Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 88
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Nature ; 541(7635): 81-86, 2017 01 05.
Article in English | MEDLINE | ID: mdl-28002404

ABSTRACT

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10-7, range P = 9.2 × 10-8 to 6.0 × 10-46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10-6, range P = 5.5 × 10-6 to 6.1 × 10-35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.


Subject(s)
Adiposity/genetics , Body Mass Index , DNA Methylation/genetics , Diabetes Mellitus, Type 2/genetics , Epigenesis, Genetic , Epigenomics , Genome-Wide Association Study , Obesity/genetics , Adipose Tissue/metabolism , Asian People/genetics , Blood/metabolism , Cohort Studies , Diabetes Mellitus, Type 2/complications , Europe/ethnology , Female , Genetic Markers , Genetic Predisposition to Disease , Humans , India/ethnology , Male , Obesity/blood , Obesity/complications , Overweight/blood , Overweight/complications , Overweight/genetics , White People/genetics
2.
Circ Res ; 124(9): 1337-1349, 2019 04 26.
Article in English | MEDLINE | ID: mdl-30892142

ABSTRACT

RATIONALE: The ETS (E-26 transformation-specific) transcription factor ERG (ETS-related gene) is essential for endothelial homeostasis, driving expression of lineage genes and repressing proinflammatory genes. Loss of ERG expression is associated with diseases including atherosclerosis. ERG's homeostatic function is lineage-specific, because aberrant ERG expression in cancer is oncogenic. The molecular basis for ERG lineage-specific activity is unknown. Transcriptional regulation of lineage specificity is linked to enhancer clusters (super-enhancers). OBJECTIVE: To investigate whether ERG regulates endothelial-specific gene expression via super-enhancers. METHODS AND RESULTS: Chromatin immunoprecipitation with high-throughput sequencing in human umbilical vein endothelial cells showed that ERG binds 93% of super-enhancers ranked according to H3K27ac, a mark of active chromatin. These were associated with endothelial genes such as DLL4 (Delta-like protein 4), CLDN5 (claudin-5), VWF (von Willebrand factor), and CDH5 (VE-cadherin). Comparison between human umbilical vein endothelial cell and prostate cancer TMPRSS2 (transmembrane protease, serine-2):ERG fusion-positive human prostate epithelial cancer cell line (VCaP) cells revealed distinctive lineage-specific transcriptome and super-enhancer profiles. At a subset of endothelial super-enhancers (including DLL4 and CLDN5), loss of ERG results in significant reduction in gene expression which correlates with decreased enrichment of H3K27ac and MED (Mediator complex subunit)-1, and reduced recruitment of acetyltransferase p300. At these super-enhancers, co-occupancy of GATA2 (GATA-binding protein 2) and AP-1 (activator protein 1) is significantly lower compared with super-enhancers that remained constant following ERG inhibition. These data suggest distinct mechanisms of super-enhancer regulation in endothelial cells and highlight the unique role of ERG in controlling a core subset of super-enhancers. Most disease-associated single nucleotide polymorphisms from genome-wide association studies lie within noncoding regions and perturb transcription factor recognition sequences in relevant cell types. Analysis of genome-wide association studies data shows significant enrichment of risk variants for cardiovascular disease and other diseases, at ERG endothelial enhancers and super-enhancers. CONCLUSIONS: The transcription factor ERG promotes endothelial homeostasis via regulation of lineage-specific enhancers and super-enhancers. Enrichment of cardiovascular disease-associated single nucleotide polymorphisms at ERG super-enhancers suggests that ERG-dependent transcription modulates disease risk.


Subject(s)
Enhancer Elements, Genetic/genetics , Gene Expression Profiling , Gene Expression Regulation , Cell Line, Tumor , Cells, Cultured , Claudin-5/genetics , Claudin-5/metabolism , GATA2 Transcription Factor/genetics , GATA2 Transcription Factor/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism , Transcriptional Regulator ERG/genetics
3.
Phys Chem Chem Phys ; 23(14): 8318-8325, 2021 Apr 14.
Article in English | MEDLINE | ID: mdl-33875996

ABSTRACT

Very recently, an important two-dimensional material, MoSi2N4, was successfully synthesized. However, pure MoSi2N4 has some inherent shortcomings when used in photocatalytic water splitting to produce hydrogen, especially a low separation rate of photogenerated electron-hole pairs and a poor visible light response. Interestingly, we find that the MoSi2N4 can be used as a good modification material, and it can be coupled with C2N to form an efficient heterojunction photocatalyst. Here, using density functional theory, a type-II heterojunction, C2N/MoSi2N4, is designed and systematically studied. Based on AIMD simulations and phonon dispersion verification, C2N/MoSi2N4 shows sufficient thermodynamic stability. As well as its perfect interface electronic properties, its large interlayer charge transfer and good visible light response lay the foundation for its excellent photocatalytic performance. In addition, the oxidation and reduction potentials of the C2N/MoSi2N4 heterojunction not only can meet the requirements of water splitting well but can also maintain a delicate balance between oxidation and reduction reactions. More importantly, the |ΔGH*| value of the C2N/MoSi2N4 heterojunction is very close to zero, indicating great application potential in the field of photocatalytic water splitting. In brief, our research paves the way for the design of future MoSi2N4-based efficient heterojunction photocatalysts.

4.
Phys Chem Chem Phys ; 23(4): 2812-2818, 2021 Feb 04.
Article in English | MEDLINE | ID: mdl-33470254

ABSTRACT

Searching for economical low-dimensional materials to construct the highly efficient type-II heterojunction photocatalysts for splitting water into hydrogen is very strategic. In this study, using the first-principles calculations, we construct a novel SiH/CeO2(111) type-II heterojunction with a very small lattice mismatch of less than 1%. Based on AIMD simulation and phonon dispersion calculations, the SiH/CeO2(111) heterojunction reveals sufficient stability, and is easy to synthesize. Due to the vdW interaction between SiH and CeO2(111) components, electron and hole accumulation regions form at the heterojunction interface, which is very conducive to the separation of photoexcited electron-hole pairs. Besides, the SiH/CeO2(111) heterojunction has good visible light response, and even a strong absorption peak of up to 8.7 × 105 cm-1 in the high-energy visible region. More importantly, the SiH/CeO2(111) heterojunction exhibits good OER and HER performance because its oxidation and reduction potentials well meet the requirements of water splitting. Consequently, SiH/CeO2(111) is a potential photocatalyst for splitting water to hydrogen.

5.
Dev Biol ; 456(1): 40-46, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31283921

ABSTRACT

We present a detailed analysis of gene expression in the 2-day (HH12) embryonic chick heart. RNA-seq of 13 micro-dissected regions reveals regionalised expression of 15,570 genes. Of these, 132 were studied by in situ hybridisation and a subset (38 genes) was mapped by Optical Projection Tomography or serial sectioning to build a detailed 3-dimensional atlas of expression. We display this with a novel interactive 3-D viewer and as stacks of sections, revealing the boundaries of expression domains and regions of overlap. Analysis of the expression domains also defines some sub-regions distinct from those normally recognised by anatomical criteria at this stage of development, such as a previously undescribed subdivision of the atria into two orthogonal sets of domains (dorsoventral and left-right). We also include a detailed comparison of expression in the chick with the mouse and other species.


Subject(s)
Heart/anatomy & histology , Heart/embryology , Imaging, Three-Dimensional/methods , Anatomy, Artistic/methods , Animals , Atlases as Topic , Chick Embryo , Chickens/genetics , Gene Expression/genetics , Gene Expression Regulation, Developmental/genetics , In Situ Hybridization/methods
6.
J Nanosci Nanotechnol ; 18(10): 7058-7063, 2018 10 01.
Article in English | MEDLINE | ID: mdl-29954533

ABSTRACT

The porous SnO2 nanospheres were fabricated by hydrothermal method and then the carbon layer was coated as a buffer cushion through a facile hydrothermal process in aqueous D-glucose followed by a subsequent calcination at 500 °C in a nitrogen (N2) atmosphere. The materials were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetric analysis and Raman spectra. Based on the experimental results, the thickness of carbon layer could be well-controlled by hydrothermal time and D-glucose concentration. The typical as-prepared carbon-coated porous SnO2 nanospheres show an initial discharge capacity of 711.26 mAhg-1 and a stabilized capacity at 414 mAhg-1 after 50 cycles. It was shown that the carbon-coated porous SnO2 nanospheres exhibited better electrochemical properties in terms of high Columbic efficiency and rate performance, which are attributed to the porous structure and the outer carbon layer.

7.
J Mater Sci Mater Med ; 28(9): 130, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28730462

ABSTRACT

Mg-5.6Zn-0.5Zr alloy (ZK60) tends to degrade too rapid for orthopedic application, in spite of its natural degradation, suitable strength and good biocompatibility. In this study, Nd was alloyed with ZK60 via laser melting method to enhance its corrosion resistance. The microstructure features, mechanical properties and corrosion behaviors of ZK60-xNd (x = 0, 1.8, 3.6, 5.4 wt.%) were investigated. Results showed that laser melted ZK60-xNd were composed of fine ɑ-Mg grains and intermetallic phases along grain boundaries. And the precipitated intermetallic phases experienced successive changes: divorced island-like MgZn phase → honeycomb-like T phase → coarsened and agglomerated W phase with Nd increasing. It was worth noting that ZK60-3.6Nd with honeycomb-like T phase exhibited an optimal corrosion behavior with a corrosion rate of 1.56 mm year-1. The improved corrosion behavior was ascribed to: (I) dense surface film caused by the formation of Nd2O3 hindered the invasion of immersion solution; (II) the three-dimensional honeycomb structure of intermetallic phases formed a tight barrier to restrain the propagation of corrosion. Moreover, ZK60-3.6Nd exhibited good biocompatibility. It was suggested that ZK60-3.6Nd was a preferable candidate for biodegradable bone implant.


Subject(s)
Alloys , Bone-Implant Interface , Neodymium/chemistry , Absorbable Implants , Animals , Bone and Bones , Cell Line, Tumor , Corrosion , Humans , Materials Testing , Mechanical Phenomena , Osteosarcoma , Surface Properties , Zirconium
8.
J Mater Sci Mater Med ; 28(1): 13, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27995491

ABSTRACT

The rapid degradation rate of Magnesium (Mg) alloy limits its biomedical application even though it possesses outstanding biological performance and biomechanical compatibility. In this study, a combined method of laser rapid melting and alloying Zinc (Zn) was proposed to decrease the degradation rate of Mg-Sn alloy. The microstructure, degradation behaviors and mechanical properties of the laser-melted Mg-5Sn-xZn (x = 0, 2, 4, 6 and 8 wt.%) alloys were investigated. The results indicated that the grain size of the alloys decreased with increasing Zn content, due to the increased number of nucleation particles formed in the process of solidification. Moreover, the laser-melted Mg-Sn alloys possessed finer grains compared with traditional as-cast and as-rolled Mg-Sn alloys. The degradation rate of the alloys decreased with increasing Zn content (0-4 wt.%), which was ascribed to the grain refinement and the formation of Zn(OH)2 protective layer. However, the degradation rate increased as the Zn content further increased (4-8 wt.%), which was caused by the galvanic corrosion between the Mg matrix and the generated Mg7Zn3 phase. Besides, Zn also increased the hardness of the alloys owing to the grain refinement strengthening and solid solution strengthening.


Subject(s)
Alloys/chemistry , Magnesium/chemistry , Tin/chemistry , Zinc/chemistry , Absorbable Implants , Biocompatible Materials/chemistry , Biomechanical Phenomena , Corrosion , Crystallization , Crystallography, X-Ray , Hardness , Humans , Lasers , Materials Testing/methods , Powders , Solutions , Stress, Mechanical
9.
Molecules ; 22(4)2017 Mar 23.
Article in English | MEDLINE | ID: mdl-28333113

ABSTRACT

Diopside (DIOP) was introduced into polyetheretherketone/polyglycolicacid (PEEK/PGA) scaffolds fabricated via selective laser sintering to improve bioactivity. The DIOP surface was then modified using a silane coupling agent, 3-glycidoxypropyltrimethoxysilane (KH570), to reinforce interfacial adhesion. The results showed that the tensile properties and thermal stability of the scaffolds were significantly enhanced. It could be explained that, on the one hand, the hydrophilic group of KH570 formed an organic covalent bond with the hydroxy group on DIOP surface. On the other hand, there existed relatively high compatibility between its hydrophobic group and the biopolymer matrix. Thus, the ameliorated interface interaction led to a homogeneous state of DIOP dispersion in the matrix. More importantly, an in vitro bioactivity study demonstrated that the scaffolds with KH570-modified DIOP (KDIOP) exhibited the capability of forming a layer of apatite. In addition, cell culture experiments revealed that they had good biocompatibility compared to the scaffolds without KDIOP. It indicated that the scaffolds with KDIOP possess potential application in tissue engineering.


Subject(s)
Silanes/chemical synthesis , Silicic Acid/chemistry , Cell Line , Humans , Silanes/chemistry , Surface Properties
10.
Micromachines (Basel) ; 15(9)2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39337816

ABSTRACT

Magnesium alloy ZK60 shows great promise as a medical metal material, but its corrosion resistance in the body is inadequate. Hydroxyapatite (HA), the primary inorganic component of human and animal bones, can form chemical bonds with body tissues at the interface, promoting the deposition of phosphorus products and creating a dense calcium and phosphorus layer. To enhance the properties of ZK60, HA was added to create HA/ZK60 composite materials. These composites, fabricated using the advanced technique of LPBF, demonstrated superior corrosion resistance and enhanced bone inductive capabilities compared to pristine ZK60. Notably, the incorporation of 3 wt% led to a significant reduction in bulk porosity, achieving a value of 0.8%. The Ecorr value increased from -1.38 V to -1.32 V, while the minimum Icorr value recorded at 33.9 µA·cm-2. Nano-HA achieved the lowest volumetric porosity and optimal corrosion resistance. Additionally, these composites significantly promoted osteogenic differentiation in bone marrow stromal cells (BMSCs), as evidenced by increased alkaline phosphatase (ALP) activity and robust calcium nodule formation, highlighting their excellent biocompatibility and osteo-inductive potential. However, when increasing the HA content to 6 wt%, the bulk porosity rose significantly to 3.3%. The Ecorr value was -1.3 V, with the Icorr value being approximately 50 µA·cm-2. This increase in porosity and weaker interfacial bonding, ultimately accelerated electrochemical corrosion. Therefore, a carefully balanced amount of HA significantly enhances the performance of the ZK60 magnesium alloy, while excessive amounts can be detrimental.

11.
Front Bioeng Biotechnol ; 12: 1386534, 2024.
Article in English | MEDLINE | ID: mdl-38655386

ABSTRACT

Extensive research on zeolitic imidazolate framework (ZIF-8) and its derivatives has highlighted their unique properties in nanomedicine. ZIF-8 exhibits advantages such as pH-responsive dissolution, easy surface functionalization, and efficient drug loading, making it an ideal nanosystem for intelligent drug delivery and phototherapy. These characteristics have sparked significant interest in its potential applications in tissue regeneration, particularly in bone, skin, and nerve regeneration. This review provides a comprehensive assessment of ZIF-8's feasibility in tissue engineering, encompassing material synthesis, performance testing, and the development of multifunctional nanosystems. Furthermore, the latest advancements in the field, as well as potential limitations and future prospects, are discussed. Overall, this review emphasizes the latest developments in ZIF-8 in tissue engineering and highlights the potential of its multifunctional nanoplatforms for effective complex tissue repair.

12.
Micromachines (Basel) ; 15(8)2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39203618

ABSTRACT

In high-tech areas such as nuclear fusion, aerospace, and high-performance tools, tungsten and its alloys are indispensable due to their high melting point, low thermal expansion, and excellent mechanical properties. The rise of Additive Manufacturing (AM) technologies, particularly Laser Powder Bed Fusion (L-PBF), has enabled the precise and rapid production of complex tungsten parts. However, cracking and densification remain major challenges in printing tungsten samples, and considerable efforts have been made to study how various processing conditions (such as laser power, scanning strategy, hatch spacing, scan speed, and substrate preheating) affect print quality. In this review, we comprehensively discuss various critical processing parameters and the impact of oxygen content on the control of the additive manufacturing process and the quality of the final parts. Additionally, we introduce additive manufacturing-compatible W materials (pure W, W alloys, and W-based composites), summarize the differences in their mechanical properties, densification, and microstructure, and further provide a clear outlook for developing additive manufactured W materials.

13.
Materials (Basel) ; 17(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38793268

ABSTRACT

Commercial oxygen-free copper sheets were cold-rolled with reduction rates ranging from 20% to 87% and annealed at 400, 500 and 600 °C. The microstructure and texture evolution during the cold-rolling and annealing processes were studied using optical microscopy (OM), scanning electron microscopy (SEM) and electron back-scattered diffraction (EBSD). The results show that the deformation textures of {123}<634> (S), {112}<111> (Copper) and {110}<112> (Brass) were continuously enhanced with the increase in cold-rolling reduction. The orientations along the α-oriented fiber converged towards Brass, and the orientation density of ß fiber obviously increased when the rolling reduction exceeded 60%. The recrystallization texture was significantly affected by the cold-rolling reduction. After 60% cold-rolling reduction, Copper and S texture components gradually decreased, and the {011}<511> recrystallization texture component formed with the increase in annealing temperature. After 87% cold-rolling reduction, a strong Cube texture formed, and other textures were inhibited with the increase in annealing temperature. The strong Brass and S deformation texture was conducive to the formation of a strong Cube annealing texture. The density of the annealing twin boundary decreased with the increase in annealing temperature, and more annealing twin boundaries formed in the oxygen-free copper sheets with the increase in cold-rolling reduction.

14.
PLoS One ; 19(1): e0294187, 2024.
Article in English | MEDLINE | ID: mdl-38227585

ABSTRACT

Ten-Eleven-Translocase (TET) enzymes contribute to the regulation of the methylome via successive oxidation of 5-methyl cytosine (5mC) to derivatives which can be actively removed by base-excision-repair (BER) mechanisms in the absence of cell division. This is particularly important in post-mitotic neurons where changes in DNA methylation are known to associate with changes in neural function. TET3, specifically, is a critical regulator of both neuronal differentiation in development and mediates dynamic changes in the methylome of adult neurons associated with cognitive function. While DNA methylation is understood to regulate transcription, little is known of the specific targets of TET3-dependent catalytic activity in neurons. We report the results of an unbiased transcriptome analysis of the neuroblastoma-derived cell line; Neuro2A, in which Tet3 was silenced. Oxidative phosphorylation (OxPhos) was identified as the most significantly down-regulated functional canonical pathway, and these findings were confirmed by measurements of oxygen consumption rate in the Seahorse bioenergetics analyser. The mRNA levels of both nuclear- and mitochondrial-encoded OxPhos genes were reduced by Tet3-silencing, but we found no evidence for differential (hydroxy)methylation deposition at these gene loci. However, the mRNA expression of genes known to be involved in mitochondrial quality control were also shown to be significantly downregulated in the absence of TET3. One of these genes; EndoG, was identified as a direct target of TET3-catalytic activity at non-CpG methylated sites within its gene body. Accordingly, we propose that aberrant mitochondrial homeostasis may contribute to the decrease in OxPhos, observed upon Tet3-downregulation in Neuro2A cells.


Subject(s)
DNA-Binding Proteins , Dioxygenases , Dioxygenases/genetics , Dioxygenases/metabolism , DNA Methylation , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Neurons/metabolism , Respiration , RNA, Messenger/metabolism , Animals , Mice
15.
Biomaterials ; 314: 122808, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39270626

ABSTRACT

Postoperative tumor treatment necessitates a delicate balance between eliminating residual tumor cells and promoting surgical wound healing. Addressing this challenge, we harness the innovation and elegance of nature's ingenuity to develop a butterfly-wing-inspired photoactive nanofiber patch (WingPatch), aimed at advancing postoperative care. WingPatch is fabricated using a sophisticated combination of electrostatic spinning and spraying techniques, incorporating black rice powder (BRP) and konjac glucomannan (KGM) into a corn-derived polylactic acid (PLA) nanofiber matrix. This fabrication process yields a paclitaxel-infused porous nanofiber architecture that mirrors the delicate patterns of butterfly wings. Meanwhile, all-natural composites have been selected for their strategic roles in postoperative recovery. BRP offers the dual benefits of photothermal therapy and antibacterial properties, while KGM enhances both antibacterial effectiveness and tissue regeneration. Responsive to near-infrared light, WingPatch ensures robust tissue adhesion and initiates combined photothermal and chemotherapeutic actions to effectively destroy residual tumor cells. Crucially, it simultaneously prevents infections and promotes wound healing throughout the treatment process. Its effectiveness has been confirmed by animal studies, and WingPatch significantly improves treatment outcomes in both breast and liver tumor models. Thus, WingPatch exemplifies our dedication to leveraging natural world's intricate patterns and inventiveness to propel postoperative care forward.

16.
J Colloid Interface Sci ; 678(Pt A): 260-271, 2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39197369

ABSTRACT

The demand for breast mesh with antitumor properties is critical in post-mastectomy breast reconstruction to prevent local tumor recurrence. Molybdenum-based oxide (MoOx) exhibits enzyme-like activities by catalyzing endogenous hydrogen peroxide to produce reactive oxygen species for inducing tumor cell apoptosis. However, its catalytic activity is limited by insufficient active sites. Herein, a defect engineering strategy is proposed to create redox nanozymes with multiple enzymatic activities by incorporating Fe into MoOx (Fe-MoOv). Fe-MoOv is subsequently integrated into polycaprolactone (PCL) to fabricate breast meshes for establishing an enzyme-catalyzed antitumor platform. The doping of Fe into MoOx formed numerous defect sites, including oxygen vacancies (OV) and Fe substitution sites, synergistically boosting the binding capacity and catalytic activity of Fe-MoOv. Density functional theory calculations demonstrated that the outstanding peroxidase-like catalytic activity of Fe-MoOv resulted from the synergy between OV and Fe sites. Additionally, OV contributes to the localized surface plasmon resonance effect, enhancing the photothermal capability of the PCL/Fe-MoOv mesh. Upon near-infrared laser exposure, the catalytic activity of the PCL/Fe-MoOv mesh is further improved, leading to increased generation of reactive oxygen species and enhanced antitumor efficacy, achieving 86.7% tumor cell mortality, a 264% enhancement compared to the PCL/MoOx mesh.

17.
Acta Biomater ; 182: 139-155, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38750914

ABSTRACT

Additively manufactured (AM) biodegradable zinc (Zn) alloys have recently emerged as promising porous bone-substituting materials, due to their moderate degradation rates, good biocompatibility, geometrically ordered microarchitectures, and bone-mimicking mechanical properties. While AM Zn alloy porous scaffolds mimicking the mechanical properties of trabecular bone have been previously reported, mimicking the mechanical properties of cortical bone remains a formidable challenge. To overcome this challenge, we developed the AM Zn-3Mg alloy. We used laser powder bed fusion to process Zn-3Mg and compared it with pure Zn. The AM Zn-3Mg alloy exhibited significantly refined grains and a unique microstructure with interlaced α-Zn/Mg2Zn11 phases. The compressive properties of the solid Zn-3Mg specimens greatly exceeded their tensile properties, with a compressive yield strength of up to 601 MPa and an ultimate strain of >60 %. We then designed and fabricated functionally graded porous structures with a solid core and achieved cortical bone-mimicking mechanical properties, including a compressive yield strength of >120 MPa and an elastic modulus of ≈20 GPa. The biodegradation rates of the Zn-3Mg specimens were lower than those of pure Zn and could be adjusted by tuning the AM process parameters. The Zn-3Mg specimens also exhibited improved biocompatibility as compared to pure Zn, including higher metabolic activity and enhanced osteogenic behavior of MC3T3 cells cultured with the extracts from the Zn-3Mg alloy specimens. Altogether, these results marked major progress in developing AM porous biodegradable metallic bone substitutes, which paved the way toward clinical adoption of Zn-based scaffolds for the treatment of load-bearing bony defects. STATEMENT OF SIGNIFICANCE: Our study presents a significant advancement in the realm of biodegradable metallic bone substitutes through the development of an additively manufactured Zn-3Mg alloy. This novel alloy showcases refined grains and a distinctive microstructure, enabling the fabrication of functionally graded porous structures with mechanical properties resembling cortical bone. The achieved compressive yield strength and elastic modulus signify a critical leap toward mimicking the mechanical behavior of load-bearing bone. Moreover, our findings reveal tunable biodegradation rates and enhanced biocompatibility compared to pure Zn, emphasizing the potential clinical utility of Zn-based scaffolds for treating load-bearing bony defects. This breakthrough opens doors for the wider adoption of zinc-based materials in regenerative orthopedics.


Subject(s)
Alloys , Cortical Bone , Zinc , Alloys/chemistry , Alloys/pharmacology , Zinc/chemistry , Zinc/pharmacology , Animals , Mice , Cortical Bone/drug effects , Porosity , Magnesium/chemistry , Magnesium/pharmacology , Materials Testing , Compressive Strength , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Absorbable Implants , Elastic Modulus , Cell Line
18.
Materials (Basel) ; 16(18)2023 Sep 17.
Article in English | MEDLINE | ID: mdl-37763526

ABSTRACT

Biodegradable magnesium (Mg) and its alloys show tremendous potential as orthopedic materials. Nevertheless, the fast degradation and insufficient osteogenic properties hinder their applications. In this study, mesoporous bioglass (MBG) with an ordered branch-like structure was synthesized via a modified sol-gel method and showed a high specific surface area of 656.45 m2/g. A Mg-based composite was prepared by introducing the MBG into a Mg matrix via powder metallurgy. Degradation tests showed that the introduction of MBG increased the adsorption sites for Ca and P ions, thus promoting the formation of a Ca-P protective layer on the Mg matrix. The Ca-P protective layer became thick and dense with an increase in the immersion time, improving the protection ability of the Mg matrix, as proven by electrochemical impedance spectroscopy measurements. Meanwhile, the Mg-based composite also exhibited excellent biocompatibility and osteogenic properties. This study demonstrated the advantages of MBG in the preparation of Mg-based bone implants and validated the feasibility of improving Mg matrix corrosion resistance and enhancing osteogenesis by introducing MBG.

19.
J Mech Behav Biomed Mater ; 144: 105978, 2023 08.
Article in English | MEDLINE | ID: mdl-37339536

ABSTRACT

Over the past few years, biodegradable ceramic scaffolds have gained significant attention in the field of bone repair. Calcium phosphate (Ca3(PO4)2)- and magnesium oxide (MgO)-based ceramics are biocompatible, osteogenic, and biodegradable, making them attractive for potential applications. However, the mechanical properties of Ca3(PO4)2 are limited. We developed a magnesium oxide/calcium phosphate composite bio-ceramic scaffold characterized by a high melting point difference, using vat photopolymerization (VP) technology to address this issue. The primary goal was to fabricate high-strength ceramic scaffolds using biodegradable materials. In this study, we investigated ceramic scaffolds with varying MgO contents and sintering temperatures. We also discussed the co-sintering densification mechanism of high and low melting-point materials associated with composite ceramic scaffolds. During sintering, a liquid phase was generated, which filled up the pores generated during the vaporization of additives (such as resin) under the influence of capillary force. This led to an increase in the extent of ceramic densification realized. Moreover, we found ceramic scaffolds with 80 wt% MgO exhibited the best mechanical performance. This kind of composite scaffold performed better than pure MgO scaffold. The results reported herein highlight that high-density composite ceramic scaffolds can be potentially used in the field of bone repair.


Subject(s)
Magnesium Oxide , Tissue Scaffolds , Oxides , Calcium Phosphates , Printing, Three-Dimensional , Ceramics , Tissue Engineering , Porosity
20.
Nanomaterials (Basel) ; 13(21)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37947674

ABSTRACT

The integration of hydroxyapatite (HA) with broad-spectrum bactericidal nano-silver within biopolymer-based bone scaffolds not only promotes new bone growth, but also effectively prevents bacterial infections. However, there are problems such as a poor interface compatibility and easy agglomeration. In this project, zeolitic imidazolate frameworks (ZIF-8) were grown in situ on nano-HA to construct a core-shell structure, and silver was loaded into the ZIF-8 shell through ion exchange. Finally, the core-shell structure (HA@Ag) was composited with polylactic acid (PLLA) to prepare bone scaffolds. In this case, the metal zinc ions of ZIF-8 could form ionic bonds with the phosphate groups of HA by replacing calcium ions, and the imidazole ligands of ZIF-8 could form hydrogen bonds with the carboxyl groups of the PLLA, thus enhancing the interface compatibility between the biopolymers and ceramics. Additionally, the frame structure of MOFs enabled controlling the release of silver ions to achieve a long-term antibacterial performance. The test results showed that the HA@Ag nanoparticles endowed the scaffold with good antibacterial and osteogenic activity. Significantly, the HA@Ag naoaprticle exhibited a good interfacial compatibility with the PLLA matrix and could be relatively evenly dispersed within the matrix. Moreover, the HA@ZIF-8 also effectively enhanced the mechanical strength and degradation rate of the PLLA scaffold.

SELECTION OF CITATIONS
SEARCH DETAIL