Jialin Niu

Microstructure, mechanical properties, biocorrosion behavior, and cytotoxicity of as-extruded Mg–Nd–Zn–Zr alloy with different extrusion ratios

Recently, commercial magnesium (Mg) alloys containing Al (such as AZ31 and AZ91) or Y (such as WE43) have been studied extensively for biomedical applications. However, these Mg alloys were developed as structural materials, not as biomaterials. In this study, a patented Mg-Nd-Zn-Zr (denoted as JDBM) alloy was investigated as a biomedical material. The microstructure, mechanical properties, biocorrosion behavior, and cytotoxicity of the alloy extruded at 320 °C with extrusion ratios of 8 and 25 were studied. The results show that the lower extrusion ratio results in finer grains and higher strength, but lower elongation, while the higher extrusion ratio results in coarser grains and lower strength, but higher elongation. The biocorrosion behavior of the alloy was investigated by hydrogen evolution and mass loss tests in simulated body fluid (SBF). The results show that the alloy extruded with lower extrusion ratio exhibits better corrosion resistance. The corrosion mode of the alloy is uniform corrosion, which is favorable for biomedical applications. Aging treatment on the as-extruded alloy improves the strength and decreases the elongation at room temperature, and has a small positive influence on the corrosion resistance in SBF. The cytotoxicity test indicates that the as-extruded JDBM alloy meets the requirement of cell toxicity.

In vitro degradation behavior and biocompatibility of Mg–Nd–Zn–Zr alloy by hydrofluoric acid treatment

In this paper, Mg-Nd-Zn-Zr alloy (denoted as JDBM) coated with hydrofluoric acid (HF) chemical conversion film (MgF2) was researched as a potential biodegradable cardiovascular stent material. The microstructures, in vitro degradation and biocompatibility were investigated. The field emission scanning electron microscopy (FE-SEM) and X-ray photoelectron spectroscopy (XPS) showed that a compact MgF2 film was formed on the surface of JDBM. The corrosion rate decreased in artificial plasma from 0.337 to 0.253 mm·y(-1) and the electrochemical measurement demonstrated that the corrosion resistance of JDBM alloy could be obviously improved due to the protective MgF2 film on the surface of the substrate. Meanwhile, the hemolysis ratio of JDBM decreased from 52.0% to 10.1% and the cytotoxicity met the requirement of cellular application after HF treatment. In addition, JDBM and MgF2 film showed good anti-platelet adhesion, which is a very favorable property for implant material in contact with blood directly.

Enhanced biocorrosion resistance and biocompatibility of degradable Mg-Nd-Zn-Zr alloy by brushite coating.

To further improve the corrosion resistance and biocompatibility of Mg-Nd-Zn-Zr alloy (JDBM), a biodegradable calcium phosphate coating (Ca-P coating) with high bonding strength was developed using a novel chemical deposition method. The main composition of the Ca-P coating was brushite (CaHPO4·2H2O). The bonding strength between the coating and the JDBM substrate was measured to be over 10 MPa, and the thickness of the coating layer was about 10-30 μm. The in vitro corrosion tests indicated that the Ca-P treatment improved the corrosion resistance of JDBM alloy in Hanks solution. Ca-P treatment significantly reduced the hemolysis rate of JDBM alloy from 48% to 0.68%, and induced no toxicity to MC3T3-E1 cells. The in vivo implantation experiment in New Zealands rabbit tibia showed that the degradation rate was reduced obviously by the Ca-P treatment and less gas was produced from Ca-P treated JDBM bone plates and screws in early stage of the implantation, and at least 10weeks degradation time can be prolonged by the present coating techniques. Both Ca-P treated and untreated JDBM Mg alloy induced bone growth. The primary results indicate that the present Ca-P treatment is a promising technique for the degradable Mg-based biomaterials for orthopedic applications.

Enhancement of Osteogenesis and Biodegradation Control by Brushite Coating on Mg–Nd–Zn–Zr Alloy for Mandibular Bone Repair

To diminish incongruity between bone regeneration and biodegradation of implant magnesium alloy applied for mandibular bone repair, a brushite coating was deposited on a matrix of a Mg-Nd-Zn-Zr (hereafter, denoted as JDBM) alloy to control the degradation rate of the implant and enhance osteogenesis of the mandible bone. Both in vitro and in vivo evaluations were carried out in the present work. Viability and adhesion assays of rabbit bone marrow mesenchyal stem cells (rBM-MSCs) were applied to determine the biocompatibility of a brushite-coated JDBM alloy. Osteogenic gene expression was characterized by quantitative real-time polymerase chain reaction (RT-PCR). Brushite-coated JDBM screws were implanted into mandible bones of rabbits for 1, 4, and 7 months, respectively, using 316L stainless steel screws as a control group. In vivo biodegradation rate was determined by synchrotron radiation X-ray microtomography, and osteogenesis was observed and evaluated using Van Giesons picric acid-fuchsin. Both the naked JDBM and brushite-coated JDBM samples revealed adequate biosafety and biocompatibility as bone repair substitutes. In vitro results showed that brushite-coated JDBM considerably induced osteogenic differentiation of rBM-MSCs. And in vivo experiments indicated that brushite-coated JDBM screws presented advantages in osteoconductivity and osteogenesis of mandible bone of rabbits. Degradation rate was suppressed at a lower level at the initial stage of implantation when new bone tissue formed. Brushite, which can enhance oeteogenesis and partly control the degradation rate of an implant, is an appropriate coating for JDBM alloys used for mandibular repair. The Mg-Nd-Zn-Zr alloy with brushite coating possesses great potential for clinical applications for mandibular repair.

Research on a Zn-Cu alloy as a biodegradable material for potential vascular stents application

Zn-based alloys have been viewed as new potential materials for biodegradable implants, such as cardiovascular stents, mainly in consideration of their lower corrosion rate when compared with that of Mg alloys. In this study we developed a new Zinc-4wt.%Copper (Zn-4Cu) alloy as a biodegradable material. Hot extrusion was applied to Zn-4Cu to refine the microstructure and consequently improve its mechanical properties and corrosion resistance. After extrusion, dendritic CuZn5 phases were broken and distributed along the extrusion direction. The grains were refined obviously due to dynamical recrystallization. The yield strength (YS), ultimate tensile strength (UTS) and elongation of the as-extruded alloy are 250±10MPa, 270±10MPa and 51±2%, respectively. The corrosion rate of the as-extruded alloy in Hanks solution is about 9.41(±1.34)μmyear(-1). In vitro evaluation shows that Zn-4Cu presents acceptable toxicity to human endothelial cells, and could effectively inhibit bacteria adhesion and biofilm formation. The present study indicates that the as-extruded Zn-4Cu alloy exhibits excellent strength and ductility, uniform and slow degradation, good biocompatibility and significant antibacterial effect, which make it an excellent candidate material for biodegradable implants, especially for cardiovascular stents application.

In vivo degradation behavior and biocompatibility of Mg-Nd-Zn-Zr alloy at early stage

The neotype magnesium alloy, Mg-Nd-Zn-Zr (NZK) alloy, was implanted into the rabbit femur to investigate its in vivo degradation behavior and biocompatibility. Seventy-two New Zealand white rabbits were randomly divided into the NZK alloy group, titanium alloy group and sham-operated group. Then NZK alloy rods were embedded in the rabbit femur in the NZK alloy group, titanium alloy rods were embedded in the titanium alloy group, and only bone tunnel was established in the sham-operated group. Prior to surgery and at 1, 7, 14, 28 and 56 days after operation, the serum alanine transaminase, creatinine, creatine kinase and magnesium ion concentration were examined in each group. An X-ray of the implanted region was taken at 7, 14, 28 and 56 days after implantation. The pathological changes in heart, liver, kidney and bone from the implant region were examined at 28 and 56 days postoperatively. The degradation behavior of the NZK alloy was observed using scanning electron microscope with an energy dispersive spectroscopy system. There were no significant differences in serum alanine transaminase, creatinine, creatine kinase and magnesium ion concentrations among each group at the same time point (P>0.05). The histology of heart, liver, kidney and bone from implant region was altered. The results demonstrate that the NZK alloy implanted into the rabbit femur could be absorbed gradually, and that the NZK alloy has excellent biocompatibility in vivo.

The processing of Mg alloy micro-tubes for biodegradable vascular stents

In this study, through a combination of hot extrusion, cold rolling and drawing, three Mg alloys, Mg-Nd-Zn-Zr (abbr. JDBM), AZ31 and WE43, were successfully fabricated into the high-quality micro-tubes with 3.00mm outer diameter and 180μm thickness for biodegradable stents. This processing method overcame the shortcoming of the poor workability of Mg alloys and could be applied to fabricate sufficiently long tubes with low dimensional errors within 2.8%. Microstructure observation demonstrated that the as-annealed JDBM, AZ31 and WE43 micro-tubes had more uniformly distributed grains with an average size of 10.9μm, 12.9μm and 15.0μm, respectively. Tensile mechanical test results showed that the as-annealed JDBM, AZ31 and WE43 micro-tubes respectively exhibited the yield strength of 123MPa, 172MPa and 113MPa, and significantly different breaking elongation of 26%, 16% and 10%. The following SEM observation showed microvoid coalescence, quasi-cleavage and cleavage fracture, respectively. In addition, EBSD analyses revealed that the as-annealed AZ31 tubes had a strong texture component 21¯1¯0 with a low Schmid factor for basal slip, while JDBM and WE43 tubes respectively exhibited weak textures 101¯0 and 101¯0+202¯1 with a similarly high Schmid factor for basal slip.

Potential biodegradable Zn-Cu binary alloys developed for cardiovascular implant applications

Binary Zn-Cu alloy system is developed as potential biodegradable materials for cardiovascular implant application. The microstructure, tensile properties, in vitro corrosion behavior, cytotoxicity and antibacterial property of as-extruded Zn-xCu (x=1, 2, 3, and 4wt%) alloys are investigated systematically. It shows that as Cu content increases more CuZn5 phase precipitates. After extrusion, the CuZn5 phases are broken and the grains of Zn-xCu alloys are refined. Tensile test shows that Cu addition could significantly improve the mechanical properties of Zn-xCu alloys. Particularly, the elongation of the Zn-4Cu reaches 50.6±2.8%, which could facilitate the micro-tubes processing for stent fabrication. The micro-tubes of 3mm in outer diameter and 0.2mm in thickness as well as vascular stents have been fabricated successfully using the Zn-Cu binary alloy. The degradation rates of Zn-xCu alloys in c-SBF solution are quite low, which vary from 22.1±4.7 to 33.0±1.0μmyear-1. With increasing Cu concentration, the corrosion rates of the Zn-xCu alloys generally exhibit a little increase compared with pure Zn, which show no significant difference among Zn-xCu alloys. In vitro test shows that Zn-xCu alloys exhibit acceptable cytotoxicity to human endothelial cells and the antibacterial property (S. aureus) is perfect when Cu concentration is higher than 2wt%. Therefore, the newly developed Zn-xCu binary alloys could be promising candidates for biodegradable cardiovascular implant application due to their excellent combination of strength and ductility, low degradation rates, acceptable cytotoxicity and good antibacterial property.

Facile Preparation of Poly(lactic acid)/Brushite Bilayer Coating on Biodegradable Magnesium Alloys with Multiple Functionalities for Orthopedic Application

Recently magnesium and its alloys have been proposed as a promising next generation orthopedic implant material, whereas the poor corrosion behavior, potential cytotoxicity, and the lack of efficient drug delivery system have limited its further clinical application, especially for the local treatment of infections or musculoskeletal disorders and diseases. In this study, we designed and developed a multifunctional bilayer composite coating of poly(lactic acid)/brushite with high interfacial bonding strength on a Mg-Nd-Zn-Zr alloy, aiming to improve the biocorrosion resistance and biocompatibility of the magnesium-based substrate, as well as to further incorporate the biofunctionality of localized drug delivery. The composite coating consisted of an inner layer of poly(lactic acid) serving as a drug carrier and an outer layer composed of brushite generated through chemical solution deposition, where a facile pretreatment of UV irradiation was applied to the poly(lactic acid) coating to facilitate the heterogeneous nucleation of brushite. The in vitro degradation results of electrochemical measurements and immersion tests indicated a considerable reduction of magnesium degradation provided the composite coating. A systematic investigation of cellular response with cell viability, adhesion, and ALP assays confirmed the coated Mg alloy induced no toxicity to MC3T3-E1 osteoblastic cells but rather fostered cell attachment and proliferation and promoted osteogenic differentiation, revealing excellent biosafety and biocompatibility and enhanced osteoinductive potential. An in vitro drug release profile of paclitaxel from the composite coating was monitored with UV-vis spectroscopy, showing an alleviated initial burst release and a sustained and controlled release feature of the drug-loaded composite coating. These findings suggested that the bilayer poly(lactic acid)/brushite coating provided effective protection for Mg alloy, greatly enhanced cytocompatibility and bioactivity, and, moreover, possessed local drug delivery capability; hence magnesium alloy with poly(lactic acid)/brushite coating presents great potential in orthopedic clinical applications, especially for localized bone therapy.

Enhanced corrosion resistance and cytocompatibility of biodegradable Mg alloys by introduction of Mg(OH) 2 particles into poly (L-lactic acid) coating

A strategy of suppressing the fast degradation behaviour of Mg-based biomaterials by the introduction of one of Mg degradation products Mg(OH)2 was proposed according to the following degradation mechanism, Mg + 2H2O ⇋ Mg(OH)2 + H2↑. Specifically, Mg(OH)2 submicron particles were mixed into poly (L-lactic acid) (PLLA) to synthesize a composite coating onto hydrofluoric acid-pretreated Mg-Nd-Zn-Zr alloy. The in vitro degradation investigations showed that the addition of Mg(OH)2 particles not only slowed down the corrosion of Mg matrix, but also retarded the formation of gas pockets underneath the polymer coating. Correspondingly, cytocompatibility results exhibited significant improvement of proliferation of endothelial cells, and further insights was gained into the mechanisms how the introduction of Mg(OH)2 particles into PLLA coating affected the magnesium alloy degradation and cytocompatibility. The present study provided a promising surface modification strategy to tailor the degradation behaviour of Mg-based biomaterials.