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Assessment of Spinal Tumor Treatment Using Implanted 3D-Printed Vertebral Bodies with Robotic Stereotactic Radiotherapy

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The Innovation 2020年第2期1卷 8-12,7页

作者： Hongqing Zhuang Feng Wei Liang Jiang Yuxia Wang zhongjun liu Department of Radiation Oncology Peking University Third Hospital49 North Garden RoadHaidian DistrictBeijing 100191P.R.China Orthopedic Department Peking University Third Hospital49 North Garden RoadHaidian DistrictBeijing 100191P.R.China These authors contributed equally

To investigate the feasibility and early efficacy of 3D-printed vertebral body implantation combined with robotic radiosurgery in the treatment of spinal *** study included 14 patients with spinal tumors from December 2017 to June *** surgery,all patients were subjected to CT scan and 3D data of the corresponding vertebral segments were *** alloy formed 3D-printed vertebral body implantation and robotic stereotactic radiotherapy were performed because of the risk of postoperative residual,high risk of recovery,or recurrence after *** main outcomes included the remission of symptoms,vertebral body stability,robotic stereotactic surgical precision,and local tumor *** patients received complete and successful combination therapy,and all healed primarily without complica*** error of the coverage accuracy for robotic radiosurgery was less than 0.5 mm,and the error of the rotation angle was less than 0.5.The therapeutic toxicity was limited(mainly in grades 1–2),and adverse events were *** evaluation of vertebral body stability and histocompatibility for all patients met the postoperative clinical *** patients with post spinal injury,the pain symptoms were reduced or disappeared(93%),and nerve function was improved or even recovered after treatment(100%).During our follow-up period,most tumors were locally well controlled(93%).3D-printed vertebral body implantation combined with robotic radiosurgery may offer a new treatment of spinal *** clinical trial registry:ChiCTR-ONN-17013946.

关键词： 3D-PRINTED TECHNOLOGY SPINAL TUMOR VERTEBRAL BODY IMPLANTATION ROBOTIC STEREOTACTIC RADIOTHERAPY

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Osteoporosis affects both post-yield microdamage accumulation and plasticity degradation in vertebra of ovariectomized rats

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Acta Mechanica Sinica 2017年第2期33卷 267-273页

作者： Siwei Li Guodong Niu Neil X. Dong Xiaodu Wang zhongjun liu Chunli Song Huijie Leng Department of Orthopedics Peking University Third Hospital Beijing 100191 China Department of Orthopedics Ansteel Group HospitalAnshan 114003 China Beijing Key Lab of Spine Diseases Beijing 100191 China Department of Health and Kinesiology University of Texas at Tyler Tyler TX 75799 USA Department of Mechanical Engineering University of Texas at San Antonio San Antonio TX 78249 USA

Estrogen withdrawal in postmenopausal women increases bone loss and bone fragility in the vertebra. Bone loss with osteoporosis not only reduces bone mineral density (BMD), but actually alters bone quality, which can be comprehensively represented by bone post-yield behaviors. This study aimed to provide some information as to how osteoporosis induced by estrogen depletion could influence the evolution of post-yield microdamage accumulation and plastic deformation in vertebral bodies. This study also tried to reveal the part of the mechanisms of how estrogen deficiency-induced osteoporosis would increase the bone fracture risk. A rat bilateral ovariectomy (OVX) model was used to induce osteoporosis. Progressive cyclic compression loading was developed for vertebra testing to elucidate the post-yield behaviors. BMD, bone volume fraction, stiffness degradation, and plastic deformation evolution were compared among rats raised for 5 weeks (ovx5w and sham5w groups) and 35 weeks (ovx35w and sham35w groups) after sham surgery and OVX. The results showed that a higher bone loss in vertebral bodies corresponded to lower stiffness and higher plastic deformation. Thus, osteoporosis could increase the vertebral fracture risk probably through microdamage accumulation and plastic deforming degradation.

关键词： Osteoporosis Bone mineral density Vertebral body Post-yield Microdamage Plasticity

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High efficacy of tetra-PEG hydrogel sealants for sutureless dural closure

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Bioactive Materials 2022年第2期7卷 12-19页

作者： Tengjiao Zhu Hufei Wang Zehao Jing Daoyang Fan zhongjun liu Xing Wang Yun Tian Department of Orthopaedics Peking University Third HospitalBeijing100191China Beijing Key Laboratory of Spinal Disease Research Beijing100191China Engineering Research Center of Bone and Joint Precision Medicine Ministry of EducationBeijing100191China Beijing National Laboratory for Molecular Sciences Institute of ChemistryChinese Academy of SciencesBeijing100190China University of Chinese Academy of Sciences Beijing 100049China

Advances in meticulous dural closure technique remain a great challenge for watertight dural closure in the aged society,because the cerebrospinal fluid(CSF)leakage after spinal surgery is often accompanied with the disgusting wound infection,meningitis and ***,a tetra-poly(ethylene glycol)(PEG)-based hydrogel sealant is developed with collective advantages of facile operation,high safety,quick set time,easy injectability,favorable mechanical strength and powerful tissue adhesion for effective sutureless dural closure during the surgery ***,this tetra-PEG sealant can instantaneously adhere to the irregular tissue surfaces even in a liquid environment,and effectively prevent or block off the intraoperative CSF leakage for sutureless dural closure and dura ***,this sutureless tetra-PEG adhesive can be utilized as a very promising alternative for high-efficient watertight dural closure of the clinical patients who incidentally or deliberately undergo the durotomy during the spinal surgery.

关键词： CSF leakage Dural repair Watertight closure Sutureless Tetra-PEG hydrogel

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Hierarchical Micropore/Nanorod Apatite Hybrids In-Situ Grown from 3-D Printed Macroporous Ti6Al4V Implants with Improved Bioactivity and Osseointegration

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Journal of Materials Science & Technology 2017年第2期33卷 179-186页

作者： Peng Xiu Zhaojun Jia Jia Lv Chuan Yin Hong Cai Chunli Song Huijie Leng Yufeng Zheng zhongjun liu Yan Cheng Department of Orthopedics Peking University Third HospitalBelting 100191China Beijing Key Laboratory of Spinal Diseases Beijing 100191China Center for Biomedical Materials and Tissue Engineering Academy for Advanced Interdisciplinary Studies.Peking UniversityBeijing 100871China Department of Materials Science and Engineering College of EngineeringPeking UniversityBeijing 100871China

The advent of three-dimensional （3-D） printed technique provides great possibility in the fabrication of customized porous titanium （Ti） implant. However, the bioinert property of the printed Ti poses an out- standing problem. Hybrid micro-arc oxidation and hydrothermal （MAO-HT） treatment on porous metals is able to produce multi-scaled hierarchical orthopedic implant, showing great potential for surface mod- ification of 3-D printed implant. In this study, cylindrical porous Ti6Al4V （Ti64） scaffolds with pore size of 640 lure, porosity of ？3% were 3-D printed by electron beam melting process, and their surfaces were left untreated or treated by a combined MAO-HT procedure. In vitro bioactivity was tested by immer- sion in simulated body fluid for different time points. Then, 12 scaffolds in each group were implanted into the femoral condyles of New Zealand rabbit for 8 weeks. Osseointegration was evaluated by qual- itative and quantitative histological analysis, and the bone ingrowth features were probed by sequential fluorescent labeling at 3 and 6 weeks post-surgery, Following the MAO-HT treatment, the porous Ti64 scaffold was endowed with multi-scaled micro/nano-topographies and high amounts of CaP on its surface. The treated scaffold exhibited drastically enhanced apatite forming ability compared with the un- treated one. In vivo test revealed significantly that a higher amount of bone ingrowth and bone implant contact at the treated scaffold. The 2 types of scaffolds had different patterns of bone ingrowth; the treated scaffold exhibited a pattern of contact osteogenesis, by which bone formed directly on the treated implant surface, whereas bone formed distal to the implant surface of the untreated scaffold. MAO-HT treat- ment can significantly enhance the in vitro apatite-inducing ability and in vivo osseointegration capacity of 3-D porous Ti64 scaffold and may provide as a viable approach for the fabrication of bioactive 3-D printed porous implant for orthop

关键词： 3-D printing Porous Ti6Al4V Micro-arc oxidation Hydrothermal treatment Osseointegration

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Circumferential decompression via the posterior approach for the surgical treatment of multilevel thoracic ossification of the posterior longitudinal ligaments： a single institution comparative study

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Chinese Medical Journal 2014年第19期127卷 3371-3377页

作者： liu Xiao Zhu Bin liu Xiaoguang liu zhongjun Dang Gengting Department of Orthopaedics Peking University Third HospitalBeijing 100191

Background The treatment strategies for multilevel thoracic ossification of the posterior longitudinal ligaments （T-OPLL） were rarely reported. The aim of this study was to investigate the clinical outcomes and complications of circumferential decompression for multilevel T-OPLL and compare two different methods in the management of the OPLL （resection or floating）. Methods Data of sequentially treated patients who received surgical treatment for thoracic spinal stenosis caused by multilevel T-OPLL from January 2005 to February 2012 were retrospectively reviewed. Based on the surgical approaches applied, the patients were divided into two groups. Group A consisted the patients who received posterior decompression and group B consisted the patients who received circumferential decompression via the posterior approach. Group B was further divided into two subgroups： subgroup 1 （the resection group） where the OPLL was completely resected and subgroup 2 （the floating group） where the OPLL was floated. Results A total of 49 patients were included in the study. Fourteen patients with single posterior decompression were included in group A and 35 patients who received circumferential decompression were included in group B. In group B, 29 patients had complete resection of the ossified posterior longitudinal ligaments, while the other six underwent a flotation procedure. The follow-up data were available in 39 patients. Mean JOA scores improved from 5.4 ± 1.8 to 7.5 ± 2.8 in group A and from 3.7 ± 1.8 to 7.9 ± 2.4 in group B. The main complications included cerebrospinal fluid （CSF） leakage and postoperative neurelogic deterioration （ND）. Twenty-three of the 25 cases with postoperative CSF leakage achieved a complete recovery at the last follow-up and 12 of the 15 cases with ND achieved some neurological improvement at the last follow-up. Conclusions Circumferential decompression via the posterior approach is an effective surgical method for thoracic spinal stenosis caused

关键词： ossification of the posterior longitudinal ligament multilevel thoracic spinal stenosis intraoperative ultrasonography

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Diagnosis and treatment of primary diffuse-type tenosynovial giant cell tumors of the cervical spine

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Chinese Medical Journal 2014年第4期127卷 791-792页

作者： Wang Kai liu Xiaoguang liu zhongjun Yu Miao Department of Orthopaedics Peking University Third HospitalBeijing 100191 China

Diffuse-type tenosynovial giant cell tumor （D-TGCT） belongs to a group of lesions believed to arise from tendon sheaths,bursae,or the synovium of diarthrodial *** etiology of D-TGCT is *** it shares histological characteristics with pigmented villonodular synovitis,however,D-TGCT is also termed extra-articular pigmented villonodular synovitis.D-TGCT,which occurs mainly in middle-aged women （20-50 years of age1）,usually involves large load-bearing joints （e.g.,knee,ankle,and hip）.Clinical case reports of D-TGCT involving the spine are rare.2 We retrospectively analyzed a series of three patients diagnosed with cervical D-TGCT in our department over a 10-year period.

关键词： tenosynovial giant cell tumor diffuse type cervical spine spinal tumor

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Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects

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Bioactive Materials 2024年第3期33卷 223-241页

作者： Zehao Jing Wanqiong Yuan Jiedong Wang Renhua Ni Yu Qin Zhinan Mao Feng Wei Chunli Song Yufeng Zheng Hong Cai zhongjun liu Department of Orthopedics Peking University Third HospitalBeijing100191People’s Republic of China Engineering Research Center of Bone and Joint Precision Medicine Ministry of EducationBeijing100191People’s Republic of China Beijing Key Laboratory of Spinal Disease Research Beijing100191People’s Republic of China School of Materials Science and Engineering Peking UniversityBeijing100871People’s Republic of China

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment.A three-dimensional(3D)-printed porous Ti6Al4V scaffold(3DTi)is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants,including a lower elasticity modulus,stronger bone-implant interlock,and larger drug-loading *** is a multitarget drug with anti-tumor and osteogenic potential;however,its efficiency is unsatisfactory when delivered ***,simvastatin was loaded into a 3DTi using a thermosensitive poly(lactic-co-gly-colic)acid(PLGA)-polyethylene glycol(PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and oste-ogenic *** constructed simvastatin/hydrogel-loaded 3DTi(Sim-3DTi)was comprehensively appraised,and its newfound anti-osteosarcoma mechanism was ***,in a bone defect model of rabbit condyles,Sim-3DTi exhibited enhanced osteogenesis,bone in-growth,and osseointegration compared with 3DTi alone,with greater bone morphogenetic protein 2 *** our nude mice model,simvastatin loading reduced tumor volume by 59%-77%without organic damage,implying good anti-osteosarcoma activity and ***,Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivo and in ***-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects,with a ferroptosis-mediated anti-osteosarcoma effect.

关键词： 3D-printed titanium alloy Implant Simvastatin Osteosarcoma Ferroptosis

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Influence of developmental cervical stenosis on dural sac space

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Chinese Medical Journal 2014年第22期127卷 3857-3861页

作者： Tang Yanchao Yu Miao liu zhongjun Sun Yu liu Xiaoguang Department of Orthopaedics Peking University Third HospitalBeijing 100191 China

Background This retrospective study aimed to investigate the difference of the intra-dural reserving space for spinal cord in magnetic resonance imaging （MRI） between patients with and without developmental cervical stenosis and its clinical *** A total of 264 patients with cervical spondylotic myelopathy who had decompression surgeries were *** average follow-up was 29 *** on their lateral radiographs,they were divided into stenosis group and non-stenosis *** the magnetic resonance images,the ratio of the sagittal diameter of the dural sac to that of the vertebral body was measured and calculated as MRI Pavlov ratio at the mid-vertebral level on T2-weighted sagittal images from C3 to *** ratio of the transverse area of the spinal cord to that of the dural sac was measured and calculated as occupation ratio on T2-weighted axial images at the same *** MRI Pavlov ratio and occupation ratio were compared between the two *** stenosis group was further divided into space-reserving and non-space-reserving subgroups based on the occupation ratios; then clinical parameters were compared between the two subgroups to determine the clinical significance of the reserving *** The MRI Pavlov ratio of the stenosis group was significantly smaller than that of the non-stenosis group at C3-C7 （P ＜0.01）,while the occupation ratio was significantly larger only at C7 （P ＜0.05）.For the space-reserving subgroup,the postoperative recovery rate was lower （P ＜0.05）.The postoperative recovery rate was （23±6）％ in anterior approach,larger than （-23±15）％ in posterior approach （P ＜0.05）.Conclusions Developmental cervical stenosis is associated with a smaller sagittal diameter of the dural sac,but does not lead to a significant decrease in intra-dural space available for the *** patients with normal intra-dural space,the recovery after anterior decompression surgery was better than posterior approach.

关键词： cervical spondylosis developmental cervical stenosis reserving space for spinal cord cervical decompression surgery

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Surface treatment of 3D printed porous Ti6Al4V implants by ultraviolet photofunctionalization for improved osseointegration

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Bioactive Materials 2022年第1期7卷 26-38页

作者： Chuan Yin Teng Zhang Qingguang Wei Hong Cai Yan Cheng Yun Tian Huijie Leng Caimei Wang Shiqing Feng zhongjun liu Department of Orthopedics Peking University Third HospitalBeijing100191People’s Republic of China Department of Orthopedics Qilu Hospital of Shandong UniversityJinan250012People’s Republic of China Center for Biomedical Materials and Tissue Engineering Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing100871People’s Republic of China Beijing AKEC Medical Company Ltd. Beijing102200People’s Republic of China

Three-dimensional(3D)-printed porous Ti6Al4V implants play an important role in the reconstruction of bone ***,its osseointegration capacity needs to be further improved,and related methods are inadequate,especially lacking customized surface treatment ***,we aimed to design an omnidirectional radiator based on ultraviolet(UV)photofunctionalization for the surface treatment of 3D-printed porous Ti6Al4V implants,and studied its osseointegration promotion effects in vitro and in vivo,while elucidating related *** UV treatment,the porous Ti6Al4V scaffolds exhibited significantly improved hydrophilicity,cytocompatibility,and alkaline phosphatase activity,while preserving their original mechanical *** increased osteointegration strength was further proven using a rabbit condyle defect model in vivo,in which UV treatment exhibited a high efficiency in the osteointegration enhancement of porous Ti6Al4V scaffolds by increasing bone ingrowth(BI),the bone-implant contact ratio(BICR),and the mineralized/osteoid bone *** advantages of UV treatment for 3D-printed porous Ti6Al4V implants using the omnidirectional radiator in the study were as follows:1)it can significantly improve the osseointegration capacity of porous titanium implants despite the blocking out of UV rays by the porous structure;2)it can evenly treat the surface of porous implants while preserving their original topography or other morphological features;and 3)it is an easy-to-operate low-cost process,making it worthy of wide clinical application.

关键词： Three-dimensional-printed porous implants UV photofunctionalization Omnidirectional UV radiator Osseointegration

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Practical strategy to construct anti-osteosarcoma bone substitutes by loading cisplatin into 3D-printed titanium alloy implants using a thermosensitive hydrogel

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Bioactive Materials 2021年第12期6卷 4542-4557页

作者： Zehao Jing Renhua Ni Jiedong Wang Xinhong Lin Daoyang Fan Qingguang Wei Teng Zhang Yufeng Zheng Hong Cai zhongjun liu Department of Orthopedics Peking University Third HospitalBeijing100191People’s Republic of China Engineering Research Center of Bone and Joint Precision Medicine Ministry of EducationBeijing100191People’s Republic of China Beijing Key Laboratory of Spinal Disease Research Beijing100191People’s Republic of China Department of Materials Science and Engineering College of EngineeringPeking UniversityBeijing100871People’s Republic of China

Surgical resection and perioperative adjuvant chemotherapy-based therapies have improved the prognosis of patients with osteosarcoma;however,intraoperative bone defects,local tumour recurrence,and chemotherapy-induced adverse effects still affect the quality of life of *** 3D-printed titanium alloy(Ti6Al4V)implants have advantages over traditional implants in bone repair,including lower elastic modulus,lower stiffness,better bone conduction,more bone in-growth,stronger mechanical interlocking,and lager drug-loading capacity by their inherent porous ***,cisplatin,a clinical first-line anti-osteosarcoma drug,was loaded into Ti6Al4V implants,within a PLGA-PEG-PLGA thermo-sensitive hydrogel,to construct bone substitutes with both anti-osteosarcoma and bone-repair *** optimal concentrations of cisplatin(0.8 and 1.6 mg/mL)were first determined in ***,the anti-tumour effect and biosafety of the cisplatin/hydrogel-loaded implants,as well as their bone-repair potential were evaluated in vivo in tumour-bearing mouse,and bone defect rabbit models,*** loading of cisplatin reduced tumour volume by more than two-thirds(from 641.1 to 201.4 mm3)with negligible organ damage,achieving better anti-tumour effects while avoiding the adverse effects of systemic cisplatin *** bone repair was hindered by cisplatin loading at 4 weeks,no difference was observed at 8 weeks in the context of implants with versus without cisplatin,indicating acceptable long-term stability of all implants(with 8.48%-10.04%bone in-growth and 16.94%-20.53%osseointegration).Overall,cisplatin/hydrogel-loaded 3D-printed Ti6Al4V implants are safe and effective for treating osteosarcoma-caused bone defects,and should be considered for clinical use.

关键词： 3D-printed titanium alloy Orthopaedic implant Osteosarcoma Hydrogel Local chemotherapy

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