骨与软骨组织工程中骨形态发生蛋白的特征与临床应用
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摘要
背景:自从1965年美国Urist等研究发现骨形态发生蛋白有助于骨重新生长后,在全世界范围内掀起了骨诱导研究的热潮,中国对于骨形态发生蛋白的研究近年也进入大规模的临床研究试验阶段。目的:回顾近年来骨形态发生蛋白在骨与软骨组织工程的临床应用及相关研究进展。方法:以"Bone morphogenetic protein, Bone tissue engineering, Cartilage tissue engineering,Osteoarthritis,Fracture,Nonunion,Bone defect,Osteonecrosis of femoral head,Gene therapy"或"骨形态发生蛋白,骨组织工程,软骨组织工程,关节炎,骨折,骨不连,骨缺损,股骨头坏死,基因治疗"等作为检索词,由第一作者检索2000年至2018年PubMed、Medline、Embase、中国知网、万方、维普等数据库收录的与骨形态发生蛋白在骨与软骨临床应用研究相关的文献报道,并排除重复性研究,共纳入62篇文章进行综述分析。结果与结论:通过从关节炎治疗、骨折治疗、骨不连及骨缺损治疗、股骨头坏死治疗、基因治疗等5个方面进行综述讨论,系统阐述了骨形态发生蛋白在骨与软骨组织工程中的临床应用研究及临床疗效报道。骨形态发生蛋白是一种具有强大的骨诱导活性成骨因子,具有促进骨生长作用,同时还具有软骨、肌腱及韧带等促进修复作用,因其较高的有效性和安全性近年来在界内倍受推崇。多种转化生长因子相互协同、复合一起作用于骨与软骨组织工程中的临床应用将成为今后骨科研究的热点之一,有待继续深入研究。
BACKGROUND: Since the Urist et al. from the USA found that bone morphogenetic proteins contribute to bone regrowth in 1965, bone induction has been a hot spot worldwide. In recent years, the study on bone morphogenetic proteins in China has also entered the clinical trial stage.OBJECTIVE: To review the clinical application and research progress of bone morphogenetic proteins in bone and cartilage tissue engineering.METHODS: "Bone morphogenetic protein, bone tissue engineering, cartilage tissue engineering, osteoarthritis, fracture, nonunion, bone defect, osteonecrosis of femoral head, gene therapy" in English and Chinese, respectively were used as keywords. The first author retrieved the literature concerning the clinical application of bone morphogenetic proteins in bone and cartilage in Pub Med, Medline, Embase, CNKI,WanF ang, and VIP databases from 2000 to 2018. A total of 62 eligible articles were included after excluding repeated studies.RESULTS AND CONCLUSION: From five aspects including arthritis, fracture, bone nonunion, bone defect; femoral head necrosis and gene therapy, clinical researches and outcomes of BMPs in bone and cartilage tissue engineering are summarized. Bone morphogenetic proteins possess strong bone-inducing active osteogenic factor, which can not only promote bone growth, but also promote the repair of cartilage, tendons and ligaments. Because of its high effectiveness and safety, it has been highly regarded in recent years. A variety of transforming growth factors mutually applied in bone and cartilage tissue engineering will become a hot spot in orthopedic research, which needs further investigation.
BACKGROUND: Since the Urist et al. from the USA found that bone morphogenetic proteins contribute to bone regrowth in 1965, bone induction has been a hot spot worldwide. In recent years, the study on bone morphogenetic proteins in China has also entered the clinical trial stage.OBJECTIVE: To review the clinical application and research progress of bone morphogenetic proteins in bone and cartilage tissue engineering.METHODS: "Bone morphogenetic protein, bone tissue engineering, cartilage tissue engineering, osteoarthritis, fracture, nonunion, bone defect, osteonecrosis of femoral head, gene therapy" in English and Chinese, respectively were used as keywords. The first author retrieved the literature concerning the clinical application of bone morphogenetic proteins in bone and cartilage in Pub Med, Medline, Embase, CNKI,WanF ang, and VIP databases from 2000 to 2018. A total of 62 eligible articles were included after excluding repeated studies.RESULTS AND CONCLUSION: From five aspects including arthritis, fracture, bone nonunion, bone defect; femoral head necrosis and gene therapy, clinical researches and outcomes of BMPs in bone and cartilage tissue engineering are summarized. Bone morphogenetic proteins possess strong bone-inducing active osteogenic factor, which can not only promote bone growth, but also promote the repair of cartilage, tendons and ligaments. Because of its high effectiveness and safety, it has been highly regarded in recent years. A variety of transforming growth factors mutually applied in bone and cartilage tissue engineering will become a hot spot in orthopedic research, which needs further investigation.
引文
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[3]Venkatesan J,Bhatnagar I,Manivasagan P,et al.Alginate composites for bone tissue engineering:a review.Int J Biol Macromol.2015;72:269-281.
[4]杨林,徐军美,王亚平,等.骨形态发生蛋白2/4在神经系统中的作用及其研究进展[J].中南大学学报(医学版),2018,43(02):222-228.
[5]阮世强,邓江,等.聚乳酸/聚羟基乙酸共聚物支架复合骨形态发生蛋白2基因增强的脂肪干细胞促进软骨缺损修复[J].中国组织工程研究,2018,22(6):840-845.
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[9]Labibzadeh N,Emadedin M,Fazeli R,et al.Msenchymal strumal cells implantation in combination with platelet lysate product is safe for reconstruction of human long bone nonunion.Cell J.2016;18(3):302-309.
[10]Deng ZH,Li YS,Gao X,et al.Bone morphogenetic proteins for articular cartilage regeneration.Osteoarthritis Cartilage.2018 Mar 24.
[11]Varady NH,Grodzinsky AJ.steoarthritis year in review2015:mechanics.Osteoarthritis Cartilage.2016;24(1):27.
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[13]Barton KI,Shekarforoush M,Heard BJ,et al.Use of preclinical surgically induced models to understand biomechanical and biological consequences of PTOA development.J Orthop Res.2017;35(3):454.
[14]Schmal H,Niemeyer P,Zwingmann J,et al.Association between expression of the bone morphogenetic proteins 2 and7 in the repair of circumscribed cartilage lesions with clinical outcome.BMC Musculoskelet Disord 2010;11:170.
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[17]Xia X,Li J,Xia B,et al.Matrigel scaffold combined with Ad-hBMP7-transfected chondrocytes improves the repair of rabbit cartilage defect.Exp Ther Med 2017;13:542-550.
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[21]Majumdar MK,Wang E,Morris EA.BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1.J Cell Physiol2001;189:275-284.
[22]Einhorn TA,Gerstenfeld LC.Fracture healing:mechanisms and interventions.Nat Rev Rheumatol.2015;11(1):45-54.
[23]Wu M,Chen G,Li YP.TGF-b and BMP signialing in osteoblast,skeletal development,and bone fromation,bomeostasis and disease.Bone Res.2016;4:16009.
[24]Kuzyk PR,Schemitsch EH.The basic science of peri-im-plant bone healing.Indian J Orthop.2011;45(2):108-115.
[25]陈启刚,胡永军,胡海,等.锁定接骨板结合重组人骨形态发生蛋白骨修复材料治疗跟骨骨折的临床分析[J].安徽医药,2018,22(4):703-706.
[26]王军,时宁文,邱阳,等.载万古霉素硫酸钙复合BMP-2治疗创伤性骨髓炎[J].中国骨科临床与基础研究杂志,2017,9(3):133-139.
[27]印飞,孙振中,殷渠东,等.短节段椎弓根钉固定联合重组人BMP-2和同种异体骨植骨治疗胸腰椎爆裂骨折[J].中国修复重建外科杂志,2017,31(9):1080-1085.
[28]Govender S,Csimma C,Genant HK,et al.Recombinant human bone orphogenetic protein-2 for treatment of open tibial fractures:a prospective,controlled,randomized study of four hundred and fifty patients.J Bone Joint Surg Am.2002;84-A(12):2123-2134.
[29]Kokubo S,Fujimoto R,Yokota S,et al.Bone regeneration by recombineant human bone morphogenetic protein-2 and a novel biodegradable carrier in arabbit ulnar defect model.Biomaterials.2003;24(9):1643-1651.
[30]Sándor GK,Tuovinen VJ,Wolff J,et al.Adipose stem cell tissue-engineered construct used to treat large anterior mandibular defect:a case report and review of the clinical application of good manufacturing practice-level adipose stem cells for bone regeneration.J Oral Maxillofac Surg.2013;71(5):938-950.
[31]Stancoven BW,Lee J,Dixon DR,et al.Effect of bone morphogeneticprotein-2,demineralized bone matrix and systemic parathyroid hormone(1-34)on local bone formation in a rat calvaria critical size defect model.J Periodontal Res.2013;48(2):243-251.
[32]Wu G,Liu Y,Iizuka T,et al.The effect of a slow mode of BMP-2delivery on the inflammatory response provoked by bone-defect-filling polymeric scaffolds.Biomaterials.2010;31(29):7485-7493.
[33]郑昊,吕游,徐丽,等.下肢长管骨骨折合并骨不连的原因分析及治疗[J].中国临床医师杂志,2015,9(17):3286-3290.
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