Bioabsorbable Metal Research Articles

Osteogenesis or Apoptosis-Twofold Effects of Zn2+ on Bone Marrow Mesenchymal Stem Cells: An In Vitro and In Vivo Study.

Zinc (Zn) is a bioabsorbable metal that shows great potential as an implant material for orthopedic applications. Suitable concentrations of zinc ions promote osteogenesis, while excess zinc ions cause apoptosis. As a result, the conflicting impacts of Zn2+ concentration on osteogenesis could prove to be significant problems for the creation of novel materials. This study thoroughly examined the cell viability, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) cultured in various concentrations of Zn2+ in vitro and validated the osteogenesis effects of zinc implantation in vivo. The effective promotion of cell survival, proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell (BMSCs) may be achieved at a low concentration of Zn2+ (125 μM). The excessively high concentration of zinc ions (>250 μM) not only reduces BMSCs' viability and proliferation but also causes them to suffer apoptosis due to the disturbed zinc homeostasis and excessive Zn2+. Moreover, transcriptome sequencing was used to examine the underlying mechanisms of zinc-induced osteogenic differentiation with particular attention paid to the PI3K-AKT and TGF-β pathways. The present investigation elucidated the dual impacts of Zn2+ microenvironments on the osteogenic characteristics of rBMSCs and the associated processes and might offer significant insights for refining the blueprint for zinc-based biomaterials.

Bioabsorbable zinc alloys for use in urological surgery

Non-absorbable clips are widely used in urologic surgery and they may come in contact with an open urinary tract intraoperatively. As a result, stray clips in the urinary tract and associated intractable infections have been reported. We developed a bioabsorbable metal and evaluated whether it would dissolve if it strayed into the urinary tract. We prepared four types of alloys mainly comprising zinc (Zn) with small amounts of magnesium (Mg) and strontium (Sr), and the biological effects, degradability, strength, and ductility were investigated. Each alloy was implanted in the bladder of five rats for 4, 8, and 12weeks. The alloys were removed and evaluated for degradability, stone adhesion, and tissue changes. The Zn-Mg-Sr alloy had degradability and no stone adhesion in the rat experiments, and it was implanted in the bladders of five pigs for 24weeks. The Mg and Zn levels in the blood were measured, and staple changes were confirmed by cystoscopy. Zn-Mg-Sr alloys showed the best degradability of 6.51% at 12weeks. In pig experiments, the degradation rate was 3.72% at 24weeks. None of the pigs had changes in the Zn or Mg concentrations in the blood. Overall, the bladder incision was healed and the gross pathology showed wound healing. The Zn-Mg-Sr alloys were safely used in animal experiments. Furthermore, the alloys are easy to process and can be formed into various shapes, such as staples, making them useful in robotic surgery.

Facile fabrication of biodegradable endothelium-mimicking coatings on bioabsorbable zinc-alloy stents by one-step electrophoretic deposition.

The zinc-alloy stent is one of the best potential candidates for bioabsorbable metal stents because of its appropriate corrosion rate aligned to the duration of the healing process of the surrounding vessel tissues. However, excessive release of zinc ions, causing cytotoxicity of endothelial cells, and insufficient surface bio-functions of Zn-alloy stents lead to considerable challenge in their application. Herein, one-step electrophoretic deposition was employed to apply a hybrid coating of polycarbonate, tannic acid, and copper ions with tailored functions on Zn-alloy stents to enhance their corrosion resistance and provide an endothelium-mimicking surface. Specifically, the synthesized amino-functionalized aliphatic polycarbonates endowed the hybrid coating with specific surface-erosion properties, resulting in superior corrosion resistance and long-term stability in degradation tests both in vitro and in vivo. The immobilized copper ions enabled the catalytic generation of nitric oxide and promoted the adhesion and proliferation of endothelial cells on zinc alloy. The added tannic acid firmly chelated the copper ions and formed durable phenolic-copper-amine crosslinked networks by electrostatic interaction, resulting in long-term stability of the hybrid coating during the 21 day dynamic immersion test. Tannic acid exerted a synergistic antibacterial effect with copper ions as well as a reduction in the inflammatory response to the zinc substrate. In addition, the hybrid coating improved the in vitro hemocompatibility of zinc alloys. By adjusting the amount of chelated copper in the coating system, the biological function of the corresponding coatings can be controlled, providing a facile surface treatment strategy to promote the progress of zinc-alloy stents in clinical applications.

Bioabsorbable metal zinc differentially affects mitochondria in vascular endothelial and smooth muscle cells

Zinc is an essential trace element having various structural, catalytic and regulatory interactions with an estimated 3000 proteins. Zinc has drawn recent attention for its use, both as pure metal and alloyed, in arterial stents due to its biodegradability, biocompatibility, and low corrosion rates. Previous studies have demonstrated that zinc metal implants prevent the development of neointimal hyperplasia, which is a common cause of restenosis following coronary intervention. This suppression appears to be smooth muscle cell-specific, as reendothelization of the neointima is not inhibited. To better understand the basis of zinc's differential effects on rat aortic smooth muscle (RASMC) versus endothelial (RAENDO) cells, we conducted a transcriptomic analysis of both cell types following one-week continuous treatment with 5 µM or 50 µM zinc. This analysis indicated that genes whose protein products regulate mitochondrial functions, including oxidative phosphorylation and fusion/fission, are differentially affected by zinc in the two cell types. To better understand this, we performed Seahorse metabolic flux assays and quantitative imaging of mitochondrial networks in both cell types. Zinc treatment differently affected energy metabolism and mitochondrial structure/function in the two cell types. For example, both basal and maximal oxygen consumption rates were increased by zinc in RASMC but not in RAENDO. Zinc treatment increased apparent mitochondrial fusion in RASMC cells but increased mitochondrial fission in RAENDO cells. These results provide some insight into the mechanisms by which zinc treatment differently affects the two cell types and this information is important for understanding the role of zinc treatment in vascular cells and improving its use in biodegradable metal implants.

The use of bioabsorbable materials in orthopaedics

Bioabsorbable materials manufactured into fracture fixation devices dissolve slowly in the physiological environment, allowing gradual transfer of stresses to the healing tissue. This removes the need for implant removal surgery and reduces the risks of long term complications seen with bioinert materials, such as: stress shielding, migration, late infection and interference with imaging. When choosing a bioabsorbable material it is important to consider its mechanical properties and its biocompatibility. The three main categories of bioabsorbable materials available for use in trauma and orthopaedic surgery are: polymers, metals and ceramics. Bioabsorbable polymers are well established, with a number of commercially available orthopaedic devices including screws, bone anchors, sutures and drug delivery system. Polymers are limited in their capacity for use as bone fixation devices due to their weaker mechanical properties. Metals more closely align to the mechanical properties of bone. Bioabsorbable metal screws are commercially available but have unpredictable degradation profiles and are still largely in the early stages of development. To date, there have only been a few limited case series reporting their outcomes. Bioabsorbable ceramics have been used successfully as implant coatings and drug delivery systems. Their use in load bearing is limited by their brittle nature. The aim of this article is to provide an overview of the material science of bioabsorbable materials and to summarize their advantages, disadvantages, current clinical uses and potential future applications in orthopaedic surgery.

Corrosion behavior of biodegradable metals in two different simulated physiological solutions: Comparison of Mg, Zn and Fe

Bio-absorbable metals have been proposed to overcome the limitations of permanent implant materials, particularly the risk of chronic inflammation and secondary surgery for removal after healing. The most researched bio-absorbable metal is magnesium, followed by iron and zinc, but there is little work comparing the different metals under the same experimental conditions. Herein, degradation performance of Mg/Zn/Fe was investigated via immersion test (28 days) and electrochemical tests under two buffer systems, simulated body fluid solution (SBF) and Dulbecco’s Modified Eagle’s cell culture medium (DMEM). Corrosion rate was initially slower in DMEM for all metals, Mg showed the fastest corrosion rate in both SBF and DMEM. The influence of the electrolyte on the corrosion behaviour was strongest for Mg. Importantly, the ranking of the corrosion rate of the three metals changes with immersion time. Noteworthy is a strong increase of corrosion resistance of Mg with time during the first 24 h of immersion. Corrosion morphology and corrosion products were characterized with SEM, EDS, FTIR, XPS and XRD. In general, the corrosion product layers are much more uniform in DMEM, besides, the insoluble corrosion product/precipitation consisted of metallic oxides/hydroxides, phosphates and carbonates. Slower corrosion rate in DMEM solution can therefore be due to formation of a more protective precipitate layer, adsorbed amino acids, and absence of Tris-HCl that accelerates corrosion in SBF.

Development of bioabsorbable zinc-magnesium alloy wire and validation of its application to urinary tract surgeries.

Metallic medical devices are typically constructed from non-bioabsorbable metals that remains in the body and causes considerable complications. Particularly in the urinary tract, calculus, intractable infection, and misdiagnosis as calculus are often caused by non-bioabsorbable metals. Here, we developed a zinc-magnesium alloy as a new bioabsorbable metal and sought to evaluate the bioabsorbable behavior of zinc and zinc-magnesium alloy in a rat bladder implantation model. We prepared zinc-magnesium alloy wires with various proportions of magnesium and investigated the strength, shape retention, formability, and absorbability of these novel materials. Then, we implanted zinc and zinc-magnesium alloy rings formed by the wires into rat bladder. Rats were euthanized at the end of the observation period, and the rings were removed for volume evaluation. Extracted bladder tissues were subjected to histological analysis. The strength of the zinc wire was enhanced by more than fourfold upon the addition of magnesium, without loss of ductility. Linear reduction of ring volume in urine was observed based on the concentration of magnesium within the ring. Nearly all rings were covered with a thin layer of calculus. Histological findings of the transected urinary bladder tissues did not differ among groups. Zinc-magnesium alloy is a promising candidate for use as a bioabsorbable medical device in the urinary tract.

Novel zinc/tungsten carbide nanocomposite as bioabsorbable implant

There is a lack of bioabsorbable materials with adequate mechanical strength suitable for implant applications that provide temporary support while tissue integrity is restored, especially for pediatric applications. Bioabsorbable metals have emerged as an attractive choice due to their combination of strength, ductility, and biocompatibility in vivo. Zinc has shown great promise as a bioabsorbable metal, but the weak mechanical properties of pure zinc limit its application as an implant material. This study investigates zinc-tungsten carbide (Zn-WC) nanocomposite as a novel material for bioabsorbable metallic implants. Ultrasound-assisted powder compaction was used to fabricate Zn-WC nanocomposites. This study includes the material characterization of microstructure, microhardness, and degradability. Results showed that tungsten carbide nanoparticles enhanced the mechanical properties of Zn, and maintained the favorable corrosion rate of pure Zn. These results encourage further investigation of Zn-WC nanocomposites for biomedical applications with the ultimate goal of creating safe and efficacious bioabsorbable metallic implants for many clinical applications.

Multifunctional High‐Power Sources for Smart Contact Lenses

AbstractPowering an electrical contact lens is a significant challenge for wearable applications such as augmented reality displays and iontophoretic drug delivery to the eye. Here a hybrid power generation device is developed comprising a wireless power transfer system and a bioabsorbable metal–air primary battery, which provides a multifunctional direct current (DC) and/or alternating current (AC) output. The DC power is generated by Zn loop anode and a bilirubin oxidase (BOD) biocathode in an artificial tear. The Zn‐based loop anode is also used as the antenna of a wireless power transfer system that results in high power transfer efficiency of 17.6% at 13.56 MHz. The wireless‐powered AC voltage is boosted from 1.5 to 1.5 V + 0.5 Vpp by a DC offset, enabling red light‐emitting diode (LED) emission. Furthermore, the hybrid AC and DC offset voltages are boosted to 2.3 V + 0.5 Vpp by a capacitive booster circuit that provides blue LED emission. No hydrogen evolution or pH change is observed in the tear electrolyte. The present hybrid power source can potentially power wearable electronics in body fluids.

Structural Characteristics and In Vitro Biodegradation of a Novel Zn-Li Alloy Prepared by Induction Melting and Hot Rolling

Zinc shows great promise as a bioabsorbable metal; however, the low tensile strength of pure zinc limits its application for endovascular stent purposes. In this study, a new Zn-xLi alloy (with x = 2, 4, 6 at. pct) was prepared by induction melting in an argon atmosphere and processed through hot rolling. Structures of the formulated binary alloys were characterized by X-ray diffraction and optical microscopy. Mechanical testing showed that the incorporation of Li into Zn increased ultimate tensile strength from 560 MPa (x = 6 at. pct). In vitro corrosion behavior was evaluated by immersion tests in simulated body fluid. The Zn-2Li and Zn-4Li corrosion study demonstrated that corrosion rates and products resemble those observed for pure Zn in vivo, and in addition, the Zn-4Li alloy exhibits higher resistance to corrosion as compared to Zn-2Li. The findings herein encourage further exploration of Zn-Li systems for structural use in biomedical vascular support applications with the ultimate goal of simplifying stent procedures, thereby reducing stent-related complications.

Gas Formation and Its Effect After Implantation of Bioabsorbable Metal Magnesium

Category: Basic Sciences/Biologics Introduction/Purpose: Metallic biomaterials (stainless steel and titanium) are most commonly used for osteotomy and fusion surgery in foot and ankle. But it results in the physical and psychological burden to the patients owing to the second surgery (hardware removal). Bioabsorbable polymer has the disadvantages such as mechanically weak strength and osteolysis. To overcome these, bioabsorbable metal such as magnesium (Mg) implant have been developed recently and applied clinically, but it has also drawback such as gas formation by the biodegradation of magnesium alloys. However, there is no study on the characteristics of the gas formation and its effect on the surrounding tissue. The purpose of this study is to identify the characteristics of gas formation and histological reaction during the absorption of Mg on surrounding tissue using in vitro and in vivo rodent model. Methods: Pure Mg plate (15 × 15 × 2 mm) was immersed in EBSS (Earle’s balanced salt solution) for in vitro immersion test for 30 days. Intramuscular implantation of Mg plate (25×5×0.25 mm) was performed on twenty-four rat’s back muscle and divided as two groups: implantation and sham surgery. Gas volume and compositions, corrosion rate and surface morphology of Mg plate, and histological exam were evaluated at every 5 days for 30 days. Results: Gas is mainly composed of H2 (2.483 ×104± 0.028 μV), but a small amount of CO (93.428±0.14 μV) and CO2 (57.18±0.53 μV) was detected in in vitro immersion test. Gas volume shows significantly higher at 5 days (0.084 ml) than other times (0.005 mL for 30 days) after implantation, and is gradually decreased over time. Corrosion rate is also faster in at 5 days and decreased over time in both in vitro and in vivo study. Surface morphology shows a lot of cracks and the formation of apatite paticles on Mg plate. Histological examination shows that nuclei gathered densely around the small and multiple air bubble pocket at 5 days and the number of gas bubbles and their volumes were reduced over time in tissue surrounded implant, and there is no difference in kidney and liver tissue between implant and sham surgery. Conclusion: The immersion of Mg in EBSS generated H2 as the major forming gas, and CO and CO2. The in vivo implantation of Mg into rats’ back muscle generated gas pockets inside the tissues because the initial gas formation rate was faster than the gas- absorbing rate; however, gas volume decreased after 15 days as the gas formation and absorbing rates became similar. The amount of Mg ions inside the liver and kidneys changed as well, but it was within a normal range, such that inflammation and tissue deformation were not found.

Bioabsorbable zinc ion induced biphasic cellular responses in vascular smooth muscle cells.

Bioabsorbable metal zinc (Zn) is a promising new generation of implantable scaffold for cardiovascular and orthopedic applications. In cardiovascular stent applications, zinc ion (Zn2+) will be gradually released into the surrounding vascular tissues from such Zn-containing scaffolds after implantation. However, the interactions between vascular cells and Zn2+ are still largely unknown. We explored the short-term effects of extracellular Zn2+ on human smooth muscle cells (SMCs) up to 24 h, and an interesting biphasic effect of Zn2+ was observed. Lower concentrations (<80 μM) of Zn2+ had no adverse effects on cell viability but promoted cell adhesion, cell spreading, cell proliferation, cell migration, and enhanced the expression of F-actin and vinculin. Cells treated with such lower concentrations of Zn2+ displayed an elongated shape compared to controls without any treatment. In contrast, cells treated with higher Zn2+ concentrations (80–120 μM) had opposite cellular responses and behaviors. Gene expression profiles revealed that the most affected functional genes were related to angiogenesis, inflammation, cell adhesion, vessel tone, and platelet aggregation. Results indicated that Zn has interesting concentration-dependent biphasic effects on SMCs with low concentrations being beneficial to cellular functions.

Optimizing the design of a bioabsorbable metal stent using computer simulation methods

Computer simulation is used extensively in the design of permanent stents. In order to address new challenges that arise in the design of absorbable metal stents (AMSs), such as corrosion and the limited mechanical properties of bioabsorbable alloys, new simulation and design techniques are needed. In this study a new method for simulating AMS corrosion is developed to study the effects of corrosion on the mechanical performance of a range of stent designs. The corrosion model is combined with an optimization strategy to identify AMS features that give optimal corrosion performance in the body. It is found that strut width is the predominant geometrical factor in determining long-term AMS scaffolding performance. An AMS with superior scaffolding performance to a commercial design is identified, based on deployment and corrosion simulations in stenosed vessels. These simulation and design techniques give new insights into in-vivo AMS performance and the role of device geometry in determining long-term scaffolding performance.

Cold drawn bioabsorbable ferrous and ferrous composite wires: An evaluation of in vitro vascular cytocompatibility

A systematic approach is applied to quantify the impact of bioabsorbable metals on human vascular endothelial cells (EC) and aortic smooth muscle cells (SMC) with the aim of optimizing bioabsorbable endovascular stent development. Composite wires comprising novel combinations of Fe, Mn, Mg, and Zn were produced and fabricated into tubular mesh stents. The stents were incubated with primary EC in order to assess attachment and cell proliferation. Migration of SMCs from the vessel medial wall to the target lesion site following recanalization of an atherosclerotic artery is important in the process of neointimal hyperplasia. Metal ion species were assayed for their impact on cell migration and survival at concentrations ranging from 0.037 to 10mM. An MTT-based assay was used to assess cytotoxicity after insult with various metal ion concentrations. Fe2+ and Fe3+ ion species were found to repress the migration of SMCs across a porous polycarbonate track etch membrane at concentrations of 1mM. Mn2+ promoted SMC migration at a concentration of 1mM, however, this effect was quenched when Fe2+ was included. Mg2+ was found to significantly increase SMC migration at concentrations above 1mM. Cell survival was not reduced after 24h insult with concentrations of Mg2+ up to 10mM. LD50 concentrations of greater than 1mM were found for Mg2+, Fe2+, Fe3+, and Fe2+ with 35 wt.% Mn2+. Significantly greater numbers of EC attached to bioabsorbable metal species compared with 316L stainless steel. Good EC coverage and proliferation were observed for all tested materials up to 120h.

Surface modification of magnesium alloys developed for bioabsorbable orthopedic implants: A general review

As a bioabsorbable metal with mechanical properties close to bone, pure magnesium or its alloys have great potential to be developed as medical implants for clinical applications. However, great efforts should be made to avoid its fast degradation in vivo for orthopedic applications when used for fracture fixation. Therefore, how to decease degradation rate of pure magnesium or its alloys is one of the focuses in Research and Development (R&D) of medical implants. It has been recognized that surface modification is an effective method to prevent its initial degradation in vivo to maintain its desired mechanical strength. This article reviews the recent progress in surface modifications for prevention of fast degradation of magnesium or its alloys using in vitro testing model, a fast yet relevant model before moving towards time-consuming and expensive in vivo testing. Pros and cons of various surface modifications are also discussed for the goal to design available products to be applied in clinical trials.

A simplified in vivo approach for evaluating the bioabsorbable behavior of candidate stent materials

Metal stents are commonly used to revascularize occluded arteries. A bioabsorbable metal stent that harmlessly erodes away over time may minimize the normal chronic risks associated with permanent implants. However, there is no simple, low-cost method of introducing candidate materials into the arterial environment. Here, we developed a novel experimental model where a biomaterial wire is implanted into a rat artery lumen (simulating bioabsorbable stent blood contact) or artery wall (simulating bioabsorbable stent matrix contact). We use this model to clarify the corrosion mechanism of iron (≥99.5 wt %), which is a candidate bioabsorbable stent material due to its biocompatibility and mechanical strength. We found that iron wire encapsulation within the arterial wall extracellular matrix resulted in substantial biocorrosion by 22 days, with a voluminous corrosion product retained within the vessel wall at 9 months. In contrast, the blood-contacting luminal implant experienced minimal biocorrosion at 9 months. The importance of arterial blood versus arterial wall contact for regulating biocorrosion was confirmed with magnesium wires. We found that magnesium was highly corroded when placed in the arterial wall but was not corroded when exposed to blood in the arterial lumen for 3 weeks. The results demonstrate the capability of the vascular implantation model to conduct rapid in vivo assessments of vascular biomaterial corrosion behavior and to predict long-term biocorrosion behavior from material analyses. The results also highlight the critical role of the arterial environment (blood vs. matrix contact) in directing the corrosion behavior of biodegradable metals.

Bioabsorbable metal stents for percutaneous treatment of critical recoarctation of the aorta in a newborn

In neonates and infants with critical aortic coarctation, balloon angioplasty is considered for rescue therapy of heart failure. The use of conventional stents is limited because of further vessel growth, the need of redilation, and later surgical removal. However, a novel bioabsorbable magnesium stent (AMS) might overcome such restrictions of vessel stenting in newborns. Presented is the first use of an AMS for acute treatment of a newborn with severely impaired heart function due to a long segment recoarctation after a complex surgical repair. We hypothesize that bioabsorbable stents will dramatically change the treatment of coarctation and recoarctation in newborns.