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Nanograins on Ti-25Nb-3Mo-2Sn-3Zr alloy facilitate fabricating biological surface through dual-ion implantation to concurrently modulate the osteogenic functions of mesenchymal stem cells and kill bacteria

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Journal of Materials Science & Technology 2021年第14期73卷 31-44页

作者： Run Huang Lei Liu Bo Li Liang Qin Lei Huang kelvin w.k.yeung Yong Han School of Materials Science and Engineering Anhui University of Science and TechnologyHuainan232001China Department of Orthopaedics and Traumatology The University of Hong KongHong KongChina State-key Laboratory for Mechanical Behavior of Materials Xi’an Jiaotong UniversityXi'an710049China Department of Gastrointestinal Surgery Hubei Cancer HospitalWuhan430060China Shenzhen key Laboratory for Innovative Technology in Orthopaedic Trauma The University of Hong Kong Shenzhen HospitalShenzhen518053China

Surface mechanical attrition treatment(SMAT)method is an effective way to generate nanograined(NG)surface on Ti-25 Nb-3 Mo-2 Sn-3 Zr(wt.%)(named as TLM),a kind ofβ-type titanium alloy,and the achieved nanocrystalline surface was proved to promote positive functions of osteoblastic *** this work,to further endow the NG TLM alloy with both good osteogenic and antibacterial properties,magnesium(Mg),silver(Ag)ion or both were introduced onto the NG TLM surface by ion implantation process,as a comparison,the Mg and Ag ions were also co-implanted onto coarsegrained(CG)TLM *** obtained results show that subsequent ion implantation does not remarkably induce the surface roughness and topography alteration of the SMAT-treated layers,and it also has little impact on the microstructure of the SMAT-derivedβ-Ti *** addition,the implanted Mg and Ag ions are observed to exist as MgO and metallic Ag na noparticles(NPs)embedding tightly in theβ-Ti matrix with grain size of about 15 and 7 nm,*** cell adhesion and functions(including proliferation,osteo-differentiation and extracellular matrix mineralization)of rabbit bone marrow mesenchymal stem cells(rBMMSCs)and the bacterial colonization of Staphylococcus aureus(***)on the different surfaces were *** in-vitro experimental results reveal that the Mg and Ag single-ion implanted NG surface either significantly promotes the rBMMSCs response or inhibits the growth ***,whereas the Mg/Ag coimplanted NG surface could concurrently enhance the rBMMSCs functions as well as inhibit the bacterial growth compared to the NG surface,and this efficacy is more pronounced as compared to the Mg/Ag co-implantation in the CG *** SMAT-achieved nanograins in the TLM surface layer are identified to not only play a leading role in determining the fate of rBMMSCs but also facilitate fabricating dualfunctio nal surface with both good osteogenic and antibacterial activities through co-imp

关键词： β-Type titanium Nanograined surface Ion implantation Stem cells Antibacterial property

Controlled release and biocompatibility of polymer/titania nanotube array system on titanium implants

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Bioactive Materials 2017年第1期2卷 44-50页

作者： Tingting wang Zhengyang weng Xiangmei Liu kelvin w.k.yeung Haobo Pan Shuilin wu Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional MaterialsHubei Key Laboratory of Polymer MaterialsSchool of Materials Science&EngineeringHubei UniversityWuhanChina Division of Spine Surgery Department of Orthopaedics&TraumatologyLi Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong KongChina Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055China

Bacterial infection and tissue inflammation are the major causes of early failure of titanium-based orthopedic implants;thus,surgical implants with tunable drug releasing properties represent an appealing way to address some of these problems of bacterial infection and tissue inflammation in early age of orthopedic *** this work,a hybrid surface system composed of biodegradable poly(lactic-coglycolic acid)(PLGA)and titania nanotubes(TNTs)has been successfully constructed on Ti implants with the aim of preventing bacterial infection via long-term drug *** varying the size of the TNTs and the thickness of the polymer film,the drug release profile can be tuned to achieve the optimal therapeutic action throughout the treatment *** size of TNTs plays a dominant role in the drug loading dose of TNTs/PLGA hybrid *** this work,TNTs with an average size of 80 nm can achieve the largest loading *** on the polymer thickness,significant improvement in the drug release characteristics is attained,for instance,reduced burst release(from 84%to 27%)and overall release time extended from 5 to over 40 *** addition,the PLGA layers may favor the proliferation and osteogenesis of MC3T3-E1 mouse cells at an earlier ***,this TNT/PLGA hybrid surface system can be employed as an effective bioplatform for improving both self-antibacterial performance and biocompatibility of Ti-based biomaterials.

关键词： Antibacterial Biocompatibility Coating Drug delivery Implants

Puerarin@Chitosan composite for infected bone repair through mimicking the bio-functions of antimicrobial peptides

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Bioactive Materials 2023年第3期21卷 520-530页

作者： Liping Ouyang Baohui Chen Xingdan Liu Donghui wang Yang Li Yun Liao kelvin w.k.yeung Xuanyong Liu State key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050China Hongqiao International Institute of edicine Shanghai Jiao Tong University School of MedicineShanghai200336China Cixi Center of Biomaterials Surface Engineering Ningbo315300China Department of Computational Biology for Individualised Medicine Centre for Individualised Infection Medicine(CiiM)&TWINCOREJoint Ventures Between the Helmholtz-Centre for Infection Research(HZI)and the Hannover Medical School(MHH)HannoverGermany Shenzhen key Laboratory for Innovative Technology in Orthopaedic Trauma Guangdong Engineering Technology Research Center for Orthopaedic Trauma RepairDepartment of Orthopaedics and TraumatologyThe University of Hong Kong Shenzhen HospitalShenzhenChina

It is important to eliminate lipopolysaccharide(LPS)along with killing bacteria in periprosthetic joint infection(PJI)therapy for promoting bone repair due to its effect to regulate macrophages *** natural antimicrobial peptides(AMPs)offer a good solution,the unknown toxicity,high cost and exogenetic immune response hamper their applications in *** this work,we fabricated a nanowire-like composite material,named P@C,by combining chitosan and puerarin via solid-phase reaction,which can finely mimic the bio-functions of ***,serving as the bacteria membrane puncture agent,and puerarin,serving as the LPS target agent,synergistically destroy the bacterial membrane structure and inhibit its recovery,thus endowing P@C with good antibacterial *** addition,P@C possesses good osteoimmunomodulation due to its ability of LPS elimination and macrophage differentiation *** in vivo results show that P@C can inhibit the LPS induced bone destruction in the Escherichia coli infected rat.P@C exhibits superior bone regeneration in Escherichia coli infected rat due to the comprehensive functions of its superior antibacterial property,and its ability of LPS elimination and immunomodulation.P@C can well mimic the functions of AMPs,which provides a novel and effective method for treating the PJI in clinic.

关键词： Osteoimmunomodulation Antibacterial Chitosan Puerarin Lipopolysaccharide

In vitro and in vivo antibacterial performance of Zr&O PIII magnesium alloys with high concentration of oxygen vacancies

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Bioactive Materials 2021年第10期6卷 3049-3061页

作者： Tao Liang Lilan Zeng Yunzhu Shi Haobo Pan Paul k.Chu kelvin w.k.yeung Ying Zhao Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhen518055China University of Chinese Academy of Sciences Beijing100049China Department of Physics Department of Materials Science and EngineeringDepartment of Biomedical EngineeringCity University of Hong KongTat Chee AvenueKowloonHong KongChina Department of Orthopaedics and Traumatology The University of Hong KongHong KongChina

The effects of dual Zr and O plasma immersion ion implantation(Zr&O PIII)on antibacterial properties of Zk60 Mg alloys are systematically *** results show that a hydrophobic,smooth,and ZrO_(2)-containing graded film is *** assessment shows that the corrosion rate of the plasma-treated Mg alloy decreases and the decreased degradation rate is attributed to the protection rendered by the surface *** vitro and in vivo antibacterial tests reveal Zr&O PIII Zk60 presents higher antibacterial rate compared to Zr PIII Zk60 and untreated *** hydrophobic and smooth surface suppresses bacterial *** concentration of oxygen vacancies in the surface films are determined by X-ray photoelectron spectroscopy(XPS),UV-vis diffuse reflectance spectra(UV-vis DRS)and electron paramagnetic resonance(EPR)and involved in the production of reactive oxygen species(ROS).The higher level of ROS expression inhibits biofilm formation by down-regulating the expression of icaADBC genes but up-regulating the expression of icaR *** addition,Zr&O PIII improves cell viability and initial cell adhesion confirming good *** Zr&O PIII is a simple and practical means to expedite clinical acceptance of biodegradable magnesium alloys.

关键词： Magnesium alloy Plasma immersion ion implantation Degradation ZrO_(2) Antibacterial property

Enhancement of critical-sized bone defect regeneration by magnesium oxide-reinforced 3D scaffold with improved osteogenic and angiogenic properties

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Journal of Materials Science & Technology 2023年第4期135卷 186-198页

作者： Bo Chen Zhengjie Lin Qimanguli Saiding Yongcan Huang Yi Sun Xinyun Zhai Ziyu Ning Hai Liang wei Qiao Binsheng Yu kelvin w.k.yeung Jie Shen Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China D Printing Clinical Translational and Regenerative Medicine Center Shenzhen Qianhai Shekou Free Trade Zone HospitalShenzhen 518067China Shenzhen key Laboratory of Spine Surgery Department of Spine SurgeryPeking University Shenzhen HospitalShenzhen 518036China Department of Orthopaedics and Traumatology the University of Hong KongChina Hong Kong Special Administrative RegionChina Shenzhen key Laboratory for Innovative Technology in Orthopaedic Trauma the University of Hong Kong Shenzhen HospitalShenzhen 518053China School of Materials Science and Engineering Nankai UniversityTianjin 300071China Department of Pathology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Stomatology Shenzhen Qianhai Shekou Free Trade Zone HospitalShenzhen 518067China Applied Oral Sciences and Community Dental Care Faculty of Dentistrythe University of Hong KongChina Hong Kong Special Administrative RegionChina China Orthopaedic Regenerative Medicine Group(CORMed) Hangzhou 310000China

The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic *** recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may ***,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD *** composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).with the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure *** in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week ***,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.

关键词： 3D printing Magnesium Critical-sized defect Bone regeneration Angiogenesis Scaffold

Engineered polycaprolactone–magnesium hybrid biodegradable porous scaffold for bone tissue engineering

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Progress in Natural Science:Materials International 2014年第5期24卷 561-567页

作者： Hoi Man wong Paul k.Chu Frankie k.L.Leung kenneth M.C.Cheung keith D.k.Luk kelvin w.k.yeung Department of Orthopaedics and Traumatology The University of Hong Kong Shenzhen key Laboratory for Innovative Technology in Orthopaedic Trauma The University of Hong Kong Shenzhen Hospital Department of Physics and Materials Science City University of Hong Kong Peking University Shenzhen Institution

In this paper, we describe the fabrication of a new biodegradable porous scaffold composed of polycaprolactone(PCL) and magnesium(Mg)micro-particles. The compressive modulus of PCL porous scaffold was increased to at least 150% by incorporating 29% Mg particles with the porosity of 74% using Micro-CT analysis. Surprisingly, the compressive modulus of this scaffold was further increased to at least 236% when the silane-coupled Mg particles were added. In terms of cell viability, the scaffold modified with Mg particles significantly convinced the attachment and growth of osteoblasts as compared with the pure PCL scaffold. In addition, the hybrid scaffold was able to attract the formation of apatite layer over its surface after 7 days of immersion in normal culture medium, whereas it was not observed on the pure PCL scaffold. This in vitro result indicated the enhanced bioactivity of the modified scaffold. Moreover, enhanced bone forming ability was also observed in the rat model after 3 months of implantation. Though bony in-growth was found in all the implanted scaffolds. High volume of new bone formation could be found in the Mg/PCL hybrid scaffolds when compared to the pure PCL scaffold. Both pure PCL and Mg/PCL hybrid scaffolds were degraded after 3 months. However, no tissue inflammation was observed. In conclusion, these promising results suggested that the incorporation of Mg micro-particles into PCL porous scaffold could significantly enhance its mechanical and biological properties. This modified porous bio-scaffold may potentially apply in the surgical management of large bone defect fixation.

关键词： Magnesium Polycaprolactone Biodegradability Biocompatibility Mechanical properties

In vitro and in vivo studies on pure Mg, Mg-1Ca and Mg-2Sr alloys processed by equal channel angular pressing

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Nano Materials Science 2020年第1期2卷 96-108页

作者： wenting Li Yunong Shen Jie Shen Danni Shen Xiao Liu Yufeng Zheng kelvin w.k.yeung Shaokang Guan Olga B.kulyasova R.Z.Valiev Department of Materials Science and Engineering College of EngineeringPeking UniversityBeijing100871China College of Materials Science and Engineering University of Science and Technology BeijingBeijing100083China Department of Orthopaedics and Traumatology The University of Hong KongPokfulamHong KongChina School of Materials Science and Engineering Zhengzhou UniversityZhengzhou450001China Ufa State Aviation Technical University 12 Karl Marx StreetUfa450008Russia

In the present work,the biomedical as-cast pure Mg,Mg–1 Ca and Mg–2 Sr alloys were processed with equal channel angular pressing(ECAP)technique to develop ultrafine microstructure within the materials,and their microstructures,mechanical properties,degradation behavior,cytocompatibility in vitro and biocompatibility in vivo were studied ***-gained microstructures and improved mechanical properties of these three materials after ECAP were confirmed compared to their as-cast ***,after ECAP the degradation rate of pure Mg was increased while that of Mg–1 Ca or Mg–2 Sr alloys decreased compared to the ascast ***,good in vitro cytocompatibility and in vivo biocompatibility of these three materials were revealed by cell cultural tests using osteoblastic MC3 T3-E1 and human mesenchymal stem cells(h MSC)and in vivo animal tests at the lateral epicondyle of SD-rats’*** study offers an alternative powerful avenue to achieve good comprehensive properties of magnesium-based biodegradable *** might also help to extend the applied range of magnesium-based biodegradable metals in orthopedic field.

关键词： Magnesium alloys Equal channel angular pressing Mechanical property Degradation behavior Biocompatibility

Stepwise 3D-spatio-temporal magnesium cationic niche: Nanocomposite scaffold mediated microenvironment for modulating intramembranous ossification

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Bioactive Materials 2021年第2期6卷 503-519页

作者： Jie Shen Bo Chen Xinyun Zhai wei Qiao Shuilin wu Xuanyong Liu Ying Zhao Changshun Ruan Haobo Pan Paul k.Chu kenneth M.C.Cheung kelvin w.k.yeung Department of Orthopaedics and Traumatology The University of Hong KongHong KongChina Shenzhen key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and Traumatologythe University of Hong Kong-Shenzhen HospitalShenzhenChina Shanghai Institute of Traumatology and Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesRuijin HospitalSchool of MedicineShanghai Jiaotong UniversityShanghaiChina School of Materials Science and Engineering Nankai UniversityTianjinChina School of Materials Science&Engineering the Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of ChinaTianjin UniversityTianjinChina Ministry-of-Education key Laboratory for the Green Preparation and Application of Functional Materials Hubei Key Laboratory of Polymer MaterialsSchool of Materials Science&EngineeringHubei UniversityWuhanChina State key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghaiChina Cixi Center of Biomaterials Surface Engineering Shanghai Institute of CeramicsChinese Academy of SciencesNingboChina Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina Department of Physics Department of Materials Science&Engineeringand Department of Biomedical EngineeringCity University of Hong KongHong KongChina

The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical,biological,or physical cues within a local tissue *** understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue *** study aims to investigate that the regulation of magnesium cationic(Mg^2+)tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous *** was discovered that moderate Mg^2+content niche(~4.11 mM)led to superior bone regeneration,while Mg^2+-free and strong Mg^2+content(~16.44 mM)discouraged cell adhesion,proliferation and osteogenic differentiation,thereby bone formation was rarely *** magnesium ions diffused into free Mg zone from concentrated zone in late time point,new bone formation on free Mg zone became significant through intramembranous *** study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue *** knowledge of how a Mg^2+cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissuerepairing biomaterials.

关键词： Nanocomposite Magnesium ion Microenvironment 3D scaffold Bone tissue regeneration

Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration

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Bioactive Materials 2021年第8期6卷 2315-2330页

作者： Zhengjie Lin Danni Shen weixiao Zhou Yufeng Zheng Tiantian kong Xuanyong Liu Shuilin wu Paul k.Chu Ying Zhao Jun wu kenneth M.C.Cheung kelvin w.k.yeung College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen518060China Department of Orthopaedics and Traumatology The University of Hong KongHong KongChina Department of Materials Science and Engineering College of EngineeringPeking UniversityBeijing100871China Shenzhen key Laboratory for Innovative Technology in Orthopaedic Trauma The University of Hong Kong Shenzhen Hospital1 Haiyuan 1st RoadFutian DistrictShenzhenChina Guangdong key Laboratory for Biomedical Measurements and Ultrasound Imaging Department of Biomedical EngineeringSchool of MedicineShenzhen UniversityShenzhen518060China State key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050China School of Materials Science&Engineering the Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of ChinaTianjin UniversityTianjin300072China Department of Physics Department of Materials Science and EngineeringCity University of Hong KongTat Chee AvenueKowloonHong KongChina Centre for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055China State key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China

The design of orthopedic biomaterials has gradually shifted from“immune-friendly”to“immunomodulatory,”in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone *** the well-known effects of bioactive metallic ions on osteogenesis,how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been ***,we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation(Mg^(2+))in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid(PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium *** results suggest that the Mg^(2+)-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory(IL-10)and pro-osteogenic(BMP-2 and TGF-β1)cytokines *** also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem *** in vivo results further verify that a large amount of bony tissue,with comparable bone mineral density and mechanical properties,has been generated at an early post-surgical stage in rat intramedullary bone defect *** study demonstrates that the concept of in situ immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment.

关键词： Bone regeneration Osteoimmunomodulatory property Osteoimmune environment Macrophage polarization Magnesium ions