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Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration, blood vessels invasion and transport of nutrient and waste. However, efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems. In this work, biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting. Mg scaffold with better interconnectivity showed lower mechanical strength. Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration, pH value and osmolality of the degradation microenvironment due to the lower specific surface area. Nevertheless, the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit. Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size. In summary, design of interconnectivity in terms of pore size distribution could regulate mechanical strength, microenvironment in cell culture condition and cell migration potential, and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.

Mg–Nd–Zn–Zr magnesium alloy (JDBM) has been studied widely as biodegradable medical material. To process high quality JDBM wires, effects of annealing on the mechanical properties and degradation behavior after drawing were studied by microscopic observations, tensile and immersion tests. The as-extruded wires with a diameter of 3 mm could be drawn up to 9 passes without annealing until 125% cumulative drawing deformation. Complete recrystallization occurred after annealing at 325 °C for 30 min, 350 °C for 5 min or 450 °C for 3 min, respectively. Room temperature tensile tests and simulated body fluid immersion tests showed that annealing at slightly elevated temperature for short time could obtain better properties due to the finer grain size and more dispersive distribution of precipitates. For this study, annealing at 350 °C for 5 min is the best parameters which can be utilized to further fabricate fine wires.

Vascular diseases are the most prevalent cause of ischemic necrosis of tissue and organ, which even result in dysfunction and death. Vascular regeneration or artificial vascular graft, as the conventional treatment modality, has received keen attentions. However, small-diameter (diameter, Graphical abstract Image 1, Highlights • This paper reviews challenges and strategies for enhanced in situ vascularization. • Strategies for homing, adhesion and activation of EPCs and ECs are summarized. • Approaches to prevent thrombogenesis and IH for long-term lumen patency are introduced. • Immune system plays a role in modulating biological behaviors of ECs and SMCs. • Perspectives for future development of vascular grafts are proposed.

Zn alloys are promising materials for application in the fabrication of vascular stents because they have a desirable degradation rate and acceptable biocompatibility. However, the poor thermostability of Zn is one limitation that needs to be addressed in order to broaden their clinical applications. Suppression atomic diffusion is of practical significance when enhancing the thermostability of Zn alloys. The present study seeks to examine lattice diffusion associated with various alloy elements by calculating the diffusion activation energies for nineteen substitutional solutes via first-principles calculations combined with CINEB methods. The calculated activation energies depend strongly on the size and the number of d-electrons of the solute atoms. The trend to improve the thermostability and creep resistance of Zn alloys at ambient temperature can also be predicted using the Nabarro-Herring model. An anti-self-aging Zn-Cu alloy was prepared to verify our calculation results. Therefore, the present work has great significance for the design of biodegradable zinc alloys with improved thermostability. Graphic abstract

To develop a biodegradable membrane with guided bone regeneration (GBR), a Mg-2.0Zn-1.0Gd alloy (wt.%, MZG) membrane with Ca-P coating was designed and fabricated in this study. The microstructure, hydrophilicity, in vitro degradation, cytotoxicity, antibacterial effect and in vivo regenerative performance for the membrane with and without Ca-P coating were evaluated. After coating, the membrane exhibited an enhance hydrophilicity and corrosion resistance, showed good in vitro cytocompatibility upon MC3T3E-1 cells, and exhibited excellent antibacterial effect against E. coli, Staphylococcus epidermis and Staphylococcus aureus, simultaneously. In vivo experiment using the rabbit calvarial defect model confirmed that Ca-P coated MZG membrane underwent progressive degradation without inflammatory reaction and significantly improved the new bone formation at both 1.5 and 3 months after the surgery. All the results strongly indicate that MZG with Ca-P coating have great potential for clinical application as GBR membranes.

The grain size of Mg foams was innovatively refined without alteration of pore structure and relative density by subjecting multi-axial forging (MAF) process to Ti-Mg composite, an intermediary product of the fabrication process of Mg foams where the spherical Ti particles were utilized as the replication material. The feasibility of the MAF process and the grain size effect on the mechanical properties of Mg foams were discussed. The results showed that, with the appropriate strain of 0.24 applied in the MAF process, Ti-Mg composites returned to original physical appearance without generating micro-cracks. And complete recrystallization was achieved after heat treatment, with the grain size of the MAF-processed Mg foams two to three orders of magnitude smaller than that of as-cast foam. The mechanical properties of Mg foams were enhanced extensively after grain refinement with the yield strength and the plastic collapse strength increased by 147% and 50.7%, respectively. A revised model integrated by the Hall-Petch law and Gibson-Ashby model was proposed, which gave a good estimation of the yield strength and the plastic collapse strength of Mg foams from the compressive behavior of the corresponding parent material, though a knockdown factor of 0.45 was introduced for the yield strength.

Due to their capability of fabricating geometrically complex structures, additive manufacturing (AM) techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys, which exhibit appropriate mechanical properties and outstanding biocompatibility. However, many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants, such as the difficulty of Mg powder preparation, powder splash, and crack formation during the AM process. In the present work, the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed. A novel Mg-based alloy (Mg–Nd–Zn–Zr alloy, JDBM) powder with a smooth surface and good roundness was first synthesized successfully, and the AM parameters for Mg-based alloys were optimized. Based on the optimized parameters, porous JDBM scaffolds with three different architectures (biomimetic, diamond, and gyroid) were then fabricated by selective laser melting (SLM), and their mechanical properties and degradation behavior were evaluated. Finally, the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate (DCPD) coating treatment, which greatly suppressed the degradation rate and increased the cytocompatibility, indicating a promising prospect for clinical application as bone tissue engineering scaffolds.

The microstructures, mechanical properties and in vitro degradation behavior of as-extruded pure Zn and Zn−xSr (x=0.1, 0.4, 0.8 wt.%) alloys were investigated systematically. For the microstructure and mechanical properties, SrZn13 phase was newly formed due to the addition of 0.1 wt.% Sr, improving the yield strength, ultimate tensile strength and elongation from (85.33±2.86) MPa, (106.00±1.41) MPa and (15.37±0.57)% for pure Zn to (107.67±2.05) MPa, (115.67±2.52) MPa and (20.80±2.19)% for Zn−0.1Sr, respectively. However, further increase of Sr content led to the deterioration of the mechanical properties due to the stress concentration and cracks initiation caused by the coarsening SrZn13 particles during tensile tests. For in vitro degradation, since micro galvanic corrosion was enhanced owing to the formation of the inhomogeneously distributed SrZn13 phase, the corrosion mode became non-uniform. Corrosion rate is gradually increased with the addition of Sr, which is increased from (11.45±2.02) μm/a (a=year) for pure Zn to (32.59±3.40) μm/a for Zn−0.8Sr. To sum up, the as-extruded Zn−0.1Sr alloy exhibited the best combination of mechanical properties and degradation behavior.

We have developed a convenient chemical conversion method of preparing a Mg3(PO4)2 coating with a lamellar structure of about 1–5 μm width on Mg-Nd-Zn-Zr (denoted as JDBM) alloy, aiming to improve the corrosion resistance and biological response. The protective effect of the phosphate coating on JDBM alloy leads to an increase in corrosion resistance of about 25% from 0.337 ± 0.021 to 0.253 ± 0.047 mm y−1. A systematic study on in vitro cytocompatibility test shows that the phosphate coated JDBM has minimal negative effect on human umbilical vein endothelial cells (HUVECs) viability, growth and proliferation, and the coating also presents a favorable affinity for HUVECs by supporting higher adherent cell density and sufficient cell spreading. In addition, the investigation of in vitro hemocompatibility confirms reduced hemolysis ratio and excellent anti-platelet adhesion property of the phosphate coated JDBM. Furthermore, this study also presents our more recent efforts to develop an in-depth understanding of the mechanism which is involving anti-platelet adhesion on the surface of biodegradable Mg substrate.

Biodegradable magnesium alloys are promising candidates for use in biomedical applications. However, degradable particles (DPs) derived from Mg-based alloys have been observed in tissue in proximity to sites of implantation, which might result in unexpected effects. Although previous in vitro studies have found that macrophages can take up DPs, little is known about the potential phagocytic pathway and the mechanism that processes DPs in cells. Additionally, it is necessary to estimate the potential bioeffects of DPs on macrophages. Thus, in this study, DPs were generated from a Mg-2.1Nd-0.2Zn-0.5Zr alloy (JDBM) by an electrochemical method, and then macrophages were incubated with the DPs to reveal the potential impact. The results showed that the cell viability of macrophages decreased in a concentration-dependent manner in the presence of DPs due to effects of an apoptotic pathway. However, the DPs were phagocytosed into the cytoplasm of macrophages and further degraded in phagolysosomes, which comprised lysosomes and phagosomes, by heterophagy instead of autophagy. Furthermore, several pro-inflammatory cytokines in macrophages were upregulated by DPs through the induction of reactive oxygen species (ROS) production. To the best of our knowledge, this is the first study to show that DPs derived from a Mg-based alloy are consistently degraded in phagolysosomes after phagocytosis by macrophages via heterophagy, which results in an inflammatory response owing to ROS overproduction. Thus, our research has increased the knowledge of the metabolism of biodegradable Mg metal, which will contribute to an understanding of the health effects of biodegradable magnesium metal implants used for tissue repair. STATEMENT OF SIGNIFICANCE: Biomedical degradable Mg-based alloys have great promise in applied medicine. Although previous studies have found that macrophages can uptake degradable particles (DPs) in vitro and observed in the sites of implantation in vivoin vivo, few studies have been carried out on the potential bioeffects relationship between DPs and macrophages. In this study, we analyzed the bioeffects of DPs derived from a Mg-based alloy on the macrophages. We illustrated that the DPs were size-dependently engulfed by macrophages via heterophagy and further degraded in the phagolysosome rather than autophagosome. Furthermore, DPs were able to induce a slight inflammatory response in macrophages by inducing ROS production. Thus, our research enhances the knowledge of the interaction between DPs of Mg-based alloy and cells, and offers a new perspective regarding the use of biodegradable alloys.

Large-sized orbital bone defects have serious consequences that destroy orbital integrity and result in maxillofacial deformities and vision loss. The treatment of orbital bone defects is currently palliative and not reparative, suggesting an urgent demand for biomaterials that regenerate orbital bones. In this study, via alloying, extrusion and surface modification, we developed mechanobiologically optimized magnesium (Mg) scaffolds (Ca-P-coated Mg-Zn-Gd scaffolds, referred to as Ca-P-Mg) for the orthotopic reconstruction of large-sized orbital bone defects. At 6 months after transplanting the scaffolds to a clinically relevant canine large animal model, large-sized defects were successfully bridged by an abundance of new bone with normal mechanical properties that corresponded to gradual degradation of the implants. The osteogenic and ancillary cells, including vascular endothelial cells and trigeminal neurons, played important roles in this process. The scaffolds robustly enhanced bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation. In addition, the increased angiogenesis including increased ratio of the specific endothelial subtype CD31hi endomucinhi (CD31hiEmcnhi) endothelial cells can facilitate osteogenesis. Furthermore, the scaffolds trigger trigeminal neurons via transient receptor potential vanilloid subtype 1 (Trpv1) to produce the neuropeptide calcitonin gene-related peptide (CGRP), which promotes angiogenesis and osteogenesis. Overall, our investigations revealed the efficacy of Ca-P-Mg scaffolds in healing orbital bone defects and warrant further exploration of these scaffolds for clinical applications.

Zinc (Zn) alloys are a promising biodegradable material for vascular stent applications. This study aimed to fabricate biodegradable Zn-2.0Cu-0.5Mn alloy micro-tubes and vascular stents with high dimensional accuracy and suitable mechanical properties, and to investigate their microstructure, texture, mechanical properties and corrosion behavior. The micro-tubes and vascular stents were successfully fabricated by a combined process of extrusion, drawing, laser cutting and electrochemical polishing. The microstructures of as-extruded and as-drawn micro-tubes consisted of Zn matrix with near-equiaxed grains (average grain size: ∼2 µm) and second phases of ε (CuZnsub4/sub) and MnZnsub13/subwith different sizes. The texture evolved from basal planes approximately paralleling to deformation direction for as-extruded micro-tube to approximately perpendicular to deformation direction for as-drawn micro-tube, because predominant deformation mechanisms changed from basallt;agt; dislocation slip during tube extrusion to prismaticlt;agt; dislocation, pyramidallt;c+agt; dislocations, and {101¯2} twins during tube drawing. As-drawn micro-tube exhibited suitable mechanical properties with an ultimate tensile strength of about 298 MPa and elongation of about 26% as a stent material. Moreover, the processed stent with a thickness of about 125 µm possessed sufficient radial strength of about 150 kPa and good balloon expandability. In addition, as-drawn tube exhibited an in vitro corrosion rate of about 158 µm/year with a basically uniform corrosion morphology. These results indicated that biodegradable Zn-2.0Cu-0.5Mn alloy is a promising vascular stent material candidate, and the procedure for processing the micro-tube and stent is practical and effective. STATEMENT OF SIGNIFICANCE: Fabrication of micro-tubes followed by laser cutting and polishing is a common way to prepare metallic vascular stents. However, it is quite challenging to fabricate Zn-based stents using this standard method, and there is a lack of studies reporting processing details in the past. Biodegradable Zn-2.0Cu-0.5Mn alloy micro-tubes and vascular stents with high dimensional accuracy and suitable mechanical properties were successfully fabricated by a combined process in this study. As-drawn micro-tube exhibited an ultimate tensile strength of about 298 MPa and elongation of about 26%. The stent possessed sufficient radial strength of about 150 kPa and good balloon expandability. We demonstrated a practical method to fabricate biodegradable Zn-based micro-tubes and stents with high dimensional accuracy and mechanical properties.

Degradability of bone tissue engineering scaffold that matching the regeneration rate could allow a complete replacement of host tissue. However, the porous structure of biodegradable Mg scaffolds certainly generated high specific surface area, and the three-dimensional interconnected pores provided fast pervasive invasion entrance for the corrosive medium, rising concern of the structural integrity during the degradation. To clarify the structural evolution of the three-dimensional (3D) porous structure, semi-static immersion tests were carried out to evaluate the degradation performance in our previous study. Nevertheless, dynamic immersion tests mimicking the in vivo circulatory fluid through the interconnected porous structure have yet been investigated. Moreover, the effects of dynamic flow rates on the degradation deposition behavior of 3D porous Mg scaffolds were rarely reported. In this study, Mg scaffolds degraded at three flow rates exhibited different degradation rates and deposition process. A flow rate of 0.5 mL/min introduced maximum drop of porosity by accumulated deposition products. The deposition products provided limited protection against the degradation process at a flow rate of 1.0 mL/min. The three-dimensional interconnected porous structure of Mg scaffold degraded at 2.0 mL/min well retained after 14 days showing the best interconnectivity resistance to the degradation deposition process. The dynamic immersion tests disclosed the reason for the different degradation rates on account of flow rates, which may bring insight into understanding of varied in vivo degradation rates related to implantation sites.

Recently, zinc (Zn) alloy has been considered as a promising biodegradable material due to its excellent physiological degradable behavior and acceptable biocompatibility. However, poor mechanical performance limits its application as vascular stents. In this study, novel biodegradable Zn-2.2Cu-xMn (x = 0.4, 0.7, and 1.0 wt%) alloys with suitable mechanical performance were investigated. The effects of Mn addition on microstructure, mechanical properties, and in vitro degradation of Zn-2.2Cu-xMn alloys were systematically investigated. After adding Mn, dynamic recrystallization (DRX) during hot extrusion was promoted, resulting in slightly finer grain size, higher DRXed regions ratio, and weaker texture. And volume fraction and number density of second phase precipitates (micron, submicron, and nano-sized ε and MnZn

Chondral defects caused by osteoarthritis (OA) are common but difficult to manage due to their limited capacity for self-repair. Further, the activated macrophages induced by OA stimulates chondrocytes degradation and inhibits regeneration, further impeding cartilage repair. Therefore, biomaterials with the potential for blocking vicious cycles between activated macrophages and chondrocytes would be promising for use in the treatment of chondral defects caused by OA. In this study, we fabricated porous Mg-Nd-Zn-Zr alloy (denoted JDBM) scaffolds coated with polydopamine (PDA) and investigated their cytocompatibility and impact on immunoregulation. Mesenchymal stem cells (MSCs) were co-cultured in supernatant from M1-polarized macrophages pretreated with extracts from JDBM scaffolds and the anti-inflammatory effect on the NF-κB pathway and reactive oxygen species (ROS) evaluated. JDBM scaffolds could reduce M1 macrophage numbers, while promoting those of M2 macrophages; recruit MSCs; and enhance chondrogenesis. Furthermore, lipopolysaccharide (LPS)-induced p65 translocation to the nucleus was inhibited by JDBM scaffolds, with ROS production and matrix metalloproteinase (MMP) expression also suppressed. These findings suggest that JDBM scaffolds can both promote chondrogenesis and effectively attenuate local inflammatory responses by transforming macrophages from the M1 to M2 subtype and down-regulating NF-κB signaling. Hence, JDBM scaffolds could promote chondrogenesis under inflammatory microenvironment and represent a promising material for treatment of chondral defects caused by OA.

To preliminarily investigate the feasibility of bioabsorption tracheal stenting for the therapeutic application of congenital tracheal stenosis (CTS).Experimental research.Shanghai Children Medical Center, National Children's Medical Center.Five kinds of magnesium alloys with different compositions were studied in this paper, a patented Mg-Nd-Zn-Zr alloy series namely JDBM (JiaoDa BioMg) and four Mg-Ca-Zn alloys. The cytotoxicity of alloys was evaluated by the MTS ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay in rabbit tracheal epithelial cells. Specific magnesium alloys had been immersed in the cell culture medium for 24 h. The tracheal stents that were made of magnesium alloy were implanted into the trachea of New Zealand rabbits and the ablation of the stent was monitored by fiber bronchoscopy. The routine blood examination was conducted prior to and following the stent placement. The rabbits were euthanized following 2-3 months of stenting. HE staining of the main organs was conducted and the induction of apoptosis of the tracheal tissues was monitored.The cytotoxicity of the JDBM magnesium alloy was mild and lower than the remaining 4 alloys. The stents were placed successfully in five animals. The tracheal stents were successfully placed and gradually biodegradated as monitored by fiber bronchoscopy; no significant systemic inflammatory response was noted. No significant differences in the liver and/or kidney function prior to and following stent placement were noted. HE staining indicated the absence of pathological changes in the trachea, liver, heart and/or kidney tissues. The apoptotic assay indicated that the apoptosis ratio of the tracheal tissues was comparable between rabbits with and without tracheal stenting.The results suggested the feasibility of bioabsorption stents made of biodegradable magnesium alloys using in patients with tracheal stenosis, especially in infants.

Magnesium alloys are an ideal material for biodegradable vascular stents, which can be completely absorbed in the human body, and have good biosafety and mechanical properties. However, the rapid corrosion rate and excessive localized corrosion, as well as challenges in the preparation and processing of microtubes for stents, are restricting the clinical application of magnesium-based vascular stents. In the present work we will give an overview of the recent progresses on biodegradable magnesium based vascular stents including magnesium alloy design, high-precision microtubes processing, stent shape optimisation and functional coating preparation. In particular, the Triune Principle in biodegradable magnesium alloy design is proposed based on our research experience, which requires three key aspects to be considered when designing new biodegradable magnesium alloys for vascular stents application, i.e. biocompatibility and biosafety, mechanical properties, and biodegradation. This review hopes to inspire the future studies on the design and development of biodegradable magnesium alloy-based vascular stents.

The solid solution strengthening of Li, Mg, Al, Mn, Cu and Ag in biodegradable Zn-based alloys is quantitatively investigated by first-principles calculations based on density functional theory. The alloying effect on lattice parameters and elastic constants is determined. Mn is found to have the greatest impact on the lattice parameters and shear modulus, while Mg and Al exhibit the least. According to the theories proposed by Fleischer and Labusch, the strengthening capability of selected elements can be ranked as Mn > Li > Cu, Ag > Mg > Al. The different strengthening effect of solutes can be attributed to their valence electron structure. Analysis on experimental results indicates that ternary Zn-based alloys may satisfy the clinical requirements on mechanical properties with less secondary phase and suppressed mechanical instability.

Additive manufacturing (AM) has enabled the fabrication of biodegradable porous metals to satisfy the desired characteristics for orthopedic applications. The geometrical design on AM biodegradable metallic scaffolds has been found to offer a favorable opportunity to regulate their mechanical and degradation performance in previous studies, however mostly confined to static responses. In this study, we presented the effect of the geometrical design on the dynamic responses of AM Mg scaffolds for the first time. Three different types of porous structures, based on various unit cells (i.e., biomimetic, diamond, and sheet-based gyroid), were established and then subjected to selective laser melting (SLM) process using group-developed Mg-Nd-Zn-Zr alloy (JDBM) powders. The topology after dynamic electropolishing, dynamic compressive properties, and dynamic biodegradation behavior of the AM Mg scaffolds were comprehensively evaluated. It was found that dynamic electropolishing effectively removed the excessive adhered powders on the surfaces and resulted in similar geometrical deviations amongst the AM Mg scaffolds, independent of their porous structures. The geometrical design significantly affected the compressive fatigue properties of the AM Mg scaffolds, of which the sheeted-based gyroid structure demonstrated a superior fatigue endurance limit of 0.85 at 106 cycles. Furthermore, in vitro dynamic immersion behaviors of the AM Mg scaffolds revealed a decent dependence on local architectures, where the sheeted-based gyroid scaffold experienced the lowest structural loss with a relatively uniform degradation mode. The obtained results indicate that the geometrical design could provide a promising strategy to develop desirable bone substitutes for the treatment of critical-size load-bearing defects. Statement of significance Additive manufacturing (AM) has provided unprecedented opportunities to fabricate geometrically complex biodegradable scaffolds where the topological design becomes a key determinant on comprehensive performance. In this paper, we fabricate 3 AM biodegradable Mg scaffolds (i.e., biomimetic, diamond, and sheet-based gyroid) and report the effect of the geometrical design on the dynamic responses of AM Mg scaffolds for the first time. The results revealed that the sheeted-based gyroid scaffold exhibited the best combination of superior compressive fatigue properties and relatively uniform dynamic biodegradation mode, suggesting that the regulation of the porous structures could be an effective approach for the optimization of AM Mg scaffolds as to satisfy clinical requirements in orthopedic applications

BACKGROUND: Restenosis is one of the worst side effects of percutaneous coronary intervention (PCI) due to neointima formation resulting from the excessive proliferation and migration of vascular smooth muscle cells (VSMCs) and continuous inflammation. Biodegradable Mg-based alloy is a promising candidate material because of its good mechanical properties and biocompatibility, and biodegradation of cardiovascular stents. Although studies have shown reduced neointima formation after Mg-based CVS implantation in vivo, these findings were inconsistent with in vitro studies, demonstrating magnesium-mediated promotion of the proliferation and migration of VSMCs. Given the vital role of activated macrophage-driven inflammation in neointima formation, along with the well-demonstrated crosstalk between macrophages and VSMCs, we investigated the interactions of a biodegradable Mg-Nd-Zn-Zr alloy (denoted JDBM), which is especially important for cardiovascular stents, with VSMCs via macrophages. METHODS: JDBM extracts and MgCl(2) solutions were prepared to study their effect on macrophages. To study the effects of the JDBM extracts and MgCl(2) solutions on the function of VSMCs via immunoregulation of macrophages, conditioned media (CM) obtained from macrophages was used to establish a VSMC-macrophage indirect coculture system. RESULTS: Our results showed that both JDBM extracts and MgCl(2) solutions significantly attenuated the inflammatory response stimulated by lipopolysaccharide (LPS)-activated macrophages and converted macrophages into M2-type cells. In addition, JDBM extracts and MgCl(2) solutions significantly decreased the expression of genes related to VSMC phenotypic switching, migration, and proliferation in macrophages. Furthermore, the proliferation, migration, and proinflammatory phenotypic switching of VSMCs were significantly inhibited when the cells were incubated with CMs from macrophages treated with LPS + extracts or LPS + MgCl(2) solutions. CONCLUSIONS: Taken together, our results suggested that the magnesium in the JDBM extract could affect the functions of VSMCs through macrophage-mediated immunoregulation, inhibiting smooth muscle hyperproliferation to suppress restenosis after implantation of a biodegradable Mg-based stent.

Bone tissue engineering is considered as a promising pathway for bone regeneration and defect reconstruction, in which scaffolds play an important role. Zn alloy, which is a biodegradable metal material that has advantages of metallic and biodegradable characteristics, has its special features, especially the ideal degradation rate and acceptable biocompatibility, which make it worthy to be further investigated for medical applications. In this study, new biodegradable porous Zn alloy scaffolds with Ca-P coating were attempted to repair cranial bone defect, and in vitro and in vivo assays were conducted to evaluate its biocompatibility, osteo-inductivity, and osteo-conductivity. The results indicated that coated Zn alloy possessed good biocompatibility, with no cytotoxicity. It could also promote osteogenic differentiation and calcium deposition of rabbit BMSCs in vitro, and new bone formation around the scaffold in vivo. The biodegradable porous Zn alloy scaffold with Ca-P coating is considered to be promising in cranial bone defect repair.

Various kinds of biodegradable Mg alloys have been developed in recent years due to their appropriate mechanical properties, biodegradation, and good biocompatibility. In this study, Mg-2.0Zn-xGd alloys (x = 0.5, 1.0, 1.5, and 2.0 wt %) were prepared. Hot extrusion was applied in order to refine the microstructure and improve the degradation resistance. The microstructure, mechanical properties, and in vitro degradation behavior of Mg-2.0Zn-xGd alloys were investigated first. The as-extruded Mg-2.0Zn-1.0Gd alloy exhibits excellent mechanical properties (UTS 338 MPa, YS 284 MPa, elongation 24%) and low in vitro degradation rate (0.24 mm/year) with uniform degradation morphology, and then, this alloy was selected for further assessments. The cytotoxicity of as-extruded Mg-2.0Zn-1.0Gd alloy to MC3T3-E1 cell is found to be grade 0-1, indicating good biocompatibility. The in vivo experiment shows that the in vivo degradation rate of this alloy is about 0.31 mm/y after 30 days implantation in cranial defect of Sprague-Dawley rats. All of these indicate a promising prospect of Mg-2.0Zn-1.0Gd alloy as biodegradable applications, especially as orthopedic implants.