The application of microfabrication to the development of biomedical implants has produced a new generation of miniaturized technology for assisting treatment and research. Microfabricated implantable devices (μID) are an increasingly important tool, and the development of new μIDs is a rapidly growing field that requires new microtechnologies able to safely and accurately function in vivo. Here, we present a review of μID research that examines the critical role of material choice in design and fabrication. Materials commonly used for μID production are identified and presented along with their relevant physical properties and a survey of the state-of-the-art in μID development. The consequence of material choice as it pertains to microfabrication and biocompatibility is discussed in detail with a particular focus on the divide between hard, rigid materials and soft, pliable polymers.

To overcome the not negligible metallic drug-eluting stents adverse events rate, the polymeric or metallic bioresorbable scaffolds were designed to provide early drug delivery and mechanical support followed by complete resorption. However, the long-term evidence, focusing on the leading Absorb BVS technology, showed higher events compared with drug-eluting stents. This review discusses the lights and shadows of the current bioresorbable scaffolds according to their mechanical properties and biodegradation profile and suggests possible perspective on these technologies. Improved scaffold design and deployment techniques might mitigate early bioresorbable scaffolds risk enhancing the late benefit of complete resorption.Copyright © 2020 Elsevier Inc. All rights reserved.

Fully bioresorbable scaffolds (BRS) were designed to overcome the limitations of metallic drug-eluting stents, which permanently cage the vessel wall, thereby preventing normal coronary vasomotion, preclude bypass grafting and can provoke long-term foreign-body responses. Although multiple scaffolds have been or are in development, the Absorb Bioresorbable Vascular Scaffold (BVS; Abbott Vascular) was the first FDA-approved device and was widely expected to fulfil the dream of interventional cardiologists of a transient scaffold that would disappear 'when the job was done' and would not hamper further treatment options. Although early, small studies and even large, randomized trials showed beneficial outcomes up to 1 year of follow-up, longer-term results have been disappointing, with increased rates of device thrombosis and target-lesion revascularization. The Absorb BVS device was withdrawn from the market because of low demand. In this Review, we summarize the preclinical and clinical data available for BRS to understand how the vascular biological reactions to these devices differ from biological reactions to metallic drug-eluting stents and how these responses translate into clinical outcomes. We also discuss next-generation BRS and outline modifications that are needed to improve the long-term outcomes with these devices so that they eventually become a viable option for patients with symptomatic obstructive coronary artery disease.

Age-hardenability and corresponding improvement of the mechanical properties of Mg-1Al-0.7Ca and Mg-1Al-0.7Ca-0.7Y alloy sheets are addressed with respect to the microstructure and texture evolution during thermomechanical treatments. A fine grain structure and weak texture with the basal pole split into the sheet transverse direction are retained in the Mg-1Al-0.7Ca-0.7Y sheet even after the homogenization at 500 °C, due to the grain boundary pinning by Y-containing precipitates possessing a high thermal stability. Contrarily, the Mg-1Al-0.7Ca sheet shows a coarse microstructure and basal-type texture after the homogenization. The peak-aged condition is attained after the aging at 250 °C for 1800 s of both homogenized sheets, while the Y-containing sheet shows a higher hardness than the Mg-1Al-0.7Ca sheet. TEM analysis and thermodynamic calculation show the formation of metastable precipitates composed of Al, Ca, Y and Mg in the Mg-1Al-0.7Ca-0.7Y sheet at the homogenized and peak-aged conditions. A significant increase in the yield strength is obtained in the peak-aged condition from 162 MPa after the homogenization to 244 MPa, which arises from the increased size and number density of the precipitates. The high age-hardenability of the Mg-1Al-0.7Ca-0.7Y sheet attributes to the superior mechanical properties with an improved ductility promoted by the weak texture.

In recent years, zinc based alloys as a new biodegradable metal material aroused intensive interests. However, the processing of Zn alloys micro-tubes (named slender-diameter and thin-walled tubes) is very difficult due to their HCP crystal structure and unfavorable mechanical properties. This study aimed to develop a novel technique to produce micro-tube of Zn alloy with good performance for biodegradable vascular stent application. In the present work, a processing method that combined drilling, cold rolling and optimized drawing was proposed to produce the novel Zn-5Mg-1Fe (wt%) alloy micro-tubes. The micro-tube with outer diameter of 2.5?mm and thickness of 130?μm was fabricated by this method and its dimension errors are within 10?μm. The micro-tube exhibits a fine and homogeneous microstructure, and the ultimate tensile strength and ductility are more than 220?MPa and 20% respectively. In addition, the micro-tube and stents of Zn alloy exhibit superior in vitro corrosion and expansion performance. It could be concluded that the novel Zn alloy micro-tube fabricated by above method might be a promising candidate material for biodegradable stent.

Additive manufacturing (AM) can produce complicated structures accurately and freely, giving the implant a macro and micro geometry, which makes the implant match the patient's defect site and realize the needs for personalized clinical treatment. Thus, AM provides a new manufacturing method for biodegradable metals. Presently, biodegradable metals are the hotspot issues of metallic biomaterials research. Additively-manufactured biodegradable metals are new research field. In this paper, a comprehensive review on the AM of Mg-, Zn-, and Fe-based biodegradable metals, which focuses on their processes and influencing factors, mechanical properties, biodegradation behavior, and biocompatibility, is given. Finally, the future development trend of the AM biomedical metallic materials is explored.

增材制造技术由于其高精度、高自由度等特点，可赋予医用金属植入物定制化的宏观与微观结构，使植入物与患者待修复缺损部位实现更好的生物力学适配，满足临床治疗个性化方案的需求，并为医用金属植入物的制造提供新途径。可降解金属目前是医用金属的研究热点，增材制造可降解金属医用植入物是个新方向，本文重点对增材制造镁基、锌基、铁基可降解金属的工艺流程及影响因素、力学性能、降解行为、生物相容性相关结果进行分析与总结，并展望了增材制造技术在医用可降解金属植入物领域的未来发展方向。

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.Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Zinc has been described as the 'calcium of the twenty-first century'. Zinc-based degradable biomaterials have recently emerged thanks to their intrinsic physiological relevance, biocompatibility, biodegradability, and pro-regeneration properties. Zinc-based biomaterials mainly include: metallic zinc alloys, zinc ceramic nanomaterials, and zinc metal-organic frameworks (MOFs). Metallic zinc implants degrade at a desirable rate, matching the healing pace of local tissues, and stimulating remodeling and formation of new tissues. Zinc ceramic nanomaterials are also beneficial for tissue engineering and therapy thanks to their nanostructures and antibacterial properties. MOFs have large surface areas and are easily functionalized, making them ideal for drug delivery and cancer therapy. This review highlights recent developments in zinc-based biomaterials, discusses obstacles to overcome, and pinpoints directions for future research.Copyright © 2018 Elsevier Ltd. All rights reserved.

Zinc ions are key structural components of a large number of proteins. The binding of zinc stabilizes the folded conformations of domains so that they may facilitate interactions between the proteins and other macromolecules such as DNA. The modular nature of some of these zinc-containing proteins has allowed the rational design of site-specific DNA binding proteins. The ability of zinc to be bound specifically within a range of tetrahedral sites appears to be responsible for the evolution of the side range of zinc-stabilized structural domains now known to exist. The lack of redox activity for the zinc ion and its binding and exchange kinetics also may be important in the use of zinc for specific functional roles.

Zinc is known as an essential nutritional factor in the growth of the human and animals. Bone growth retardation is a common finding in various conditions associated with dietary zinc deficiency. Bone zinc content has been shown to decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting its role in bone disorder. Zinc has been demonstrated to have a stimulatory effect on osteoblastic bone formation and mineralization; the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in the cells, and it stimulates cellular protein synthesis. Zinc has been shown to stimulate gene expression of the transcription factors runt-related transcription factor 2 (Runx2) that is related to differentiation into osteoblastic cells. Moreover, zinc has been shown to inhibit osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-induced osteoclastogenesis. Zinc transporter has been shown to express in osteoblastic and osteoclastic cells. Zinc protein is involved in transcription. The intake of dietary zinc causes an increase in bone mass. beta-Alanyl-L: -histidinato zinc (AHZ) is a zinc compound, in which zinc is chelated to beta-alanyl-L: -histidine. The stimulatory effect of AHZ on bone formation is more intensive than that of zinc sulfate. Zinc acexamate has also been shown to have a potent-anabolic effect on bone. The oral administration of AHZ or zinc acexamate has the restorative effect on bone loss under various pathophysiologic conditions including aging, skeletal unloading, aluminum bone toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen deficiency, diabetes, and fracture healing. Zinc compounds may be designed as new supplementation factor in the prevention and therapy of osteoporosis.

Endothelial cells interact with blood components and the abluminal tissues, thus playing an active role in many aspects of vascular function. Numerous physiologic and pathophysiologic stimuli are often mediated by nutrients that can contribute to the overall functions of endothelial cells in the regulation of vascular tone, coagulation, cellular growth, immune and inflammatory responses. Therefore, nutrient-mediated functional changes of the endothelium and the underlying tissues may be significantly involved in disease processes such as atherosclerosis. There is evidence that individual nutrients or nutrient derivatives may either provoke or prevent metabolic and physiologic perturbations of the vascular endothelium. Diets high in fat and/or calories are considered a risk factor for the development of atherosclerosis. Our research has shown that certain diet-derived lipids and their derivatives can disrupt normal endothelial integrity, thus reducing the ability of the endothelium to act as a selectively permeable barrier to blood components. Mechanisms underlying fatty acid-mediated endothelial cell dysfunction may be related to changes in fatty acid composition as well as to an increase in cellular oxidative stress. Selective lipid accumulation and fatty acid changes in endothelial cells can modulate membrane fluidity, proteoglycan metabolism and signal transduction mechanisms. Most importantly, dietary fats rich in certain unsaturated fatty acids, may be atherogenic by enhancing the formation of reactive oxygen intermediates. A subsequent imbalance in cellular oxidative stress/antioxidant status can activate oxidative stress-responsive transcription factors, which in turn may promote cytokine production, expression of adhesion molecules on the surface of endothelial cells, and thus intensify an inflammatory response in atherosclerosis. Our data also suggest that certain nutrients, which have antioxidant and/or membrane stabilizing properties, can protect endothelial cells by interfering with lipid/cytokine-mediated endothelial cell dysfunction. These findings contribute to the understanding of the interactive role of dietary fats with inflammatory components, as well as with nutrients that exhibit antiatherogenic properties, in the development of atherosclerosis.

Bone homeostasis is regulated through osteoclasts and osteoblasts. Osteoporosis, which is induced with its accompanying decrease in bone mass with increasing age, is widely recognized as a major public health problem. Bone loss may be due to decreased osteoblastic bone formation and increased osteoclastic bone resorption. There is growing evidence that nutritional and food factors may play a part in the prevention of bone loss with aging and have been to be worthy of notice in the prevention of osteoporosis. Zinc, an essential trace element, or genistein, which are contained in soybeans, has been shown to have a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption, thereby increasing bone mass. These factors have an effect on protein synthesis and gene expression, which are related to bone formation in osteoblastic cells and bone resorption in osteoclastic cells. The combination of zinc and genistein is found to reveal the synergistic effect on bone anabolic effect. The oral administration of those factors has been shown to prevent on bone loss in ovariectomized rats, an animal model for osteoporosis, indicating a role in the prevention of osteoporosis. Supplemental intake of ingredient with the combination of zinc and genistein has been shown to have a preventive effect on osteoporosis in human subjects, suggesting a role in the prevention of bone loss.

The quantities of zinc and phytate in the diet are the primary factors determining zinc absorption. A mathematical model of zinc absorption as a function of dietary zinc and phytate can be used to predict dietary zinc requirements and, potentially, enhance our understanding of zinc absorption. Our goal was to develop a model of practical and informative value based on fundamental knowledge of the zinc absorption process and then fit the model to selected published data to assess its validity and estimate parameter values. A model of moderate mathematical complexity relating total zinc absorption to total dietary zinc and total dietary phytate was derived and fit to 21 mean data from whole day absorption studies using nonlinear regression analysis. Model validity, goodness of fit, satisfaction of regression assumptions, and quality of the parameter estimates were evaluated using standard statistical criteria. The fit had an R(2) of 0.82. The residuals were found to exhibit a normal distribution, constant variance, and independence. The parameters of the model, A(MAX), K(R), and K(P), were estimated to have values of 0.13, 0.10, and 1.2 mmol/d, respectively. Several of these estimates had wide CI attributable in part to the small number and the scatter of the data. The model was judged to be valid and of immediate value for studying and predicting absorption. A version of the model incorporating a passive absorption mechanism was not supported by the available data.

Biodegradable metals (BMs) gradually degrade by releasing corrosion products once exposed to the physiological environment in the body. Complete dissolution of biodegradable implants assists tissue healing, with no implant residues in the surrounding tissues. In recent years, three classes of BMs have been extensively investigated, including magnesium (Mg)-based, iron (Fe)-based, and zinc (Zn)-based BMs. Among these three BMs, Mg-based materials have undergone the most clinical trials. However, Mg-based BMs generally exhibit faster degradation rates, which may not match the healing periods for bone tissue, whereas Fe-based BMs exhibit slower and less complete degradation. Zn-based BMs are now considered a new class of BMs due to their intermediate degradation rates, which fall between those of Mg-based BMs and Fe-based BMs, thus requiring extensive research to validate their suitability for biomedical applications. In the present study, recent research and development on Zn-based BMs are reviewed in conjunction with discussion of their advantages and limitations in relation to existing BMs. The underlying roles of alloy composition, microstructure, and processing technique on the mechanical and corrosion properties of Zn-based BMs are also discussed.© 2020 [The Author/The Authors].

Zinc (Zn) is a promising bioresorbable implant material with more moderate degradation rate compared to magnesium (Mg) and iron (Fe). However, the low mechanical strength and localized degradation behavior of pure Zn limit its clinical applications. Alloying is one of the most effective ways to overcome these limitations. After screening the alloying element candidates regarding their potentials for improvement on the degradation and biocompatibility, we proposed Fe as the alloying element for Zn, and investigated the and performances of these alloys in both subcutaneous and femoral tissues. Results showed that the uniformly distributed secondary phase in Zn-Fe alloys significantly improved the mechanical property and facilitated uniform degradation, which thus enhanced their biocompatibility, especially the Zn-0.4Fe alloy. Moreover, these Zn-Fe alloys showed outstanding antibacterial property. Taken together, Zn-Fe alloys could be promising candidates as bioresorbable medical implants for various cardiovascular, wound closure, and orthopedic applications.© 2022 The Authors.

Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures. Biodegradable Zn metals are revolutionary materials for orthopedic implants. In this study, pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion (L-PBF) technology. First, the mechanical properties, corrosion behavior, and biocompatibility of the pure Zn porous scaffolds were characterized. The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks. The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone, as well as relatively suitable degradation rates for bone regeneration. A benign host response was observed using hematoxylin and eosin (HE) staining of the heart, liver, spleen, lungs, and kidneys. Moreover, the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability. This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.© 2022 The Authors.

The manner in which a mutually acceptable co-existence of biomaterials and tissues is developed and sustained has been the focus of attention in biomaterials science for many years, and forms the foundation of the subject of biocompatibility. There are many ways in which materials and tissues can be brought into contact such that this co-existence may be compromised, and the search for biomaterials that are able to provide for the best performance in devices has been based upon the understanding of all the interactions within biocompatibility phenomena. Our understanding of the mechanisms of biocompatibility has been restricted whilst the focus of attention has been long-term implantable devices. In this paper, over 50 years of experience with such devices is analysed and it is shown that, in the vast majority of circumstances, the sole requirement for biocompatibility in a medical device intended for long-term contact with the tissues of the human body is that the material shall do no harm to those tissues, achieved through chemical and biological inertness. Rarely has an attempt to introduce biological activity into a biomaterial been clinically successful in these applications. This essay then turns its attention to the use of biomaterials in tissue engineering, sophisticated cell, drug and gene delivery systems and applications in biotechnology, and shows that here the need for specific and direct interactions between biomaterials and tissue components has become necessary, and with this a new paradigm for biocompatibility has emerged. It is believed that once the need for this change is recognised, so our understanding of the mechanisms of biocompatibility will markedly improve.

The situations in which biomaterials are currently used are vastly different to those of just a decade ago. Although implantable medical devices are still immensely important, medical technologies now encompass a range of drug and gene delivery systems, tissue engineering and cell therapies, organ printing and cell patterning, nanotechnology based imaging and diagnostic systems and microelectronic devices. These technologies still encompass metals, ceramics and synthetic polymers, but also biopolymers, self assembled systems, nanoparticles, carbon nanotubes and quantum dots. These changes imply that our original concepts of biomaterials and our expectations of their performance also have to change. This Leading Opinion Paper addresses these issues. It concludes that many substances which hitherto we may not have thought of as biomaterials should now be considered as such so that, alongside the traditional structural biomaterials, we have substances that have been engineered to perform functions within health care where their performance is directly controlled by interactions with tissues and tissue components. These include engineered tissues, cells, organs and even viruses. This essay develops the arguments for a radically different definition of a biomaterial.

Most cast dental restorations are made from alloys or commercially pure titanium (cpTi). Many orthodontic appliances are also fabricated from metallic materials. It has been documented in vitro and in vivo that metallic dental devices release metal ions, mainly due to corrosion. Those metallic components may be locally and systemically distributed and could play a role in the etiology of oral and systemic pathological conditions. The quality and quantity of the released cations depend upon the type of alloy and various corrosion parameters. No general correlation has been observed between alloy nobility and corrosion. However, it has been documented that some Ni-based alloys, such as beryllium-containing Ni alloys, exhibit increased corrosion, specifically at low pH. Further, microparticles are abraded from metallic restorations due to wear. In sufficient quantities, released metal ions-particularly Cu, Ni, Be, and abraded microparticles-can also induce inflammation of the adjacent periodontal tissues and the oral mucosa. While there is also some in vitro evidence that the immune response can be altered by various metal ions, the role of these ions in oral inflammatory diseases such as gingivitis and periodontitis is unknown. Allergic reactions due to metallic dental restorations have been documented. Ni has especially been identified as being highly allergenic. Interestingly, from 34% to 65.5% of the patients who are allergic to Ni are also allergic to Pd. Further, Pd allergy always occurrs with Ni sensitivity. In contrast, no study has been published which supports the hypothesis that dental metallic materials are mutagenic/genotoxic or might be a carcinogenic hazard to man. Taken together, very contradictory data have been documented regarding the local and systemic effects of dental casting alloys and metallic ions released from them. Therefore, it is of critical importance to elucidate the release of cations from metallic dental restorations in the oral environment and to determine the biological interactions of released metal components with oral and systemic tissues.

In-stent restenosis is a complication which impairs the success of coronary stenting. Recently, it was supposed that a delayed hypersensitivity reaction to nickel and molybdenum might be one of the triggering factors in in-stent restenosis. We have analyzed the data collected in our centre with respect to this hypothesis. Altogether, 34 patients were investigated (24 male, 10 female). Patch tests were performed with the standard series of the German Contact Dermatitis Research Group and a metal series containing the metal components of 316 L stainless steel. A positive patch test reaction to nickel was observed in 4 (11.8%) patients. None of the patients showed sensitization to the other metals. Retrospective analysis was performed in 20 patients: 2 of these patients had a positive patch test reaction to nickel, one of whom had an in-stent restenosis, and the other not. Restenoses were predominantly observed in patients with negative patch test reactions to nickel (6/18 patients). Out of the patients who were investigated prospectively only one showed sensitization to nickel. Restenosis was observed in 2 patients: neither patient had nickel allergy. Although it still cannot be excluded that metal allergy may play a role in the restenosis process in coronary stenting, there is at present little evidence for it.

To evaluate different grades of in-stent stenosis in a nickel-titanium stent with MRI.Magnetic resonance phase velocity mapping (MR-PVM) was used to measure flow velocity through a 9-mm NiTi stent with three different degrees of stenosis in a phantom study. The tested stenotic geometries were 1) axisymmetric 75%, 2) axisymmetric 90%, and 3) asymmetric 50%. The MR-PVM data were subsequently compared with the velocities from computational fluid dynamic (CFD) simulations of identical conditions.Good quantitative agreement in velocity distribution for the 50% and 75% stenoses was observed. The agreement was poor for the 90% stenosis, most likely due to turbulence and the high-velocity gradients found in the small luminal area relative to the pixel resolution in our imaging settings.The accuracy of the MRI velocities inside the stented area renders MRI a modality that may be used to assess moderate to severe in-stent restenosis (ISR) in medium-sized vascular stents in peripheral vessels, such as the iliac, carotid, and femoral arteries. Advances in MR instrumentation may provide sufficient resolution to obtain adequate velocity information from smaller vessels, such as the coronary arteries, and allow MRI to substitute for invasive and expensive catheterization procedures currently in clinical use.(c) 2005 Wiley-Liss, Inc.

Bacterial adhesion and biofilm formation impose a heavy burden on the medical system. Bacterial adhesion on implant materials would induce inflammation and result in implant failure. The adhesion of bacteria on food-processing and handling equipment may lead to food-borne illness. To reduce and even prevent bacterial adhesion, some bacterial anti-adhesion surface designs have been developed. However, the effect of some surface properties (including surface patterning, roughness and wettability) on bacterial adhesion has not been systematically summarized. In this review, a comprehensive overview of bacterial anti-adhesion surface design is presented. Modifying the surface pattern and roughness could reduce the contact area between bacteria and surfaces to weaken the initial adhesion force. Fabricating superhydrophobic surface or modifying hydrophilic functional groups could hinder the bacterial adhesion. The analysis and discussion about influencing factors of bacterial anti-adhesion surfaces provide basic guidelines on antibacterial surface design for future researches.

Biodegradable zinc (Zn) metals, a new generation of biomaterials, have attracted much attention due to their excellent biodegradability, bioabsorbability, and adaptability to tissue regeneration. Compared with magnesium (Mg) and iron (Fe), Zn exhibits better corrosion and mechanical behaviors in orthopedic and stent applications. After implantation, Zn containing material will slowly degrade, and Zn ions (Zn) will be released to the surrounding tissue. For stent applications, the local Znconcentration near endothelial tissue/cells could be high. However, it is unclear how endothelia will respond to such high concentrations of Zn, which is pivotal to vascular remodeling and regeneration. Here, we evaluated the short-term cellular behaviors of primary human coronary artery endothelial cells (HCECs) exposed to a concentration gradient (0-140 μM) of extracellular Zn. Zn had an interesting biphasic effect on cell viability, proliferation, spreading, and migration. Generally, low concentrations of Zn promoted viability, proliferation, adhesion, and migration, while high concentrations of Zn had opposite effects. For gene expression profiles, the most affected functional genes were related to cell adhesion, cell injury, cell growth, angiogenesis, inflammation, vessel tone, and coagulation. These results provide helpful information and guidance for Zn-based alloy design as well as the controlled release of Znin stent and other related medical applications.

Zinc (Zn) and its alloys have recently been introduced as a new class of biodegradable metals with potential application in biodegradable vascular stents. Although an in vivo feasibility study pointed to outstanding biocompatibility of Zn-based implants in vascular environments, a thorough understanding of how Zn and Zn affect surrounding cells is lacking. In this comparative study, three vascular cell types-human endothelial cells (HAEC), human aortic smooth muscle cells (AoSMC), and human dermal fibroblasts (hDF)-were studied to advance the understanding of Zn/Zn-cell interactions. Aqueous cytotoxicity using a Zn insult assay resulted in LD values of 50 µM for hDF, 70 µM for AoSMC, and 265 µM for HAEC. Direct cell contact with the metallic Zn surface resulted initially in cell attachment, but was quickly followed by cell death. After modification of the Zn surface using a layer of gelatin-intended to mimic a protein layer seen in vivo-the cells were able to attach and proliferate on the Zn surface. Further experiments demonstrated a Zn dose-dependent effect on cell spreading and migration, suggesting that both adhesion and cell mobility may be hindered by free Zn.

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 (Zn) alloys have been considered as promising absorbable metals, mainly due to their moderate degradation rates ranging between magnesium alloys and iron alloys. The degradation behavior depends on the specific physiological environment. Released metallic ions and corrosion products directly influence biocompatibility. The initial contact of orthopedic implants or vascular stents after implantation will be with blood. In this study, fetal bovine serum (FBS) was used as a model system of blood components. We investigated the influence of FBS on in vitro degradation behavior and cytotoxicity of pure Zn, and Zn-4Ag and Zn-2Ag-1.8Au-0.2 V (wt%) alloys. The initial degradation rates in FBS were assessed and compared with the degradation and toxicity in four other common physiological model systems: DMEM cell culture medium ± FBS and McCoy's 5A medium ± FBS. Test samples in pure FBS showed the highest initial degradation rates, and accordingly, FBS supplemented media accelerated the degradation process as well. Moreover, an extract test according to ISO 10993-5 and -12 with L929 and Saos-2 cells was performed to investigate the role of FBS in the extraction medium. The cytotoxic effects observed in the tests were correlated with FBS-mediated Zn release. These findings have significant implications regarding the selection of appropriate media for in vitro degradation and cytotoxicity evaluation of Zn and its alloys. STATEMENT OF SIGNIFICANCE: Metallic zinc and its alloys have been considered as promising biodegradable metals, mainly due to their moderate degradation rates. However, in vitro cytotoxicity tests according to the current ISO 10993 standard series are not suitable to predict biocompatibility of Zn alloys due to the inconsistent correlation between in vitro and in vitro biocompatibility. In this study, we show that the outcomes of standardized in vitro cytotoxicity tests of Zn and Zn alloys are influenced by fetal bovine serum in the extraction vehicle because FBS promotes Zn release during the extraction process. The results of the study provide significant information for selection of appropriate model systems to evaluate in vitro degradation behavior and cytotoxicity.Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

As one of the most promising medical metal implants, magnesium (Mg) or its alloys have shown significant advantages over other candidates attributed to not only their excellent biodegradability and suitable mechanical properties but also their osteopromotive effects for bone applications. Prior to approval mandated by the governmental regulatory body, the access to the medical market for Mg-based implants requires a series of testing for assurance of their safety and efficacy via preclinical evaluations and clinical tests including phase 1 and 2 evaluations, and phase 3 of multi-center randomized double blind and placebo-controlled clinical trials. However, as the most widely used protocols for biosafety evaluation of medical devices, current ISO 10993 standards should be carefully reevaluated when directly applying them to predict potential health risks of degradable Mg based biomaterials via cytotoxicity tests due to the huge gap between in vitro and in vivo conditions. Therefore, instead of a direct adoption, modification of current ISO standards for in vitro cytotoxicity test is desirable and justified. The differences in sensitivities of cells to in vitro and in vivo Mg ions and the capability of in vivo circulation system to dilute local degradation products were fully considered to propose modification of current ISO standards. This paper recommended a minimal 6 times to a maximal 10 times dilution of extracts for in vitro cytotoxicity test specified in ISO 10993 part 5 for pure Mg developed as potential orthopedic implants based on literature review and our specifically designed in vitro and in vivo tests presented in the study. Our work may contribute to the progress of biodegradable metals involved translational work. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Hemostasis is a remarkable and a remarkably complex mechanism. It can maintain blood in a fluid state intravascularly but very quickly changes blood to a jellylike mass upon disruption of the vasculature. This review will give a synopsis of the 3 phases of hemostasis: platelet, vascular, and coagulation. Fibrinolysis and control mechanisms of hemostasis will also be covered. In addition, brief descriptions of the clinical and laboratory evaluation of patients and the diagnosis of bleeding disorders will be presented.

Platelets were discovered by G. Bizzozero in 1882 and rediscovered in the 1960s after many decades of oblivion. Interestingly enough, their role was initially more clearly associated with thrombosis than with hemostasis. For many years a serious unresolved problem was that the clotting time was normal even in severe thrombocytopenia. The concept of coagulation as an enzymatic cascade had not yet been elaborated. During the 1960s, the interest of many experts moved from the interaction of platelets with the process of blood coagulation to the interaction of these cells with the vascular wall (adhesion) and each other (aggregation). The discovery of the role of ADP as the principle of platelet aggregation stimuli was rapidly followed by other important discoveries such as the aggregating properties of collagen and thrombin, the release reaction, the metabolism of arachidonic acid, and the inhibitory effect of aspirin. The use of aspirin as a potential antithrombotic drug has made the history of clinical trials in the last 30 years. The last two decades have been characterized by an explosion of cell and molecular biology approaches. There are presently people who study platelet signal transduction or platelet-leukocyte interactions but who know almost nothing about hemostasis or thrombosis! This is due not only to the intrinsic limitations of the biological approach but also to the progressive recognition of the role of platelets in other physiopathologic and clinical conditions such as inflammation, cancer growth and dissemination, and organ transplant rejection. Overlooked for more than two centuries after the microscope was made available to hematologists, considered as an artifact or a Cinderella, the platelet has mainly been considered in the past 30 years as a dangerous cell to be inhibited by (ever more expensive) drugs. But the taming of the shrew is far from being achieved.

In the present study, pure zinc stents were implanted into the abdominal aorta of rabbits for 12 months. Multiscale analysis including micro-CT, scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM) and histological stainings was performed to reveal the fundamental degradation mechanism of the pure zinc stent and its biocompatibility. The pure zinc stent was able to maintain mechanical integrity for 6 months and degraded 41.75 ± 29.72% of stent volume after 12 months implantation. No severe inflammation, platelet aggregation, thrombosis formation or obvious intimal hyperplasia was observed at all time points after implantation. The degradation of the zinc stent played a beneficial role in the artery remodeling and healing process. The evolution of the degradation mechanism of pure zinc stents with time was revealed as follows: Before endothelialization, dynamic blood flow dominated the degradation of pure zinc stent, creating a uniform corrosion mode; After endothelialization, the degradation of pure zinc stent depended on the diffusion of water molecules, hydrophilic solutes and ions which led to localized corrosion. Zinc phosphate generated in blood flow transformed into zinc oxide and small amounts of calcium phosphate during the conversion of degradation microenvironment. The favorable physiological degradation behavior makes zinc a promising candidate for future stent applications.Copyright © 2017 Elsevier Ltd. All rights reserved.

Implanted biomedical devices are of increasing importance in modern medical care. However, surprisingly little is known of the factors that determine biocompatibility of the materials used in these devices. These materials, although generally inert and non-toxic, can mediate a variety of adverse reactions, including inflammation, fibrosis, coagulation, and infection. This brief review focuses on the inflammatory responses (including fibrosis) that commonly occur around implanted biomaterials. Host proteins that spontaneously associate with implant surfaces are important determinants of the acute inflammatory response. In this regard, adsorbed fibrinogen appears particularly pro-inflammatory. Chronic inflammatory processes, in many cases in response to fragments of implanted biomaterials, may cause implant failure. In the case of silicone-filled mammary prostheses, the extravasation of silicone gel has been held responsible for a number of complications, including silicone granuloma, synovitis, connective-tissue disease, and lymphadenopathy. In some instances, material-mediated inflammatory responses may even cause degradation of the material itself (via oxidative products released by implant-associated inflammatory cells). Overall, there is insufficient knowledge of the determinants and mechanisms of host: implant responses. A clear understanding of tissue:biomaterial interactions will be required both to explain the pathogenesis of many implant-mediated complications and to aid in the development of more biocompatible materials for implantable devices.

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 ± 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.Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Metallic zinc implanted into the abdominal aorta of rats out to 6months has been demonstrated to degrade while avoiding responses commonly associated with the restenosis of vascular implants. However, major questions remain regarding whether a zinc implant would ultimately passivate through the production of stable corrosion products or via a cell mediated fibrous encapsulation process that prevents the diffusion of critical reactants and products at the metal surface. Here, we have conducted clinically relevant long term in vivo studies in order to characterize late stage zinc implant biocorrosion behavior and products to address these critical questions. We found that zinc wires implanted in the murine artery exhibit steady corrosion without local toxicity for up to at least 20months post-implantation, despite a steady buildup of passivating corrosion products and intense fibrous encapsulation of the wire. Although fibrous encapsulation was not able to prevent continued implant corrosion, it may be related to the reduced chronic inflammation observed between 10 and 20months post-implantation. X-ray elemental and infrared spectroscopy analyses confirmed zinc oxide, zinc carbonate, and zinc phosphate as the main components of corrosion products surrounding the Zn implant. These products coincide with stable phases concluded from Pourbaix diagrams of a physiological solution and in vitro electrochemical impedance tests. The results support earlier predictions that zinc stents could become successfully bio-integrated into the arterial environment and safely degrade within a time frame of approximately 1-2years.Previous studies have shown zinc to be a promising candidate material for bioresorbable endovascular stenting applications. An outstanding question, however, is whether a zinc implant would ultimately passivate through the production of stable corrosion products or via a cell mediated tissue encapsulation process that prevented the diffusion of critical reactants and products at the metal surface. We found that zinc wires implanted in the murine artery exhibit steady corrosion for up to at least 20months post-implantation. The results confirm earlier predictions that zinc stents could safely degrade within a time frame of approximately 1-2years.Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

Bone defects are commonly caused by severe trauma, malignant tumors, or congenital diseases and remain among the toughest clinical problems faced by orthopedic surgeons, especially when of critical size. Biodegradable zinc-based metals have recently gained popularity for their desirable biocompatibility, suitable degradation rate, and favorable osteogenesis-promoting properties. The biphasic activity of Sr promotes osteogenesis and inhibits osteoclastogenesis, which imparts Zn-Sr alloys with the ideal theoretical osteogenic properties. Herein, a biodegradable Zn-Sr binary alloy system was fabricated. The cytocompatibility and osteogenesis of the Zn-Sr alloys were significantly better than those of pure Zn in MC3T3-E1 cells. RNA-sequencing illustrated that the Zn-0.8Sr alloy promoted osteogenesis by activating the wnt/β-catenin, PI3K/Akt, and MAPK/Erk signaling pathways. Furthermore, rat femoral condyle defects were repaired using Zn-0.8Sr alloy scaffolds, with pure Ti as a control. The scaffold-bone integration and bone ingrowth confirmed the favorable in vivo repair properties of the Zn-Sr alloy, which was verified to offer satisfactory biosafety based on the hematoxylin-eosin (H&E) staining and ion concentration testing of important organs. The Zn-0.8Sr alloy was identified as an ideal bone repair material candidate, especially for application in critical-sized defects on load-bearing sites due to its favorable biocompatibility and osteogenic properties in vitro and in vivo.© 2020 [The Author/The Authors].

Magnesium-based biodegradable metals (BMs) as bone implants have better mechanical properties than biodegradable polymers, yet their strength is roughly less than 350 MPa. In this work, binary Zn alloys with alloying elements Mg, Ca, Sr, Li, Mn, Fe, Cu, and Ag respectively, are screened systemically by in vitro and in vivo studies. Li exhibits the most effective strengthening role in Zn, followed by Mg. Alloying leads to accelerated degradation, but adequate mechanical integrity can be expected for Zn alloys when considering bone fracture healing. Adding elements Mg, Ca, Sr and Li into Zn can improve the cytocompatibility, osteogenesis, and osseointegration. Further optimization of the ternary Zn-Li alloy system results in Zn-0.8Li-0.4Mg alloy with the ultimate tensile strength 646.69 ± 12.79 MPa and Zn-0.8Li-0.8Mn alloy with elongation 103.27 ± 20%. In summary, biocompatible Zn-based BMs with strength close to pure Ti are promising candidates in orthopedics for load-bearing applications.

Zn-0.8 wt.% Li-0.1 wt.% Mn wire with the diameter of 0.3 mm was fabricated and further processed into gastrointestinal staple, and its in vitro and in vivo biodegradation behavior and biocompatibility were studied systematically. The experimental Zn-Li-Mn alloy staple could deform from the original U-shape to B-shape without fracture, indicating its good mechanical property. Due to the residual stress concentration caused by anastomosis deformation, the feet and leg arc part of the staple were more prone to degradation. The Zn-Li-Mn alloy staple sustained integrity after immersion in Hanks' solution and simulated gastric fluid (SGF) for 28 days, and the degradation rate in SGF was about 4 times of that in Hanks' solution. Furthermore, Zn-Li-Mn alloy staples were utilized for gastrointestinal anastomosis in pig models, with clinically-used titanium alloy staples as a comparison. No anastomotic leakage and severe inflammation were observed after operation. The Zn-Li-Mn alloy staple maintained mechanical integrity within 8 weeks' implantation. The gastrointestinal tissue healed after 12 weeks, and no obvious side effects were detected during the whole implantation period, demonstrating the good biocompatibility of Zn-Li-Mn alloy staple. Thus, Zn-Li-Mn alloy staple fabricated in this work displayed the promising potential in the gastrointestinal anastomosis.Copyright © 2020. Published by Elsevier Ltd.

Bone and joint-related infections remain the primary and most critical complications of orthopedic surgery. We have innovatively prepared Zn-Cu alloys to achieve outstanding material and antibacterial properties. In this study, we systematically assessed the material properties and antibacterial activity of these Zn-Cu alloys. Our results showed that the Zn-2Cu alloy had the best mechanical properties, biocompatibility, and osteogenic properties. Findings of microbial cultures, CLSM, SEM, and TEM indicated that Zn-2Cu alloy can inhibit both coagulase-positive and coagulase-negative staphylococci, as well as antibiotic-resistant strains (MRSA and MRSE), by preventing the bacteria adhesion and the biofilm formation. Zn-2Cu alloy could broadly affect the expression of MRSA genes associated with adhesion, autolysis, biofilm formation, virulence, and drug resistance. A rat femur intramedullary nail infection-prevention model was established and the Zn-2Cu alloy-treated group showed significant antibacterial activity against MRSA and reduced the inflammatory toxic side-effects and infection-related bone loss. Collectively, our results indicate the potential utility of Zn-Cu alloy implants with 2 wt% Cu in treating orthopedic infections. Statement of significance: Osteomyelitis is a serious complication of orthopedic surgeries. Wide use of antibiotics contributes to the appearance of multi-drug resistant strains like methicillin-resistant staphylococcus aureus (MRSA). Alternatively, anti-osteomyelitis implants with broad-spectrum antibacterial properties can be favorable. Here, the antibacterial performance of biodegradable Zn-Cu alloys was evaluated with four different bacteria strains including antibiotic-resistant strains (MRSA and MRSE). Zn-Cu alloys exert excellent bacterial killing capability in all strains. In a rat femur infection model, the alloy showed significant antibacterial activity against MRSA and reduced inflammatory toxic side-effects as well as infection-related bone loss. The antibacterial property of Zn-2Cu alloy was associated with inhibition of gene expression related to wall synthesis, adhesion, colonization, biofilm formation, autolysis, and secretion of virulence factors in MRSA.Copyright © 2020. Published by Elsevier Ltd.

Zinc (Zn) alloys are receiving increasing attention in the field of biodegradable implant materials due to their unique combination of suitable biodegradability and good biological functionalities. However, the currently existing industrial Zn alloys are not necessarily biocompatible, nor sufficiently mechanically strong and wear-resistant. In this study, a Zn-1Cu-0.1Ti alloy is developed with enhanced mechanical strength, corrosion wear property, biocompatibility, and antibacterial ability for biodegradable implant material applications. HR and HR + CR were performed on the as-cast alloy and its microstructure, mechanical properties, frictional and wear behaviors, corrosion resistance, in vitro cytocompatibility, and antibacterial ability were systematically assessed. The microstructures of the Zn-1Cu-0.1Ti alloy after different deformation conditions included a η-Zn phase, a ε-CuZn phase, and an intermetallic phase of TiZn. The HR+CR sample of Zn-1Cu-0.1Ti exhibited a yield strength of 204.2 MPa, an ultimate tensile strength of 249.9 MPa, and an elongation of 75.2%; significantly higher than those of the HR alloy and the AC alloy. The degradation rate in Hanks' solution was 0.029 mm/y for the AC alloy, 0.032 mm/y for the HR+CR alloy, and 0.034 mm/y for the HR alloy. The HR Zn-1Cu-0.1Ti alloy showed the best wear resistance, followed by the AC alloy and the alloy after HR + CR. The extract of the AC Zn-1Cu-0.1Ti alloy showed over 80% cell viability with MC3T3-E1 pre-osteoblast and MG-63 osteosarcoma cells at a concentration of ≤ 25%. The as-cast Zn-1Cu-0.1Ti alloy showed good blood compatibility and antibacterial ability. STATEMENT OF SIGNIFICANCE: This work repots a Zn-1Cu-0.1Ti alloy with enhanced mechanical strength, corrosion wear property, biocompatibility, and antibacterial ability for biodegradable implant applications. Our findings showed that Zn-1Cu-0.1Ti after hot-rolling plus cold-rolling exhibited a yield strength of 204.2 MPa, an ultimate tensile strength of 249.9 MPa, an elongation of 75.2%, and a degradation rate of 0.032 mm/y in Hanks' Solution. The hot-rolled Zn-1Cu-0.1Ti showed the best wear resistance. The extract of the as-cast alloy at a concentration of ≤ 25% showed over 80% cell viability with MC3T3-E1 and MG-63 cells. The Zn-1Cu-0.1Ti alloy showed good hemocompatibility and antibacterial ability.Copyright © 2020. Published by Elsevier Ltd.

Zinc (Zn) alloys have attracted much attention for biomedical applications due to their biodegradability, biocompatibility, and biological functionalities. Zn alloy foams have high potential to be used as regenerative medical implants by virtue of their porous structure, which allows new bone tissue ingrowth, their low elastic modulus approximating that of natural bone, and their biodegradation, which eliminates the need for follow-up surgery to remove the implants after bone tissue healing. In this context, a biodegradable Zn-Cu foam was fabricated by electrochemical deposition on a foamed Cu template and given a subsequent diffusion heat treatment. The microstructure, mechanical properties, degradation behavior, toxicity, hemolysis percentages, and antibacterial effects of the Zn-Cu foams were assessed for biomedical applications. The Zn-Cu foams exhibited a yield strength of ~12.1 MPa, a plateau strength of 16.8 MPa, and a strain over 50% under compression tests. The corrosion rate of the Zn-Cu foams measured by electrochemical polarization testing was 0.18 mm/y. The Zn-Cu foams showed good blood compatibility with a hemolysis percentage of less than 5%. Cytotoxicity assessment indicated that a 100% concentration of the Zn-Cu foam extract showed clear cytotoxicity against MC3T3-E1 osteoblast cells, but a 12.5% concentration of the extract showed > 90% cell viability. Moreover, the Zn-Cu foams showed good antibacterial effects. STATEMENT OF SIGNIFICANCE: This work reportsa biodegradable Zn-Cu foam with high mechanical strength and ductility, suitable degradation rate, good antibacterial capacity, and good hemolysis property and biocompatibility. The Zn-Cu foam exhibited a yield strength of ~12.1 MPa, a plateau strength of 16.8 MPa, and a strain over 50% under compression tests. The corrosion rate of the Zn-Cu foam measured by electrochemical polarization testing was 0.18 mm/y in Hanks' Solutions. The Zn-Cu foam showed good blood compatibility with a hemolysis percentage of less than 5%. Cytotoxicity assessment indicated that a 12.5% concentration of the foam extract showed > 90% cell viability. Moreover, the Zn-Cu foam showed good antibacterial effects against S. aureus.Copyright © 2019. Published by Elsevier Ltd.

The widespread use of orthopedic implants to support or replace bones is increasingly threatened by the risk of incurable bacterial infections, impenetrable microbial biofilms, and irreversible antibiotic resistance. In the past, the development of anti-infective biomaterials focused solely on direct antibacterial properties while ignoring the host's immune response. Inspired by the clearance of infection by the innate neutrophil response and participation in anti-infectious immunity of Zn ions, we report an innovative neutrophil extracellular traps (NETs) strategy, induced by biodegradable pure Zn, which achieved therapeutic efficacy toward biomaterial-related infections. Our and data showed that pure Zn was favorable for NETs formation by promoting the release of DNA fibers and granule proteins in a reactive oxygen species (ROS)-dependent manner, thereby retraining and degrading bacteria with an efficiency of up to 99.5%. Transcriptome analysis revealed that cytoskeletal rearrangement and toll-like receptor (TLR) signaling pathway were also involved in Zn-induced NETs formation. Furthermore, the results of a ()-infected rat model verified that pure Zn potentiated the bactericidal capability of neutrophils around implants, and promoted osseointegration in -infected rat femurs. This antibacterial immunity concept lays a foundation for the development of other antibacterial biomaterials and holds great promise for treating orthopedic infections.© 2022 The Authors.