In vitro degradation,hemolysis and MC3T3-E1 cell adhesion of biodegradable Mg–Zn alloy

In this study a kind of patent binary Mg–6 wt.%Zn magnesium alloy was investigated as degradable biomedical material. The results of in vitro degradation including electrochemical measurements and immersion tests in simulated body fluid (SBF) revealed that zinc could elevate both the corrosion potential and Faraday charge transfer resistance of magnesium and thus improve the corrosion resistance. XRD and EDS analysis proved that the corrosion products on the surface of Mg–Zn contained hydroxyapatite (HA), Mg(OH)₂ and other Mg/Ca phosphates, which could reduce the degradation rate. The degradation process of magnesium alloy and the mechanism of corrosion layer formation were also discussed in this work, i.e. the byproducts of degradation of magnesium, Mg²⁺ and OH^?, reacted with the phosphate and Ca²⁺ in the SBF, thus the corrosion layer containing HA, Mg(OH)₂ and other magnesium-substituted apatite precipitated in corrosion pits and covered the surface of magnesium alloy.The hemolysis test found that the hemolysis rate of Mg–Zn was 3.4%, which is lower than the safe value of 5% according to ISO 10993-4. For the cell culture experiments, after 2 h incubation the pre-osteoblastic cell MC3T3-E1 was able to adhere and spread on the corrosion layer of Mg–Zn alloy, indicating that despite the fluctuation of pH value of DMEM culture solution, Mg–Zn alloy could still support the earlier adhesion of pre-osteoblastic cells on the surface. Hemolysis and adhesion of cells display good biocompatibility of Mg–Zn alloy in vitro.     

Nd-induced honeycomb structure of intermetallic phase enhances the corrosion resistance of Mg alloys for bone implants

Mg-5.6Zn-0.5Zr alloy (ZK60) tends to degrade too rapid for orthopedic application, in spite of its natural degradation, suitable strength and good biocompatibility. In this study, Nd was alloyed with ZK60 via laser melting method to enhance its corrosion resistance. The microstructure features, mechanical properties and corrosion behaviors of ZK60-xNd (x?=?0, 1.8, 3.6, 5.4 wt.%) were investigated. Results showed that laser melted ZK60-xNd were composed of fine ɑ-Mg grains and intermetallic phases along grain boundaries. And the precipitated intermetallic phases experienced successive changes: divorced island-like MgZn phase?→?honeycomb-like T phase?→?coarsened and agglomerated W phase with Nd increasing. It was worth noting that ZK60-3.6Nd with honeycomb-like T phase exhibited an optimal corrosion behavior with a corrosion rate of 1.56?mm?year^?1. The improved corrosion behavior was ascribed to: (I) dense surface film caused by the formation of Nd₂O₃ hindered the invasion of immersion solution; (II) the three-dimensional honeycomb structure of intermetallic phases formed a tight barrier to restrain the propagation of corrosion. Moreover, ZK60-3.6Nd exhibited good biocompatibility. It was suggested that ZK60-3.6Nd was a preferable candidate for biodegradable bone implant.     

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 Hank's 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 Zealand's 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 10 weeks 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.     

Surface Engineering of Biodegradable Magnesium Alloys for Enhanced Orthopedic Implants

Magnesium (Mg) alloys have been promised for biomedical implants in orthopedic field, however, the fast corrosion rate and mode challenge their clinical application. To push Mg alloys materials into practice, a composite coating with biodegradable and high compatible components to improve anticorrosion property of an Mg alloy (i.e., AZ31) is designed and fabricated. The inner layer is micro‐nano structured Mg(OH)₂ through hydrothermal treatment. Then stearic acid (SA) is introduced to modify Mg(OH)₂ for better reducing the gap below a surface‐degradation polymer layer of poly(1,3‐trimethylene carbonate). Benefited by the SA modification effect, this sandwiched coating avoids corrosive medium penetration via enhancing the adhesion strength at the interface between outer and inner layers. Both in vitro and in vivo tests indicate that the composite coating modified AZ31 perform a better anticorrosion behavior and biocompatibility compared to bare AZ31. Strikingly, a 1.7‐fold improvement in volume of newly formed bone is observed surrounding the composite coating modified implant after 12 week implantation. The sandwiched biocompatible coating strategy paves a hopeful way for future translational application of Mg alloys orthopedic materials in clinics.     

Bio-corrosion characterization of Mg–Zn–X (X = Ca, Mn, Si) alloys for biomedical applications

The successful applications of magnesium-based alloys as biodegradable orthopedic implants are mainly inhibited due to their high degradation rates in physiological environment. This study examines the bio-corrosion behaviour of Mg–2Zn–0.2X (X = Ca, Mn, Si) alloys in Ringer’s physiological solution that simulates bodily fluids, and compares it with that of AZ91 magnesium alloy. Potentiodynamic polarization and electrochemical impedance spectroscopy results showed a better corrosion behaviour of AZ91 alloy with respect to Mg–2Zn–0.2Ca and Mg–2Zn–0.2Si alloys. On the contrary, enhanced corrosion resistance was observed for Mg–2Zn–0.2Mn alloy compared to the AZ91 one: Mg–2Zn–0.2Mn alloy exhibited a four-fold increase in the polarization resistance than AZ91 alloy after 168 h exposure to the Ringer’s physiological solution. The improved corrosion behaviour of the Mg–2Zn–0.2Mn alloy with respect to the AZ91 one can be ascribed to enhanced protective properties of the Mg(OH)₂ surface layer. The present study suggests the Mg–2Zn–0.2Mn alloy as a promising candidate for its applications in degradable orthopedic implants, and is worthwhile to further investigate the in vivo corrosion behaviour as well as assessed the mechanical properties of this alloy.     

Design and characterizations of novel biodegradable ternary Zn-based alloys with IIA nutrient alloying elements Mg,Ca and Sr

Apart from the industrial and automotive applications, Zn and Zn-based alloys are considered as a new kind of potential biodegradable material quite recently. However, one drawback of pure Zn as potential biodegradable metal lies in that pure Zn has quite low strength and plasticity. In the present study, three important IIA essential nutrient elements Mg, Ca and Sr and hot-rolling and hot-extrusion thermal deformations have been applied to overcome the drawback of pure Zn and benefit the biocompatibility of Zn-based potential implants. The microstructure, mechanical properties, corrosion behavior, hemocompatibility, in vitro cytocompatibility were studied systematically to investigate their feasibility as bioabsorbable implants. The results showed that the mechanical properties of the ternary Zn–1Mg–1Ca, Zn–1Mg–1Sr and Zn–1Ca–1Sr alloys are much higher than that of pure Zn, owing to both the alloying effects and thermal deformation effects. In vitro hemolytic rate test and cell viability test indicated that the addition of the IIA nutrient alloying elements Mg, Ca and Sr into Zn can benefit their hemocompatibility and cytocompatibility, which would further guarantee the biosafety of these new kind of biodegradable Zn-based implants for future clinical applications.     

Characterisation and thermodynamic calculations of biodegradable Mg–2.2Zn–3.7Ce and Mg–Ca–2.2Zn–3.7Ce alloys

In the present study, the effect of Ca (0.5–6?wt-%) content on the microstructure, phase formation, and mechanical properties and in vitro degradation behaviour of Mg–2.2Zn–3.7Ce alloys were investigated. Microstructural analysis and thermodynamic calculations also showed that Mg–2.2Zn–3.7Ce alloy contain α-Mg, Mg₁₂Ce and CeMgZn₂, while after adding 0.5?wt-% Ca to Mg–2.2Zn–3.7Ce alloy, IM1 (Ca₃Mg_xZn_15?x) (4.6?≤?x?≤?12) phase was detected. Further addition of Ca to 6?wt-% resulted in forming Mg₂Ca besides α-Mg, Mg₁₂Ce and IM1 with the absence of CeMgZn₂. The tensile strength and elongation of the Mg–Ca–2.2Zn–3.7Ce alloys increase with increasing Ca content up to 1.5?wt-%, while further addition of Ca to 6?wt-% has a reversed effect. Similarly, the degradation rate of the alloys increased first with increasing Ca content and then decreased.     

Microstructures,mechanical and cytocompatibility of degradable Mg–Zn based orthopedic biomaterials

The Mg–1Zn–xSr (x = 0.2, 0.5, 0.8 and 1 wt.%) alloys have been prepared by zone purifying solidification followed by backward extrusion (BE). The grain size was reduced and the hardness was improved with the increased concentration of strontium (Sr) after backward extrusion. The BE–Mg–1Zn–0.8Sr alloy was mostly composed of fine precipitates (MgZn and Mg₁₇Sr₂) and Mg matrix. At the same time, the mechanical properties of BE–Mg–Zn–Sr alloys were increased with the increment of strontium, which were strongly associated with fine average grain size and homogeneous secondary precipitates. The degradation rate is significantly increased when Sr content is over 0.8 wt.%. The homogenous degradation rate is achieved. The degradation products show good biocompatibility evaluated by MTT method using L929 cell line. It is demonstrated that the micro-alloying element of Sr is a potential approach to develop novel Mg–Zn based biomaterials.     

Mechanical and bio-corrosion properties of quaternary Mg–Ca–Mn–Zn alloys compared with binary Mg–Ca alloys

Binary Mg–xCa alloys and the quaternary Mg–Ca–Mn–xZn were studied to investigate their bio-corrosion and mechanical properties. The surface morphology of specimens was characterized by X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The results of mechanical properties show that the yield strength (YS), ultimate tensile strength (UTS) and elongation of quaternary alloy increased significantly with the addition of zinc (Zn) up to 4 wt.%. However, further addition of Zn content beyond 4 wt.% did not improve yield strength and ultimate tensile strength. In contrast, increasing calcium (Ca) content has a deleterious effect on binary Mg–Ca alloys. Compression tests of the magnesium (Mg) alloys revealed that the compression strength of quaternary alloy was higher than that of binary alloy. However, binary Mg–Ca alloy showed higher reduction in compression strength after immersion in simulated body fluid. The bio-corrosion behaviour of the binary and quaternary Mg alloys were investigated using immersion tests and electrochemical tests. Electrochemical tests shows that the corrosion potential (E_corr) of binary Mg–2Ca significantly shifted toward nobeler direction from −1996.8 to −1616.6 mV_SCE with the addition of 0.5 wt.% manganese (Mn) and 2 wt.% Zn content. However, further addition of Zn to 7 wt.% into quaternary alloy has the reverse effect. Immersion tests show that the quaternary alloy accompanied by two secondary phases presented higher corrosion resistance compared to binary alloys with single secondary phase. The degradation behaviour demonstrates that Mg–2Ca–0.5Mn–2Zn alloy had the lowest degradation rate among quaternary alloys. In contrast, the binary Mg–2Ca alloy demonstrated higher corrosion rates, with Mg–4Ca alloy having the highest rating. Our analysis showed the Mg–2Ca–0.5Mn–2Zn alloy with suitable mechanical properties and excellent corrosion resistance can be used as biodegradable implants.     

The influence of HF treatment on corrosion resistance and <Emphasis Type="Italic">in vitro</Emphasis> biocompatibility of Mg-Zn-Zr alloy

The samples made of a Mg-2.5wt.%Zn-0.5wt.%Zr alloy were immersed in the 20% hydrofluoric acid (HF) solution at room temperature for different time, with the aim of improving the properties of magnesium (Mg) alloy in applications as biomaterials. The corrosion resistance and in vitro biocompatibility of untreated and fluoride-coated samples were investigated. The results show that the optimum process is to immerse Mg alloys in the 20% HF solution for 6 h. After the immersion, a dense magnesium fluoride (MgF₂) coating of 0.5 μm was synthesized on the surface of Mg-Zn-Zr alloy. Polarization tests recorded a reduction in the corrosion current density from 2.10 to 0.05 μA/cm² due to the MgF₂ protective coating. Immersion tests in the simulated body fluid (SBF) also reveal a much milder corrosion on the fluoride-coated samples, and its corrosion rate was calculated to be 0.05 mm/yr. Hemolysis test suggests that the conversion coated Mg alloy has no obvious hemolysis reaction. The hemolysis ratio (HR) of the samples decreases from 11.34% to 1.86% with the HF treatment, which meets the requirements of biomaterials (HR < 5%). The coculture of 3T3 fibroblasts with Mg alloy results in the adhesion and proliferation of cells on the surface of fluoride-coated samples. All the results show that the MgF₂ conversion coating would markedly improve the corrosion resistance and in vitro biocompatibility of Mg-Zn-Zr alloy.     

The influence of HF treatment on corrosion resistance and in vitro biocompatibility of Mg-Zn-Zr alloy

The samples made of a Mg-2.5wt.%Zn-0.5wt.%Zr alloy were immersed in the 20% hydrofluoric acid (HF) solution at room temperature for different time, with the aim of improving the properties of magnesium (Mg) alloy in applications as biomaterials. The corrosion resistance and in vitro biocompatibility of untreated and fluoride-coated samples were investigated. The results show that the optimum process is to immerse Mg alloys in the 20% HF solution for 6 h. After the immersion, a dense magnesium fluoride (MgF₂) coating of 0.5 μm was synthesized on the surface of Mg-Zn-Zr alloy. Polarization tests recorded a reduction in the corrosion current density from 2.10 to 0.05 μA/cm² due to the MgF₂ protective coating. Immersion tests in the simulated body fluid (SBF) also reveal a much milder corrosion on the fluoride-coated samples, and its corrosion rate was calculated to be 0.05 mm/yr. Hemolysis test suggests that the conversion coated Mg alloy has no obvious hemolysis reaction. The hemolysis ratio (HR) of the samples decreases from 11.34% to 1.86% with the HF treatment, which meets the requirements of biomaterials (HR < 5%). The coculture of 3T3 fibroblasts with Mg alloy results in the adhesion and proliferation of cells on the surface of fluoride-coated samples. All the results show that the MgF₂ conversion coating would markedly improve the corrosion resistance and in vitro biocompatibility of Mg-Zn-Zr alloy.     

Effects of Ca on microstructure, mechanical and corrosion properties and biocompatibility of Mg–Zn–Ca alloys

Zn and Ca were selected as alloying elements to develop an Mg–Zn–Ca alloy system for biomedical application due to their good biocompatibility. The effects of Ca on the microstructure, mechanical and corrosion properties as well as the biocompatibility of the as-cast Mg–Zn–Ca alloys were studied. Results indicate that the microstructure of Mg–Zn–Ca alloys typically consists of primary α-Mg matrix and Ca₂Mg₆Zn₃/Mg₂Ca intermetallic phase mainly distributed along grain boundary. The yield strength of Mg–Zn–Ca alloy increased slightly with the increase of Ca content, whilst its tensile strength increased at first and then decreased. Corrosion tests in the simulated body fluid revealed that the addition of Ca is detrimental to corrosion resistance due to the micro-galvanic corrosion acceleration. In vitro hemolysis and cytotoxicity assessment disclose that Mg–5Zn–1.0Ca alloy has suitable biocompatibility.     

Effect of minor content of Gd on the mechanical and degradable properties of as-cast Mg-2Zn-xGd-0.5Zr alloys

RE-containing Mg alloys used as biodegradable medical implants exhibit good promising application due to their good mechanical properties and degradation resistance. In this work, effect of Gd on the microstructure, mechanical properties and biodegradation of as-cast Mg-2Zn-xGd-0.5Zr alloys was investigated. The results showed that there were mainly α-Mg, I-phase, W-phase and MgZn2 phase in Mg-Zn-Gd-Zr alloys. With increase of the Gd content, the strength of the alloys was enhanced due to the second phase strengthening and grain refinement. The degradation resistance of Mg-2Zn-0.5Zr alloy was increased by adding 0.5%–1% Gd due to the uniformly distributed second phases which acted as a barrier to prevent the pitting corrosion. However, increasing Gd content to 2% reduced the degradation resistance of the alloy due to the galvanic corrosion between the matrix and the second phases.The good degradation resistance and mechanical properties of as-cast Mg-2Zn-1Gd-0.5Zr alloy makes it outstanding for biomaterial application.     

Nano-SiC reinforced Zn biocomposites prepared via laser melting:Microstructure,mechanical properties and biodegradability

Zn has been regarded as new kind of potential implant biomaterials due to the desirable biodegradability and good biocompatibility,but the low strength and ductility limit its application in bone repairs.In the present study,nano-SiC was incorporated into Zn matrix via laser melting,aiming to improve the mechanical performance.The microstructure analysis showed that nano-SiC distributed along Zn grain boundaries.During the laser rapid solidification,nano-SiC particles acted as the sites for heterogeneous nucleation,which resulted in the reduction of Zn grain size from 250 μm to 15 μm with 2 wt%SiC(Zn-2 SiC).Meanwhile,nano-SiC acted as a reinforcer by virtue of Orowan strengthening and dispersion strengthening.As a consequence,the nanocomposites showed maximal compressive yield strength(121.8±5.3 MPa) and high microhardness(72.24±3.01 HV),which were increased by 441% and 78%,respectively,compared with pure Zn.Moreover,fracture analysis indicated a more ductile fracture of the nanocomposites after the incorporation of nano-SiC In addition,the nanocomposites presented favorable biocompatibility and accelerated degradation caused by intergranular corrosion.These findings suggested that the nano-SiC reinforced Zn biocomposites may be the potential candidates for orthopedic implants.     

Preliminary study of biodegradation of AZ31B magnesium alloy

Magnesium alloys are potential to be developed as a new type of biodegradable implant material by use of their active corrosion behavior. Both in vitro and in vivo biodegradation properties of an AZ31B magnesium alloy were investigated in this work. The results showed that AZ31B alloy has a proper degradation rate and much lower hydrogen release in Hank’s solution, with a degradation rate of about 0.3 mm/year and hydrogen release below 0.15 mL/cm². The animal implantation test showed that the AZ31B alloy could slowly biodegrade in femur of the rabbit and form calcium phosphate around the alloy sample, with the Ca/P ratio close to the natural bone.     

Challenges and Solutions for the Additive Manufacturing of Biodegradable Magnesium Implants

Due to their capability of fabricating geometrically complex structures, additive manufacturing (AM) techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys, which exhibit appropriate mechanical properties and outstanding biocompatibility. However, many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants, such as the difficulty of Mg powder preparation, powder splash, and crack formation during the AM process. In the present work, the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed. A novel Mg-based alloy (Mg–Nd–Zn–Zr alloy, JDBM) powder with a smooth surface and good roundness was first synthesized successfully, and the AM parameters for Mg-based alloys were optimized. Based on the optimized parameters, porous JDBM scaffolds with three different architectures (biomimetic, diamond, and gyroid) were then fabricated by selective laser melting (SLM), and their mechanical properties and degradation behavior were evaluated. Finally, the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate (DCPD) coating treatment, which greatly suppressed the degradation rate and increased the cytocompatibility, indicating a promising prospect for clinical application as bone tissue engineering scaffolds.     

Microstructure,Mechanical Properties and In Vitro Degradation Behavior of a Novel Biodegradable Mg-1.5Zn-0.6Zr-0.2Sc Alloy

A novel Mg-l.5Zn-0.6Zr-0.2Sc(denoted as ZK21-0.2Sc) alloy was developed as potential biodegradable implant materials.The microstmcture,mechanical properties,and in vitro degradation behavior of the as-cast ZK21-0.2Sc alloy were investigated and compared with ZK21 alloy and pure Mg.The ZK21-0.2Sc alloy showed a single-phase structure with fine equiaxed grains.The alloy exhibited a good balance between strength and ductility.Both immersion tests and electrochemical tests showed that the ZK21-0.2Sc alloy had the lowest degradation rate in Hank's solution.The excellent degradation behavior of ZK21-0.2Sc alloy could be explained by the single-phase and fine grain structure,the more effective protection corrosion film,and the beneficial alloying effects of Zn,Zr and Sc.     

Effects of scandium addition on the in vitro degradation behavior of biodegradable Mg–1.5Zn–0.6Zr alloy

Heretofore, recognitions of the systematic effects of scandium addition on corrosion behavior of biodegradable magnesium alloys are not yet clear. In the present study, a series of Mg–1.5Zn–0.6Zr–xSc (ZK21–xSc, x?=?0, 0.2, 0.5, 1.0 wt.%) alloys were casted and investigated with respect to the immersion and electrochemical degradation behavior. The hydrogen evolution, pH monitoring, ion release and mass loss results demonstrated that ZK21–0.2Sc alloy exhibited the lowest corrosion rate. The surface morphology analyses displayed that an obvious uniform corrosion occurred in ZK21–xSc alloys with Sc content below 0.5, while localized corrosion occurred in ZK21–1.0Sc alloy. Corrosion potentials of ZK21–xSc alloys shifted toward more positive with the increasing Sc content. But ZK21–0.2Sc alloy exhibited the lowest corrosion current density and the largest corrosion film resistance. Compared with other developed Mg alloys, the ZK21–0.2Sc alloy demonstrated a superior degradation behavior.     

Material processing of hydroxyapatite and titanium alloy (HA/Ti) composite as implant materials using powder metallurgy: A review

The bio-active and biodegradable properties of hydroxyapatite (HA) make this material a preferred candidate for implants such as bone replacement in replacing natural tissues damaged by diseases and accidents. However, the low mechanical strength of HA hinders its application. Combining HA with a biocompatible material with a higher mechanical strength, such as a titanium (Ti) alloy, to form a composite has been of interest to researchers. A HA/Ti composite would possess characteristics essential to modern implant materials, such as bio-inertness, a low Young’s modulus, and high biocompatibility. However, there are issues in the material processing, such as the rheological behavior, stress-shielding, diffusion mechanism and compatibility between the two phases. This paper reviews the HA and Ti alloy interactions under various conditions, in vitro and in vivo tests for HA/Ti composites, and common powder metallurgy processes for HA/Ti composites (e.g., pressing and sintering, isostatic pressing, plasma spraying, and metal injection molding).     

Thermal characteristics and corrosion behaviour of Mg–xZn alloys for biomedical applications

The thermal parameters of Mg–xZn cast alloys with 0·5–9 wt% Zn were evaluated by using computer aided cooling curve thermal analysis (CA–CCTA), whereas the corrosion behaviour was investigated by potentiodynamic polarization and immersion tests. Thermal analysis results revealed that the dendrite coherency temperature (T _DCP ) decreased from 642·2 to 600 °C with the addition of Zn from 0·5 to 9 wt%. The liquid fraction at coherency point ( ${f}_{ L}^{ DCP}$ ) increased by 72% when Zn was increased up to 9 wt%. MgZn intermetallic phase was observed in samples with <3 wt% Zn. At higher percentages of Zn, the Mg ₅₁Zn ₂₀ intermetallic phase was also detected in addition to α-Mg and MgZn by first derivative cooling curves under non-equilibrium solidification. All these phases were observed along the grain boundary when Zn was rejected from the solid/liquid interface and enriched in the triple conjunction of grain boundary. The grain size decreased from 185·2 to 71·5 μm when Zn content was increased. The addition of Zn content had a significant effect on the corrosion rate and the corresponding mechanisms. The corrosion rate decreased from 2·1 to 1·81 mmpy as Zn content increased from 0·5 to 3 wt%; afterwards, however, this value increased with further increase of Zn. Mg–3Zn also had the lowest degradation rate and highest corrosion resistance which can be fully utilized for biodegradable orthopedic applications.