[Biological characteristics and osteogenic differentiation of magnesium-doped nanoporous titanium coating].

PURPOSE: Bioactive magnesium ions were successfully incorporated into the nanoporous titanium base coating by micro-arc oxidation(MAO), and its physical properties and osteogenic effects were explored. METHODS: Non-magnesium-containing and magnesium-containing titanium porous titanium coatings(MAO, MAO-mg) were prepared by changing the composition of MAO electrolyte and controlling the doping of magnesium in porous titanium coatings. The samples were characterized by scanning electron microscope (SEM), roughness, contact angle and energy dispersive X-ray spectrometer (EDS). Mg2+ release ability of magnesium-doped nanoporous titanium coatings was determined by inductively coupled plasma/optical emission spectrometer(ICP-OES). The structure of the cytoskeleton was determined by live/dead double staining, CCK-8 detection of material proliferation-toxicity, and staining of ß-actin using FITC-phalloidin. The effects of the coating on osteogenic differentiation in vitro were determined by alizarin red (ARS), alkaline phosphatase (ALP) staining and real-time polymerase chain reaction (qRT-PCR). SPSS 25.0 software package was used for statistical analysis. RESULTS: The MAO electrolyte with magnesium ions did not change the surface characteristics of the porous titanium coating. Each group prepared by MAO had similar microporous structure(P＞0.05). There was no significant difference in surface roughness and contact angle between MAO treatment group (MAO, MAO-mg)(P＞0.05), but significantly higher than that of Ti group (P＜0.05). With the passage of cell culture time, MAO-mg group promoted cell proliferation (P＜0.05). MAO-mg group was significantly higher than other groups in ALP and ARS staining. The expression of Runx2 mRNA (P＜0.05), ALP(P＜0.05) and osteocalcin OCN(P＜0.05) in MAO-mg group was significantly higher than that in Ti and MAO groups. CONCLUSIONS: MAO successfully prepared magnesium-containing nanoporous titanium coating, and showed a significant role in promoting osteogenic differentiation.

High performance injectable Mg doped bioactive glass bone cement for the regulation of osteogenic immune microenvironment.

Although calcium phosphate has been extensively utilized in orthopedic applications such as spine, limbs, dentistry, and maxillofacial surgery, the lack of osteoinductive properties often hinders its effectiveness in treating bone defects resulting from pathological micro-environment such as tumor surgery, osteoporosis, osteomyelitis, and diabetic. Therefore, a novel bone cement based on magnesium-doped bioactive glass was developed in this study. The moderate release of magnesium ions improved the mechanical properties by controlling the crystal size of hydroxyapatite. Through detailed discussion of element content and heat treatment temperature, it was found that 2Mg-BG-800 was suitable for the construction of bone cement. 2Mg-BG-BC exhibited favorable initial (15 min) and final (30 min) setting time, compressive strength (29.45 MPa), compressive modulus (1851.49 MPa), injectability, and shape-adaptability. Furthermore, Mg-BG-BC demonstrated the ability to enhance the osteogenic differentiation of BMSCs, and induce macrophage polarization towards the M2 phenotype, suggesting its potential for osteoporotic fracture regeneration.

Differential Protective Effect of Zinc and Magnesium for the Hepatic and Renal Toxicity Induced by Acetaminophen and Potentiated with Ciprofloxacin in Rats.

Background and Objectives: The purpose of this study was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally induced with acetaminophen (AAPh) and potentiated by a ciprofloxacin addition in rats. Material and Methods: The experiment was performed on five animal groups: group 1-control, treated for 6 weeks with normal saline, 1 mL/kg; group 2-AAPh, treated for 6 weeks with AAPh, 100 mg/kg/day; group 3-AAPh + C, treated for 6 weeks with AAPh 100 mg/kg/day and ciprofloxacin 50 mg/kg/day, only in the last 14 days of the experiment; group 4-AAPh + C + Mg, with the same treatment as group 3, but in the last 14 days, MgCl2 10 mg/ kg/day was added; and group 5-AAPh + C + Zn, with the same treatment as group 3, but in the last 14 days, zinc gluconate (ZnG), 10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (p < 0.001 group 2 vs. group 1 for all mentioned parameters). Furthermore, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, at 0.001 < p < 0.01 and 0.01 < p < 0.05, respectively). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days, resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine (0.01 < p < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against the increase in liver enzymes, and a more pronounced protection against the increase in serum urea and creatinine (0.001 < p < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < p < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in the case of ZnG, to a higher extent, especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < p < 0.05 group 5 vs. group 4). Conclusions: This study presents further proof for the beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney's function, and the antioxidant profile improvement has a key role, especially in the case of zinc gluconate.

Mechanical biomimetic silk nano fiber-magnesium ion complex/hydroxyethylcellulose/glycerol hydrogel dressing with angiogenic capacity for accelerating scarless diabetic wound healing.

Quick scarless healing remains a key issue for diabetic wounds. Here, a stretchable elastomeric hydrogel dressing composed of hydroxyethylcellulose (HEC), silk nano fiber-magnesium ion complex (Mg2+-SNF) and glycerol (Gly) was developed to optimize mechanical niche, anti-inflammatory and angiogenic behavior simultaneously. The composite hydrogel dressing exhibited skin-like elasticity (175.1 ± 23.9 %) and modulus (156.7 ± 2.5 KPa) while Mg2+-SNF complex endowed the dressing with angiogenesis, both favoring quick scarless skin regeneration. In vitro cell studies revealed that the hydrogel dressing stimulated fibroblast proliferation, endothelial cell migration and vessel-like tube formation, and also induced anti-inflammatory behavior of macrophages. In vivo results revealed accelerated healing of diabetic wounds. The improved granulation ingrowth and collagen deposition suggested high quality repair. Both thinner epidermal layer and low collagen I/III ratio of the regenerated skin confirmed scarless tissue formation. This bioactive hydrogel dressing has promising potential to address the multifaceted challenges of diabetic wound management.

A magnesium screw with optimized geometry exhibits improved corrosion resistance and favors bone fracture healing.

Stress-induced corrosion impairs the mechanical integrity of magnesium (Mg) and its alloys as potential orthopedic implants. Although there has been extensive work reporting the effects of stress on Mg corrosion in vitro, the geometric design principles of the Mg-based orthopedic devices still remain largely unknown. In this work, a numerical simulation model mimicking fractured bone fixation and surgical animal models were applied to investigate the effects of the geometric design of Mg screws on the stress distribution and the stress-induced degradation behavior. Finite element (FE) analysis was used for calculation of stress concentrations around the Mg screws, with different thread type, thread pitch, and thread width. Afterward, the Mg screws of the pre-optimization and post-optimization groups exhibiting the highest and lowest stress concentrations, respectively, were implanted in the fractured distal femora and back subcutaneous tissue of rabbits. Encouragingly, there was a significant difference between the pre-optimization and the post-optimization groups in the degradation rate of the stressed screw parts located around the fracture line. Interestingly, there was no significant difference between the two groups in the degradation rate of the non-stressed screw parts. Consistently, the Mg screw post-optimization exhibited a significantly lower degradation rate than that pre-optimization in the back subcutaneous implantation model, which generated stress in the whole screw body. The alteration in geometric design did not affect the corrosion rate of the Mg screws in an immersion test without load applied. Importantly, an accelerated new bone formation with less fibrous encapsulation around the screws was observed in the Mg group post-optimization relative to the Mg group pre-optimization and the poly (lactic acid) group. Geometry optimization may be a promising strategy to reduce stress-induced corrosion in Mg-based orthopedic devices. STATEMENT OF SIGNIFICANCE: Stress concentrations influence corrosion characteristics of magnesium (Mg)-based implants. The geometric design parameters, including thread type, thread pitch, and thread width of the Mg screws, were optimized through finite element analysis to reduce stress concentrations in a fractured model. The Mg screws with triangular thread type, 2.25 mm pitch, and 0.3 mm thread width, exhibiting the lowest maximum von Mises stress, showed a significant decrease in the volume loss relative to the Mg screws pre-optimization. Compared with the Mg screw pre-optimization and the poly(lactic acid) screw, the Mg screw post-optimization favored new bone formation while inhibiting fibrous encapsulation. Collectively, optimization in the geometric design is a promising approach to reduce stress-induced corrosion in Mg-based implants.

Comparative transcriptional analysis of Candida auris biofilms following farnesol and tyrosol treatment.

Candida auris is frequently associated with biofilm-related invasive infections. The resistant profile of these biofilms necessitates innovative therapeutic options, where quorum sensing may be a potential target. Farnesol and tyrosol are two fungal quorum-sensing molecules with antifungal effects at supraphysiological concentrations. Here, we performed genome-wide transcript profiling with C. auris biofilms following farnesol or tyrosol exposure using transcriptome sequencing (RNA-Seq). Since transition metals play a central role in fungal virulence and biofilm formation, levels of intracellular calcium, magnesium, and iron were determined following farnesol or tyrosol treatment using inductively coupled plasma optical emission spectrometry. Farnesol caused an 89.9% and 73.8% significant reduction in the calcium and magnesium content, respectively, whereas tyrosol resulted in 82.6%, 76.6%, and 81.2% decrease in the calcium, magnesium, and iron content, respectively, compared to the control. Genes involved in biofilm events, glycolysis, ergosterol biosynthesis, fatty acid oxidation, iron metabolism, and autophagy were primarily affected in treated cells. To prove ergosterol quorum-sensing molecule interactions, microdilution-based susceptibility testing was performed, where the complexation of farnesol, but not tyrosol, with ergosterol was impeded in the presence of exogenous ergosterol, resulting in a minimum inhibitory concentration increase in the quorum-sensing molecules. This study revealed several farnesol- and tyrosol-specific responses, which will contribute to the development of alternative therapies against C. auris biofilms. IMPORTANCE: Candida auris is a multidrug-resistant fungal pathogen, which is frequently associated with biofilm-related infections. Candida-derived quorum-sensing molecules (farnesol and tyrosol) play a pivotal role in the regulation of fungal morphogenesis and biofilm development. Furthermore, they may have remarkable anti-biofilm effects, especially at supraphysiological concentrations. Innovative therapeutic approaches interfering with quorum sensing may be a promising future strategy against C. auris biofilms; however, limited data are currently available concerning farnesol-induced and tyrosol-related molecular effects in C. auris. Here, we detected several genes involved in biofilm events, glycolysis, ergosterol biosynthesis, fatty acid oxidation, iron metabolism, and autophagy, which were primarily influenced following farnesol or tyrosol exposure. Moreover, calcium, magnesium, and iron homeostasis were also significantly affected. These results reveal those molecular and physiological events, which may support the development of novel therapeutic approaches against C. auris biofilms.

Heterogeneous nucleation induced A. pernyi/B. mori silk fibroin coatings on AZ31 biometals with enhanced corrosion resistance, adhesion and biocompatibility.

Silk fibroin coatings on biomedical magnesium alloys have garnered significant attention due to their enhanced corrosion resistance and biocompatibility. However, the utilization of wild A. pernyi silk fibroin, known for its RGD sequence that facilitates tissue regeneration, presents a challenge for corrosion-resistant coatings on magnesium alloys due to its weak adhesion and high dissolution rate. In this study, we employed hexafluoroisopropanol as a solvent to blend A. pernyi silk fibroin with B. mori silk fibroin. The resulting blended fibroin coating at a 3:7 mass ratio exhibited a heterogeneous nucleation effect, enhancing ß-sheet content (32.3 %) and crystallinity (28.6 %). This improved ß-sheet promoted the "labyrinth effect" with an Icorr of 2.15 × 10-6 A cm-2, resulting in significantly improved corrosion resistance, which is two orders of magnitude lower than that of pure magnesium alloy. Meanwhile, the increased content of exposed serine in zigzag ß-sheet contributes to a higher adhesion strength. Cell cytotoxicity evaluation confirmed the enhanced cell adhesion and bioactivity. This work provides a facile approach for wild A. pernyi silk fibroin coatings on magnesium alloys with enhanced corrosion resistance, adhesion and biocompatibility.

Engineered MgO nanoparticles for cartilage-bone synergistic therapy.

The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg2+ on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.

Methyl Jasmonate-induced Increase in Intracellular Magnesium Promotes Apoptosis in Breast Cancer Cells.

BACKGROUND/AIM: Methyl jasmonate (MeJa) is a botanical stress hormone that serves as a defense mechanism to inhibit growth in stressed plants. It is well known that MeJa exhibits an anticancer effect by reducing intracellular ATP, activating reactive oxygen species (ROS) production, and promoting mitogen-activated protein kinase (MAPK) activity. Presently, no report has been published on MeJa-induced changes in intracellular Mg2+ concentration ([Mg2+]i), and TRPM7 as an Mg2+ transporter in cancer cells. Therefore, this study aimed to investigate the Mg2+ homeostatic changes and apoptotic effects following MeJa treatment using the MCF-7 human breast cancer cell line. MATERIALS AND METHODS: The MTT assay was used to assess the cell viability and half-inhibitory concentration, microscopic two-photon excitation wavelength spectrophotometry was used to measure the [Mg2+]i, a luminescent assay determined intracellular ATP levels, western blot assay measured TRPM7 levels, antioxidant capacities, endoplasmic reticulum (ER) stress, and MAPK signaling pathways, while the fluorescence assay evaluated ROS concentrations and the cell apoptotic index. RESULTS: This study provides evidence that MeJa has an antiapoptotic effect on MCF-7 cells. The increase in [Mg2+]i led to decreased TRPM7 expression, which is related to elevated ROS production, in addition to elevated ER stress and MAPK signaling pathway activity and decreased ATP content. CONCLUSION: The increase in [Mg2+]i leads to decreased TRPM7 expression and may be the epicenter of MeJa-induced apoptotic cell death in MCF-7 cells.

Mg-based implants with a sandwiched composite coating simultaneously facilitate antibacterial and osteogenic properties.

Insufficient antibacterial effects and over-fast degradation are the main limitations of magnesium (Mg)-based orthopedic implants. In this study, a sandwiched composite coating containing a triclosan (TCS)-loaded poly(lactic acid) (PLA) layer inside and brushite (DCPD) layer outside was prepared on the surface of the Mg-Nd-Zn-Zr (denoted as JDBM) implant. In vitro degradation tests revealed a remarkable improvement in the corrosion resistance and moderate degradation rate. The drug release profile demonstrated a controllable and sustained TCS release for at least two weeks in vitro. The antibacterial rates of the implant were all over 99.8% for S. aureus, S. epidermidis, and E. coli, demonstrating superior antibacterial effects. Additionally, this coated JDBM implant exhibited no cytotoxicity but improved cell adhesion and proliferation, indicating excellent cytocompatibility. In vivo assays were conducted by implant-related femur osteomyelitis and osseointegration models in rats. Few bacteria were attached to the implant surface and the surrounding bone tissue. Furthermore, the coated JDBM implant exhibited more new bone formation than other groups due to the synergistic biological effects of released TCS and Mg2+, revealing excellent osteogenic ability. In summary, the JDBM implant with the sandwiched composite coating could significantly enhance the antibacterial activities and osteogenic properties simultaneously by the controllable release of TCS and Mg2+, presenting great potential for clinical transformation.

Functionalized magnesium alloys obtained by superplastic forming process retain osteoinductive and antibacterial properties: An in-vitro study.

OBJECTIVES: This study aimed to investigate the biocompatibility, osteogenic and antibacterial activity of biomedical devices based on Magnesium (Mg) Alloys manufactured by Superplastic Forming process (SPF) and subjected to Hydrothermal (HT) and Sol-Gel Treatment (Sol-Gel). METHODS: Mg-SPF devices subjected to Hydrothermal (Mg-SPF+HT) and Sol-Gel Treatment (Mg-SPF+Sol-Gel) were investigated. The biocompatibility of Mg-SPF+Sol-Gel and Mg-SPF+HT devices was observed by indirect and direct cytotoxicity assays, whereas the colonization of sample surfaces was assessed by confocal microscopy. qRT-PCR analysis and microbial growth curve analyses were employed to evaluate the osteogenic and antibacterial activity of both SPF-Mg treated devices, respectively. RESULTS: Mg-SPF+HT and Mg-SPF+Sol-Gel showed a high degree of biocompatibility. Analysis of mRNA expression of osteogenic genes in cells cultured on Mg-treated devices revealed a significant upregulation of the expression levels of BMP2 and Runx-2. Furthermore, the bacterial growth in strains developed in contact with both the Mg-SPF+HT and Mg-SPF+Sol-Gel devices was lower than that observed in the control. SIGNIFICANCE: Hydrothermal and Sol-Gel Treatments of Mg alloys obtained through the SPF process demonstrated bioactive, osteogenic and antibacterial activity, offering a promising alternative to conventional Mg-based devices. The obtained Mg-based materials may have the potential to enhance the tunability of temporary devices in maxillary reconstruction, eliminating the need for second surgeries, and ensuring a good bone reconstruction and a reduced implant failure rate due to bacterial infections.

Magnesium-lithium thin films for neurological applications-An in vitro investigation of glial cytocompatibility and neuroinflammatory response.

Lithium (Li), a widely used drug for bipolar disorder management, is associated with many side effects due to systemic exposure. The localized delivery of lithium through implants could be an approach to overcome this challenge, for which biodegradable magnesium (Mg)-based materials are a promising choice. In this study, we focus on Mg-Li thin film alloys as potential Li-releasing implants. Therefore, we investigated the in vitro short-term corrosion behavior and cytocompatibility of two alloys, Mg-1.6wt%Li and Mg-9.5wt%Li. As glial cells are the key players of foreign body responses to implants, we used human glial cell lines for cytocompatibility studies, and a murine brain slice model for a more holistic view at the neuroinflammatory response. We found that Mg-1.6wt%Li corrodes approximately six times slower than Mg-9.5wt%Li. Microscopic analysis showed that the material surface (Mg-1.6wt%Li) is suitable for cell adhesion. The cytocompatibility test with Mg-1.6wt%Li and Mg-9.5wt%Li alloy extracts revealed that both cell types proliferated well up to 10 mM Mg concentration, irrespective of the Li concentration. In the murine brain slice model, Mg-1.6wt%Li and Mg-9.5wt%Li alloy extracts did not provoke a significant upregulation of glial inflammatory/ reactivity markers (IL-1ß, IL-6, FN1, TNC) after 24 h of exposure. Furthermore, the gene expression of IL-1ß (up to 3-fold) and IL-6 (up to 16-fold) were significantly downregulated after 96 h, and IL-6 downregulation showed a Li concentration dependency. Together, these results indicate the acute cytocompatibility of two Mg-Li thin film alloys and provide basis for future studies to explore promising applications of the material. STATEMENT OF SIGNIFICANCE: We propose the idea of lithium delivery to the brain via biodegradable implants to reduce systemic side effects of lithium for bipolar disorder therapy and other neurological applications. This is the first in vitro study investigating Mg-xLi thin film degradation under physiological conditions and its influence on cellular responses such as proliferation, viability, morphology and inflammation. Utilizing human brain-derived cell lines, we showed that the material surface of such a thin film alloy is suitable for normal cell attachment. Using murine brain slices, which comprise a multicellular network, we demonstrated that the material extracts did not elicit a pro-inflammatory response. These results substantiate that degradable Mg-Li materials are biocompatible and support the further investigation of their potential as neurological implants.

Dietary Magnesium Replacement for Prevention of Hypomagnesemia in Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy.

PURPOSE: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment. MATERIALS AND METHODS: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined as ≥60% completion of dietary recalls and ≥280 mg average daily dietary magnesium intake across all patients. RESULTS: Twenty-one of 26 patients enrolled completed at least five chemotherapy cycles and were included in the analysis. Adherence to the study diet was 76%. Daily dietary magnesium intake was 100.5 mg at baseline and increased throughout each cycle: 6% of patients at baseline, 24% after the first cycle, and 67% after the fifth cycle reached ≥280-mg/day magnesium intake. Seven (33%) of 21 had at least one incident of hypomagnesemia. Patients who were adherent had significantly lower incidence of hypomagnesemia (19% v 80%, P = .03) and less need for intravenous magnesium (6% v 60%, P = .03) than those who were nonadherent. CONCLUSION: The study achieved primary feasibility objectives of retention and adherence to the study intervention. Weekly education about magnesium-rich diets was effective in increasing dietary magnesium intake. Adequate dietary magnesium appeared to be protective against hypomagnesemia.

Selective Laser Melting of the Porous Ta Scaffold with Mg-Doped Calcium Phosphate Coating for Orthopedic Applications.

Addressing the repair of large-scale bone defects has become a hot research topic within the field of orthopedics. This study assessed the feasibility and effectiveness of using porous tantalum scaffolds to treat such defects. These scaffolds, manufactured using the selective laser melting (SLM) technology, possessed biomechanical properties compatible with natural bone tissue. To enhance the osteogenesis bioactivity of these porous Ta scaffolds, we applied calcium phosphate (CaP) and magnesium-doped calcium phosphate (Mg-CaP) coatings to the surface of SLM Ta scaffolds through a hydrothermal method. These degradable coatings released calcium and magnesium ions, demonstrating osteogenic bioactivity. Experimental results indicated that the Mg-CaP group exhibited biocompatibility comparable to that of the Ta group in vivo and in vitro. In terms of osteogenesis, both the CaP group and the Mg-CaP group showed improved outcomes compared to the control group, with the Mg-CaP group demonstrating superior performance. Therefore, both CaP and magnesium-CaP coatings can significantly enhance the osseointegration of three-dimensional-printed porous Ta, thereby increasing the surface bioactivity. Overall, the present study introduces an innovative approach for the biofunctionalization of SLM porous Ta, aiming to enhance its suitability as a bone implant material.

Nanosized Silk-Magnesium Complexes for Promotion of Angiogenic and Osteogenic Activities.

Injectable hydrogels with osteogenic and angiogenetic properties are of interest in bone tissue engineering. Since the bioactivity of ions is concentration-dependent, nanosized silk-magnesium (Mg) complexes were previously developed and assembled into hydrogels with angiogenic capabilities but failed to control both osteogenic and angiogenetic activities effectively. Here, nanosized silk particles with different sizes were obtained by using ultrasonic treatment to control silk-Mg coordination and particle formation, resulting in silk-Mg hydrogels with different types of bioactivity. Fourier transform infrared and X-ray diffraction results revealed that different coordination intensities were present in the different complexes as a basis for the differences in activities. Slow Mg ion release was controlled by these nanosized silk-Mg complexes through degradation. With the same amount of Mg ions, the different silk-Mg complexes exhibited different angiogenic and osteogenic capacities. Complexes with both angiogenic and osteogenic capacities were developed by optimizing the sizes of the silk particles, resulting in faster and improved quality of bone formed in vivo than complexes with the same composition of silk and Mg but only angiogenic or osteogenic capacities. The biological selectivity of silk-Mg complexes should facilitate applications in tissue regeneration.

Magnesium hydride attenuates intestinal barrier injury during hemorrhage shock by regulating neutrophil extracellular trap formation via the ROS/MAPK/PAD4 pathway.

Magnesium hydride (MgH2) is a hydrogen storage material that is known for its high capacity and safety and is capable of releasing hydrogen in a controlled manner when administered orally. This release of hydrogen has been associated with a range of biological effects, including anti-inflammatory properties, antioxidant activity, and protection of the intestinal barrier. Previous research has shown that neutrophil extracellular traps (NETs) play a role in the dysfunction of the intestinal barrier in conditions such as sepsis and critical illnesses. However, it remains unclear as to whether MgH2 can protect the intestinal barrier by inhibiting NET formation, and the underlying mechanisms have yet to be elucidated. A rat model of hemorrhagic shock was created, and pretreatment or posttreatment procedures with MgH2 were performed. After 24 h, samples from the small intestine and blood were collected for analysis. In vitro, human neutrophils were incubated with either phorbol-12-myristate-13-acetate (PMA) or MgH2. Reactive oxygen species generation and the expression of key proteins were assessed. The results demonstrated that MgH2 administration led to a decrease in inflammatory cytokines in the serum and mitigated distant organ dysfunction in rats with HS. Furthermore, MgH2 treatment reversed histopathological damage in the intestines, improved intestinal permeability, and enhanced the expression of tight junction proteins (TJPs) during HS. Additionally, MgH2 treatment was found to suppress NET formation in the intestines. In vitro pretreatment with MgH2 alleviated intestinal monolayer barrier disruption that was induced by NETs. Mechanistically, MgH2 pretreatment reduced ROS production and NET formation, inhibited the activation of ERK and p38, and suppressed the expression of the PAD4 protein. These findings indicated that MgH2 may inhibit NET formation in a ROS/MAPK/PAD4-dependent manner, which reduces NET-related intestinal barrier damage, thus offering a novel protective role in preventing intestinal barrier dysfunction during HS.

A Cu(â ¡)-eluting coating through silk fibroin film on ZE21B alloy designed for in situ endotheliazation biofunction.

In the cardiovascular field, coating containing copper used to catalyze NO (nitric oxide) production on non-degradable metal surfaces have shown unparalleled expected performance, but there are few studies on biodegradable metal surfaces. Magnesium-based biodegradable metals have been applied in cardiovascular field in large-scale because of their excellent properties. In this study, the coating of copper loaded in silk fibroin is fabricated on biodegradable ZE21B alloy. Importantly, the different content of copper is set to investigate the effects of on the degradation performance and cell behavior of magnesium alloy. Through electrochemical and immersion experiments, it is found that high content of copper will accelerate the corrosion of magnesium alloy. The reason is the spontaneous micro-batteries between copper and magnesium with the different standard electrode potentials, that is, the galvanic corrosion accelerates the corrosion of magnesium alloy. Moreover, the coating formed through silk fibroin by the right amount copper not only have a protective effect on the ZE21B alloy substrate, but also promotes the adhesion and proliferation of endothelial cells in blood vessel micro-environment. The production of NO catalyzed by copper ions makes this trend more significant, and inhibits the excessive proliferation of smooth muscle cells. These findings can provide guidance for the amount of copper in the coating on the surface of biodegradable magnesium alloy used for cardiovascular stent purpose.

Degradation protection and enhanced biocompatibility of Mg alloys pretreated with plasma proteins.

After implantation of the Mg alloy in the human body, the adsorption of plasma protein on surface will cause a series of cell reactions and affect the degradation of Mg alloys. Herein, in vitro biological reactions of the ZK60 and AZ31 Mg alloys are analyzed in plasma protein environment. Combined with mass spectrometry analysis of the type of adsorbed proteins, it is shown that proteins such as fibrinogen, vitronectin, fibronectin, and prothrombin are prone to get adsorbed on the surface of the alloys than other proteins, leading to the promotion of MG63 cell adhesion and proliferation. The effect of selected proteins (fibrinogen, fibronectin, and prothrombin) on degradation of ZK60 and AZ31 Mg alloys is investigated using immersion tests. The degradation of AZ31 Mg alloy is significantly restrained with the presence of proteins. This is due to the protein adsorption effect on the sample surface. The molecular dynamics simulation results indicate that both fibrinogen and fibronectin tend to adsorb onto the AZ31 rather than ZK60, forming a stable protein layer on the AZ31 Mg alloy retarding the degradation of the samples. As to ZK60 alloy, the addition of protein inhibits the degradation in the short term, however, the degradation increases after a long time of immersion. This phenomenon is particularly pronounced in fibronectin solution.

An oxidized dextran-composite self-healing coated magnesium scaffold reduces apoptosis to induce bone regeneration.

Self-healing coatings have shown promise in controlling the degradation of scaffolds and addressing coating detachment issues. However, developing a self-healing coating for magnesium (Mg) possessing multiple biological functions in infectious environments remains a significant challenge. In this study, a self-healing coating was developed for magnesium scaffolds using oxidized dextran (OD), 3-aminopropyltriethoxysilane (APTES), and nano-hydroxyapatite (nHA) doped micro-arc oxidation (MHA), named OD-MHA/Mg. The results demonstrated that the OD-MHA coating effectively addresses coating detachment issues and controls the degradation of Mg in an infectious environment through self-healing mechanisms. Furthermore, the OD-MHA/Mg scaffold exhibits antibacterial, antioxidant, and anti-apoptotic properties, it also promotes bone repair by upregulating the expression of osteogenesis genes and proteins. The findings of this study indicate that the OD-MHA coated Mg scaffold possessing multiple biological functions presents a promising approach for addressing infectious bone defects. Additionally, the study showcases the potential of polysaccharides with multiple biological functions in facilitating tissue healing even in challenging environments.

Self-Healing Micro Arc Oxidation and Dicalcium Phosphate Dihydrate Double-Passivated Coating on Magnesium Membrane for Enhanced Bone Integration Repair.

Magnesium is a revolutionary biomaterial for orthopedic implants, owing to its eminent mechanical properties and biocompatibility. However, its uncontrolled degradation rate remains a severe challenge for its potential applications. In this study, we developed a self-healing micro arc oxidation (MAO) and dicalcium phosphate dihydrate (DCPD) double-passivated coating on a magnesium membrane (Mg-MAO/DCPD) and investigated its potential for bone-defect healing. The Mg-MAO/DCPD membrane possessed a feasible self-repairing ability and good cytocompatibility. In vitro degradation experiments showed that the Mg contents on the coating surface were 0.3, 3.8, 4.1, 6.1, and 7.9% when the degradation times were 0, 1, 2, 3, and 4 weeks, respectively, exhibiting available corrosion resistance. The slow and sustained release of Mg2+ during the degradation process activated extracellular matrix proteins for bone regeneration, accelerating osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The extract solutions of Mg-MAO/DCPD considerably promoted the activation of the Wnt and PI3K/AKT signaling pathways. Furthermore, the evaluation of the rat skull defect model manifested the outstanding bone-healing efficiency of the Mg-MAO/DCPD membrane. Taken together, the Mg-MAO/DCPD membrane demonstrates an optimized degradation rate and excellent bioactivity and is believed to have great application prospects in bone tissue engineering.