可降解镁基金属骨缺损修复材料的研究探索

doi:10.11900/0412.1961.2017.00279

金属学报

2017, Vol. 53

Issue (10): 1197-1206 DOI: 10.11900/0412.1961.2017.00279

研究论文

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可降解镁基金属骨缺损修复材料的研究探索

东家慧^1,², 谭丽丽¹, 杨柯¹(

)

1 中国科学院金属研究所沈阳 110016
2 中国科学技术大学材料科学与工程学院沈阳 110016

Research of Biodegradable Mg-Based Metals as Bone Graft Substitutes

Jiahui DONG^1,², Lili TAN¹, Ke YANG¹(

)

1 Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, China
2 School of Materials Science and Engineering, University of Science and Technology of China, Shenyang 110016, China

引用本文:

东家慧, 谭丽丽, 杨柯. 可降解镁基金属骨缺损修复材料的研究探索[J]. 金属学报, 2017, 53(10): 1197-1206.
Jiahui DONG, Lili TAN, Ke YANG. Research of Biodegradable Mg-Based Metals as Bone Graft Substitutes[J]. Acta Metall Sin, 2017, 53(10): 1197-1206.

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摘要:

由于各种原因所造成的骨缺损的修复是临床上一项具有挑战的难题,理想的骨修复材料应同时具备良好的生物相容性、骨传导、骨诱导以及成骨功能。自体骨虽然被视为骨修复材料的“金标准”,却存在取骨量有限和取骨区并发症等问题,而人工合成骨修复材料则还不具备骨诱导能力以及成骨性能,因此临床常用的骨移植材料以及骨移植替代材料都存在各自的应用局限。可降解镁基金属(纯Mg和镁合金)由于具有生物可降解、良好的生物相容性以及与骨组织接近的弹性模量和密度等特性受到人们的广泛关注。本文较系统地综述了镁基金属在骨填充应用研究中的生物学行为,包括良好的促成骨、骨传导能力,潜在的骨诱导作用,以及抗菌、抗肿瘤等独特的生物功能,虽然其在临床应用上仍需要继续研究探索,但不可否认其在骨缺损修复方面具有巨大的优势和潜力,有望成为新一代骨缺损修复替代材料。

关键词 ：骨缺损, 骨修复, 促成骨, 镁基金属, 生物可降解

Abstract：

Bone defects are very challenging in orthopedic practice due to a variety of reasons. Bone repair requires four critical elements, biocompatibility, osteoconduction, osteoinduction and osteogenesis. The autografts still exist some problems for applications such as the limitation of available autogenous bones and post-operative complications, although they are considered as the “gold standard” in bony defect repairs. Generally the synthetic bone substitutes do not possess osteoinductive and osteogenic activities. Therefore, the clinical bone grafts and bone-graft substitutes have their own shortcomings in the repair of bone defects. Biodegradable magnesium-based metals, including pure magnesium and magnesium alloys, have been concerned and studied recently due to their biodegradation, good biocompatibility and similar elastic modulus and density with bone tissue. This paper summarizes the biological behavior of magnesium-based metals for bone defects repair application, including ability of promoting osteogenesis, osteoconduction and potential osteoinduction, as well as some particular biofunctions such as antibacterial and antitumor properties. The great advantages and potentials of magnesium in bone defects repair can not be denied as a promising class of bone substitutes, although further researches are still needed for clinical applications.

Key words： bone defect bone repair osteogenesis Mg-based metal biodegradable

收稿日期: 2017-07-06

ZTFLH:

R318.08

基金资助:国家自然科学基金项目Nos.81401773 和31500777

作者简介:

作者简介东家慧,女,1993年生

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https://www.ams.org.cn/CN/10.11900/0412.1961.2017.00279 或 https://www.ams.org.cn/CN/Y2017/V53/I10/1197

图1 不同骨修复材料的抗压强度及与人体骨骼力学性能对比[21]

图2 Mg-6Zn合金棒植入动物体内6和18周后周围组织切片的HE染色[26]

图3 镁合金组和CaSO4 组植入2和4个月后骨缺损处的CT三维重建[27]

图4 植入物释放的Mg2+诱导骨膜来源干细胞(PDSC)成骨分化的机制图[29]

图5 组织学观察(利用Laczkó-Lévai方法染色,染色后粉色处为硬骨质,蓝色处为软骨,灰色处为纤维组织)[37]

图6 利用Levai-Laczko染色后的植入物处的组织切片观察 [39]

图7 金黄色葡萄球菌(S.aureus)在37 ℃条件下分别与不同材料(Mg、Mg-Sr、316L SS)及现有骨修复材料(CaSO4、HA、β-TCP)共培养24 h后剩余菌落数结果[40]

图8 纯Mg以及表面改性后的纯Mg样品在SBF溶液中浸泡后的H2释放量,不同系统中羟基浓度的吸光度(OD)值大小,将纯Mg与表面改性后纯Mg与MG63共培养4、6、8 h后自由基浓度的OD值[51]

[1]	Greenwald A S, Boden S D, Goldberg V M, et al.Bone-graft substitutes: Facts, fictions, and applications[J]. J. Bone Joint Surg. Am., 2001, 83: 98
[2]	Finkemeier C G.Bone-grafting and bone-graft substitutes[J]. J. Bone Joint Surg. Am., 2002, 84: 454
[3]	van Heest A, Swiontkowski M. Bone-graft substitutes[J]. Lancet, 1999, 353: S28
[4]	Calori G M, Mazza E, Colombo M, et al.The use of bone-graft substitutes in large bone defects: Any specific needs?[J]. Injury, 2011, 42: S56
[5]	Einhorn T A.Enhancement of fracture-healing[J]. J. Bone Joint Surg. Am., 1995, 77: 940
[6]	Giannoudis P V, Dinopoulos H, Tsiridis E.Bone substitutes: An update[J]. Injury, 2005, 36: S20
[7]	van der Stok J. Bone graft substitutes developed for trauma and orthopaedic surgery[J]. Ned. Tijdschr. Trauma., 2015, 23: 84
[8]	Bhatt R A, Rozental T D.Bone graft substitutes[J]. Hand Clin., 2012, 28: 457
[9]	Campana V, Milano G, Pagano E, et al.Bone substitutes in orthopaedic surgery: From basic science to clinical practice[J]. J. Mater. Sci. Mater. Med., 2014, 25: 2445
[10]	Morone M A, Boden S D, Hair G, et al.The Marshall R. Urist young investigator award. gene expression during autograft lumbar spine fusion and the effect of bone morphogenetic protein 2[J]. Clin. Orthop. Relat. Res., 1998, (351): 252
[11]	Goldberg V M.The biology of bone grafts[J]. Orthopedics, 2003, 26: 923
[12]	Zipfel G J, Guiot B H, Fessler R G.Bone grafting[J]. Neurosurg Focus, 2003, 14: e8
[13]	Baumhauer J, Pinzur M S, Donahue R, et al.Site selection and pain outcome after autologous bone graft harvest[J]. Foot Ankle Int., 2014, 35: 104
[14]	Charalambides C, Beer M, Cobb A G.Poor results after augmenting autograft with xenograft (Surgibone) in hip revision surgery[J]. Acta Orthop., 2005, 76: 544
[15]	Nandi S K, Roy S, Mukherjee P, et al.Orthopaedic applications of bone graft & graft substitutes: A review[J]. Indian J. Med. Res., 2010, 132: 15
[16]	Robin B N, Chaput C D, Zeitouni S, et al.Cytokine-mediated inflammatory reaction following posterior cervical decompression and fusion associated with recombinant human bone morphogenetic protein-2: A case study[J]. Spine, 2010, 35: E1350
[17]	Song G L, Atrens A.Corrosion mechanisms of magnesium alloys[J]. Adv. Eng. Mater., 1999, 1: 11
[18]	Thormann U, Alt V, Heimann L, et al.The biocompatibility of degradable magnesium interference screws: An experimental study with sheep[J]. Biomed. Res. Int., 2015, 2015: 943603
[19]	Witte F, Ulrich H, Rudert M, et al.Biodegradable magnesium scaffolds: Part 1: Appropriate inflammatory response[J]. J. Biomed. Mater. Res., 2007, 81A: 748
[20]	Staiger M P, Pietak A M, Huadmai J, et al.Magnesium and its alloys as orthopedic biomaterials: A review[J]. Biomaterials, 2006, 27: 1728
[21]	Liu C, Wan P, Tan L L, et al.Preclinical investigation of an innovative magnesium-based bone graft substitute for potential orthopaedic applications[J]. J. Orthop. Trans., 2014, 2: 139
[22]	Xie X W, Huang J, Li N, et al.Progress of magnesium ions and magnesium alloy implant application in the clinical orthopaedics[J]. Chin. J. Tiss. Eng. Res., 2012, 16: 7317(谢兴文, 黄晋, 李宁等. 镁及镁合金植入体在骨科临床中的应用与进展[J]. 中国组织工程研究, 2012, 16: 7317)
[23]	Gu X N, Zheng Y F, Cheng Y, et al.In vitro corrosion and biocompatibility of binary magnesium alloys[J]. Biomaterials, 2009, 30: 484
[24]	Gao J C, Qiao L Y, Li L C, et al.Hemolysis effect and calcium-phosphate precipitation of heat-organic-film treated magnesium[J]. Trans. Nonferrous Met. Soc. China, 2006, 16: 539
[25]	Li L C, Gao J C, Wang Y.Evaluation of cyto-toxicity and corrosion behavior of alkali-heat-treated magnesium in simulated body fluid[J]. Surf. Coat. Technol., 2004, 185: 92
[26]	Zhang S X, Zhang X N, Zhao C L, et al.Research on an Mg-Zn alloy as a degradable biomaterial[J]. Acta Biomater., 2010, 6: 626
[27]	Zhang Q, Lin X, Qi Z R, et al.Magnesium alloy for repair of lateral Tibial Plateau defect in minipig model[J]. J. Mater. Sci. Technol., 2013, 29: 539
[28]	Witte F, Ulrich H, Palm C, et al.Biodegradable magnesium scaffolds: Part II: Peri-implant bone remodeling[J]. J. Biomed. Mater. Res., 2007, 81A: 757
[29]	Zhang Y F, Xu J K, Ruan Y C, et al.Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats[J]. Nat. Med., 2016, 22: 1160
[30]	Burmester A, Willumeit-R?mer R, Feyerabend F.Behavior of bone cells in contact with magnesium implant material[J]. J. Biomed. Mater. Res. Appl. Biomater., 2017, 105B: 165
[31]	Zhai Z J, Qu X H, Li H W, et al.The effect of metallic magnesium degradation products on osteoclast-induced osteolysis and attenuation of NF-κB and NFATc1 signaling[J]. Biomaterials, 2014, 35: 6299
[32]	Zreiqat H, Howlett C R, Zannettino A, et al.Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants[J]. J. Biomed. Mater. Res., 2002, 62: 175
[33]	Yoshizawa S, Brown A, Barchowsky A, et al.Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation[J]. Acta Biomater., 2014, 10: 2834
[34]	Willbold E, Kalla K, Bartsch I, et al.Biocompatibility of rapidly solidified magnesium alloy RS66 as a temporary biodegradable metal[J]. Acta Biomater., 2013, 9: 8509
[35]	Yang T T, Ni Y X, Zhai J J, et al.Microstructure, mechanical properties, In Vitro degradation and cytotoxicity of Mg-4Zn-3HA alloy for biodegradable implant materials[J]. J. Hard Tiss. Biol., 2014, 23: 111
[36]	Asagiri M, Takayanagi H.The molecular understanding of osteoclast differentiation[J]. Bone, 2007, 40: 251
[37]	Castellani C, Lindtner R A, Hausbrandt P, et al.Bone-implant interface strength and osseointegration: Biodegradable magnesium alloy versus standard titanium control[J]. Acta Biomater., 2011, 7: 432
[38]	Lindtner R A, Castellani C, Tangl S, et al.Comparative biomechanical and radiological characterization of osseointegration of a biodegradable magnesium alloy pin and a copolymeric control for osteosynthesis[J]. J. Mech. Behav. Biomed. Mater., 2013, 28: 232
[39]	Kraus T, Fischerauer S F, H?nzi A C, et al.Magnesium alloys for temporary implants in osteosynthesis: In vivo studies of their degradation and interaction with bone[J]. Acta Biomater., 2012, 8: 1230
[40]	Liu C, Fu X K, Pan H B, et al.Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long-lasting antibacterial effects[J]. Sci. Rep., 2016, 6: 27374
[41]	Boyan B D, Weesner T C, Lohmann C H, et al.Porcine fetal enamel matrix derivative enhances bone formation induced by demineralized freeze dried bone allograft in vivo[J]. J. Periodontol., 2000, 71: 1278
[42]	Huang J J, Ren Y B, Zhang B C, et al.Study on biocompatility of magnesium and its alloys[J]. Rare Met. Mater. Eng., 2007, 36: 1102(黄晶晶, 任伊宾, 张炳春等. 镁及镁合金的生物相容性研究[J]. 稀有金属材料与工程, 2007, 36: 1102)
[43]	Reifenrath J, Badar M, Dziuba D, et al.Assessment of cellular reactions to magnesium as implant material in comparison to titanium and to glyconate using the mouse tail model[J]. J. Appl. Biomater. Funct. Mater., 2013, 11: e89
[44]	Ren L, Lin X, Tan L L, et al.Effect of surface coating on antibacterial behavior of magnesium based metals[J]. Mater. Lett., 2011, 65: 3509
[45]	Krulwich T A, Sachs G, Padan E.Molecular aspects of bacterial pH sensing and homeostasis[J]. Nat. Rev. Microbiol., 2011, 9: 330
[46]	Li Y, Liu L N, Wan P, et al.Biodegradable Mg-Cu alloy implants with antibacterial activity for the treatment of osteomyelitis: In vitro and in vivo evaluations[J]. Biomaterials, 2016, 106: 250
[47]	Zhang Y, Ren L, Li M, et al.Preliminary study on cytotoxic effect of biodegradation of magnesium on cancer cells[J]. J. Mater. Sci. Technol., 2012, 28: 769
[48]	?ekin E, Ipcioglu O M, Erkul B E, et al.The association of oxidative stress and nasal polyposis[J]. J. Int. Med. Res., 2009, 37: 325
[49]	Valko M, Rhodes C J, Moncol J, et al.Free radicals, metals and antioxidants in oxidative stress-induced cancer[J]. Chem. Biol. Interact., 2006, 160: 1
[50]	Dole M, Wilson F R, Fife W P.Hyperbaric hydrogen therapy: Apossible treatment for cancer[J]. Science, 1975, 190: 152
[51]	Ma N, Chen Y M, Yang B C.Magnesium metal—A potential biomaterial with antibone cancer properties[J]. J. Biomed. Mater. Res., 2014, 102A: 2644

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