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The most critical factor determining the success of biodegradable bone implants is the host tissue response, which greatly depends on their degradation behaviors. Here, a new magnesium-based implant, namely magnesium-silicon-calcium (Mg-0.2Si-1.0Ca) alloy, that coordinates its biodegradation along with the bone regenerative process via a self-assembled, multilayered bone-implant interface is designed. At first, its rapid biocorrosion contributes to a burst release of Mg 2+ , leading to a pro-osteogenic immune microenvironment in bone. Meanwhile, with the simultaneous intervention of Ca and Si in the secondary phases of the new alloy, a hierarchical layered calcified matrix is rapidly formed at the degrading interface that favored the subsequent bone mineralization. In contrast, pure Mg or Mg-0.2Si alloy without the development of this interface at the beginning will unavoidably induce detrimental bone loss. Hence, it is believed this biomimicking interface justifies its bioadaptability in which it can modulate its degradation in vivo and accelerate bone mineralization., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Despite the widespread observations on the osteogenic effects of magnesium ion (Mg 2+ ), the diverse roles of Mg 2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg 2+ in bone repair. During the early inflammation phase, Mg 2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg 2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg 2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg 2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg 2+ . Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg 2+ in bone healing.

High-pressure torsion (HPT) can refine the microstructure and consequently modify the properties, such as mechanical and corrosion properties, of Mg and its alloys. Biodegradable magnesium materials alloyed with the essential elements of life, such as Ca and Sr, are a current research frontier. In this study, biodegradable ultrafine-grained pure Mg, Mg-Ca alloy, and Mg-Sr alloy were prepared using HPT processing. The microstructure, mechanical properties, biodegradable behaviors, and biocompatibility in vitro and in vivo of these materials were systematically investigated. Our results revealed that HPT pure Mg with a bimodal and ultrafine-grained microstructure showed higher mechanical strength, ductility, and degradation rate compared with the as-received materials. The good biocompatibility of HPT pure Mg was confirmed both in vitro and in vivo. The HPT Mg-Ca alloy and Mg-Sr alloy with homogeneous ultrafine-grained microstructures showed higher mechanical strength and lower degradation rate than their as-cast counterparts. The good biocompatibility of the HPT Mg-Ca alloy and Mg-Sr alloy was also revealed. All these findings indicate that HPT is an alternative avenue to fabricate biodegradable Mg-based materials.

Magnesium biometals exhibit great potentials for orthopeadic applications owing to their biodegradability, bioactive effects and satisfactory mechanical properties. However, rapid corrosion of Mg implants in vivo combined with large amount of hydrogen gas evolution is harmful to bone healing process which seriously confines their clinical applications. Enlightened by the superior biocompatibility and corrosion resistance of passive titanium oxide layer automatically formed on titanium alloy, we employ the Ti and O dual plasma ion immersion implantation (PIII) technique to construct a multifunctional TiO 2 based nano-layer on ZK60 magnesium substrates for enhanced corrosion resistance, osteoconductivity and antimicrobial activity. The constructed nano-layer (TiO 2 /MgO) can effectively suppress degradation rate of ZK60 substrates in vitro and still maintain 94% implant volume after post-surgery eight weeks. In animal study, a large amount of bony tissue with increased bone mineral density and trabecular thickness is formed around the PIII treated group in post-operation eight weeks. Moreover, the newly formed bone in the PIII treated group is well mineralized and its mechanical property almost restores to the level of that of surrounding mature bone. Surprisingly, a remarkable killing ratio of 99.31% against S. aureus can be found on the PIII treated sample under ultra-violet (UV) irradiation which mainly attributes to the oxidative stress induced by the reactive oxygen species (ROS). We believe that this multifunctional TiO 2 based nano-layer not only controls the degradation of magnesium implant, but also regulates its implant-to-bone integration effectively. STATEMENT OF SIGNIFICANCE: Rapid corrosion of magnesium implants is the major issue for orthopaedic applications. Inspired by the biocompatibility and corrosion resistance of passive titanium oxide layer automatically formed on titanium alloy, we construct a multifunctional TiO 2 /MgO nanolayer on magnesium substrates to simultaneously achieve superior corrosion resistance, satisfactory osteoconductivity in rat intramedullary bone defect model and excellent antimicrobial activity against S. aureus under UV irradiation. The current findings suggest that the specific TiO 2 /MgO nano-layer on magnesium surface can achieve the three objectives aforementioned and we believe this study can demonstrate the potential of biodegradable metals for future clinical applications., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Rapid corrosion of biodegradable magnesium alloys under in vivo condition is a major concern for clinical applications. Inspired by the stability and biocompatibility of titanium oxide (TiO 2 ) passive layer, a functionalized TiO 2 /Mg 2 TiO 4 nano-layer has been constructed on the surface of WE43 magnesium implant by using plasma ion immersion implantation (PIII) technique. The customized nano-layer not only enhances corrosion resistance of Mg substrates significantly, but also elevates the osteoblastic differentiation capability in vitro due to the controlled release of magnesium ions. In the animal study, the increase of new bone formation adjacent to the PIII-treated magnesium substrate is 175% higher at post-operation 12 weeks, whereas the growth of new bone on titanium control and untreated magnesium substrate are only 97% and 29%, respectively. In addition, its Young's modulus can be restored to about 82% as compared with the surrounding matured bone. Furthermore, this specific TiO 2 /Mg 2 TiO 4 layer even exhibits photoactive bacteria disinfection capability when irradiated by ultraviolet light which is attributed to the intracellular reactive oxygen species (ROS) production. With all these constructive observations, it is believed that the TiO 2 /Mg 2 TiO 4 nano-layer on magnesium implants can significantly promote new bone formation and suppress bacterial infection, while the degradation behavior can be controlled simultaneously., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A range of magnesium ions (Mg 2+ ) used has demonstrated osteogenic tendency in vitro. Hence, we propose to actualize this concept by designing a new system to precisely control the Mg 2+ delivery at a particular concentration in vivo in order to effectively stimulate in-situ bone regeneration. To achieve this objective, a monodisperse core-shell microsphere delivery system comprising of poly (lactic-co-glycolic acid) (PLGA) biopolymer, alginate hydrogel, and magnesium oxide nano-particles has been designed by using customized microfluidic capillary device. The PLGA-MgO sponge-like spherical core works as a reservoir of Mg 2+ while the alginate shell serves as physical barrier to control the outflow of Mg 2+ at ∼50 ppm accurately for 2 weeks via its adjustable surface micro-porous network. With the aid of controlled release of Mg 2+ , the new core-shell microsphere system can effectively enhance osteoblastic activity in vitro and stimulate in-situ bone regeneration in vivo in terms of total bone volume, bone mineral density (BMD), and trabecular thickness after operation. Interestingly, the Young's moduli of formed bone on the core-shell microsphere group have been restored to ∼96% of that of the surrounding matured bone. These findings indicate that the concept of precisely controlled release of Mg 2+ may potentially apply for in-situ bone regeneration clinically., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To achieve enhanced biological response and controlled degradation of magnesium alloy, a modified biodegradable polymer coating called polycaprolactone (PCL) is fabricated by a thermal approach in which the heat treatment neither alters the chemical composition of the PCL membrane nor the rate of magnesium ion release, pH value, or weight loss, compared with the untreated sample. The changes in the crystallinity, hydrophilicity, and oxygen content of heat-treated PCL coating not only improve the mechanical adhesion strength between the coating and magnesium substrate but also enhance the biological properties. Moreover, the thermally modified sample can lead to higher spreading and elongation of osteoblasts, due to the enhanced hydrophilicity and CO to CO functional group ratio. In the analyses of microcomputed tomography from one to four weeks postoperation, the total volume of new bone formation on the heat-treated sample is 10%-35% and 70%-90% higher than that of the untreated and uncoated controls, respectively. Surprisingly, the indentation modulus of the newly formed bone adjacent to the heat-treated sample is ≈20% higher than that of both controls. These promising results reveal the clinical potential of the modified PCL coating on magnesium alloy in orthopedic applications., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Magnesium alloys are potential biodegradable materials and have received increasing attention due to their outstanding biological performance and mechanical properties. However, rapid degradation in the physiological environment and potential toxicity limit clinical applications. Recently, special magnesium-calcium (Mg-Ca) and magnesium-strontium (Mg-Sr) alloys with biocompatible chemical compositions have been reported, but the rapid degradation still does not meet clinical requirements. In order to improve the corrosion resistance, a rough, hydrophobic and ZrO(2)-containing surface film is fabricated on Mg-Ca and Mg-Sr alloys by dual zirconium and oxygen ion implantation. Weight loss measurements and electrochemical corrosion tests show that the corrosion rate of the Mg-Ca and Mg-Sr alloys is reduced appreciably after surface treatment. A systematic investigation of the in vitro cellular response and antibacterial capability of the modified binary magnesium alloys is performed. The amounts of adherent bacteria on the Zr-O-implanted and Zr-implanted samples diminish remarkably compared to the unimplanted control. In addition, significantly enhanced cell adhesion and proliferation are observed from the Zr-O-implanted sample. The results suggest that dual zirconium and oxygen ion implantation, which effectively enhances the corrosion resistance, in vitro biocompatibility and antimicrobial properties of Mg-Ca and Mg-Sr alloys, provides a simple and practical means to expedite clinical acceptance of biodegradable magnesium alloys., (Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In this paper, we describe a new biodegradable composite composed of polycaprolactone and magnesium. Incorporation of magnesium micro-particles into the polycaprolactone matrix yields mechanical properties close to those of human cancellous bone, and in vitro studies indicate that the silane-coated Mg/PCL composites have excellent cytocompatibility and osteoblastic differentiation properties. The bioactivity of the composites is manifested by the formation of calcium and phosphate after immersion in simulated body fluids. The bulk mechanical properties can be maintained for 2 months before obvious degradation takes place. The in vivo animal study reveals a larger amount of new bone formation on the silane-coated Mg/PCL composites compared to conventional PMMA and pure polycaprolactone and our results suggest potential clinical applications of the sliane-coated Mg/PCL composites., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Magnesium and its alloys may potentially be applied as degradable metallic materials in orthopaedic implantations due to their degradability and resemblance to human cortical bone. However, the high corrosion rate and accumulation of hydrogen gas upon degradation hinders its clinical application. In this study, we adopt a new approach to control the corrosion rate by coating a controllable polymeric membrane fabricated by polycaprolactone and dichloromethane onto magnesium alloys, in which the pore size was controlled during the manufacturing process. The addition of the polymeric membrane was found to reduce the degradation rate of magnesium, and the bulk mechanical properties were shown to be maintained upon degradation. The in-vitro studies indicated good cytocompatibility of eGFP and SaOS-2 osteoblasts with the polymer-coated samples, which was not observed for the uncoated samples. The in-vivo study indicated that the uncoated sample degraded more rapidly than that of the polymer-coated samples. Although new bone formation was found on both samples, as determined by Micro-CT, higher volumes of new bone were observed on the polymer-coated samples. Histological analysis indicated no inflammation, necrosis or hydrogen gas accumulation on either of the samples during degradation. Collectively, these data suggest that the use of polymeric membrane may be potentially applied for future clinical use., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)