How surface-to-volume ratio affects degradation of magnesium: in vitro and in vivo studies.

Despite the many studies carried out over the past decade to determine the biodegradation performance of magnesium and its alloys, few studies focused on the effect of altered surface area to volume ratio on in vitro and in vivo degradation rate and osteogenesis. Here, high purity magnesium cylindrical rods with gradient of surface area to volume ratio were processed by excavating different numbers of grooves on the side surface. The immersion test in SBF solution and the rat femoral condylar bone defect model were used to evaluate the degradation of magnesium rods in vitro and in vivo, respectively. We demonstrated that, the increased number of grooves on the HP magnesium surface represented a decrease in the percentage of residual volume over time, not necessarily an increase in absolute degradation volume or a regular change in corrosion rate. Furthermore, there were strong linear correlations between the relative degradation volume and the initial surface-to-volume ratio of HP magnesium rods both in vitro and in vivo. The difference in the slope of this relationship in vitro and in vivo might help to determine the possible range of in vivo degradation rates via in vitro data. In addition, the corrosion rate is more suitable for evaluating bone formation surrounding the different HP magnesium rods. Our findings in this work may facilitate adjusting the in vivo degradation and osteogenesis of different kinds of orthopedic implants made of the same magnesium-based material, and thus, accelerate the clinical popularization and application.

Nanomechanical probing of bacterial adhesion to biodegradable Zn alloys.

Bacterial infections on implants cause an inflammatory response and even implant failure. Bacterial adhesion is an initial and critical step during implant infection. The prevention of bacterial adhesion to implant materials has attracted much attention, especially for biodegradable metals. A deep understanding of the mechanisms of bacterial adhesion to biodegradable metals is urgently needed. In this work, a bacterial probe based on atomic force spectroscopy was employed to determine the bacterial adhesion to Zn alloy, which depended on surface charge, roughness, and wettability. Negative surface charges of Zn, Zn-0.5Li, and 316L generated electrostatic repulsion force towards bacteria. The surface roughness of Zn-0.5Li was significantly increased by localized corrosion. Bacterial adhesion forces on Zn, Zn-0.5Li, and 316L were 325.2 pN, 519.1 pN, and 727.7 pN, respectively. The density of attached bacteria (early-stage bacterial adhesion) on these samples exhibited a positive correlation with the bacterial adhesion force. The bacterial adhesion force and adhesion work provide a quantitative determination of the interactions between bacteria and biodegradable alloys. These results provide a deeper understanding of early bacterial adhesion on Zn alloys, which can further guide the antibacterial surface design of biodegradable materials for clinical application.

Surface-Roughness-Induced Plasticity in a Biodegradable Zn Alloy.

Improving plasticity has been an eternal theme of developing metallic materials. It is difficult to increase room-temperature elongation of metallic materials over 100% without sacrificing strength using existing methods. Herein, surface-roughness-induced plasticity (SRIP) is discovered in biodegradable Zn-0.4Mn alloy. Surprisingly, in the good surface range that meets the international standard ISO 6892, reducing surface roughness results in significant increase in plasticity without loss of strength. From unground to 5000# sandpaper ground states, the surface roughness Ra of the alloy decreases from 0.63 to 0.05 µm, while its room temperature elongation increases from 74% to 143%. SRIP is the synergistic result of increased microstructure damage tolerance and decreased surface roughness. It provides a new method for improving plasticity.

Development of a high-strength Zn-Mn-Mg alloy for ligament reconstruction fixation.

Although various biodegradable materials have been investigated for ligament reconstruction fixation in the past decades, only few of them possess a combination of high mechanical properties, appropriate degradation rate, good biocompatibility, and osteogenic effect, thus limiting their clinical applications. A high-strength Zn-0.8Mn-0.4Mg alloy (i.e., Zn08Mn04Mg) with yield strength of 317 MPa was developed to address this issue. The alloy showed good biocompatibility and promising osteogenic effect in vitro. The degradation effects of Zn08Mn04Mg interference screws on the interface between soft tissue and bone were investigated in anterior cruciate ligament (ACL) reconstruction in rabbits. Compared to Ti6Al4V, the Zn alloy screws significantly accelerated the formation of new bone and further induced partial tendon mineralization, which promoted tendon-bone integration. The newly developed screws are believed to facilitate early joint function recovery and rehabilitation training and also avoid screw breakage during insertion, thereby contributing to an extensive clinical prospect.

Insight into role and mechanism of Li on the key aspects of biodegradable ZnLi alloys: Microstructure evolution, mechanical properties, corrosion behavior and cytotoxicity.

ZnLi based alloys have been proved as desirable candidates for biodegradable materials accounting for its high mechanical performance and great biocompatibility. However, effects of Li on microstructure and comprehensive properties of Zn alloys are seldom investigated and need to be addressed. Herein, Zn-(0.1-1.4 wt%)Li alloys are fabricated and systematically analyzed. Lath-like Zn precipitates are observed in the primary ß-LiZn4 (ß) phase of Zn-(0.5-1.4 wt%)Li alloys, leading to the formation of dense ß/Zn lamellar structure with an inter-spacing of 0.8 µm. Mechanical tests show that the strengths of the ZnLi alloys have at least tripled due to the formation of dense ß/Zn lamellar structure. Early degradation behaviors of the ZnLi alloys in simulated body fluid (SBF) reveal a competitive releasing of Li+ and Zn2+. As the priority of Li+ releasing becomes more obvious with increasing Li content in the alloys, aqueous insoluble Li-rich corrosion products containing LiOH and Li2CO3 form a passivation film on Zn-(0.5-1.4 wt%)Li alloys. Consequently, corrosion rate decreases significantly from 45.76 µm/y of pure Zn to 14.26 µm/y of Zn-1.4Li alloy. Importantly, observations of white light interferometer microscope and transmission electron microscope demonstrate that ß phase degrades prior to Zn in the alloys, suggesting that biomedical implants made of ZnLi alloys are likely to degrade completely in human body. Cytotoxicity tests of the alloys exhibit no cytotoxicity in 10% extracts. The most tolerated Zn2+/Li+ concentrations of the alloy extracts to L-929 cells are calculated, which provides guidance for future design of Zn alloys containing Li.

Enhancement in mechanical and corrosion resistance properties of a biodegradable Zn-Fe alloy through second phase refinement.

Biodegradable Zn alloys containing Fe suffer from a common problem that FeZn13 second phase particles are coarse. This problem roots thermodynamically from the negligible solid solubility of Fe in Zn and priority of FeZn13 solidification over Zn. In this paper, bottom circulating water-cooled casting method is successfully developed to significantly refine FeZn13 particles in Zn-0.3Fe alloy, owing to its cooling speed about 8 times of that of conventional casting. The second phase refinement alleviates brittleness of the alloy, increases the ultimate tensile strength by about 62%, and decreases electrochemical corrosion rate (CR) by about 19%, but immersion CR by only about 4% due to barrier effect of corrosion products. Viability of human umbilical vein endothelial cells maintains at a high level over 95% in 25-100% extracts. A great potential is shown for improving comprehensive properties of biodegradable Zn alloys without changing its chemical compositions through such a physical method.

Design biodegradable Zn alloys: Second phases and their significant influences on alloy properties.

Alloying combined with plastic deformation processing is widely used to improve mechanical properties of pure Zn. As-cast Zn and its alloys are brittle. Beside plastic deformation processing, no effective method has yet been found to eliminate the brittleness and even endow room temperature super-ductility. Second phase, induced by alloying, not only largely determines the ability of plastic deformation, but also influences strength, corrosion rate and cytotoxicity. Controlling second phase is important for designing biodegradable Zn alloys. In this review, knowledge related to second phases in biodegradable Zn alloys has been analyzed and summarized, including characteristics of binary phase diagrams, volume fraction of second phase in function of atomic percentage of an alloying element, and so on. Controversies about second phases in Zn-Li, Zn-Cu and Zn-Fe systems have been settled down, which benefits future studies. The effects of alloying elements and second phases on microstructure, strength, ductility, corrosion rate and cytotoxicity have been neatly summarized. Mg, Mn, Li, Cu and Ag are recommended as the major alloying elements, owing to their prominent beneficial effects on at least one of the above properties. In future, synergistic effects of these elements should be more thoroughly investigated. For other nutritional elements, such as Fe and Ca, refining second phase is a matter of vital concern.

Hemocompatibility of biodegradable Zn-0.8 wt% (Cu, Mn, Li) alloys.

Zinc alloys have been explored as potential materials for biodegradable vascular stents due to their tolerable corrosion rates and tunable mechanical properties. However, the performances of Zn alloys were not supported with enough toxicity or biological compatibility evaluation, particularly hemocompatibility for vascular scaffolding application. In this work, the hemocompatibility of three zinc alloys (Zn-0.8Cu, Zn-0.8Mn and Zn-0.8Li) was evaluated with 316 L stainless steel and pure zinc as controls. The hemolysis ratios of 316 L stainless steel, pure Zn, Zn-0.8Cu, Zn-0.8Mn and Zn-0.8Li were 0.38 ±â€¯0.08%, 1.04 ±â€¯0.21%, 0.47 ±â€¯0.21%, 0.57 ±â€¯0.14% and 0.52 ±â€¯0.22%, respectively, for direct contact method. Platelets aggregation on the 316 L stainless steel was observed, while the adhered platelets on the Zn alloys exhibited round shape with few pseudopodia spreading. The number of adhered platelets on the three zinc alloys (Zn-0.8Cu, Zn-0.8Mn and Zn-0.8Li) had no statistically difference compared with 316 L stainless steel, while significant fewer than the pure Zn group. None remarkable platelet activation, hematocyte aggregation, coagulation or complement activation was observed in any Zn alloy group. Furthermore, the Zn alloys prolonged prothrombin time and partial thromboplastin time, demonstrating a potential function of anticoagulation. The results demonstrated that Zn alloys presented in this work are indeed meeting the hemocompatible requirements of implant and showing the promise for perspective application as biodegradable stent.

Long-term in vivo study of biodegradable Zn-Cu stent: A 2-year implantation evaluation in porcine coronary artery.

In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ±â€¯13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. STATEMENT OF SIGNIFICANCE: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.

Effects of Ag, Cu or Ca addition on microstructure and comprehensive properties of biodegradable Zn-0.8Mn alloy.

Zn-0.8Mn (in wt%) alloy with good ductility is used for design of novel Zn-0.8Mn-0.4x (x = Ag, Cu or Ca) alloys. Hot extrusion not only eliminates brittleness of the as-cast alloys but also significantly improves their strengths. Among them, Zn-0.8Mn-0.4Ca exhibits the highest strength, Zn-0.8Mn-0.4Ag exhibits the highest ductility, but Zn-0.8Mn-0.4Cu exhibits the best combination of strength and ductility. The minor addition of Ag, Cu or Ca accelerates alloy degradation in simulated body fluid. However, Cu addition much improves in vitro biocompatibility and endows antibacterial ability of Escherichia coli. Overall, Zn-0.8Mn-0.4Cu alloy has the best comprehensive properties.