Osteosarcoma (OS) poses a severe threat to human health, and the standard clinical treatment involves prosthetic replacement after surgical removal combined with radiotherapy and chemotherapy. However, the recurrence of residual tumors and extensive bone defects leads to a poor prognosis for patients. Zoledronic acid (ZA) is clinically used for tumor treatment and osteoclast inhibition. Nevertheless, intravenous infusion of ZA has poor targeting and significant toxicity to normal tissues. Biodegradable Mg alloys have excellent mechanical and biological compatibility, making them ideal for orthopedic implants. However, their application is limited due to poor corrosion resistance. This work applied a multi-composite layered double hydroxide (LDH)-ZA/PDA coating to the surface of ZE21C alloy. The composite coating adsorbed ZA in weakly alkaline or neutral conditions and released ZA under near-infrared (NIR) irradiation in the tumor microenvironment (TME). The stimuli-responsive release of ZA was confirmed to be related to the NIR-TME-triggered change in LDH interlayer spacing. In vitro and in vivo experiments showed that this multi-composite coating improved corrosion resistance, responded to TME and NIR stimuli to release ZA and reactive oxygen species, effectively targeting and killing tumor cells and osteoclasts through the AKT/GSK-3β signaling pathway. It also transformed OS from “cold tumors” into “hot tumors”, reactivated macrophage-mediated tumor immunity, and promoted osteogenesis. The chemo-thermal-therapeutic approach of the composite coating achieves a “three-birds-with-one-stone” effect. This study offers new insights into applying Mg alloys in prosthetic replacements after OS surgery.
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Open Access
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Bio-magnesium (Mg) alloys exhibit excellent biocompatibility and biodegradability, making them highly promising for implant applications. However, their limited strength-ductility balance remains a critical challenge restricting widespread use. In this study, ultra-fine-grained and homogeneous Mg alloys were fabricated using double-sided friction stir processing (DS-FSP) with liquid CO2 rapid cooling, leading to a significant enhancement in the strength-ductility synergy of the stirred zone. The results demonstrate that DS-FSP samples exhibit simultaneous improvements in ultimate tensile strength (UTS) and elongation, reaching 334.1 ± 15 MPa and 28.2 ± 7.3%, respectively. Compared to the non-uniform fine-grained microstructure obtained through single-sided friction stir processing, DS-FSP generates a uniform ultra-fine-grained structure, fundamentally altering the fracture behavior and mechanisms of Mg alloys. The DS-FSP samples exhibit irregular fracture patterns due to variations in basal slip system activation among different grains. In contrast, single-sided friction stir processing samples, characterized by a fine-grained yet heterogeneous microstructure, display flat shear fractures dominated by high-density dislocation initiation induced by twin formation, with fracture propagation dictated by the non-uniform texture. By achieving an ultra-fine grain size and homogeneous texture, DS-FSP effectively modifies the fracture mechanisms, thereby enhancing the strength-ductility balance of bio-magnesium alloys.
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Vascular scaffolds are one of the important application fields of biodegradable Mg alloys, and related research has been carried out for more than 20 years. In recent years, the application expansion of Mg alloy vascular scaffolds has brought new challenges to the research of related fields. This review focuses on the relevant advances in the field of Mg alloys for both cardio-/cerebrovascular scaffolds. The frequently investigated alloy series for vascular scaffolds were reviewed. The bottleneck of processing of Mg alloy minitubes was elucidated. The idea of functionalized surface modification was also pointed out in this review, and the authors put forward guidelines based on research experience in terms of scaffold structural design and degradation behavior evaluation. Finally, suggestions for further research directions of Mg alloy vascular scaffolds were provided.
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Cardiovascular stent has been widely applied to treat cardiovascular disease (CVD), which is the major disease contribution to mortality in the world wide. Biodegradable magnesium (Mg) alloys are the encouraging materials in cardiovascular stents benefit from absorbability and biocompatibility. While, the ability of degradation is a double-edged sword for manufacture stent, modifying the surface to decrease the excessive degradation rate and promote the surface endothelialization could expand the prospect of the further application. In this work, the biodegradable Mg-Zn-Y-Nd alloy was modified by MgF2 and dopamine polymer film (PDA) as the corrosion resistance layer and the bonding layer respectively, and then the exosome, a natural nanoparticle contains mRNAs and proteins, was tailored to give the surface better biocompatibility. The electrochemical test and weight loss test reflected the MgF2-PDA/exosome coating increase the corrosion resistance of the Mg-Zn-Y-Nd alloy. The cytocompatibility data indicated the novel MgF2-PDA/exosome coating selectively reduced the tumor necrosis factor (TNF-α) expression and ROS release from macrophage, and promoted the α-SMA expression of smooth muscle cells. In addition, the MgF2-PDA/exosome coating also improved the adhesion, proliferation, CD31 expression and nitric oxide (NO) release of vascular endothelial cells (ECs), all of which contribute to the surface endothelialization. And the mechanism experiments showed the exosome released from the coating uptake by the ECs and assemble around the lysosome and mitochondria, and the released rate of the exosome on the coating is around 5 to 7 days, indicating excellent multi-functions of MgF2-PDA/exosome coating in cardiovascular stent.
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Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect biocompatibility and delayed re-endothelialization still lead to a considerable challenge for its application. In this work, to overcome these shortcomings, a compound of catalyzing nitric oxide (NO) generation containing copper ions (Cu2+) and hyaluronic acid (HA), an important component of the extracellular matrix, were covalently immobilized on a hydrofluoric acid (HF)-pretreated ZE21B alloy via amination layer for improving its corrosion resistance and endothelialization. Specifically, the Cu2+chelated firmly with a cyclen 1,4,7,10-tetraazacyclododecane-N, N′, N″, N″′- tetraacetic acid (DOTA) could form a stability of hybrid coating, avoiding the explosion of Cu2+. The chelated Cu2+enabled the catalytic generation of NO and promoted the adhesion and proliferation of endothelial cells (ECs) in vascular micro-environment. In this case, the synergistic effect of NO-generation and endothelial glycocalyx molecules of HA lead to efficient ECs promotion and smooth muscle cells (SMCs) inhibition. Meanwhile, the blood compatibility also had achieved a marked improvement. Moreover, the standard electrochemical measurements indicated that the functionalized ZE21B alloy had better anti-corrosion ability. In a conclusion, the dual-functional coating displays a great potential in the field of biodegradable magnesium-based implantable cardiovascular stents.
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Mg-Nd-Zn-Zr (JDBM) alloy was studied as a candidate for biodegradable implant material because of its moderate mechanical properties, good biocompatibility, and favorable uniform degradation behavior. To verify whether JDBM alloy exhibits electroplasticity effect and then study the mechanism of electropulsing treatment on JDBM alloy, in this study, homogenized and pre-tensile deformed samples were treated by electropulsing. After the electropulsing treatment, the average grain size was refined due to recrystallization, micron-scale Mg12Nd secondary phases precipitated slightly, while the morphology of nanoscale Zr particles changed from rodlike to ellipsoidal shape. The elongation to failure (EL) increased obviously for the homogenized and pre-tensile deformed JDBM alloy samples after electropulsing treatment, accompanying with no obvious sacrifice of the yield strength (YS) for the former and an evident decrease of YS for the latter, mainly due to the reduction of the dislocation density. The YS decrement and EL increment (77.57%) for the latter are more apparent attributed to the higher density of dislocations introduced by pre-tensile deformation. Therefore, the electropulsing treatment can obviously improve the mechanical properties of JDBM alloy, especially for the plasticity. The present work opens a new window for the fabrication of JDBM alloy profiles with high mechanical properties, especially for the plasticity, such as the cold drawing wires and tubes for biomedical applications. It also could provide theoretical references for other magnesium alloy processing.
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Constructing a functional hybrid coating appears to be a promising strategy for addressing the poor corrosion resistance and insufficient endothelialization of Mg-based stents. Nevertheless, the steps for preparing composite coatings are usually complicated and time-consuming. Herein, a novel composite coating, composed of bioactive magnesium thioctic acid (MTA) layer formed by deposition and corrosion-resistant magnesium hydroxide (Mg(OH)2) layer grown in situ, is simply fabricated on ZE21B alloys via one-step electrodeposition. Scanning electron microscopy (SEM) shows that the electrodeposited coating has a compact and uniform structure. And the high adhesion of the MTA/Mg(OH)2 hybrid coating is also confirmed by the micro-scratch test. Electrochemical test, scanning kelvin probe (SKP), and hydrogen evolution measurement indicate that the hybrid coating effectively reduces the degradation rate of Mg substrates. Haemocompatibility experiment and cell culture trial detect that the composite coating is of fine biocompatibility. Finally, the preparation mechanism of MTA/Mg(OH)2 hybrid coatings is discussed and proposed. This coating shows a great potential application for cardiovascular stents.
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Recently, functional molecules such as Polydopamine (PDA), Hyaluronic Acid (HA) and heparin have been widely studied in the field of surface modification of magnesium (Mg) alloy stents for better degradation behavior and biocompatibility, but their further application is limited by undesirable anticoagulant function, uncontrollable degradation and easy bleeding, respectively.
Regarding to this consideration, a magnesium Fluoride/Polydopamine/Sulphonated hyaluronic acid (MgF2/PDA/S-HA) composite coating was successfully prepared by applying S-HA with sulfur content of 9.71 wt% on the surface of ZE21B alloy in this study. The results showed that the composite coating with a unique mesh structure not only inherited the anticoagulant effect of sulfonic acid group and the excellent cyto-compatibility of S-HA with high sulfur content, but also significantly improved the corrosion performance of ZE21B alloy. These results indicate a great application potential of the composite coating in the field of cardiovascular biomaterials.
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Protein adsorption preferentially occurs and significantly affects the physicochemical reactions once the biodegradable magnesium alloys as bone replacements have been implanted. To date, interactions mechanisms between Mg implants and proteins remain unclear at a molecular level. Thereby, a combination of molecular dynamic (MD) simulations and experimental exploration is used to investigate the adsorption behavior and conformational change of bovine serum albumin (BSA), a representative protein of blood plasma, upon the surface of micro-arc oxidation (MAO) coated Mg alloy AZ31. The influences of absorbed proteins on the cytocompatibility of MAO coating are evaluated by virtue of cytotoxicity assay. Results indicate that the negatively charged O atoms (BSA) exhibit strong interaction with Mg2+ ions of Mg(OH)2, revealing that BSA molecules are ionically adsorbed on the AZ31 surface. Interestingly, MD simulation reveals that MAO coating demonstrates superior ability to capture BSA molecules during the process of adsorption owing to strong electric attraction between the negatively charged O atoms in BSA molecules with Mg atoms of MgO in MAO coating. Moreover, the α-helix part of absorbed BSA molecules on AZ31 substrate and MAO coating markedly decreases with an increase in β-sheet, β-turn and unordered contents, which is attributed to the reduction in the number of hydrogen bonds in BSA molecules. Furthermore, the adsorbed BSA molecules improve the cytocompatibility of MAO coating since the positively charged -NH3+ group and β-sheet content of absorbed BSA molecules mediate the cell adhesion by interacting with the negatively charged cell membrane.
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Research Article
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In the present work, the biomedical as-cast pure Mg, Mg–1Ca and Mg–2Sr alloys were processed with equal channel angular pressing (ECAP) technique to develop ultrafine microstructure within the materials, and their microstructures, mechanical properties, degradation behavior, cytocompatibility in vitro and biocompatibility in vivo were studied comprehensively. Finer-gained microstructures and improved mechanical properties of these three materials after ECAP were confirmed compared to their as-cast counterparts. Moreover, after ECAP the degradation rate of pure Mg was increased while that of Mg–1Ca or Mg–2Sr alloys decreased compared to the as-cast counterparts. Additionally, good in vitro cytocompatibility and in vivo biocompatibility of these three materials were revealed by cell cultural tests using osteoblastic MC3T3-E1 and human mesenchymal stem cells (hMSC) and in vivo animal tests at the lateral epicondyle of SD-rats’ femur. This study offers an alternative powerful avenue to achieve good comprehensive properties of magnesium-based biodegradable metals. It might also help to extend the applied range of magnesium-based biodegradable metals in orthopedic field.
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