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静电纺纤维滴鼻液实现脑室内给药

Science Bulletin 2024年第9期69卷 1249-1262页

作者：王娟王秋云符一飞卢敏陈亮刘志恒付晓晗杜习羽于布为陆菡崔文国 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 Department of Anesthesiology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Anesthesiology Shenzhen Second People’s HospitalThe First Afﬁliated Hospital of Shenzhen UniversityShenzhen 518035China Department of Anesthesiology Huadong Hospital Afﬁliated to Fudan UniversityShanghai 200040China

Adequate drug delivery across the blood–brain barrier(BBB) is a critical factor in treating central nervous system(CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization,the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2(LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine(PLL)and negatively charged surface of fibers;this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.

关键词： Nasal drops Electrospun short fibers Nasal mucosa Intraventricular administration Brain diseases

Influence of layer thickness on formation quality,microstructure,mechanical properties,and corrosion resistance of WE43 magnesium alloy fabricated by laser powder bed fusion

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Journal of Magnesium and Alloys 2024年第4期12卷 1367-1385页

作者： Bangzhao Yin Jinge Liu Bo Peng Mengran Zhou Bingchuan Liu Xiaolin Ma Caimei Wang Peng Wen Yun Tian Yufeng Zheng State Key Laboratory of Tribology in Advanced Equipment Beijing100084China Department of Mechanical Engineering Tsinghua UniversityBeijing 100084China institute for Precision Medicine Tsinghua UniversityBeijing102218China Department of orthopaedics Peking University Third HospitalBeijing 100191China Beijing AKEC Medical Co. Ltd.Beijing 102200China School of Materials Science and Engineering Peking UniversityBeijing 100871China Engineering Research Center of Bone and Joint Precision Medicine Ministry of EducationBeijing 100191China

Laser powder bed fusion(L-PBF)of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical *** thickness(LT)is of great significance to the L-PBF process but has not been studied for Mg *** this study,WE43 Mg alloy bulk cubes,porous scaffolds,and thin walls with layer thicknesses of 10,20,30,and 40μm were *** required laser energy input increased with increasing layer thickness and was different for the bulk cubes and porous *** tended to occur at the connection joints in porous scaffolds for LT40 and could be eliminated by reducing the laser energy *** thin wall parts,a large overhang angle or a small wall thickness resulted in porosity when a large layer thicknesses was used,and the porosity disappeared by reducing the layer thickness or laser energy input.A deeper keyhole penetration was found in all occasions with porosity,explaining the influence of layer thickness,geometrical structure,and laser energy input on the *** the samples achieved a high fusion quality with a relative density of over 99.5%using the optimized laser energy *** increased layer thickness resulted to more precipitation phases,finer grain sizes and decreased grain *** the similar high fusion quality,the tensile strength and elongation of bulk samples were significantly improved from 257 MPa and 1.41%with the 10μm layer to 287 MPa and 15.12%with the 40μm layer,in accordance with the microstructural *** effect of layer thickness on the compressive properties of porous scaffolds was ***,the corrosion rate of bulk samples accelerated with increasing the layer thickness,mainly attributed to the increased number of precipitation phases.

关键词： Magnesium alloy WE43 Laser powder bed fusion Layer thickness Process optimization

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Bone Research 2024年第1期12卷 122-136页

作者： Nan-Yu Zou Ran Liu Mei Huang Yu-Rui Jiao Jie Wei Yangzi Jiang Wen-Zhen He Min Huang Yi-Li Xu Ling Liu Yu-Chen Sun Mi Yang Qi Guo Yan Huang Tian Su Ye Xiao Wei-Shan Wang Chao Zeng Guang-Hua Lei Xiang-Hang Luo Chang-Jun Li Department of Endocrinology Endocrinology Research CenterXiangya Hospital of Central South UniversityChangshaHunan 410008China Department of orthopaedics Xiangya Hospital of Central South UniversityChangshaHunan 410008China Department of Epidemiology and Health Statistics Xiangya School of Public HealthCentral South UniversityChangshaChina Hunan Key Laboratory of Joint Degeneration and Injury ChangshaHunan 410008China Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment Ministry of EducationXiangya HospitalCentral South UniversityChangshaChina School of Biomedical Sciences Institute for Tissue Engineering and Regenerative MedicineFaculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Department of orthopaedics The First Affiliated Hospital of Shihezi UniversityShiheziXinjiangChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Skeletal stem/progenitor cell(SSPC)senescence is a major cause of decreased bone regenerative potential with aging,but the causes of SSPC senescence remain *** this study,we revealed that macrophages in calluses secrete prosenescent factors,including grancalcin(GCA),during aging,which triggers SSPC senescence and impairs fracture *** injection of human rGCA in young mice induced SSPC senescence and delayed fracture *** deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC ***,GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction,resulting in cellular *** of Plxnb2 in SSPCs impaired fracture *** of GCA-neutralizing antibody enhanced fracture healing in aged ***,our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence,and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

关键词： healing union senescence

Ultrastable in-situ silver nanoparticle dressing for effective prevention and treatment of wound infection in emergency

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Engineered Regeneration 2024年第1期5卷 111-123页

作者： Wei Wang Ziwei Hu Wanying Mo Min Ouyang Shihao Lin Xiang Li Chengxinqiao Wang Feng Yu Yupeng Wang Dongfang Zhou Key Laboratory of Mental Health of the Ministry of Education NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China institute of Otolaryngology Head and neck surgery Guangzhou Red Croee Hospital of Jinan UniversityGuangzhou 510282China c Department of orthopaedics and Traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China

The use of antibacterial dressings is crucial in the prevention and treatment of wound infection in emergency ***,the efficacy of dressings is compromised by long-term storage or exposure to harsh ***,an ultrastable in-situ silver nanoparticle dressing(AgSNP@CD)was prepared for effective prevention and treatment of wound infection in *** fabrication process of AgSNP@CD is simple,suitable for large-scale *** to the strong interaction between the in-situ synthesized AgNPs and the cotton fabric,AgSNP@CD owned remarkable stability,thus retaining its antimicrobial efficacy even after long-term storage(up to 2 years)and under extreme conditions(damp heat,low temperatures,low-oxygen,water immersion,acid-alkali erosion).Both in vitro and in vivo results demonstrated the extraordinary antibacterial efficacy and stability of AgSNP@CD,facilitating infection prevention and wound healing in extreme *** particular,AgSNP@CD exhibited a superior treatment effect on severe bacteria-infected trauma and can prevent the occur-rence of sepsis *** exceptional stability and antibacterial efficacy of AgSNP@CD under complex and extreme conditions make it a well-suited dressing strategy for the prevention and treatment of wound infection in emergency.

关键词： Bacteria-infected wounds Silver nanoparticle dressing Ultra stability Infection prevention In emergency

Analysis of causes for revision in unicompartmental knee arthroplasty

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World Journal of Clinical Cases 2024年第25期12卷 5642-5645页

作者： Sujit Kumar Tripathy Siddharth Satyakam Pradhan Shahnawaz Khan Hursch Patel Department of orthopaedics All India Institute of Medical SciencesBhubaneswar 751019OdishaIndia Department of Orthopedics All India Institute of Medical SciencesBhubaneswar 751019India Department of Medicine Kansas City University of Medicine and BiosciencesKansas CityMO 64106United States

The study by Zhao et al identifies the factors leading to the failure of unicompartmental knee arthroplasty(UKA)in their *** factors include substandard suturing of the wound,the presence of osteophytes and intra-articular loose bodies causing impingement,premature loosening of the tibial component,choosing unsuitable patients for the procedure,dislocation of the movable insert,and damage to the anterior cruciate ligament and medial collateral *** findings suggest that employing the correct surgical techniques and indications is essential for successful outcomes in the UKA.

关键词： Unicompartmental knee arthroplasty Arthroplasty Knee Failure Conversion TKA

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

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World Journal of Stem Cells 2024年第5期16卷 575-590页

作者： Han Duan Ning Tao Lin Lv Kai-Xin Yan Yong-Gang You Zhuang Mao Chang-Yao Wang Xue Li Jia-Yan Jin Chu-Tse Wu Hua Wang School of Life Sciences Hebei UniversityBaoding 071002Hebei ProvinceChina Beijing institute of Radiation Medicine Beijing 100850China Department of Cardiology The Sixth Medical CentreChinese People’s Liberation Army General HospitalBeijing 100037China Department of orthopaedics The Fourth Medical CentreChinese People’s Liberation Army General HospitalBeijing 100853China Third Cadet Regiment School of Basic Medical ScienceAir Force Medical UniversityXi’an 710032Shaanxi ProvinceChina

BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular *** pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related *** growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune *** To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular *** ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the *** in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western *** factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling *** DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced *** treatment had no effect on serum lipoprotein *** FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and ***-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tu

关键词： Atherosclerosis Apolipoprotein E-knockout mice Cell therapy Dental pulp stem cells Hepatocyte growth factor

Delivering Microrobots in the Musculoskeletal System

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Nano-Micro Letters 2024年第11期16卷 585-617页

作者： Mumin Cao Renwang Sheng Yimin Sun Ying Cao Hao Wang Ming Zhang Yunmeng Pu Yucheng Gao Yuanwei Zhang Panpan Lu Gaojun Teng Qianqian Wang Yunfeng Rui Department of orthopaedics Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsuPeople’s Republic of China School of Medicine Southeast UniversityNanjing 210009People’s Republic of China Orthopaedic Trauma institute(OTI) Southeast UniversityNanjing 210009People’s Republic of China Jiangsu Key Laboratory for Design and Manufacture of Micro‑Nano Biomedical Instruments School of Mechanical EngineeringSoutheast UniversityNanjing 210009People’s Republic of China Center of Interventional Radiology and Vascular Surgery Department of RadiologyZhongda HospitalSchool of MedicineSoutheast UniversityNanjing 210009People’s Republic of China

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited *** often suffer chronic pain and might eventually have to undergo end-stage ***,future treatments should focus on early detection and intervention of regional *** have been gradually used in organisms due to their advantages of intelligent,precise and minimally invasive targeted *** the combination of control and imaging systems,microrobots with good biosafety can be delivered to the desired area for *** the musculoskeletal system,microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the *** to traditional biomaterial and tissue engineering strategies,active motion improves the efficiency and penetration of local targeting of cells/*** review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal *** summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

关键词： Microrobot Musculoskeletal system Targeted delivery Microrobotic systems Magnetic actuation

Mitochondrial dysfunction:mechanisms and advances in therapy

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2362-2390页

作者： Yao Zong Hao Li Peng Liao Long Chen Yao Pan Yongqiang Zheng Changqing Zhang Delin Liu Minghao Zheng Junjie Gao Centre for Orthopaedic Research Medical SchoolThe University of Western AustraliaNedlandsWA 6009Australia Department of orthopaedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China institute of Microsurgery on Extremities and Department of Orthopedic SurgeryShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Sixth People’s Hospital Fujian No.16Luoshan SectionJinguang RoadLuoshan StreetJinjiang CityQuanzhouFujianChina

Mitochondria,with their intricate networks of functions and information processing,are pivotal in both health regulation and disease ***,mitochondrial dysfunctions are identified in many common pathologies,including cardiovascular diseases,neurodegeneration,metabolic syndrome,and ***,the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to ***,these complexities do not prevent mitochondria from being among the most important therapeutic *** recent years,strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical *** intervention such as using healthy mitochondria to replenish or replace damaged mitochondria,has shown promise in preclinical trials of various *** components,including mtDNA,mitochondria-located microRNA,and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue ***,we review current knowledge of mitochondrial pathophysiology in concrete examples of common *** also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies,as well as the clinical translational situation of related pharmacology ***,this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

关键词： dysfunction injuries replace

Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects

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Regenerative Biomaterials 2024年第4期3卷 66-81页

作者： Shichao Lian Zhiyu Mu Zhengchao Yuan Muhammad Shafiq Xiumei Mo Weidong Mu Department of Traumatic orthopaedics Shandong Provincial HospitalShandong UniversityJinanShandong 250012China Zoucheng People’s Hospital ZouchengShandong 273500China Department of Medical Physics and Biomedical Engineering University of LondonLondon WC1E 6BTUK State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative MedicineCollege of Biological Science and Medical EngineeringDonghua UniversityShanghai 201620PR China Innovation Center of NanoMedicine(iCONM) Kawasaki Institute of Industrial PromotionKawasaki-KuKawasaki 210-0821Japan

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties,biocompatibility,biodegradability,vasculogenic ability and *** objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma(PRP)-loaded gelatin methacrylate(GM)and employ them for the regeneration of large-sized bone *** performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors(GFs)from *** GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue *** biofunction assay,the GM@PRP hydrogels significantly improved cell migration and ***,transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP *** GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in *** defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis,biomineralization,and collagen *** on the biocompatibility and biological function of GM@PRP hydrogels,a new strategy is provided for the regenerative repair of large-size bone defects.

关键词： large-sized bone defect repair platelet-rich plasma hydrogel tissue scaffold gelatin methacrylate