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Evolving concepts in bone infection: redefining “biofilm”,“acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

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Bone research 2019年第3期7卷 225-242页

作者： Elysia A. Masters Ryan P. Trombetta Karen L. de Mesy Bentley Brendan F Boyce Ann Lindley Gill Steven R. Gill Kohei Nishitani Masahiro Ishikawa Yugo Morita Hiromu Ito Sheila N. Bello-Irizarry Mark Ninomiya James D. Brodell Jr. Charles C. Lee Stephanie P. Hao Irvin Oh Chao Xie Hani A. Awad John L. Daiss John R. Owen Stephen L. Kates Edward M. Schwarz Gowrishankar Muthukrishnan Center for Musculoskeletal research University of Rochester Medical Center Rochester NY USA department of Biomedical Engineering University of Rochester Medical Center Rochester NY USA department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester NY USA department of orthopaedics University of Rochester Medical Center Rochester NY USA department of Microbiology & Immunology University of Rochester Medical Center Rochester NY USA department of orthopaedic Surgery Kyoto University Kyoto Japan department of orthopaedic Surgery Virginia Commonwealth University Medical Center Richmond VA USA

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, *** intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

关键词： disease caused by soft tissue necrotic tissuel

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Risk factors for chronic ankle instability after first episode of lateral ankle sprain:A retrospective analysis of 362 cases

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Journal of Sport and Health Science 2023年第5期12卷 606-612页

作者： Jieyuan Zhang Kai Yang Cheng Wang Wenqi Gu Xueqian Li Shaoling Fu Guoxun Song Jiazheng Wang Chenglin Wu Hongyi Zhu Zhongmin Shi National Center for orthopaedics Shanghai Sixth People’s HospitalShanghai 200233China department of Orthopedic Surgery Shanghai Sixth People’s HospitalShanghai 200233China department of Radiology Shanghai Sixth People’s HospitalShanghai 200233China institute of Clinical research National Center for OrthopaedicsShanghai Sixth People’s HospitalShanghai 200233China

Background:Chronic ankle instability(CAI) is a common sequela following an acute lateral ankle sprain(LAS).To treat an acture LAS more effectively and efficiently,it is important to identify patients at substantial risk for developing *** study identifies magnetic resonance imaging(MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these ***:All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1,2017 to December 1,2019 were *** were collected using the Cumberland Ankle Instability Tool at final *** and other related clinical variables,including age,sex,body mass index,and treatment were also *** and multivariable analyses were performed successively to identify risk factors for CAI after first-episode ***:A total 131 out of 362 patients with a mean follow-up of 3.0± 0.6 years(mean ± SD;2.0—4.1 years) developed CAI after first-episode *** to multivariable regression,development of CAI after first-episode LAS was associated with 5 prognostic factors:age(odds ratio(OR)=0.96,95% confidence interval(95%CI):0.93-1.00,p=0.032);body mass index(OR=1.09,95%CI:1.02-1.17,p=0.009);posterior talofibular ligament injury(OR=2.17,95%CI:1.05-4.48,p=0.035);large bone marrow lesion of the talus(OR=2.69,95%CI:1.30-5.58,p=0.008),and Grade 2 effusion of the tibiotalar joint(OR=2.61,95%CI:1.39-4.89,p=0.003).When patients had at least 1 positive clinical finding in the 10-m walk test,anterior drawer test,or inversion tilt test,they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by ***:MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the10-m walk test,anterior drawer test,and inversion tilt

关键词： Chronic ankle instability Lateral ankle sprain MRI Risk factorsTagedAPTARAEnd

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Osteoblastic microRNAs in skeletal diseases:Biological functions and therapeutic implications

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Engineered Regeneration 2022年第3期3卷 241-257页

作者： Lei Yu Wenming Li Peng Yang Wei Zhang Huaqiang Tao Gaoran Ge Huilin Yang Jiaxiang Bai Huaiyu Wang Dechun Geng department of orthopaedics The First Affiliated Hospital of Soochow University188 Shizi StreetSuzhouJiangsu 215006China Center for Human Tissues and Organs Degeneration Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China orthopaedic institute Medical CollegeSoochow UniversitySuzhouJiangsu 215000China

Skeletal diseases normally represents a grievous imbalance between osteoblasts for bone formation and osteoclasts for bone resorption.A lack of osteogenic function can make it difficult to repair pathological bone ***,substantial efforts have been made to remedy these issues,with the aid of bioactive molecules,herbs and *** recent insights,the importance of epigenetic gene regulation is increasingly evident,especially *** can silence target genes by inhibiting mRNA translation or degrading mRNA molecules by binding to their 3′-untranslated *** is accumulating evidence indicating that the miRNAs significantly involved in osteogenic gene expression,signaling pathway intervention and programmed cell ***,numerous new target drugs(microRNA inhibitors or agonists)have been proposed to exploit its value in skeletal physiology and *** this review,we mainly discuss the role of microRNAs in the context of skeletal disease-associated osteoblast differentiation,the applications of microRNA polymorphisms as biomarkers for diagnostic and therapeutic targets,and the challenges to meet this *** summary provides novel horizon for improving the therapeutic effect of microRNAs,which may be beneficial to the further clinical translation of microRNAs in the treatments of skeletal diseases.

关键词： Skeletal diseases Osteogenesis Apoptosis MicroRNA Diagnosis Drug delivery

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Sustained Akt signaling in articular chondrocytes causes osteoarthritis via oxidative stress-induced senescence in mice

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Bone research 2019年第3期7卷 318-326页

作者： Jing Xie Jingting Lin Min Wei Yan Teng Qi He Guan Yang Xiao Yang State Key Laboratory of Proteomics Beijing Proteome Research Center National Center for Protein Sciences (Beijing) Beijing Institute of Lifeomics Beijing 102206 China department of orthopaedics Chinese PLA General Hospital Beijing 100853 China

Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial *** mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^(ERT2) developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient ***, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore,inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA.

关键词： chondrocyte accumulation of Osteoarthritis(OA)

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Cephalomedullary fixation for femoral neck/intertrochanteric and ipsilateral shaft fractures： surgical tips and pitfalls

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Chinese Journal of Traumatology 2013年第1期16卷 40-45页

作者： Kamal Bali Nitesh Gahlot Sameer Aggarwal Vijay Goni department of orthopaedic Surgery Post GraduateInstitute of Medical Education and Research ChandigarhIndia department of orthopaedics University of CalgaryAlberta Canada

Objective： Surgical management options for femoral shaft fracture and ipsilateral proximal fe- mur fracture vary from single-implant to double-implant fixation. Cephalomedullary fixation in such fractures has rela- tive advantages over other techniques especially because of less soft tissue dissection and immediate postoperative weight beating with accelerated rehabilitation. However, the surgery is technically demanding and there is a paucity of literature describing the surgical techniques for this fixation. The aim of the study was to describe the surgical technique of cephalomedullary fixation for femoral shaft fracture and ipsilateral proximal femur fracture. Methods： Sixteen cases （10 males and 6 females with a mean age of 41.8 years） of ipsilateral proximal femur and shaft fractures were treated by single-stage cephalomedullary fixation at tertiary level trauma center in northern India. The fractures were classified according to AO classification. An intraoperative record of duration of surgery as well as technical challenges unique to each fracture pattern was kept for all the patients. Results： The most common proximal femoral pattern was AO B2.1 observed in 9 of our patients. The AO B2.3 fractures were seen in 4 patients while the AO A1.2 fractures in 3 patients. Four of the AO B2.1 and 2 of the AO B2.3 frac- tures required open reduction with Watson-Jones approach. The mean operative time was around 78 minutes, which tended to decrease as the surgical experience increased. There was only one case of malreduction, which required revision surgery. Conclusion： Combination of ipsilateral femoral shaft fracture and neck/intertrochanteric fracture is a difficult frac- ture pattern for trauma surgeons. Cephalomedullary nail is an excellent implant for such fractures but it requires careful insertion to avoid complications. Surgery is technically demanding with a definite learning curve. Nevertheless, a majority of these fractures can be surgically managed by

关键词： Femoral fractures Fracture fixation, internal Nails

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Mid-term outcomes of microfragmented adipose tissue plus arthroscopic surgery for knee osteoarthritis:A randomized,activecontrol,multicenter clinical trial

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World Journal of Stem Cells 2023年第12期15卷 1063-1076页

作者： Cong-Zi Wu Zhen-Yu Shi Zhen Wu Wen-Jun Lin Wei-Bo Chen Xue-Wen Jia Si-Cheng Xiang Hui-Hui Xu Qin-Wen Ge Kai-Ao Zou Xu Wang Jia-Li Chen Ping-Er Wang Wen-Hua Yuan Hong-Ting Jin Pei-Jian Tong institute of orthopaedics and Traumatology of Zhejiang Province The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina epartment of Orthopedic Surgery The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006Zhejiang ProvinceChina department of orthopaedic Surgery Tongde Hospital of Zhejiang ProvinceHangzhou 310012China department of orthopaedic Surgery The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325015Zhejiang ProvinceChina department of orthopaedic Surgery Ruian Hospital of Traditional Chinese MedicineWenzhou 325299Zhejiang ProvinceChina department of orthopaedics Ningbo First HospitalNingbo 315010Zhejiang ProvinceChina The First College of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina

BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint *** the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical *** regenerative therapies,such as those involving platelet-rich plasma,mesenchymal stem cells,and microfragmented adipose tissue(MFAT),have been pushed to the forefront of treatment to prevent the progression of ***,MFAT has been successfully applied to treat different types of orthopedic *** To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA(KOA).METHODS A randomized,multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang,***,302 patients diagnosed with KOA(Kellgren-Lawrence grades 2-3)were randomized to the MFAT group(n=151,were administered MFAT following arthroscopic surgery),or the control group(n=151,were administered hyaluronic acid following arthroscopic surgery).The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,the visual analog scale(VAS)score,the Lequesne index score,the Whole-Organ Magnetic Resonance Imaging Score(WORMS),and safety over a 24-mo period from *** The changes in the WOMAC score(including the three subscale scores),VAS pain score,and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups,as well as when comparing values at the posttreatment visit and those at baseline(P<0.001).The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group(P<0.05).Furthermore,the WOMAC stiffness score,WOMAC function score,and Lequesne index score differed significantly between the groups at 12 and 24 mo(P<0.05).However,no signicant between-group differences were observed in the WORMS at 24 mo(P=0.367).No serious adverse events

关键词： Osteoarthritis Microfragmented adipose tissue Lipogems Arthroscopic surgery Knee

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Application of Novel Design Bone Grafting for Treatment of Segmental Acetabular Rim Defects During Revision Total Hip Arthroplasty

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Journal of Bionic Engineering 2021年第6期18卷 1369-1377页

作者： Xin Zhao Haowen Xue Yang Sun Aobo Zhang Yang Liu Hao Chen Qian Wan Jiangbo Zhang Jianlin Xiao Chenyu Wang Qing Han Jincheng Wang orthopaedic Medical Center The 2nd Hospital of Jilin UniversityChangchun130041China department of orthopaedics China-Japan Union Hospital of Jilin UniversityChangchun130033China department of Plastic and Reconstructive Surgery First Bethune Hospital of Jilin UniversityChangchun130021China

The study aimed to develop efficient techniques with different novel graft structures to enhance the treatment of acetabular bone *** inhomogeneous material properties Finite Element Analysis(FEA)model was reconstructed according to computed tomography images based on a healthy patient without any peri-acetabular bony defect according to the American Academy of Orthopedic Surgeons(AAOS).The FEA model of acetabular bone deficiency was performed to simulate and evaluate the mechanical performances of the grafts in different geometric structures,with the use of fixation implants(screws),along with the stress distribution and the relative micromotion of graft *** stress distribution mainly concentrated on the region of contact of the screws and superolateral *** the different structures,the mortise-tenone structure provided better relative micromotion,with suitable biomechanical property even without the use of *** novel grafting structures could provide sufficient biomechanical stability and bone remodeling,and the mortise-tenone structure is the optimal treatment option for acetabulum reconstruction.

关键词： Segmental defects of the acetabular rim Bone grafting Finite element analysis method Structure optimization Revision total hip arthroplasty

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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

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Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis

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Bioactive Materials 2021年第10期6卷 3596-3607页

作者： Ying Han Jielai Yang Weiwei Zhao Haimang Wang Yulong Sun Yuji Chen Jing Luo Lianfu Deng Xiangyang Xu Wenguo Cui Hongyu Zhang State Key Laboratory of Tribology Department of Mechanical EngineeringTsinghua UniversityBeijing100084China 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 MedicineShanghai200025China Beijing research institute of Automation for Machinery Industry Co. LtdBeijing100120China

The occurrence of osteoarthritis(OA)is highly associated with the reduced lubrication property of the joint,where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the *** this study,bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel,we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA ***,the lubricating microspheres(GelMA@DMA-MPC)were fabricated by dip coating a self-adhesive polymer(DMA-MPC,synthesized by free radical copolymerization)on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres(GelMA,prepared via microfluidic technology),and encapsulated with an anti-inflammatory drug of diclofenac sodium(DS)to achieve the dual-functional *** tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC *** addition,the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model,and the biological tests including qRT-PCR,immunofluorescence staining assay,X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of *** summary,the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release,therefore representing a facile and promising technique for the treatment of OA.

关键词： Microfluidics Hydrogel microspheres Catecholamine chemistry Hydration lubrication Drug delivery

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Fretting corrosion of screws contribute to the fixation failure of the femoral neck:a case report

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Biosurface and Biotribology 2019年第4期5卷 118-123页

作者： Jiajun Luo Sara Ajami Hai-Ming Yu Shuanhong Ma Shen-Mao Chen Feng Zhou Pei-Wen Wang Xue-Dong Yao Chaozong Liu Division of Surgery&Interventional Science Institute of Orthopaedic&Musculoskeletal ScienceUniversity College LondonRoyal National Orthopaedic HospitalStanmore HA74LPUK department of orthopaedics Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000People’s Republic of China State Key Laboratory of Solid Lubrication Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000People’s Republic of China

Fretting corrosion of metal implants has been associated with implant failure and revision *** report describes the fixation failure of a femoral neck fracture in a 61-year-old male patient due to corrosion of three cannulated *** evaluation at the time of primary surgery demonstrated well-positioning of the cannulated *** patient had no significant medical comorbidities at the time of ***,screw loosening and avascular necrosis were diagnosed after 5 *** the revision surgery,inflammatory serological markers,C-reactive protein and erythrocyte sedimentation rate showed no signs of infections,and screws were *** electron microscopy observations showed that all screws were subjected to fretting corrosion which led to discolouration,pitting attack,and ***,Fretting corrosion may have contributed to the failure of the fixation of screws.

关键词： corrosion pitting fracture

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