The search for biodegradable metals with mechanical properties equal or higher to those of currently used permanent biomaterials, such as stainless steels, cobalt chromium and titanium alloys, desirable in vivo degradation rate and uniform corrosion is still an open challenge. Magnesium (Mg), iron (Fe) and zinc (Zn)-based alloys have been proposed as biodegradable metals for medical applications. Over the last two decades, extensive research has been done on Mg and Fe. Fe-based alloys show appropriate mechanical properties, but their degradation rate is an order of magnitude below the benchmark value. In comparison, alongside the insufficient mechanical performance of most of its alloys, Mg degradation rate has proven to be too high in a physiological environment and corrosion is rarely uniform. During the last few years, Zn alloys have been explored by the biomedical community as potential materials for bioabsorbable vascular stents due to their tolerable corrosion rates and tunable mechanical properties. This review summarizes recent progress made in developing Zn alloys for vascular stenting application. Novel Zn alloys are discussed regarding their microstructural characteristics, mechanical properties, corrosion behavior and in vivo performance.Numerous studies on magnesium and iron materials have been reported to date, in an effort to formulate bioabsorbable stents with tailorable mechanical characteristics and corrosion behavior. Crucial concerns regarding poor ductility and remarkably rapid corrosion of magnesium, and very slow degradation of iron, seem to be still not desirably fulfilled. Zinc was introduced as a potential implant material in 2013 due to its promising biodegradability and biocompatibility. Since then, extensive investigations have been made toward development of zinc alloys that meet clinical benchmarks for vascular scaffolding. This review critically surveys the zinc alloys developed since 2013 from metallurgical and biodegradation points of view. Microstructural features, mechanical, corrosion and in vivo performances of these new alloys are thoroughly reviewed and evaluated.Copyright © 2018 Acta Materialia Inc. All rights reserved.

Zinc is one of the most abundant nutritionally essential elements in the human body. It is found in all body tissues with 85% of the whole body zinc in muscle and bone, 11% in the skin and the liver and the remaining in all the other tissues. In multicellular organisms, virtually all zinc is intracellular, 30-40% is located in the nucleus, 50% in the cytoplasm, organelles and specialized vesicles (for digestive enzymes or hormone storage) and the remainder in the cell membrane. Zinc intake ranges from 107 to 231 micromol/d depending on the source, and human zinc requirement is estimated at 15 mg/d. Zinc has been shown to be essential to the structure and function of a large number of macromolecules and for over 300 enzymic reactions. It has both catalytic and structural roles in enzymes, while in zinc finger motifs, it provides a scaffold that organizes protein sub-domains for the interaction with either DNA or other proteins. It is critical for the function of a number of metalloproteins, inducing members of oxido-reductase, hydrolase ligase, lyase family and has co-activating functions with copper in superoxide dismutase or phospholipase C. The zinc ion (Zn(++)) does not participate in redox reactions, which makes it a stable ion in a biological medium whose potential is in constant flux. Zinc ions are hydrophilic and do not cross cell membranes by passive diffusion. In general, transport has been described as having both saturable and non-saturable components, depending on the Zn(II) concentrations involved. Zinc ions exist primarily in the form of complexes with proteins and nucleic acids and participate in all aspects of intermediary metabolism, transmission and regulation of the expression of genetic information, storage, synthesis and action of peptide hormones and structural maintenance of chromatin and biomembranes.

In recent years, Zn-based materials provide a new option as biodegradable metals for orthopedic applications. To improve the low strength and brittle nature of pure Zn, small amounts of alloying element Mn (0.1, 0.4 and 0.8 wt.%) were added into Zn to fabricate binary Zn-Mn alloys. An extremely high elongation (83.96 ± 2.36%) was achieved in the resulting Zn-0.8 wt.%Mn alloy. Moreover, Zn-Mn alloys displayed significantly improved cytocompatibility as compared to pure Zn, according to cell proliferation and morphology analyses. More importantly, a significantly improved osteogenic activity was verified after adding Mn regarding ALP activity and osteogenic expression. Furthermore, Zn-0.8 wt.%Mn alloy scaffolds were implanted into the rat femoral condyle for repairing bone defects with pure Ti as control. Enhanced osteogenic activities were confirmed for Zn-0.8Mn alloy in contrast to pure Ti based on Micro-CT and histological results, and favorable in vivo biosafety of Zn-0.8Mn alloy was verified by H&E staining and blood tests. The exceptional mechanical performance and favorable osteogenic capability render Zn-Mn alloy a promising candidate material in the treatment of bone defects or fracture repair. STATEMENT OF SIGNIFICANCE: The element Mn, on the one hand, as an essential trace element in the human body, promotes cell proliferation, adhesion, spreading, and regulates bone metabolism; on the other hand, it could significantly improve the ductility of Zn alloys. Here, we systematically reported the biocompatibility and biofunctionality of binary biodegradable Zn-Mn alloys in the bone environment. The Zn-Mn alloys promoted MC3T3-E1 cell proliferation, adhesion, spreading, and osteogenic differentiation in vitro. Furthermore, a rat femoral condyle defect model was established; porous Zn-Mn alloy scaffolds were manufactured to repair the bone defects. Significant bone regenerations, considerable bone ingrowth, and desirable biosafety were confirmed in vivo. Therefore, biodegradable Zn-Mn with promising osteogenic properties may become new options for orthopedic implant materials.Copyright © 2020. Published by Elsevier Ltd.

In the present work Zn-Mg alloys containing up to 3wt.% Mg were studied as potential biodegradable materials for medical use. The structure, mechanical properties and corrosion behavior of these alloys were investigated and compared with those of pure Mg, AZ91HP and casting Zn-Al-Cu alloys. The structures were examined by light and scanning electron microscopy (SEM), and tensile and hardness testing were used to characterize the mechanical properties of the alloys. The corrosion behavior of the materials in simulated body fluid with pH values of 5, 7 and 10 was determined by immersion tests, potentiodynamic measurements and by monitoring the pH value evolution during corrosion. The surfaces of the corroded alloys were investigated by SEM, energy-dispersive spectrometry and X-ray photoelectron spectroscopy. It was found that a maximum strength and elongation of 150MPa and 2%, respectively, were achieved at Mg contents of approximately 1wt.%. These mechanical properties are discussed in relation to the structural features of the alloys. The corrosion rates of the Zn-Mg alloys were determined to be significantly lower than those of Mg and AZ91HP alloys. The former alloys corroded at rates of the order of tens of microns per year, whereas the corrosion rates of the latter were of the order of hundreds of microns per year. Possible zinc doses and toxicity were estimated from the corrosion behavior of the zinc alloys. It was found that these doses are negligible compared with the tolerable biological daily limit of zinc.Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

在过去的20年间,随着对可降解金属研究的不断深入,从合金成分设计到熔炼制造加工,从毛细管到支架激光加工和药物涂覆等相关技术不断成熟。可降解金属支架也从一个概念发展为实际产品,并形成3个材料体系分支：可降解镁合金支架已经开展了大量的动物实验和临床实验,结果显示其良好的表现和临床安全性,Biotronik公司生产的可降解镁合金产品Magmaris在2016年获得CE认证;可降解铁合金支架目前处在动物实验阶段,注氮铁合金支架具有优异的力学性能,动物实验结果显示注氮铁支架具有良好的生物相容性;可降解锌合金支架近几年才得到人们的关注,目前的体内动物实验研究结果显示,纯Zn丝在小鼠体内具有良好的降解性能和生物相容性,暂未见体内支架研究报道。本文在综合评述可降解金属支架材料的研究现状基础上,展望了可降解金属支架在性能优化、药物洗脱和智能化方面的未来发展趋势。

Zinc has been identified as one of the most promising biodegradable metals along with magnesium and iron. Zinc appears to address some of the core engineering problems associated with magnesium and iron when applied to biomedical implant applications; hence the increase in the amount of research investigations on the metal in the last few years. In this review, the current state-of-the-art on biodegradable Zn, including recent developments, current opportunities and future directions of research are discussed. The discussions are presented with a specific focus on reviewing the relationships that exist between mechanical properties, biodegradability, and biocompatibility of zinc with alloying and fabrication techniques. This work hopes to guide future studies on biodegradable Zn that will help in advancing this field of research. STATEMENT OF SIGNIFICANCE: (i) The review offers an up-to-date and comprehensive review of the influence of alloying and fabrication technique on mechanical properties, biodegradability and biocompatibility of Zn; (ii) the work cites the most relevant biodegradable Zn fabrication processes including additive manufacturing techniques; (iii) the review includes a listing of research gap and future research directions for the field of biodegradable Zn.Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Zinc and its alloys have emerged as a new research direction of biodegradable metals (BMs) due to the significant physiological functions of Zn ions in human body. However, low inhibitory concentration threshold value to cause cytotoxicity by Zn ions during in vitro study and delayed osseointegration in vivo are two key flaws for the bulk Zn-based BMs. To combat these issues, we constructed a barrier layer of ZrO nanofilm on the surface of Zn-0.1(wt.%) Li alloy via atomic layer deposition (ALD). A decreased release of Zn ions accompanied with accelerated release of Li ions was observed on account of galvanic coupling between the coating compositions and Zn-0.1Li alloy substrate. Cytocompatibility assay reflected that ZrO nanofilm coated Zn-0.1Li alloy exhibited improved cell adhesion and viability. Histological analysis also demonstrated better in vivo osseointegration for the ZrO nanofilm coated Zn-0.1Li alloy. Hence, the present study elucidated that the ALD of ZrO nanofilm on Zn-based BMs can effectively promote osseointegration and control their biodegradation behavior. STATEMENT OF SIGNIFICANCE: Zn-Li binary alloy was reported recently to be the promising biodegradable metals with ultimate tensile strength over 500 MPa, yet the low inhibitory concentration threshold value to cause cytotoxicity by Zn ions is the obstacle needed to be overcome. As a pilot study, a systematic investigation on the ZrO nanofilm coated Zn-Li alloy, prepared by atomic layer deposition (ALD) technique, was conducted in the present study, which involved in the formation process, in vitro and in vivo degradation behavior as well as biocompatibility evaluation. We found a controllable corrosion rate and better in vivo osseointegration can be achieved by ZrO nanofilm coating on Zn-Li alloy, which provides new insight into the surface modification on biodegradable Zn alloys for usage within bone.Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Rare earth elements are promising alloying element candidates for magnesium alloys used as biodegradable devices in biomedical applications. Rare earth elements have significant effects on the high temperature strength as well as the creep resistance of alloys and they improve magnesium corrosion resistance. We focused on lanthanum, neodymium and cerium to produce magnesium alloys with commonly used rare earth element concentrations. We showed that low concentrations of rare earth elements do not promote bone growth inside a 750 μm broad area around the implant. However, increased bone growth was observed at a greater distance from the degrading alloys. Clinically and histologically, the alloys and their corrosion products caused no systematic or local cytotoxicological effects. Using microtomography and in vitro experiments, we could show that the magnesium-rare earth element alloys showed low corrosion rates, both in in vitro and in vivo. The lanthanum- and cerium-containing alloys degraded at comparable rates, whereas the neodymium-containing alloy showed the lowest corrosion rates.Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.