GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> As a lightweight metal with mechanical properties similar to natural bone, a natural ionic presence with significant functional roles in biological systems, and in vivo degradation via corrosion in the electrolytic environment of the body, magnesium-based implants have the potential to serve as biocompatible, osteoconductive, degradable implants for load-bearing applications. This review explores the properties, biological performance, challenges and future directions of magnesium-based biomaterials. <s> BIB001 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> The in vivo corrosion of magnesium alloys might provide a new mechanism which would allow degradable metal implants to be applied in musculo-skeletal surgery. This would particularly be true if magnesium alloys with controlled in vivo corrosion rates could be developed. Since the magnesium corrosion process depends on its corrosive environment, the corrosion rates of magnesium alloys under standard in vitro environmental conditions were compared to corrosion rates in an in vivo animal model. Two gravity-cast magnesium alloys (AZ91D, LAE442) were used in these investigations. Standardized immersion and electrochemical tests according to ASTM norms were performed. The in vivo corrosion tests were carried out by intramedullar implantation of sample rods of the magnesium alloys in guinea pig femura. The reduction in implant volume was determined by synchrotron-radiation-based microtomography. We found that in vivo corrosion was about four orders of magnitude lower than in vitro corrosion of the tested alloys. Furthermore, the tendency of the corrosion rates obtained from in vitro corrosion tests were in the opposite direction as those obtained from the in vivo study. The results of this study suggest, that the conclusions drawn from current ASTM standard in vitro corrosion tests cannot be used to predict in vivo corrosion rates of magnesium alloys. <s> BIB002 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> The chemical and physical processes of magnesium in simulated body fluid (SBF) were investigated. The corrosion rate of magnesium was measured after 3, 5, 7, 14 and 21 days of immersion, respectively. It was found that the corrosion rate decreased with increasing immersion time, while the pH of SBF changed inversely. Network-like cracks and pits were the main damages resulting from corrosion, and the localized buildup of chloride ions was the major cause of pit formation. <s> BIB003 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Abstract The aim of this work was to collect and compare data from different published reports which focused on the description of the influence of different electrochemical setups for the assessment of magnesium corrosion. Based on this, a comparison with our own results, obtained for LAE 442 and AZ 31, was made and discussed. As the collection of data has shown, the reported inconsistencies between in vivo and electrochemical data depend greatly on the electrochemical medium used, on the alloy composition and on surface preparation. Nevertheless, these differences also exist when comparing different in vitro results using different methodologies and even different Mg alloys, and need therefore to be discussed more thoroughly in the future. The simulation of transport conditions of the in vivo interface should become a focus of research interest in order to gain a better understanding of the influence of connecting processes on the degradation of the biomaterials. <s> BIB004 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Magnesium alloy stent has been employed in animal and clinical experiment in recent years. It has been verified to be biocompatible and degradable due to corrosion after being implanted into blood vessel. Mg–Y–Gd–Nd alloy is usually used to construct an absorbable magnesium alloy stent. However, the corrosion resistant of as cast Mg–Y–Gd–Nd alloy is poor relatively and the control of corrosion rate is difficult. Aiming at the requirement of endovascular stent in clinic, a new biomedical Mg–Zn–Y–Nd alloy with low Zn and Y content (Zn/Y atom ratio 6) was designed, which exists quasicrystals to improve its corrosion resistance. Additionally, sub-rapid solidification processing was applied for preparation of corrosion-resisting Mg–Zn–Y–Nd and Mg–Y–Gd–Nd alloys. Compared with the as cast sample, the corrosion behavior of alloys in dynamic simulated body fluid (SBF) (the speed of body fluid: 16 ml/800 ml min−1) was investigated. The results show that as sub-rapid solidification Mg–Zn–Y–Nd alloy has the better corrosion resistance in dynamic SBF due to grain refinement and fine dispersion distribution of the quasicrystals and intermetallic compounds in α-Mg matrix. In the as cast sample, both Mg–Zn–Y–Nd and Mg–Y–Gd–Nd alloys exhibit poor corrosion resistance. Mg–Zn–Y–Nd alloy by sub-rapid solidification processing provides excellent corrosion resistance in dynamic SBF, which open a new window for biomedical materials design, especially for vascular stent application. <s> BIB005 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> The use of magnesium and its alloys as biodegradable metallic implant materials requires that their corrosion behavior can be controlled. We tailored the Mg release kinetics and cell adhesion properties of commercially pure Mg by chemical surface treatments in simulated body fluid, in Dulbecco's Modified Eagle's cell culture medium in the presence or absence of fetal bovine serum (FBS), or in 100% FBS. HeLa cells were cultured for 24 h on these Mg surfaces to characterize their biocompatibility. Cell density on all treated surfaces was significantly increased compared with a polished Mg surface, where almost no cells survived. This low biocompatibility of pure Mg was not caused by the high Mg ion release with concentrations of up to 300 mg/L in the cell culture medium after 24 h, as cells grown on a glass substrate showed no adverse reactions to high Mg ion concentrations. Rather, the most critical factor for cell adhesion was a sufficiently reduced initial dissolution rate of the surface. A comparison among all surface treatments showed that an incubation of the Mg samples in cell culture medium gave the lowest dissolution rate and resulted in the best cell adhesion and spreading behavior. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011. <s> BIB006 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Abstract Magnesium alloys have got extensive attention as biodegradable implant materials due to their biodegradability in the physiological environment and similar elastic modulus to natural bone. But their poor corrosion resistance is a dominant problem that limits their clinical application due to the inhomogeneous distribution of the second phase. Nevertheless, after high pressure torsion (HPT) treatment, the second phase became nano-sized particles and distributed uniformly in grain interiors instead of along grain boundaries. The immersion tests indicated that the HPT-treated sample exhibited homogeneous corrosion resulting from the uniform distribution of the second phase. The results of the potentiodynamic polarization experiments showed that, compared with the as-cast alloy, the corrosion current density of the HPT-treated alloy decreased from 5.3 × 10 − 4 A/cm 2 to 3.3 × 10 − 6 A/cm 2 . <s> BIB007 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Abstract The mechanical property and in particular the corrosion behavior of an Mg–Al–Mn–Ca alloy produced by spinning water atomization process (SWAP) were investigated and compared to those of the alloys made by gravity cast and hot extrusion. It is found that the SWAPed alloy has not only superior mechanical properties but also distinguished corrosion resistance. The corrosion resistance of the SWAPed alloy is about 2.5 and 10 times higher than that of the hot-extruded and as-cast alloys, respectively, when immersed in 0.1 M NaCl solution. Potentiodynamic polarization shows that both the anodic and cathodic current densities of the three alloys in 0.1 M NaCl solution are in the order of SWAPed alloy <s> BIB008 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Friction stir processing (FSP) was successfully adopted to fabricate nano-hydroxyapatite (nHA) reinforced AZ31 magnesium alloy composite as well as to achieve fine grain structure. The combined effect of grain refinement and the presence of embedded nHA particles on enhancing the biomineralization and controlling the degradation of magnesium were studied. Grain refinement from 56 to ~4 and 2 μm was observed at the stir zones of FSP AZ31 and AZ31–nHA composite respectively. The immersion studies in super saturated simulated body fluid (SBF 5×) for 24 h suggest that the increased wettability due to fine grain structure and nHA particles present in the AZ31–nHA composite initiated heterogeneous nucleation which favored the early nucleation and growth of calcium-phosphate mineral phase. The nHA particles as nucleation sites initiated rapid biomineralization in the composite. After 72 h of immersion the degradation due to localized pitting was observed to be reduced by enhanced biomineralization in both the FSPed AZ31 and the composite. Also, best corrosion behavior was observed for the composite before and after immersion test. MTT assay using rat skeletal muscle (L6) cells showed negligible toxicity for all the processed and unprocessed samples. However, cell adhesion was observed to be more on the composite due to the small grain size and incorporated nHA. <s> BIB009 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Abstract Biodegradable magnesium-based alloys are very promising materials for temporary implants. However, the clinical use of magnesium-based alloys is often limited by rapid corrosion and by insufficient mechanical stability. Here we investigated RS66, a magnesium-based alloy with extraordinary physicochemical properties of high tensile strength combined with a high ductility and a homogeneous grain size of ∼1 μm which was obtained by rapid solidification processing and reciprocal extrusion. Using a series of in vitro and in vivo experiments, we analyzed the biodegradation behavior and the biocompatibility of this alloy. In vitro, RS66 had no cytotoxic effects in physiological concentrations on the viability and the proliferation of primary human osteoblasts. In vivo, RS66 cylinders were implanted into femur condyles, under the skin and in the muscle of adult rabbits and were monitored for 1, 2, 3, 4 and 8 weeks. After explantation, the RS66 cylinders were first analyzed by microtomography to determine the remaining RS66 alloy and calculate the corrosion rates. Then, the implantation sites were examined histologically for healing processes and foreign body reactions. We found that RS66 was corroded fastest subcutaneously followed by intramuscular and bony implantation of the samples. No clinical harm with transient gas cavities during the first 6 weeks in subcutaneous and intramuscular implantation sites was observed. No gas cavities were formed around the implantation site in bone. The corrosion rates in the different anatomical locations correlated well with the local blood flow prior to implantation. A normal foreign body reaction occurred in all tissues. Interestingly, no enhanced bone formation could be observed around the corroding samples in the condyles. These data show that RS66 is biocompatible, and due to its interesting physicochemical properties, this magnesium alloy is a promising material for biodegradable implants. <s> BIB010 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Abstract Recently, magnesium (Mg) alloys have received significant attention as potential biomaterials for degradable implants, and this study was directed at evaluating the suitability of Mg for craniofacial bone screws. The objective was to implant screws fabricated from commercially available pure Mg and alloy AZ31 in vivo in a rabbit mandible. First, Mg and AZ31 screws were compared to stainless steel screws in an in vitro pull-out test and determined to have a similar holding strength (∼40 N). A finite-element model of the screw was created using the pull-out test data, and this model can be used for future Mg alloy screw design. Then, Mg and AZ31 screws were implanted for 4, 8 and 12 weeks, with two controls of an osteotomy site (hole) with no implant and a stainless steel screw implanted for 12 weeks. Microcomputed tomography was used to assess bone remodeling and Mg/AZ31 degradation, both visually and qualitatively through volume fraction measurements for all time points. Histological analysis was also completed for the Mg and AZ31 at 12 weeks. The results showed that craniofacial bone remodeling occurred around both Mg and AZ31 screws. Pure Mg had a different degradation profile than AZ31; however, bone growth occurred around both screw types. The degradation rate of both Mg and AZ31 screws in the bone marrow space and the muscle were faster than in the cortical bone space at 12 weeks. Furthermore, it was shown that by alloying Mg, the degradation profile could be changed. These results indicate the promise of using Mg alloys for craniofacial applications. <s> BIB011 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Abstract In order to select a good cost-performance ratio magnesium alloy as anode material, the electrochemical properties of AZ31B magnesium alloy under different processing conditions were investigated by electrochemical workstation, optical microscope (OM), scanning electron microscopy (SEM) and energy dispersed spectroscopy (EDS). Extruded, rolled, cast-rolled and as-cast AZ31 magnesium alloys were prepared as the anode materials. The results show that under different processing conditions, the extruded alloy is the best cost-performance ratio anode material among the four alloys. It possesses the most negative equilibrium potential, the lowest corrosion current density and the smallest free corrosion rate indicating the highest electrochemical activity due to the uniform fine grains and the second phase. Its corrosiun products are loose, dispersing uniformly on the extruded anode surface, prone to falling off which decrease the polarization and increase the utilization of the anode. The electrochemical activity and the corrosion resistance of the rolled and the cast-rolled alloys are relatively low, compared with the extrude samples. Due to the coarse grains, as-cast defects and coarse second phase distributed along the grain boundaries, the as-cast alloy has unstable discharge curve and positive discharge potential. The corrosions of AZ31 magnesium alloy under different conditions are almost pitting corrosion. <s> BIB012 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Magnesium is a biodegradable metal that has significant potential advantages as an implant material. However, the fast degradation rate in the biological environment has limits the application. In this article, corrosion behaviors of as-cast and hot rolled pure magnesium in 0.9% NaCl, Ringer’s, and Tas-SBF solutions were studied. Potentiodynamic polarization and hydrogen evolution test were employed to assess the corrosion behaviors. The magnesium specimens were characterized using field emission scanning electron microscopy equipped with energy-dispersive X-ray analysis and X-ray diffraction. The as-cast specimens in 0.9% NaCl and Ringer’s solutions had lower corrosion potentials and corrosion rates than the hot rolled specimens. However, the as-cast specimen in the Tas-SBF solution had a higher corrosion potential and a lower corrosion rate than the hot rolled specimen. Only the specimens in the Tas-SBF solution showed passivation behavior due to the presence of HCO3 − ions. The hot rolled specimen could form apatite more easily on its surface than the as-cast specimen in Tas-SBF. <s> BIB013 </s> GRAIN REFINEMENT TECHNIQUES TO REDUCE BIODEGRADATION RATE OF MAGNESIUM ALLOY AS A POTENTIAL BIODEGRADABLE IMPLANT MATERIAL: A REVIEW <s> INTRODUCTION <s> Abstract Each year, millions of Americans suffer bone fractures, often requiring internal fixation. Current devices, like plates and screws, are made with permanent metals or resorbable polymers. Permanent metals provide strength and biocompatibility, but cause long-term complications and may require removal. Resorbable polymers reduce long-term complications, but are unsuitable for many load-bearing applications. To mitigate complications, degradable magnesium (Mg) alloys are being developed for craniofacial and orthopedic applications. Their combination of strength and degradation make them ideal for bone fixation. Previously, we conducted a pilot study comparing Mg and titanium devices with a rabbit ulna fracture model. We observed Mg device degradation, with uninhibited healing. Interestingly, we observed bone formation around degrading Mg, but not titanium, devices. These results highlighted the potential for these fixation devices. To better assess their efficacy, we conducted a more thorough study assessing 99.9% Mg devices in a similar rabbit ulna fracture model. Device degradation, fracture healing, and bone formation were evaluated using microcomputed tomography, histology and biomechanical tests. We observed device degradation throughout, and calculated a corrosion rate of 0.40 ± 0.04 mm/year after 8 weeks. In addition, we observed fracture healing by 8 weeks, and maturation after 16 weeks. In accordance with our pilot study, we observed bone formation surrounding Mg devices, with complete overgrowth by 16 weeks. Bend tests revealed no difference in flexural load of healed ulnae with Mg devices compared to intact ulnae. These data suggest that Mg devices provide stabilization to facilitate healing, while degrading and stimulating new bone formation. <s> BIB014
Today, more than 200 years after the first production of metallic magnesium by Sir Humphry Davy in 1808, as a lightweight metal with mechanical properties similar to natural bone, magnesium-based materials as potential candidates for degradable temporary implants have been gaining wide popularity  BIB001 . The dominant reason is because of their mechanical properties which are close to that of natural bone compared to other metals, their good biocompatibility, nontoxicity and biodegradability BIB001  BIB011 BIB014  . Many new magnesium alloys and composites have been produced and evaluated for biomaterial applications BIB004 , Hermawan, Sunil et al., 2014a BIB009  BIB006 . However, the applications are seriously limited due to the excessively rapid degradation rate in the physiological environment BIB001 BIB004 BIB006 BIB002 BIB003 BIB012 BIB013 BIB007 BIB005 . Furthermore, rapid solidification is another effective way to refine the microstructures of Mg alloys BIB005 BIB010 BIB008 . Since the late 1930s, a number of approaches have been developed to obtain grain refinement in magnesium alloys that contain aluminum. These are briefly summarized as hot plastic deformation and rapid solidification. Hot plastic deformation is a useful method to refine grains and obtain a homogeneous microstructure. A fine microstructure can often be achieved by common deformation, such as single extrusion (SE) and rolling BIB012 BIB013 . Moreover, when BIB007 studied the corrosion behavior of the Mg-Zn-Ca alloy in SBF using an HPT process, they found that the second phase has been refined to nano-sized particles and distributed homogeneously in the interior of α-Mg grains. As a result, the alloy shows a uniform corrosion mode, indicating that severe plastic deformation is also useful for improving the corrosion mode of Mg alloys. Rapid solidification has been shown to refine the microstructure of Mg alloys due to the increased solidification rate BIB005 BIB010 . The corrosion resistance is also enhanced by rapid solidification because of grain refinement and fine dispersion of the quasi-crystals and intermetallic compounds in the α-Mg matrix. BIB008 