The Microstructural Evolution and Corrosion Behavior of Zn-Mg Alloys and Hybrids Processed Using High-Pressure Torsion.

Zinc (Zn) alloys, particularly those incorporating magnesium (Mg), have been explored as potential bioabsorbable metals. However, there is a continued need to enhance the corrosion characteristics of Zn-Mg alloys to fulfill the requirements for biodegradable implants. This work involves a corrosion behavior comparison between severe-plastic-deformation (SPD) processed cast Zn-Mg alloys and their hybrid counterparts, having equivalent nominal compositions. The SPD processing technique used was high-pressure torsion (HPT), and the corrosion behavior was studied as a function of the number of turns (1, 5, 15) for the Zn-3Mg (wt.%) alloy and hybrid and as a function of composition (Mg contents of 3, 10, 30 wt.%) for the hybrid after 15 turns. The results indicated that HPT led to multimodal grain size distributions of ultrafine Mg-rich grains containing MgZn2 and Mg2Zn11 nanoscale intermetallics in a matrix of coarser dislocation-free Zn-rich grains. A greater number of turns resulted in greater corrosion resistance because of the formation of the intermetallic phases. The HPT hybrid was more corrosion resistant than its alloy counterpart because it tended to form the intermetallics more readily than the alloy due to the inhomogeneous conditions of the materials before the HPT processing as well as the non-equilibrium conditions imposed during the HPT processing. The HPT hybrids with greater Mg contents were less corrosion resistant because the addition of Mg led to less noble behavior.

Immobilization of blood coagulant factor VII on polycaprolactone membrane through polydopamine grafting.

Postoperative bleeding following cardiac surgeries is still an issue that deranges the medical resources and cost. The oral and injection administrations of blood coagulation protein, Factor VII (FVII), is effective to stop the bleeding. However, its short half-life has limited the effectiveness of this treatment and frequent FVII intake may distress the patients. Instead, incorporating FVII into synthetic biodegradable polymers such as polycaprolactone (PCL) that is commonly used in drug delivery applications should provide a solution. Therefore, this study aimed to immobilize FVII on PCL membranes through a cross-linkage polydopamine (PDA) grafting as an intermediate layer. These membranes are intended to provide a solution for cardiac bleeding in coagulating blood and sealing the sutured region. The membranes were evaluated in terms of its physio-chemical properties, thermal behavior, FVII release profile and biocompatibility properties. The ATR-FTIR was used to analyze the chemical functionalities of the membranes. Further validation was done with XPS where the appearances of 0.45 ± 0.06% sulfur composition and C-S peak have confirmed the immobilization of FVII on the PCL membranes. The cross-linked FVIIs were viewed in spherical immobilization on the PCL membranes with a size range between 30 and 210 nm. The surface roughness and hydrophilicity of the membranes were enhanced with a slight shift of melting temperature. The PCL-PDA-FVII0.03 and PCL-PDA-FVII0.05 membranes, with wide area of FVII immobilization released approximately only 22% of FVII into the solution within 60 days period and, it is found that the PCL-PDA-FVIIx membranes projected the Higuchi release model with non-Fickian anomalous transport. While the cytotoxic and hemocompatibility analyses showed advance cell viability, identical coagulation time and low hemolysis ratio on the PCL-PDA-FVIIx membranes. The erythrocytes were viewed in polyhedrocyte coagulated structure under SEM visualization. These results validate the biocompatibility of the membranes and its ability to prolong blood coagulation, thus highlighting its potential application as cardiac bleeding sealant.

Processing and properties optimisation of carbon nanofibre-reinforced magnesium composites for biomedical applications.

In the last decade, magnesium alloys have been considered as absorbable metals for biomedical applications, while some have reached their clinical use as temporary bone implants. However, their widespread use is still limited by its strength and degradability. One way of improvement can be done by reinforcing magnesium alloys with carbon nanofibres to form composites. This work aims at developing carbon nanofibre-reinforced magnesium-zinc (Mg-Zn/CNF) composites with optimum strength and degradability while ensuring their biocompatibility. A response surface method was used to determine their optimum process parameters (composition, compaction pressure, and sintering temperature), and analyse the resulting properties (elastic modulus, hardness, weight loss, and cytocompatibility). Results showed that the optimal parameters were reached at 1.8% of CNF, 425 MPa of compaction pressure, and 500 °C of sintering temperature, whereby it gave an elastic modulus of 5 GPa, hardness of 60 Hv, and a weight loss of 51% after three days immersion in PBS. The composites exhibited a hydrophobic surface that controlled the liberation of Mg2+ and Zn2+ ions, leading to more than 70% osteoblast cells viability up to seven days of incubation. This study can also serve as a starting point for future researchers interested in finding methods to fabricate Mg-Zn/CNF composites with high mechanical characteristics, corrosion resistance, and biocompatibility.

Potential bioactive coating system for high-performance absorbable magnesium bone implants.

Magnesium alloys are considered the most suitable absorbable metals for bone fracture fixation implants. The main challenge in absorbable magnesium alloys is their high corrosion/degradation rate that needs to be controlled. Various coatings have been applied to magnesium alloys to slow down their corrosion rates to match their corrosion rate to the regeneration rate of the bone fracture. In this review, a bioactive coating is proposed to slow down the corrosion rate of magnesium alloys and accelerate the bone fracture healing process. The main aim of the bioactive coatings is to enhance the direct attachment of living tissues and thereby facilitate osteoconduction. Hydroxyapatite, collagen type I, recombinant human bone morphogenetic proteins 2, simvastatin, zoledronate, and strontium are six bioactive agents that show high potential for developing a bioactive coating system for high-performance absorbable magnesium bone implants. In addition to coating, the substrate itself can be made bioactive by alloying magnesium with calcium, zinc, copper, and manganese that were found to promote bone regeneration.

Special Issue "Absorbable Metals for Biomedical Applications".

Current temporary metal implants made from titanium or stainless steel are not absorbable [...].

Synthesis, Characterization, and Antibacterial Evaluation of a Cost-Effective Endodontic Sealer Based on Tricalcium Silicate-White Portland Cement.

Mineral trioxide aggregate (MTA) is an ideal yet costly endodontic sealer material. Tricalcium silicate-white Portland cement (TS-WPC) seems to have similar characteristics to those of MTA. This work aims to characterize a modified TS-WPC and evaluate its antibacterial properties as a potential endodontic sealer material. The modified TS-WPC was synthesized from a 4:1 mixture of sterilized Indocement TS-WPC and bismuth trioxide using a simple solution method with 99.9% isopropanol. The mixture was stirred until it was homogenous, centrifuged, and dried. The material was then characterized using infrared spectroscopy, X-ray diffraction, and electron microscopy and subjected to antibacterial evaluation against Enterococcus faecalis using a Mueller-Hinton agar inhibition test. The results showed that the material was characterized by main functional groups of hydroxyls, silicate, bismuth trioxide, and tricalcium silicate, like those of a commercial MTA-based sealer, both tested after hydration. Modified TS-WPC before hydration showed similar powder morphology and size to the commercial one, indicating the ease of manipulation. Both materials exhibited antibacterial activity due to calcium dihydroxide's ability to absorb carbon dioxide, which is essential for the anaerobic E. faecalis, with minimum inhibitory effect and bactericidal concentrations of 12,500 ppm and 25,000 ppm, respectively. The modified TS-WPC has the potential to become a cost-effective alternative endodontic sealer material.

In Vitro Degradation, Hemocompatibility, and Cytocompatibility of Nanostructured Absorbable Fe-Mn-Ag Alloys for Biomedical Application.

The addition of noble elements such as Ag was shown as a successful method to accelerate the corrosion rate of absorbable Fe-based alloys. One major concern of Ag addition is its effect on hemocompatibility and biocompatibility. In this study, in vitro degradation and surface analysis of Fe-30Mn-xAg (x = 0, 1, and 3 wt %) alloys as well as their effects on hemocompatibility and cell viability of human umbilical vein endothelial cells (HUVECs) were investigated. The static degradation rate of the alloys was 4.97, 4.69, and 4.49 mg/cm2 for Fe-30Mn, Fe-30Mn-1Ag, and Fe-30Mn-3Ag, respectively. The surface analysis after degradation showed that γ-FeOOH was formed on Fe-30Mn-3Ag, while α-FeOOH was more dominant on Fe-30Mn and Fe-30Mn-1Ag. As γ-FeOOH is more soluble than α-FeOOH, it assists further degradation of Fe-30Mn-3Ag alloy. The high amount of Ag, which induced the hemolysis ratio, however, inhibited coagulation by decreasing the platelet adhesion. Fe-30Mn-1Ag and Fe-30Mn-3Ag alloys show an improved cell viability as compared to that of Fe-Mn alloy. Shear yield strength and shear elastic modulus of the samples after immersion tests were increased, while the ultimate shear strength was not affected. On the basis of the acceptable hemolysis rate, low platelet adhesion, acceptable cell viability, and appropriate mechanical properties after degradation, Fe-30Mn-1Ag can be considered as a suitable blood-contacting Fe-based absorbable alloy.

Biological Assessment of Zn-Based Absorbable Metals for Ureteral Stent Applications.

The use of ureteral stents to relieve urinary tract obstruction is still challenged by the problems of infection, encrustation, and compression, leading to the need for early removal procedures. Biodegradable ureteral stents, commonly made of polymers, have been proposed to overcome these problems. Recently, absorbable metals have been considered as potential materials offering both biodegradation and strength. This work proposed zinc-based absorbable metals by firstly evaluating their cytocompatibility toward normal primary human urothelial cells using 2D and 3D assays. In the 2D assay, the cells were exposed to different concentrations of metal extracts (i.e., 10 mg/mL of Zn-1Mg and 8.75 mg/mL of Zn-0.5Al) for up to 3 days and found that their cytoskeletal networks were affected but were recovered at day 3, as observed by immunofluorescence. In the 3D ureteral wall tissue construct, the cells formed a multilayered urothelium, as found in native tissue, with the presence of tight junctions at the superficial layer and laminin at the basal layer, indicating a healthy tissue condition even with the presence of the metal samples for up to 7 days of exposure. The basal cells attached to the metal surface as seen in a natural spreading state with pseudopodia and fusiform morphologies, indicating that the metals were non-toxic.

Current status and perspectives of zinc-based absorbable alloys for biomedical applications.

Absorbable metals have the potential to serve as the next generation of temporary medical implant devices by safely dissolving in the human body upon vascular tissue healing and bone regeneration. Their implementation in the market could greatly reduce the need of costly and risky additional surgeries for either implant replacement or removal, often required in current permanent implants. Despite the extensive research done over the last two decades on magnesium (Mg) and iron (Fe) based alloys, they have not generally shown a satisfactory combination of mechanical properties, biocompatibility and controlled degradation rate in the physiological environment. Consequently, zinc (Zn) based alloys were introduced in the last few years as alternative materials to overcome the limitations of Fe and Mg-based alloys. The blend of different alloying elements and processing conditions have led to a wide variety of Zn-based alloys having tunable mechanical properties and corrosion rates. This review provides the most recent progress in the development of absorbable Zn-based alloys for biomedical implant applications, primarily for cardiovascular and orthopedic devices. Their biocompatibility, processability and metallurgical aspects, as well as their mechanical behavior and corrosion properties are presented and discussed, including their opportunities, limitations and future research directions. STATEMENT OF SIGNIFICANCE: Temporary orthopedic bioimplants have become increasingly popular as they offer an alternative to prevent complications, like infections or secondary surgeries, often related to the implantation of permanent devices. Iron and magnesium alloys were extensively studied as candidates for absorbable medical applications, but they generally failed to provide a desirable mechanical performance and corrosion characteristics in the physiological environment. Zinc was introduced in the last decade as a potential implant material after showing outstanding biocompatibility and biodegradability. This review summarizes the research advances to date and provides a thorough discussion of the future challenges of absorbable zinc alloys to satisfy the demanding clinical benchmarks for absorbable medical applications. Their biocompatibility, mechanical, and corrosion aspects, both in vitro and in vivo, are comprehensively reviewed and assessed accordingly.

In Vitro Degradation of Absorbable Zinc Alloys in Artificial Urine.

Absorbable metals have potential for making in-demand rigid temporary stents for the treatment of urinary tract obstruction, where polymers have reached their limits. In this work, in vitro degradation behavior of absorbable zinc alloys in artificial urine was studied using electrochemical methods and advanced surface characterization techniques with a comparison to a magnesium alloy. The results showed that pure zinc and its alloys (Zn⁻0.5Mg, Zn⁻1Mg, Zn⁻0.5Al) exhibited slower corrosion than pure magnesium and an Mg⁻2Zn⁻1Mn alloy. The corrosion layer was composed mostly of hydroxide, carbonate, and phosphate, without calcium content for the zinc group. Among all tested metals, the Zn⁻0.5Al alloy exhibited a uniform corrosion layer with low affinity with the ions in artificial urine.

Updates on the research and development of absorbable metals for biomedical applications.

Absorbable metals, metals that corrode in physiological environment, constitute a new class of biomaterials intended for temporary medical implant applications. The introduction of these metals has shifted the established paradigm of metal implants from preventing corrosion to its direct application. Interest toward absorbable metals has been growing in the past decade. This is proved by the rapid increase in scientific publication, progressive development of standards, and launching the first commercial products. Iron, magnesium, zinc, and their alloys are the current three absorbable metals families. Magnesium-based metals are the most progressing family with a large data set obtained from both basic and translational research. Iron-based metals are still facing a major challenge of low in vivo corrosion rate despite the significant efforts that have been put to overcome its weakness. Zinc-based metals are the new alternative absorbable metals with moderate corrosion rates that fall between those of iron and magnesium. This manuscript provides a brief review on the latest progress in the research and development of absorbable metals, the most important findings, the remaining challenges, and the perspective on the future direction.

Novel antibacterial biodegradable Fe-Mn-Ag alloys produced by mechanical alloying.

Various compositions and synthesis methods of biodegradable iron-based alloys have been studied aiming for the use of temporary medical implants. However, none is focused on nano-structured alloy and on adding antibacterial property to the alloy. In this study, new Fe-30Mn-(1-3)Ag alloys were synthesized by means of mechanical alloying and assessed for their microstructure, mechanical properties, corrosion rate, antibacterial activity and cytotoxicity. Results showed that the alloy with 3 wt% Ag content displayed the highest relative density, shear strength, micro hardness and corrosion rate. However, optimum cytotoxicity and the antibacterial activity were reached by the alloy with 1 wt% Ag content. The compositional and processing effects of the alloys' properties are further discussed in this work.

Bioinspired surface functionalization of metallic biomaterials.

Metallic biomaterials are widely used for clinical applications because of their excellent mechanical properties and good durability. In order to provide essential biofunctionalities, surface functionalization is of particular interest and requirement in the development of high-performance metallic implants. Inspired by the functional surface of natural biological systems, many new designs and conceptions have recently emerged to create multifunctional surfaces with great potential for biomedical applications. This review firstly introduces the metallic biomaterials, important surface properties, and then elaborates some strategies on achieving the bioinspired surface functionalization for metallic biomaterials.

Antibacterial efficacy of triple-layered poly(lactic-co-glycolic acid)/nanoapatite/lauric acid guided bone regeneration membrane on periodontal bacteria.

A guided bone regeneration (GBR) membrane has been extensively used in the repair and regeneration of damaged periodontal tissues. One of the main challenges of GBR restoration is bacterial colonization on the membrane, constitutes to premature membrane degradation. Therefore, the purpose of this study was to investigate the antibacterial efficacy of triple-layered GBR membrane composed of poly(lactic-co-glycolic acid) (PLGA), nanoapatite (NAp) and lauric acid (LA) with two types of Gram-negative periodontal bacteria, Fusobacterium nucleatum and Porphyromonas gingivalis through a disc diffusion and bacterial count tests. The membranes exhibited a pattern of growth inhibition and killing effect against both bacteria. The increase in LA concentration tended to increase the bactericidal activities which indicated by higher diameter of inhibition zone and higher antibacterial percentage. It is shown that the incorporation of LA into the GBR membrane has retarded the growth and proliferation of Gram-negative periodontal bacteria for the treatment of periodontal disease.

Drug-eluting coating of ginsenoside Rg1 and Re incorporated poly(lactic-co-glycolic acid) on stainless steel 316L: Physicochemical and drug release analyses.

Active ingredients of ginsenoside, Rg1 and Re, are able to inhibit the proliferation of vascular smooth muscle cells and promote the growth of vascular endothelial cells. These capabilities are of interest for developing a novel drug-eluting stent to potentially solve the current problem of late-stent thrombosis and poor endotheliazation. Therefore, this study was aimed to incorporate ginsenoside into degradable coating of poly(lactic-co-glycolic acid) (PLGA). Drug mixture composed of ginseng extract and 10% to 50% of PLGA (xPLGA/g) was coated on electropolished stainless steel 316L substrate by using a dip coating technique. The coating was characterized principally by using attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy and contact angle analysis, while the drug release profile of ginsenosides Rg1 and Re was determined by using mass spectrometry at a one month immersion period. Full and homogenous coating coverage with acceptable wettability was found on the 30PLGA/g specimen. All specimens underwent initial burst release dependent on their composition. The 30PLGA/g and 50PLGA/g specimens demonstrated a controlled drug release profile having a combination of diffusion- and swelling-controlled mechanisms of PLGA. The study suggests that the 30PLGA/g coated specimen expresses an optimum composition which is seen as practicable for developing a controlled release drug-eluting stent.

Immobilization of antibacterial chlorhexidine on stainless steel using crosslinking polydopamine film: Towards infection resistant medical devices.

Chlorhexidine (CHX) is known for its high antibacterial substantivity and is suitable for use to bio-inert medical devices due to its long-term antibacterial efficacy. However, CHX molecules require a crosslinking film to be stably immobilized on bio-inert metal surfaces. Therefore, polydopamine (PDA) was utilized in this study to immobilize CHX on the surface of 316L type stainless steel (SS316L). The SS316L disks were pre-treated, modified with PDA film and immobilized with different concentrations of CHX (10mM-50mM). The disks were then subjected to various surface characterization analyses (ATR-FTIR, XPS, ToF-SIMS, SEM and contact angle measurement) and tested for their cytocompatibility with human skin fibroblast (HSF) cells and antibacterial activity against Escherichia coli and Staphylococcus aureus. The results demonstrated the formation of a thin PDA film on the SS316L surface, which acted as a crosslinking medium between the metal and CHX. CHX was immobilized via a reduction process that covalently linked the CHX molecules with the functional group of PDA. The immobilization of CHX increased the hydrophobicity of the disk surfaces. Despite this property, a low concentration of CHX optimized the viability of HSF cells without disrupting the morphology of adherent cells. The immobilized disks also demonstrated high antibacterial efficacy against both bacteria, even at a low concentration of CHX. This study demonstrates a strong beneficial effect of the crosslinked PDA film in immobilizing CHX on bio-inert metal, and these materials are applicable in medical devices. Specifically, the coating will restrain bacterial proliferation without suffocating nearby tissues.

The effect of hydrogen gas evolution of magnesium implant on the postimplantation mortality of rats.

BACKGROUND/OBJECTIVE: Hydrogen gas cavity is formed during in vivo degradation of magnesium implants. In many studies, the gas cavity is mostly punctured out subcutaneously. However, this procedure becomes inapplicable in certain internal surgeries; therefore, the effect of this gas cavity is worth further assessment. METHODS: In this study, we investigated the effect of hydrogen gas evolution on the mortality of rats and analysed the whole body capacity to relieve the gas. Porous pure-magnesium implants were implanted in the femoral bone defect of adult Sprague-Dawley rats up to 18 days, and their survival rate was calculated while the gas cavity size was measured, and its effect was analysed with support of radiographic and blood analysis. RESULTS: The gas cavity was rapidly formed surrounding the implantation site and obviously decreased the rats' survival rate. The gas was observed to swell the surrounding implantation site by filling the loose compartments and then dispersing subcutaneously to other areas. CONCLUSION: The rat's whole body capacity was unable to tolerate the rapid and persistent hydrogen gas cavity formation as shown by high postimplantation mortality.

Controlling the degradation kinetics of porous iron by poly(lactic-co-glycolic acid) infiltration for use as temporary medical implants.

Iron and its alloy have been proposed as biodegradable metals for temporary medical implants. However, the formation of iron oxide and iron phosphate on their surface slows down their degradation kinetics in both in vitro and in vivo scenarios. This work presents new approach to tailor degradation behavior of iron by incorporating biodegradable polymers into the metal. Porous pure iron (PPI) was vacuum infiltrated by poly(lactic-co-glycolic acid) (PLGA) to form fully dense PLGA-infiltrated porous iron (PIPI) and dip coated into the PLGA to form partially dense PLGA-coated porous iron (PCPI). Results showed that compressive strength and toughness of the PIPI and PCPI were higher compared to PPI. A strong interfacial interaction was developed between the PLGA layer and the iron surface. Degradation rate of PIPI and PCPI was higher than that of PPI due to the effect of PLGA hydrolysis. The fast degradation of PIPI did not affect the viability of human fibroblast cells. Finally, this work discusses a degradation mechanism for PIPI and the effect of PLGA incorporation in accelerating the degradation of iron.

Structure-property relationships of iron-hydroxyapatite ceramic matrix nanocomposite fabricated using mechanosynthesis method.

Hydroxyapatite (HAp) is an attractive bioceramics due to its similar composition to bone mineral and its ability to promote bone-implant interaction. However, its low strength has limited its application as load bearing implants. This paper presented a work focusing on the improvement of HAp mechanical property by synthesizing iron (Fe)-reinforced bovine HAp nanocomposite powders via mechanosynthesis method. The synthesis process was performed using high energy milling at varied milling time (3, 6, 9, and 12h). The samples were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM). Its mechanical properties were investigated by micro-Vicker's hardness and compression tests. Results showed that milling time directly influenced the characteristics of the nanocomposite powders. Amorphous BHAp was formed after 9 and 12h milling in the presence of HPO4(2-) ions. Continuous milling has improved the crystallinity of Fe without changing the HAp lattice structure. The nanocomposite powders were found in spherical shape, agglomerated and dense after longer milling time. The hardness and Young's modulus of the nanocomposites were also increased at 69% and 66%, respectively, as the milling time was prolonged from 3 to 12h. Therefore, the improvement of the mechanical properties of nanocomposite was attributed to high Fe crystallinity and homogenous, dense structure produced by mechanosynthesis.

Evidences of in vivo bioactivity of Fe-bioceramic composites for temporary bone implants.

Iron-bioceramic composites have been developed as biodegradable implant materials with tailored degradation behavior and bioactive features. In the current work, in vivo bioactivity of the composites was comprehensively studied by using sheep animal model. Five groups of specimens (Fe-HA, Fe-TCP, Fe-BCP composites, and pure-Fe and SS316L as controls) were surgically implanted into medio proximal region of the radial bones. Real-time ultrasound analysis showed a decreased echo pattern at the peri-implant biodegradation site of the composites indicating minimal tissue response during the wound healing process. Peripheral whole blood biomarkers monitoring showed a normal dynamic change of blood cellular responses and no stress effect was observed. Meanwhile, the released Fe ion concentration was increasing along the implantation period. Histological analysis showed that the composites corresponded with a lower inflammatory giant cell count than that of SS316L. Analysis of the retrieved implants showed a thicker degradation layer on the composites compared with pure-Fe. It can be concluded that the iron-bioceramic composites are bioactive and induce a preferable wound healing process.