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Enhanced antibacterial activity,corrosion resistance and endothelialization potential of Ti-5Cu alloy by oxygen and nitrogen plasma-based surface modification

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Journal of Materials Science & Technology 2024年第1期168卷 250-264页

作者： Xiaotong Zhao Jiali Hu Jingjun Nie Dafu Chen Gaowu Qin Erlin Zhang Key lab.for Anisotropy and Texture of Materials Education Ministry of ChinaSchool of Materials Science and EngineeringNortheastern UniversityShenyang 110819China Research Center for Metallic Wires Northeastern UniversityShenyang 110819China laboratory of bone Tissue Engineering Beijing Laboratory of Biomedical MaterialsNational Center for OrthopaedicsBeijing Research Institute of Traumatology and OrthopaedicsBeijing Jishuitan HospitalBeijing 100035China

Antibacterial Ti-5Cu alloy is a promising substitute material for Ti-made cardiovascular implants,so its surface engineering is crucial to expediting clinical implementation.Given the antibacterial and cardiovas-cular biological benefits of Cu^(2+)and titanium-nitride-oxide(TiN x O y)coatings,a Cu_(2)O/CuO-TiN x O y coating with upregulated Cu^(2+)release was successfully deposited on Ti-5Cu alloy for the first time using oxygen and nitrogen plasma-based surface modification.The superhydrophilic and nanostructured Cu_(2)O/CuO-TiN x O y coating had a dense structure and was well bonded to the substrate,resulting in enhanced cor-rosion resistance,while CuO/Cu_(2)O in the coating released Cu^(2+)faster than Ti_(2)Cu phase in the matrix.More gratifying,the coating demonstrated perfect antibacterial properties(R>99.9%against S.aureus),owing primarily to direct contact sterilization of Cu_(2)O/CuO.The most encouraging phenomenon was that the coating dramatically accelerated HUVEC adhesion(1.4 times),proliferation(RGR:106%-116%),and particularly migration(RMR:158%-247%)compared with the control Ti.The coating extract also signifi-cantly stimulated in vitro angiogenesis capacity.The rapid endothelialization for Cu_(2)O/CuO-TiN x O y coating was attributed to the surface nanostructure and Cu^(2+)/NO_(2)−release,which upregulated the angiogenesis-related gene expression of HIF-1α,VEGF,and eNOS to increase VEGF secretion and NO production.All of the findings indicated that the Cu_(2)O/CuO-TiN x O y coating could enhance the corrosion resistance,an-tibacterial properties,and endothelialization potential of Ti-Cu alloy,displaying great clinical potential in cardiovascular applications.

关键词： Titanium-copper alloy Titanium-nitride-oxide(TiNxOy) Cu^(2+)release Antibacterial property Cell compatibility

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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew Rawlings Marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(lab)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon printing.The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay bone 3D bioprinting

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Full-Scale Isogeometric Topology Optimization of Cellular Structures Based on Kirchhoff-Love Shells

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Computer Modeling in Engineering & Sciences 2024年第6期139卷 2479-2505页

作者： Mingzhe Huang Mi Xiao Liang Gao Mian Zhou Wei Sha Jinhao Zhang State Key lab of Intelligent Manufacturing Equipment and Technology Huazhong University of Science and TechnologyWuhan430074China

Cellular thin-shell structures are widely applied in ultralightweight designs due to their high bearing capacity and strength-to-weight ratio.In this paper,a full-scale isogeometric topology optimization(ITO)method based on Kirchhoff-Love shells for designing cellular tshin-shell structures with excellent damage tolerance ability is proposed.This method utilizes high-order continuous nonuniform rational B-splines(NURBS)as basis functions for Kirchhoff-Love shell elements.The geometric and analysis models of thin shells are unified by isogeometric analysis(IGA)to avoid geometric approximation error and improve computational accuracy.The topological configurations of thin-shell structures are described by constructing the effective density field on the controlmesh.Local volume constraints are imposed in the proximity of each control point to obtain bone-like cellular structures.To facilitate numerical implementation,the p-norm function is used to aggregate local volume constraints into an equivalent global constraint.Several numerical examples are provided to demonstrate the effectiveness of the proposed method.After simulation and comparative analysis,the results indicate that the cellular thin-shell structures optimized by the proposed method exhibit great load-carrying behavior and high damage robustness.

关键词： Cellular thin-shell structures isogeometric analysis full-scale topology optimization Kirchhoff–Love shells

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Liquid metal biomaterials: translational medicines,challenges and perspectives

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National Science Review 2024年第2期11卷 264-284页

作者： Hanchi Xu Jincheng Lu Yikuang Xi Xuelin Wang Jing Liu Department of Biomedical Engineering School of Medicine Tsinghua University Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Shanghai World Foreign Language Academy Beijing Advanced Innovation Center for Biomedical Engineering School of Engineering MedicineBeihang University Beijing Key lab of Cryo-Biomedical Engineering and Key lab of Cryogenics Technical Institute of Physics and Chemistry Chinese Academy of Sciences

Until now, significant healthcare challenges and growing urgent clinical requirements remain incompletely addressed by presently available biomedical materials. This is due to their inadequate mechanical compatibility, suboptimal physical and chemical properties, susceptibility to immune rejection, and concerns about long-term biological safety. As an alternative, liquid metal(LM) opens up a promising class of biomaterials with unique advantages like biocompatibility, flexibility, excellent electrical conductivity,and ease of functionalization. However, despite the unique advantages and successful explorations of LM in biomedical fields, widespread clinical translations and applications of LM-based medical products remain limited. This article summarizes the current status and future prospects of LM biomaterials, interprets their applications in healthcare, medical imaging, bone repair, nerve interface, and tumor therapy, etc.Opportunities to translate LM materials into medicine and obstacles encountered in practices are discussed.Following that, we outline a blueprint for LM clinics, emphasizing their potential in making new-generation artificial organs. Last, the core challenges of LM biomaterials in clinical translation, including bio-safety,material stability, and ethical concerns are also discussed. Overall, the current progress, translational medicine bottlenecks, and perspectives of LM biomaterials signify their immense potential to drive future medical breakthroughs and thus open up novel avenues for upcoming clinical practices.

关键词： liquid metal biomaterials translational medicine clinical device healthcare therapeutics

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Microtubule actin crosslinking factor 1 functions as a novel therapeutic target in lung metastasis of osteosarcoma

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Genes & Diseases 2023年第2期10卷 325-328页

作者： Chaofei Yang Ye Tian Fan Zhao Qian Huang Zhiyong Liu Chenyang He Hui Li Yu li Zhiping Miao Airong Qian lab for bone metabolism Xi'an Key Laboratory of Special Medicine and Health EngineeringKey Lab for Space Biosciences and BiotechnologyResearch Center for Special Medicine and Health Systems EngineeringNPU-UAB Joint Laboratory for Bone MetabolismSchool of Life SciencesNorthwestern Polytechnical UniversityXi'anShaanxi 710072China Department of Oncology The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxi 710004China Honghui Hospital Xi'anShaanxi 710054China

Lung metastasis is the primary cause of death in osteosarcoma(OS)patients.1 A better understanding of the molecular mechanisms underlying OS tumorigenesis and metastasis is urgently needed to identify therapeutic targets.Microtubule actin crosslinking factor 1(MACF1),which belongs to the spectraplakin family of cytoskeletal crosslinking proteins,2 is critical for cell migration and polarization due to its regulation of the cytoskeleton.Recently,MACF1 was indicated to be involved in the metastatic invasion of some human cancers,3 but the function of MACF1 in OS is still unclear.

关键词： metastasis osteosarcoma therapeutic

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An integrated genome-wide analysis identifies HUR/ELAVL1 as a positive regulator of osteogenesis through enhancing theβ-catenin signaling activity

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Genes & Diseases 2023年第2期10卷 377-380页

作者： Ying Huai Zhihao Chen Xiaoni Deng Xue Wang Wenjing Mao Zhiping Miao Yu Li Hui Li Xiao Lin Airong Qian lab for bone metabolism Xi'an Key Laboratory of Special Medicine and Health EngineeringSchool of Life SciencesNorthwestern Polytechnical UniversityXi'anShaanxi 710072China Key lab for Space Biosciences and Biotechnology School of Life SciencesNorthwestern Polytechnical UniversityXi'anShaanxi 710072China Research Center for Special Medicine and Health Systems Engineering School of Life SciencesNorthwestern Polytechnical UniversityXi'anShaanxi 710072China NPU-UAB Joint laboratory for bone metabolism School of Life SciencesNorthwestern Polytechnical UniversityXi'anShaanxi 710072China Honghui Hospital Xi'an Jiaotong University College of MedicineXi'anShaanxi 710054China

Osteoporosis is a prevalent multifactorial bone disease with a strong genetic contribution.The heritability of traits that contribute to osteoporosis(bone mass,bone mineral density(BMD),bone size,bone loss and fractures)ranges from 50 to 85%,suggesting that a comprehensive understanding of the genetic basis may help identify new therapeutic targets.1 However,the genetic characteristics remain obscure,and the existing drug targets are associated with various challenges.Numerous studies have demonstrated that high-throughput sequencing data analysis is fruitful for identifying novel targets of human diseases.2 We therefore integrated GWAS and transcriptome analyses through Multi-marker Analysis of GenoMic Annotation(MAGMA)and weighted gene co-expression network analysis3(WGCNA)to identify new network modules and potential therapeutic genes for osteoporosis.As an illustration,the flow chart presenting the process of the present study was shown in Figure S1.

关键词： osteoporosis analysis Figure

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Degradable magnesium alloy suture promotes fibrocartilaginous interface regeneration in a rat rotator cuff transosseous repair model

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Journal of Magnesium and Alloys 2024年第1期12卷 384-393页

作者： Baoxiang Zhang Wen Zhang Fei Zhang Chao Ning Mingyang An Ke Yang Lili Tan Qiang Zhang Department of Sports Medicine Chinese PLA General HospitalBeijing 100853China Shi-changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China Medical School of PLA Beijing 100853China Institute of Orthopedics Chinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Lab of Musculoskeletal Trauma&War Injuries of Chinese PLABeijing 100853China

Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation,the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures.In the present work,degradable magnesium(Mg)alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4±0 absorbable suture as control.The shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4,8,and 12 weeks after operation.The Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to failure.Gross observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture groups.In the histological analysis,for Mg alloy suture groups,chondrocytes appear to proliferate at 4 weeks postoperatively,and the tendon-bone interface showed an orderly structural transition zone at 8 weeks postoperatively.The collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed,where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous enthesis.In vivo degradation of the magnesium alloy wire was completed within 12 weeks.The results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.

关键词： Rotator cuff repair Mg alloy wire Tendon-bone healing Fibrocartilaginous interface

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Observation of liver indexes in patients with relapsed/refractory multiple myeloma treated with CAR-T-cells based on BCMA

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China Medical Abstracts(Internal Medicine) 2024年第1期41卷 58-58页

作者：孙乾 Hematol Instit Xuzhou Med UnivHematol DeptAffil HospXuzhou Med UnivJiangsu Prov Key LabBone Marrow Stem CellXuzhou 221002

Objective To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CART-cells based on BCMA.Methods Retrospective analysis was performed on patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD 19 CAR-T-cells at our center between June 1,2019,and February 28,2023.

关键词： BCMA CAR liver

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Global gene expression profiling of blast lung injury of goats exposed to shock wave

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Chinese Journal of Traumatology 2020年第5期23卷 249-257页

作者： Hong Wang Wen-Juan Zhang Jun-Hong Gao Jin-Ren Liu Zhi-Yong Liu Bao-Qing Xia Xiao-Lin Fan Cun-Zhi Li Ai-Rong Qian lab for bone metabolism Xi'an Key Laboratory of Special Medicine and Health EngineeringKey Lab for Space Biosciences and BiotechnologyResearch Center for Special Medicine and Health Systems EngineeringNPU-UAB Joint Laboratory for Bone MetabolismSchool of Life SciencesNorthwestern Polytechnical UniversityXi'an 710072China Research Center for Toxicological and Biological Effects Institute for Hygiene of Ordnance IndustryXi'an 710065China

Purpose:Blast lung injury(BLI)is the most common damage resulted from explosion-derived shock wave in military,terrorism and industrial accidents.However,the molecular mechanisms underlying BLI induced by shock wave are still unclear.Methods:In this study,a goat BLI model was established by a fuel air explosive power.The key genes involved in were identified.The goats of the experimental group were fixed on the edge of the explosion cloud,while the goats of the control group were 3 km far away from the explosive environment.After successful modeling for 24 h,all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)analysis were performed to identify the main enriched biological functions of differentially expressed genes(DEGs).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to verify the consistency of gene expression.Results:Of the sampled goat lungs,895 genes were identified to be significantly differentially expressed,and they were involved in 52 significantly enriched GO categories.KEGG analysis revealed that DEGs were highly enriched in 26 pathways,such as cytokine-cytokine receptor interaction,antifolate resistance,arachidonic acid metabolism,amoebiasis and bile secretion,JAK-STAT,and IL-17 signaling pathway.Furthermore,15 key DEGs involved in the biological processes of BLI were confirmed by qRTPCR,and the results were consistent with RNA sequencing.Conclusion:Gene expression profiling provide a better understanding of the molecular mechanisms of BLI,which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

关键词： Blast lung injury Shock wave Differentially expressed genes RNA sequencing Transcriptome

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Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

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Oncology Research 2024年第4期32卷 691-702页

作者： JIJIE XIAO HONG XIAO YUJUN CAI JIANWEI LIAO JUE LIU LIN YAO SHAOLIN LI Department of Radiology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai510900China Department of Ultrasound The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou528405China PCFM lab of Ministry of Education School of Materials Science and EngineeringGuangzhou510275China

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

关键词： Immunotherapy Osteosarcoma Nanodrug Photodynamic therapy CD47

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