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ROLE OF TRANSFORMING GROWTH FACTOR β(TGF-β)IN REPAIRING OF bone defects

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Chinese Medical Sciences Journal 1996年第4期11卷 209-214页

作者：孙玉鹏张皖清陆裕朴胡蕴玉马富成陈万禄 InstituteofTraumatologyandOrthopaedics XijingHospitaltheFourthMilitaryMedicalUniversityXian710032 DepartmentofMaxillofacialSurgery StomatologicalCollegetheFourthMilitaryMedicalUniversity DepartmentofPathology XijingHospitaltheFourthMilitaryMedicalUniversity

TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repair. A rabbit radial bone defect model was used to evaluate the effect of TGF-β, which was extracted and purified from bovine blood platelets, on the healing of a large segmental osteoperiosteal defect. A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adult rabbits. The defect was filled with implant containing TGF-β that consisted of carrier and bovine TGF-β. Limbs served as controls received carrier alone. The defectswere examined radiographically and histologically at 4, 8,12 , 16 and 20 weeks after implantation. The results showed that in TGF-β implant group . the defect areas at 12 weeks post operation were bridged by uniform new bone and the cut ends of cortex could not be seen;while in control group, the defects remained clear. Only a small amount of new bone formed as a cap on the cut bone ends. In the experimental group, new lamellar and woven bone formed in continuity with the cut ends of the cortex. An early medullar canal appears to be forming and contained normal-appearancing marrow elements; while the control group displayed entirely fibrous tissue within the defect site. Remnants of the cancellous bone carrier were observed in the control specimen. These data demonstrate that exogenous TGF-β initiate osteogenesis and stimulate the bone defects repair in animal model.

关键词： transforming growth factor beta bone defects bone repair

Effect of vascular endothelial growth factor 165 gene transfection on bone defects and its mRNA expression in rabbits

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Chinese Medical Journal 2007年第13期120卷 1187-1191页

作者： ZHAO Dong-mei WANG Hai-bin YANG Jia-feng WU Shi-qing LIU Jun-li XU Fu-yu QIU Li-ping CAI Jing-long Department of Orthopaedics Shandong University Jinan 250033 China Department of Plastics Shandong University Jinan 250033 China Second Hospital Key Laboratory of Liquid Structure and Heredity of Materials Ministry of Education Shandong University Jinan 250033 China

Background Gene therapy has been a hot spot in repair of bone defects in recent years. This study aimed to construct a recombinant plasmid pcDNA3.1-VEGF165, and to observe the effect of vascular endothelial growth factor 165 （VEGF165） gene therapy on bone defects in rabbits. Methods Total RNA was extracted from rabbit bone tissues. VEGF165 cDNA fragment was prepared by reverse transcription and the gene was cloned by polymerase chain reaction （PCR）. Plasmid pMD18-T/VEGF165 combined with pcDNA3.1 was cloned to reconstruct pcDNA3.1-VEGF165 plasmid. Thirty New Zealand white rabbits weighing （2.50±0.13）kg were used to establish models of bone defects （1 cm in length） of the bilateral radii. The bone defects were repaired with absorbable gelatin sponge. After the operation, physiological sodium chloride solution was injected into the injured site in one of the forelegs of the rabbits as the control group, and pcDNA3.1-VEGF165 plasmid （0.2 ml, 200 ng） was injected into the opposite foreleg as the experiment groups. At weeks 1, 2, 4, 6, 8, and 12 after the treatments, the bones were examined by X-ray, and the specimens of the bone defects were collected, stained with HE, and observed under a light microscope. The expression of VEGF165 mRNA was examined by real-time quantitative polymerase chain reaction （RQ-PCR）. Results The pcDNA3.1-VEGF165 plasmid with a correct sequence was constructed successfully. Postoperative X-ray found no difference between the two groups at week 1. In the experiment group, callus and synostosis were observed after 2 weeks, and osteosis structure was normal at week 12; these phenomena occurred much later in the control group. In the experiment group, HE staining showed a large amount of newly formed blood vessels after 2 weeks, a number of bone trabeculae with osteoblasts proliferation at 4 weeks, and fresh bone cortex and reformed medullary cavity at 12 weeks; whereas in the control group these structures formed in later phases. The VEGF165 m

关键词： gene transfection vascular endothelial growth factor bone defects

Two-site osteotomy bone transport for large segmental defects of tibia and soft tissue

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Two-site osteotomy bone transport for large segmental defect...

An Experimental Study of Sponge and Putty of Demineralized bone Matrix （DBM）in the Repair of Segmental defects

第三届全军创伤骨科学术大会

作者： XU Yong-qing ZHU Yue-liang FAN Xing-yu Othopaedic Research Institute of Kunming General Hospital Chengdu Military Command PLA

Objective To do two-site osteotomy of tibial bone transport of for large defects of the tibia and sort tissue and evaluate its role in accelerating the bone union and soft tissue *** From May 2009 to May 2011,6 cases of large tibial and soft tissue defects were treated in our *** cases were all open fractures of Gustilo IIIB,with an average of *** causes include 5cases of accidental trauma,1 case of machine *** size of soft tissue of the anterior leg ranged from 8cm×4cm to 24cm×11cm,and the defect length of the tibia defect was from *** debridement,the half-ring external fixator were used to fix the *** osteotomy were made on the proximal and distal metaphsis of the tibia,and the bone transport were made at a speed of 1mm/d for each osteotomy *** The follow up ranged from 106 months(averaging 16months).All the soft tissue of the legs healed whileall the tibia defects were *** discrepancy of the two legs were within 2 *** Two-site osteotomy of bone transport is effective and will accelerate the healing of large defects of the tibia and soft tissue.

关键词： Tibial bone defects Soft Tissue Ddefects Distraction Osteogenesis

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An Experimental Study of Sponge and Putty of Demineralized B...

Synergistic injection of the thermosensitive hydrogel and Bi-based alloy bone cement for orthopaedic repair

第2届世界华人生物医学工程研讨会

作者： SUN Mingxue HUANG Jingxiang WANG Aiyuan et al (Institute of Orthopaedics PLA General Hospital Fuxing Road No.28 100853 Beijing China)

OBJECTIVE This study was to evaluate the osteogenic effects of demineralized bone matrix(DBM) in the forms of sponge and putty. METHODS Rabbits DBM particles and fibers were prepared by demineralize

关键词： demineralized bone matrix osteoinduction bone defects

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Science China(Technological Sciences) 2024年第7期67卷 2153-2163页

作者： LIU SiCong LI Lei JIANG ChanYuan WANG QianYu DENG ZhongShan Key Laboratory of Cryogenic Science and Technology Technical Institute of Physics and ChemistryChinese Academy of SciencesBeijing 100190China Department of Cleft Lip and Palate Plastic Surgery HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100144China School of Future Technology University of Chinese Academy of SciencesBeijing 100049China

Low-melting-point alloys have the advantages of good biocompatibility, plasticity, and near-bone mechanical strength, making them suitable as bone defect-filling materials for direct injection into defective bone sites. However, using low-melting-point alloys for orthopedic implants poses the challenge of causing thermal damage to the surrounding bone tissue during injection. In this study, a thermosensitive hydrogel is prepared and synergistically injected into the bone defect site with BiInSn. BiInSn solidifies and releases heat during injection, while the thermosensitive hydrogel absorbs heat and transforms into a gel state,encapsulating BiInSn. Therefore, the surrounding bone tissue is effectively protected from thermal damage. When BiInSn and the thermosensitive hydrogel were injected synergistically, in vitro thermal experiments revealed that the maximum temperature of the surrounding bone tissue reached 42℃. This temperature is below the 47℃ threshold, which causes permanent damage to bone tissues. In vivo experiments demonstrated that rats in the BiInSn-thermosensitive hydrogel group exhibited better recovery at the bone defect sites. These results suggest that the synergistic injection of Bi-based alloy and thermosensitive hydrogel is beneficial in reducing thermal damage to bone tissue, guiding bone tissue growth, and effectively facilitating the repair of bone defects.

关键词： bone defects thermosensitive hydrogel thermal damage to tissue bismuth-based alloy bone cement

bone remodeling effect of a chitosan and calcium phosphate-based composite

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Regenerative Biomaterials 2019年第4期6卷 241-247页

作者： Lilja Kjalarsdottir Arna Dyrfjord Atli Dagbjartsson Elin H.Laxdal Gissur Orlygsson Johannes Gislason Jon M.Einarsson Chuen-How Ng Halldor Jonsson Jr Department of Orthopaedic Surgery Landspı´tali University HospitalReykjavik 108Iceland Faculty of Medicine University of IcelandReykjavik 101Iceland Genis hf. Siglufjordur 580Iceland Department of Materials Biotechnology and EnergyInnovation Center IcelandReykjavik 112Iceland Department of Vascular Surgery Landspitali University HospitalReykjavik 108Iceland

Chitosan is a biocompatible polymer that has been widely studied for tissue engineering *** aim of this research was to assess bone regenerative properties of an injectable chitosan and calcium phosphate-based composite and identify optimal degree of deacetylation(%DDA)of the chitosan *** holes were generated on the left side of a mandible in Sprague-Dawley rats,and the hole was either left empty or filled with the *** animals were sacrificed at several time points after surgery(7–22 days)and bone was investigated using micro-CT and *** significant new bone formation was observed in the implants themselves at any time ***,substantial new bone formation was observed in the rat mandible further away from the drill *** changes indicating bone formation were found in specimens explanted on Day 7 in animals that received *** bone formation pattern was seen in control animals with an empty drill hole at later time points but not to the same extent.A second experiment was performed to examine if the%DDA of the chitosan polymer influenced the bone remodeling *** results suggest that chitosan polymers with%DDA between 50 and 70%enhance the natural bone remodeling mechanism.

关键词： bone remodeling bone implant bone defects chitosan degree of deacetylation micro-CT rat mandible

bone tissue engineering scaffold materials: Fundamentals, advances, and challenges

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Chinese Chemical Letters 2024年第2期35卷 176-186页

作者： Chang Xu Zhize Liu Xi Chen Yang Gao Wenjun Wang Xijing Zhuang Hao Zhang Xufeng Dong Department of Cardiovascular Surgery Central Hospital of Dalian University of TechnologyDalian 116089China School of Materials Science and Engineering Dalian University of TechnologyDalian 116024China Department of Orthopaedics Central Hospital of Dalian University of TechnologyDalian 116089China Department of Dermatology Allergologyand VenereologyUniversity of LübeckLübeck 23562Germany

bone damage caused by trauma and tumors is a serious problem for human health, therefore, three-dimensional (3D) scaffolding materials that stimulate and promote the regeneration of broken bone tissues have become the focus of current research in the field of bone damage *** this regard, a preferential combination of materials and preparation techniques is considered crucial for the preparation of advanced bone tissue engineering scaffolds to better facilitate the regeneration of broken *** this review, current research advances and challenges in bone tissue engineering scaffolds are discussed and analyzed in ***, we elucidated the structure and self-healing mechanism of bone ***, the main applications of different materials, including inorganic and organic materials, in bone tissue engineering scaffolds are ***, we overview the latest research progress of the mainstream preparation strategies of bone tissue engineering scaffolds, and provide an in-depth analysis of the different advantages of each ***, promising future directions and challenges of bone tissue engineering scaffolds are systematically discussed.

关键词： Biomaterials bone defects Tissue engineering Scaffolds Osteogenesis

Biodegradable materials for bone defect repair

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Military Medical Research 2021年第2期8卷 202-229页

作者： Shuai Wei Jian-Xiong Ma Lai Xu Xiao-Song Gu Xin-Long Ma Tianjin Hospital Tianjin UniversityTianjin 300211China Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair Key Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationNantong UniversityNantongJiangsu 226001China

Compared with non-degradable materials,biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects,and have attracted extensive attention from *** the treatment of bone defects,scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role,which will eventually be degraded and absorbed in the body and be replaced by the new bone *** biodegradable materials include polymers,ceramics and metals,which have been used in bone defect repairing for many *** these materials have more or fewer shortcomings,they are still the cornerstone of our development of a new generation of degradable *** the rapid development of modern science and technology,in the 21 st century,more and more kinds of new biodegradable materials emerge in endlessly,such as new intelligent micro-nano materials and cell-based *** the same time,there are many new fabrication technologies of improving biodegradable materials,such as modular fabrication,3 D and 4 D printing,interface reinforcement and *** review will introduce various kinds of biodegradable materials commonly used in bone defect repairing,especially the newly emerging materials and their fabrication technology in recent years,and look forward to the future research direction,hoping to provide researchers in the field with some inspiration and reference.

关键词： Biodegradable materials bone defects bone repair Intelligent material Modular fabrication

Synthesis and potential osteogenic applications of Wnt3a-loaded ZIF-8 nanoparticles

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Chinese Chemical Letters 2024年第3期35卷 399-405页

作者： Hengfei Wang Song Chen Zihan He Junyu Chen Zhou Zhu Qianbing Wan Jian Wang Xibo Pei State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of ProsthodonticsWest China Hospital of StomatologySichuan UniversityChengdu 610041China Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationStomatological Hospital of Chongqing Medical UniversityChongqing 400016China

The Wnt signaling pathway plays a critical role in bone homeostasis,and the related protein therapy strategies have been reported to have great potential in osseointegration;however,they face formidable challenges such as complex external environments and unavoidable protein *** this work,we report a novel approach combining the synthesis of metal–organic frameworks(MOFs)and protein encapsulation in a one-pot process based on zeolitic imidazolate framework-8(ZIF-8)and Wnt3a protein,with improved biomechanical behavior and enhanced protein biological *** combination was designed to enhance the Wnt3a protein function through the improved chemical stability provided by the ZIF-8 ***,the zinc ions contained in the ZIF-8 crystals induced bone homeostasis,further favoring the *** results showed that the Wnt3a protein-loaded ZIF-8 crystals served as efficient drug delivery vehicles to promote osteogenesis,preventing protein *** particular,Wnt3a-loaded ZIF-8 nanoparticles(Wnt3a@ZIF-8 NPs)had higher efficacy on bone marrow mesenchymal stem cells(BMSCs)than ZIF-8 NPs or Wnt3a proteins,contributing to the osteogenesis through ZIF-8 crystals and intracellular Wnt3a proteins released from Wnt3a@ZIF-8 ***,polymerase chain reaction(PCR)analysis showed that the osteogenic pathways were ***,the present one-pot process can open up new avenues to develop signaling protein-delivery systems for applications in protein therapy strategies.

关键词： Metal–organic frameworks Nanoparticle Drug release Osteogenesis bone defects