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Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction

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Research 2024年第2期2023卷 431-447页

作者： Zhenyu Zhao Huitong Ruan Aopan chen Wei Xiong Mingzhu Zhang Ming cai Wenguo cui department of orthopaedics Shanghai Tenth People's HospitalSchool of MedicineTongji University No.301 Middle Yanchang RoadShanghai 200072China department of orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University Schoolof Medicine197 Rujin 2nd RoadShanghai 200025China department of Foot and Ankle Surgery Beijing Tongren HospitalCapital Medical University1 Dongjiao MinxiangBeijing 100730China

Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered in situ cross-linking and cell gene transfection, and finally complete in situ gene therapy to promote bone reconstruction. First, ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen. Simultaneously, liposome loaded with Zinc-finger E-box-binding homeobox 1 (ZEB1) gene plasmid (Lip-ZEB1) was combined to construct an ultrasound-triggered in situ cross-linked hydrogels that can deliver Lip-ZEB1. Second, ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release, and then acted on the ZEB1/Notch signal pathway of cells, promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering. Overall, this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.

关键词： sustained release linking

Biophysical-driven piezoelectric and aligned nanofibrous scaffold promotes bone regeneration by re-establishing physiological electrical microenvironment

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Nano Research 2024年第8期17卷 7376-7393页

作者： Aoao Wang Xinbo Ma Yafeng Yang Guoliang Shi Liwei Han Xiantong Hu Rui Shi Jun Yan Quanyi Guo Yantao Zhao Senior department of Orthopedics the Fourth Medical Center of PLA General HospitalBeijing 100048China department of chemistry Capital Normal UniversityBeijing 100048China National center for orthopaedics Beijing Research Institute of Traumatology and OrthopaedicsBeijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Xijing 986 hospital department The Fourth Military Medical UniversityXi'an 710032China Institute of Orthopedics Chinese PLA General HospitalBeijing Key Laboratory of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLABeijing 100853China

The initial healing stages of bone fracture is a complex physiological process involving a series of spatially and temporally overlapping events,including pathogen clearance,immunological modulation,and *** this study,we have developed a piezoelectric and aligned nanofibrous scaffold composed of ZnO@PcL/PVDF with multiple antibacterial,immunomodulatory,and osteogenic effects using electrospinning *** scaffold’s piezoelectric signal output under ultrasound(US)control can be similar to the physiological electrical signals of healthy bone tissue,creating a truly biomimetic electrical microenvironment in the bone *** vitro studies have shown that ZnO@PcL/PVDF scaffold significantly enhances the proliferation,migration,and osteogenic differentiation of Mc3T3-E1 cells under piezoelectric drive provided by ***,the scaffold exhibits inhibitory effects on the growth of *** and ***,as well as the ability to induce M2 macrophage polarization,indicating potent antibacterial and immunomodulatory *** vivo experiments demonstrated that the ZnO@PcL/PVDF scaffold can accelerate the repair of mandibular defects in rats,effectively inhibit bacterial colonization,and reduce inflammatory ***,this study confirms that the newly developed ZnO@PcL/PVDF scaffold effectively promotes bone repair by truly mimicking the endogenous electrical microenvironment and precisely regulating the temporospatial disorders of initial bone healing,thus providing a simple and effective solution for bone defects.

关键词： piezoelectricity bone defect bacterial infection ZnO nanoparticles immunomodulation osteogenesis

High formability Mg-Zn-Gd wire facilitates AcL reconstruction via its swift degradation to accelerate intra-tunnel endochondral ossification

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Journal of Magnesium and Alloys 2024年第1期12卷 295-315页

作者： Xuan He Ye Li Hongwei Miao Jiankun Xu Michael Tim-yun Ong chenmin Wang Lizhen Zheng Jiali Wang Le Huang Haiyue Zu Zhi Yao Jie Mi Bingyang Dai Xu Li Patrick Shu-hang Yung Guangyin Yuan Ling Qin Musculoskeletal Research Laboratory of department of orthopaedics&traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongHong KongChina National Engineering Research center of Light Alloy Net Forming School of Materials Science&EngineeringShanghai Jiao Tong UniversityShanghaiChina department of orthopaedics and traumatology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Orthopaedic department Peking University Third HospitalBeijingChina department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong KongChina

After reconstructing the anterior cruciate ligament(AcL),unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing *** good biological features and high formability,Magnesium-Zinc-Gadolinium(ZG21)wires are developed to bunch the tendon graft for matching the bone tunnel during ***,tensile strength,degradation,and cytotoxicity of ZG21 wire are *** rabbit model is used for assessing the biological effects of ZG21 wire by Micro-cT,histology,and mechanical *** SEM/EDS,immunochemistry,and in vitro assessments are performed to investigate the underlying *** tests demonstrate the high formability of ZG21 wire as surgical ***-cT shows ZG21 wire degradation accelerates tunnel bone formation,and histologically with earlier and more fibrocartilage regeneration at the healing *** mechanical test shows higher ultimate load in the ZG21 *** SEM/EDS presents ZG21 wire degradation triggered calcium phosphate(ca-P)*** results demonstrate upregulation of Wnt3a,BMP2,and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of *** vitro tests also confirmed the ca-P in the metal extract could elevate the expression of Wnt3a,βcatenin,ocn and opn to stimulate *** vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon *** conclusion,the ZG21 wire is feasible for tendon graft *** degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in AcL reconstruction.

关键词： Magnesium wire AcL reconstruction Magnesium alloy Biomaterials Endochondral ossification

Histone demethylase Kdm5c regulates osteogenesis and bone formation via PI3K/Akt/HIF1α and Wnt/β-catenin signaling pathways

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Genes & Diseases 2024年第1期11卷 64-66页

作者： Ying Li Lingli Ding Yage Zhang Bingyu Zhou Gene chi Wai Man Min Wang Jinglan Li Yamei Liu Weiping Lin Haibin Wang Sien Lin Liangliang Xu Key Laboratory of orthopaedics&traumatology Lingnan Medical Research CenterThe First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineGuangzhouGuangdong 510000China department of orthopaedics&traumatology Faculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong SAR 999077China departments of Diagnostics of Traditional chinese Medicine Guangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Orthopaedic Research Lab Affiliated Hospital of Guangdong Medical UniversityGuangdong Medical UniversityZhanjiangGuangdong 524001China

Fractures have an extraordinarily negative impact on individuals'quality of life and functional *** or disability of fracture is a major health issue with important clinical,social,and economic implications.1 Mesenchymal stem cells(MScs)play an indispensable role in the initiation of the fracture repair process including the formation of a callus which is replaced by new *** use of MScs in the treatment of fractures is very attractive as they can reduce the time of healing and occurrence of nonunion.

关键词： PI3K/Akt HIF1α healing

实现无缝合手术的未来之路:自粘性强韧水凝胶（英文）

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Science Bulletin 2024年第15期 2307-2310页

作者：项雷赵鼎李毅焓齐曼古丽·塞丁崔文国 department of orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Surgical sutures serve as foundational elements in surgical procedures, facilitating wound closure, exudation minimization, infection prevention, structural support maintenance, and healing promotion. The classification of traditional surgical suturing methods is intricate, and contingent upon variables such as tissue type,wound morphology, and desired healing outcomes.

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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

Outcome of percutaneous reconstruction of chronic lateral collateral ligament rupture

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chinese Journal of traumatology 2024年第1期27卷 58-62页

作者： Soliudeen Adebayo Arojuraye Ibrahim Abolaji Alabi Ibrahim Usman Mustapha department of orthopaedics National Orthopaedic Hospital Dala-KanoNigeria department of Surgery Bayero University KanoNigeria

Purpose:Many techniques have been described for the reconstruction of chronic lateral collateral ligament(LcL)rupture with different autograft *** advantages of percutaneous LcL reconstruction include small incisions,minimal soft tissue disruption,less postoperative pain,and speedy rehabilitation and *** aim of this study was to report the functional outcome of percutaneous LcL reconstruction and overall patient satisfaction in ***:This prospective and interventional study involving 51 patients with chronic LcL rupture who had percutaneous LcL reconstruction using peroneus longus autograft was conducted between January 2021 and December 2022 in National Orthopaedic hospital,Dala-Kano,*** inclusion criteria were patients between the ages of 18 and 45 years with chronic isolated LcL and not more than 1 injury of knee *** criteria were active infection,and multi-ligament knee injury requiring 2-staged *** knee functions were assessed preoperatively,3 months,6 months,and 12 months postoperatively using the Lysholm scoring *** satisfaction with the outcome of the treatment was assessed using a 5-point Likert *** information was recorded into Microsoft Excel sheet and data was analyzed using SPSS version 23.0 for *** paired samples t-test was used to compare the clinical outcomes as continuous *** significance was considered at pcores were 44.33±12.97 and 97.96±1.23,***:Percutaneous LcL reconstruction using peroneus longus autograft significantly improves patient knee function and results in excellent patient satisfaction。

关键词： rupture ligament percutaneous

Ipsilateral fractures of the acromion and coracoid processes of the scapula

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chinese Journal of traumatology 2024年第2期27卷 121-124页

作者： Yusuf Omar Qalib Srinivasa Reddy Medagam Sunil Dachepalli department of orthopaedics The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai519000GuangdongChina department of orthopaedics Yashoda HospitalsSomajigudaHyderabadTelangana500082India

A fracture of the acromion and coracoid processes of scapula is rarely seen in the outpatient clinic,due to the acromion's anatomical position and shape,as well as the strong ligaments and muscles that are attached to *** fractures are caused by either direct or indirect high-energy trauma injuries to the shoulder joint,leading to severe pain and a grossly restricted range of *** acromial classifications were reported,but this type of longitudinal plane fracture of the acromion process in our case is yet to be described in the current *** present a rare combination of the coracoid process and unstable acromion bony projection fractures that have not previously been noted for this type of *** closest to this is Kuhn's type III classification.A 51-year-old male presented to our emergency department complaining of the right shoulder pain and difficulty raising his arm following a 2-wheeler *** patient was managed by open reduction and internal fixation with 3 cannulated cancellous screws fixation and progressed well with no postoperative *** was asymptomatic postoperatively and regained full range of motion after 4 months.

关键词： Acromion Scapular fracture coracoid process

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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