Zhanyong Zhao

Electrodeposition of hydroxyapatite coating on Mg‐4.0Zn‐1.0Ca‐0.6Zr alloy and in vitro evaluation of degradation, hemolysis, and cytotoxicity

A novel biodegradable Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy was successfully produced using a series of metallurgical processes; including melting, casting, rolling, and heat treatment. The hardness and ultimate tensile strength of the alloy sheets increased to 71.2HV and 320 MPa after rolling and then aging for 12 h at 175°C. These mechanical properties were sufficient for load-bearing orthopedic implants. A hydroxyapatite (HA) coating was deposited on the Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy using a novel coating process combining alkali heat pretreatment, electrodeposition, and alkali heat posttreatment. The microstructure, composition, and phases of the Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy and HA coating were characterized using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). The degradation, hemolysis, and cytocompatibility of the HA-coated and uncoated Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy were studied in vitro. The corrosion potential (E(corr)) of Mg-4.0Zn-1.0Ca-0.6Zr alloy (-1.72 V) was higher than Mg (-1.95 V), Mg-0.6Ca alloy (-1.91 V) and Mg-1.0Ca alloy (-1.97 V), indicating the Mg-Zn-Ca-Zr alloy would be more corrosion resistant. The initial corrosion potential of the HA-coated Mg alloy sample (-1.51 V) was higher than the uncoated sample (-1.72 V). The hemolysis rates of the HA-coated and uncoated Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy samples were both <5%, which met the requirements for implant materials. The HA-coated and uncoated Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy samples demonstrated the same cytotoxicity score as the negative control. The HA-coated samples showed a slightly greater relative growth rate (RGR%) of fibroblasts than the uncoated samples. Both the HA-coated and uncoated Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy provided evidence of acceptable cytocompatibility for medical applications.

Development and evaluation of a magnesium–zinc–strontium alloy for biomedical applications — Alloy processing, microstructure, mechanical properties, and biodegradation

A new biodegradable magnesium-zinc-strontium (Mg-Zn-Sr) alloy was developed and studied for medical implant applications. This first study investigated the alloy processing (casting, rolling, and heat treatment), microstructures, mechanical properties, and degradation properties in simulated body fluid (SBF). Aging treatment of the ZSr41 alloy at 175 °C for 8h improved the mechanical properties when compared to those of the as-cast alloy. Specifically, the aged ZSr41 alloy had an ultimate tensile strength of 270 MPa, Vickers hardness of 71.5 HV, and elongation at failure of 12.8%. The mechanical properties of the ZSr41 alloy were superior as compared with those of pure magnesium and met the requirements for load-bearing medical implants. Furthermore, the immersion of the ZSr41 alloy in SBF showed a degradation mode that progressed cyclically, alternating between pitting and localized corrosion. The steady-state average degradation rate of the aged ZSr41 alloy in SBF was 0.96 g/(m(2)·hr), while the pH of SBF immersion solution increased. The corrosion current density of the ZSr41 alloy in SBF solution was 0.41 mA/mm(2), which was much lower than 1.67 mA/mm(2) for pure Mg under the same conditions. In summary, compared to pure Mg, the mechanical properties of the new ZSr41 alloy improved while the degradation rate decreased due to the addition of Zn and Sr alloying elements and specific processing conditions. The superior mechanical properties and corrosion resistance of the new ZSr41 alloy make it a promising alloy for next-generation implant applications.

Investigation of magnesium-zinc-calcium alloys and bone marrow derived mesenchymal stem cell response in direct culture.

Crystalline Mg-Zn-Ca ternary alloys have recently attracted significant interest for biomedical implant applications due to their promising biocompatibility, bioactivity, biodegradability and mechanical properties. The objective of this study was to characterize as-cast Mg-xZn-0.5Ca (x=0.5, 1.0, 2.0, 4.0wt.%) alloys, and determine the adhesion and morphology of bone marrow derived mesenchymal stem cells (BMSCs) at the interface with the Mg-xZn-0.5Ca alloys. The direct culture method (i.e. seeding cells directly onto the surface of the sample) was established in this study to probe the highly dynamic cell-substrate interface and thus to elucidate the mechanisms of BMSC responses to dynamic alloy degradation. The results showed that the BMSC adhesion density on these alloys was similar to the cell-only positive control and the BMSC morphology appeared more anisotropic on the rapidly degrading alloy surfaces in comparison with the cell-only positive control. Importantly, neither culture media supplemented with up to 27.6mM Mg(2+) ions nor media intentionally adjusted up to alkaline pH 9 induced any detectable adverse effects on BMSC responses. We speculated that degradation-induced dynamic surface topography played an important role in modulating cell morphology at the interface. This study presents a clinically relevant in vitro model for screening bioresorbable alloys, and provides useful design guidelines for determining the degradation rate of implants made of Mg-Zn-Ca alloys.

Cytocompatibility and early inflammatory response of human endothelial cells in direct culture with Mg-Zn-Sr alloys

Crystalline Mg-Zinc (Zn)-Strontium (Sr) ternary alloys consist of elements naturally present in the human body and provide attractive mechanical and biodegradable properties for a variety of biomedical applications. The first objective of this study was to investigate the degradation and cytocompatibility of four Mg-4Zn-xSr alloys (x=0.15, 0.5, 1.0, 1.5wt%; designated as ZSr41A, B, C, and D respectively) in the direct culture with human umbilical vein endothelial cells (HUVEC) in vitro. The second objective was to investigate, for the first time, the early-stage inflammatory response in cultured HUVECs as indicated by the induction of vascular cellular adhesion molecule-1 (VCAM-1). The results showed that the 24-h in vitro degradation of the ZSr41 alloys containing a β-phase with a Zn/Sr at% ratio ∼1.5 was significantly faster than the ZSr41 alloys with Zn/Sr at% ∼1. Additionally, the adhesion density of HUVECs in the direct culture but not in direct contact with the ZSr41 alloys for up to 24h was not adversely affected by the degradation of the alloys. Importantly, neither culture media supplemented with up to 27.6mM Mg2+ ions nor media intentionally adjusted up to alkaline pH 9 induced any detectable adverse effects on HUVEC responses. In contrast, the significantly higher, yet non-cytotoxic, Zn2+ ion concentration from the degradation of ZSr41D alloy was likely the cause for the initially higher VCAM-1 expression on cultured HUVECs. Lastly, analysis of the HUVEC-ZSr41 interface showed near-complete absence of cell adhesion directly on the sample surface, most likely caused by either a high local alkalinity, change in surface topography, and/or surface composition. The direct culture method used in this study was proposed as a valuable tool for studying the design aspects of Zn-containing Mg-based biomaterials in vitro, in order to engineer solutions to address current shortcomings of Mg alloys for vascular device applications. STATEMENT OF SIGNIFICANCE Magnesium (Mg) alloys specifically designed for biodegradable implant applications have been the focus of biomedical research since the early 2000s. Physicochemical properties of Mg alloys make these metallic biomaterials excellent candidates for temporary biodegradable implants in orthopedic and cardiovascular applications. As Mg alloys continue to be investigated for biomedical applications, it is necessary to understand whether Mg-based materials or the alloying elements have the intrinsic ability to direct an immune response to improve implant integration while avoiding cell-biomaterial interactions leading to chronic inflammation and/or foreign body reactions. The present study utilized the direct culture method to investigate for the first time the in vitro transient inflammatory activation of endothelial cells induced by the degradation products of Zn-containing Mg alloys.

In vitro interactions of blood, platelet, and fibroblast with biodegradable magnesium-zinc-strontium alloys

Magnesium (Mg) alloy is an attractive class of metallic biomaterial for cardiovascular applications due to its biodegradability and mechanical properties. In this study, we investigated the degradation in blood, thrombogenicity, and cytocompatibility of Magnesium-Zinc-Strontium (Mg-Zn-Sr) alloys, specifically four Mg-4 wt % Zn-xSr (x = 0.15, 0.5, 1, and 1.5 wt %) alloys, together with pure Mg control and relevant reference materials for cardiovascular applications. Human whole blood and platelet rich plasma (PRP) were used as the incubation media to investigate the degradation behavior of the Mg-Zn-Sr alloys. The results showed that the PRP had a greater pH increase and greater concentration of Mg(2+) ions when compared with whole blood after 2 h of incubation with the same respective Mg alloys, suggesting that the Mg alloys degraded faster in PRP than in whole blood. The Mg alloy with 4 wt % Zn and 0.15 wt % Sr (named as ZSr41A) was identified as the most promising alloy for cardiovascular stent applications, because it showed slower degradation and less thrombogenicity, as indicated by the lower concentrations of Mg(2+) ions released and less deposition of platelets. Additionally, ZSr41 alloys were cytocompatible with fibroblasts in direct exposure culture in which the cells adhered and proliferated around the samples, with no statistical difference in cell adhesion density compared with the blank reference. Future studies on the ZSr41 alloys are necessary to investigate their direct interactions with other important cells in cardiovascular system, such as vascular endothelial cells and smooth muscle cells.

A Novel Semisolid Rheo-Rolling Process of AZ31 Alloy with Vibrating Sloping Plate

A novel semisolid rheo-rolling process of AZ31 alloy was achieved by combining the shape rolling mill with the vibrating sloping plate device. The process is expected to be developed as a high-speed, semisolid roll-casting technique. During the process, due to the strong cooling rate by the sloping plate and stirrings caused by vibration and metal flow, three mechanisms—heterogenous nucleation, eruptive nucleation, and nucleus multiplication—exist, which lead to fine spherical or rosette grains formation. Two grain-growing styles, direct globular growth, dendrite growth, and fracture happen on the sloping plate surface, which also devotes to the fine non dendrite formation. During the rolling process, the solid grain of the slurry is elongated a little, and its original shape is basically maintained. If the casting temperature is too high, the liquid segregation occurs. At the casting temperature range of 650–690°C, AZ31 alloy strip with a cross section size of 4 × 160 mm was prepared by the proposed process. The product has good quality surface and homogenous microstructure. The mechanical properties of the product are higher than that produced by conventional roll casting.

Microstructure formation mechanism during a novel semisolid rheo-rolling process of AZ91 magnesium alloy

A novel semisolid rheo-rolling process of AZ91 alloy was proposed. The microstructure formation mechanism of AZ91 magnesium alloy during the process was studied. The results reveal that the eruptive nucleation and the heterogeneous nucleation exist. During the grain growth process, the grain breakage took place and transformed into fine spherical or rosette grains on the sloping plate gradually, the other grain growth style is direct globular growth. Due to the secondary crystallization of the remnant liquids in the roll gap, the microstructure of the strip becomes finer with the increment of the casting temperature from 650 °C to 690 °C. But when the casting temperature reached 710 °C, a part of the liquid alloy transformed into the eutectic phases, and the primary grains ripened to form coarse dendrites. In the casting temperature range from 650 °C to 690 °C, AZ91 alloy strip with fine spherical or rosette grains was prepared by the proposed process.

Effects of Electromagnetic Stirring, Shearing, and Extrusion on TiB2 and TiAl3 Particles in Al–5Ti–1B(wt.%) Alloy

Electromagnetic stirring induced metal flow and led to homogenous dispersion of TiAl3 particles. Fragmentation mechanism induced by electromagnetic stirring also contributed to TiAl3 particle refining. TiAl3 particle size decreased with the increases of stirring temperature and time. Shearing force among different melt layers under the shear action of roll in the roll-shoe gap increased with the decrease of casting temperature and the increase of melt viscosity, and the fragmentation of TiAl3 phase became obvious correspondingly. Under the optimal process parameters, Al–5Ti–1B(wt.%) alloy wire with excellent inner microstructure and high surface quality was produced. The average sizes of TiAl3 are less than 20 µm, and TiB2 phases are less than 0.5 µm, respectively. Al–5Ti–1B(wt.%) alloy wire manufactured by present method has a high refining ability on pure aluminum and an excellent ability of refining effectiveness.

Process parameter optimizing and studies on microstructure and properties of AZ31 alloy prepared by semisolid rolling process

A novel continuous semisolid rolling process for producing AZ31 alloy strip was developed. The process parameters were optimized, and microstructure and properties of AZ31 alloy prepared by the process were studied. The results reveal that primary grains of the strip become coarse, and the grain structure transforms from round shape to dendrite with the increment of casting temperature gradually. Eutectic phase fraction and primary grain size increase with the increment of roll speed. The primary grain size decreases firstly and then increases with the increment of the vibration frequency correspondingly. When the casting temperature is from 650 °C to 690 °C, the roll speed is 0.069 m·s−1, and the vibration frequency is about 80 Hz, AZ31 alloy strip with a cross section size of 4 mm×160 mm was prepared by the proposed process. The ultimate tensile strength and elongation are improved 1% and 57%, respectively.

Boundary layer distributions and cooling rate of cooling sloping plate process

According to the principle of grain refining and slurry preparation by cooling sloping plate process, the distributions of boundary layers during melt treatment by cooling sloping plate were studied, and mathematic model of cooling rate was established. The calculation value approximately agrees with the experimental result. Laminar flow and turbulent flow exist on sloping plate surface commonly. The thickness of velocity boundary layer and the critical transfer distance from laminar flow to turbulent flow increase with the decrease of initial flow velocity. The thickness of temperature boundary layer increases with the increment of flow distance and the decrease of initial flow velocity. The melt cooling rate and melt thickness have an inverse proportion relationship. The melt cooling rate increases along the plate direction gradually when the initial flow velocity is lower than 1 m/s, the melt cooling rate keeps nearly a constant when the initial flow velocity is 1 m/s, when the initial flow velocity is higher than 1 m/s, the melt cooling rate decreases gradually. The melt cooling rate of cooling sloping plate process can reach 102–103 K/s and belongs to meta-rapid solidification scope.