a 20 month observation was carried out after the bare Mg-Nd-Zn-Zr (abbr. JDBM) stent prototype was implanted into the common carotid artery of New Zealand white rabbit in order to evaluate its safety, efficacy and especially degradation behavior. The degradation of the main second phase Mg12Nd was also studied. Results showed that the bare JDBM stent had good safety and efficacy with a complete re-endothelialization within 28 days. The JDBM stent struts were mostly replaced in situ by degradation products in 4 month. The important finding was that the volume and Ca concentration of the degradation products decreased in the long term, eliminating the clinicians' concern of possible vessel calcification. In addition, the alloying elements Mg and Zn in the stent could be safely metabolized as continuous enrichment in any of the main organs were not detected although Nd and Zr showed an abrupt increase in spleen and liver after 1 month implantation. Collectively, the long term in vivo results showed the rapid re-endothelialization of JDBM stent and the long term safety of the degradation products, indicating its great potential as the backbone of the fully degradable vascular stent. STATEMENT OF SIGNIFICANCE: Mg-based stent is a promising candidate of the next generation fully degradable stents, especially after the recent market launch of one of its kind (Magmaris). However the fundamental question about the long term degradation and metabolic mechanism of Mg-based stent and its degradation products remain unanswered. We implanted our patented Mg-Nd-Zn-Zr bare stent into the common carotid artery of rabbits and conducted a 20 months observation. We found that the Ca containing degradation products could be further degraded in vivo. All the alloying elements showed no continuous enrichment in the main organs of rabbits. These findings eliminate the clinicians' concern of possible vessel calcification and element enrichment after the implantation of Mg alloy based stents to some extent.

Metal release and cell biological compatibility of beta-type Ti-40Nb containing indium.

Small indium (In) additions up to 5 wt % to the beta-type Ti-40Nb alloy effectively improve its mechanical biofunctionality. The impact on its biocompatibility is addressed in this work. Comparative electrochemical polarization studies and inductively coupled plasma optical emission spectrometry analyses were conducted in Tris-buffered saline (on the basis of 150 mM NaCl) with pH 7.6 and 2.0 at 310 ± 1 K with Ti-6Al-4V as reference. The metal ion releases from beta-type alloys were generally very low, for example, those of In3+ ions from (Ti-40Nb)-4In specimens were below 6 × 10-7 mmol/cm2 . X-ray photoelectron spectroscopy revealed the passivation mainly by Ti- and Nb-oxides with traces of In-oxides as the dominating surface process. In vitro studies demonstrate a better human bone marrow stromal cells (hBMSC) activity on the beta-type alloys in comparison to CP-Ti (grade 2), which is mainly due to their high Nb content. At 24 h after seeding on (Ti-40Nb)-4In the metabolic activity of hBMSC was 1.5-fold higher and after 11 days, the tissue non-specific alkaline phosphatase activity was 1.8-fold higher relative to values for CP-Ti. Surface treatments, like chemical etching or plasma oxidation, change the surface topography and the thickness and composition of the oxide layers, but they are not effective in further improving the cell response. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1686-1697, 2018.

Macrophage phagocytosis of biomedical Mg alloy degradation products prepared by electrochemical method.

Biomedical Mg alloy is promising for its widespread use clinically. In vitro and in vivo studies showed that the degradation products of biomedical Mg alloy were composed of O, P, Ca, Mg and other alloying elements. However, little is known about the metabolism of the degradation products. In this study, the in vitro macrophage phagocytosis of the degradation products of a biomedical Mg-Nd-Zn-Zr alloy was directly observed. This result affirms the necessity to investigate the long-term fate of Mg alloy degradation products in physiological environments. Besides, an electrochemical method was proposed to prepare enough amount of degradation products in vitro efficiently.

In vitro and in vivo corrosion and histocompatibility of pure Mg and a Mg-6Zn alloy as urinary implants in rat model.

Pure Mg and a Mg-6wt.% Zn alloy were investigated as potential candidates for biodegradable implants for the urinary system. The in vitro corrosion behavior was studied by potentiodynamic polarization and immersion tests in simulated body fluid (SBF) at 37°C. The in vivo degradation and histocompatibility were examined through implantation into the bladders of Wistar rats. The alloying element Zn elevated the passivation potential and increased the cathodic current density. Both in vitro and in vivo degradation tests showed a faster corrosion rate for the Mg-6Zn alloy. Tissues stained with hematoxylin and eosin (HE) suggested that both pure Mg and Mg-6Zn alloy exhibited good histocompatibility in the bladder indwelling implantation and no differences between pure Mg and Mg-6Zn groups were found in bladder, liver and kidney tissues during the 2weeks implantation. Overall, this work presented instructive information on the degradation properties and histocompatibility of pure Mg and the Mg-6Zn alloy in the urinary system.

Bi-directional controlled release of ibuprofen and Mg(2+) from magnesium alloys coated by multifunctional composite.

Two major problems for magnesium alloy implant are the high degradation rate and easy infection associated with implantation. Herein, a surface drug delivery system (Mg/Epoxy resin-ZnO/PCL-Ibuprofen) which can realize bi-directional controlled release of ibuprofen and Mg(2+) was designed via a dip coating process followed by spraying. The in vitro test demonstrated that the ibuprofen in drug-eluting compound material showed sustained release profiles for 22days, which can effectively solve the local cellular rejection and inflammation during the early stage of implantation. Besides, the drug carrier also exhibited improved corrosion resistance duel to the high combining strength between Epoxy resin-ZnO coating and magnesium alloy, so Mg(2+) can release slowly at first and then speeded up later. This approach may be suitable for coating other implant materials such as stainless steel, titanium alloy etc.

A biokinetic model for nickel released from cardiovascular devices.

Many alloys used in cardiovascular device applications contain high levels of nickel, which if released in sufficient quantities, can lead to adverse health effects. While nickel release from these devices is typically characterized through the use of in-vitro immersion tests, it is unclear if the rate at which nickel is released from a device during in-vitro testing is representative of the release rate following implantation in the body. To address this uncertainty, we have developed a novel biokinetic model that combines a traditional toxicokinetic compartment model with a physics-based model to estimate nickel release from an implanted device. This model links the rate of in-vitro nickel release from a cardiovascular device to serum nickel concentrations, an easily measured endpoint, to estimate the rate and extent of in-vivo nickel release from an implanted device. The model was initially parameterized using data in the literature on in-vitro nickel release from a nickel-containing alloy (nitinol) and baseline serum nickel levels in humans. The results of this first step were then used to validate specific components of the model. The remaining unknown quantities were fit using serum values reported in patients following implantation with nitinol atrial occluder devices. The model is not only consistent with levels of nickel in serum and urine of patients following treatment with the atrial occluders, but also the optimized parameters in the model were all physiologically plausible. The congruity of the model with available data suggests that it can provide a framework to interpret nickel biomonitoring data and use data from in-vitro nickel immersion tests to estimate in-vivo nickel release from implanted cardiovascular devices.