纳米羟基磷灰石/胶原复合材料修复猪下颌骨缺损后血管内皮生长因子的变化
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摘要
背景:纳米羟基磷灰石/胶原复合材料可促进下颌骨缺损的修复,但其作用机制尚不明确。目的:探讨纳米羟基磷灰石/胶原复合材料对家猪下颌骨缺损中血管内皮生长因子的影响。方法:取家猪60只(河北医科大学第一医院医学动物实验中心提供),随机分3组,每组20只:假手术组不做任何处理;模型对照组建立10 mm×5 mm×1 mm下颌骨缺损模型;观察组建立10 mm×5 mm×1 mm下颌骨缺损模型,将纳米羟基磷灰石/胶原复合材料植入骨缺损处。术后12周,取下颌骨缺损部位,分别进行苏木精-伊红染色、免疫组织化学染色、X射线检查。实验获得河北医科大学第一医院伦理委员会批准。结果与结论:(1)苏木精-伊红染色显示,观察组材料中心区部分材料降解,大量代谢旺盛的细胞分散在材料空洞中,周围可见大量骨小梁;模型对照组缺损区域被纤维肉芽组织覆盖,未见明显成骨发生;假手术组下颌骨部位组织排列整齐;观察组新生骨小梁面积大于模型对照组(P <0.05);(2)X射线显示,模型对照组可见明显缺损部位;观察组缺损面积明显小于模型对照组;(3)免疫组织化学染色显示,观察组血管内皮生长因子表达高于模型对照组(P <0.05);(4)结果表明,纳米羟基磷灰石/胶原复合材料可促进猪下颌骨缺损的愈合,提高血管内皮生长因子水平。
BACKGROUND: Nano-hydroxyapatite/collagen composites can promote the repair of mandibular defects, but the mechanism is still unclear. OBJECTIVE: To investigate the effect of nano-hydroxyapatite/collagen composites on vascular endothelial growth factors in mandibular defects of domestic pigs. METHODS: Sixty domestic pigs(provided by the Laboratory Animal Center of the First Hospital of Hebei Medical University, China) were randomized into three groups(n=20/group): sham group(no intervention), control group(model of mandibular defect with 10 mm×5 mm×1 mm), and observation group(model of mandibular defect with 10 mm×5 mm×1 mm, and implantation of nano-hydroxyapatite/collagen composite material). At 12 weeks after surgery, the mandibular defect areas were removed for hematoxylin-eosin staining, immunohistochemistry and X-ray examination. The study was approved by the Animal Ethics Committee of the First Hospital of Hebei Medical University. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that some materials in the central part of the material in the observation group were degraded, and a large number of metabolically active cells were dispersed in the material cavity, which was surrounded by numerous trabecular bones. The defect area in the control group was covered by fibrous granulation tissue without obvious osteogenesis. The tissues in the mandibular part of sham group arranged regularly. The area of newly born bone in the observation group was significantly larger than that in the control group(P < 0.05). X-ray examination revealed that there was obvious defect in the control group, and the defect area in the observation group was significantly smaller than that in the control group. Immunohistochemistry results indicated that the expression level of vascular endothelial growth factor in the observation group was significantly higher than that in the control group(P < 0.05). In summary, nano-hydroxyapatite/collagen composite can promote the healing of pig mandibular defect, and increase vascular endothelial growth factor level.
BACKGROUND: Nano-hydroxyapatite/collagen composites can promote the repair of mandibular defects, but the mechanism is still unclear. OBJECTIVE: To investigate the effect of nano-hydroxyapatite/collagen composites on vascular endothelial growth factors in mandibular defects of domestic pigs. METHODS: Sixty domestic pigs(provided by the Laboratory Animal Center of the First Hospital of Hebei Medical University, China) were randomized into three groups(n=20/group): sham group(no intervention), control group(model of mandibular defect with 10 mm×5 mm×1 mm), and observation group(model of mandibular defect with 10 mm×5 mm×1 mm, and implantation of nano-hydroxyapatite/collagen composite material). At 12 weeks after surgery, the mandibular defect areas were removed for hematoxylin-eosin staining, immunohistochemistry and X-ray examination. The study was approved by the Animal Ethics Committee of the First Hospital of Hebei Medical University. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that some materials in the central part of the material in the observation group were degraded, and a large number of metabolically active cells were dispersed in the material cavity, which was surrounded by numerous trabecular bones. The defect area in the control group was covered by fibrous granulation tissue without obvious osteogenesis. The tissues in the mandibular part of sham group arranged regularly. The area of newly born bone in the observation group was significantly larger than that in the control group(P < 0.05). X-ray examination revealed that there was obvious defect in the control group, and the defect area in the observation group was significantly smaller than that in the control group. Immunohistochemistry results indicated that the expression level of vascular endothelial growth factor in the observation group was significantly higher than that in the control group(P < 0.05). In summary, nano-hydroxyapatite/collagen composite can promote the healing of pig mandibular defect, and increase vascular endothelial growth factor level.
引文
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[26]陈贵征,孙玥,刘显,等.负载BMP-2的形状记忆支架修复兔下颌骨缺损的研究[J].口腔颌面外科杂志,2017,27(1):19-24.
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[31]罗有福,高金鉴,高浩然,等.负载重组人骨形态发生蛋白2的α型半水硫酸钙/纳米羟基磷灰石复合植骨材料的成骨性能研究[J].中国脊柱脊髓杂志,2016,26(4):348-353.
[32]吕春堂,张庆福.计算机辅助设计和3D打印技术与下颌骨缺损的个体化重建[J].口腔颌面外科杂志,2017,27(1):1-7.
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[2]许莹莹,王敬,韩尚志,等.载辛伐他汀/纳米羟基磷灰石胶原复合组织工程材料对家猪牙槽骨缺损的修复作用[J].山东医药,2017,57(42):43-45.
[3]Wang X,Wu X,Xing H,et al.Porous nano-hydroxyapatite/collagen scaffolds loading insulin PLGA particles for restoration of critical size bone defect.ACS Appl Mater Interfaces.2017;9(13):11380-11391.
[4]范田堂,陈景帝,刘小翠,等.Fe3O4-壳聚糖-胶原-纳米羟基磷灰石原位复合支架的仿生制备及表征[J].复合材料学报,2017,34(11):2593-2597.
[5]李冬梅,刘新晖,李庆星.纳米级细胞型组织工程人工骨的构建:修复下颌骨缺损[J].中国组织工程研究,2018,22(14):2146-2151.
[6]He S,Lin KF,Sun Z,et al.Effects of Nano-hydroxyapatite/Poly(DL-lactic-co-glycolic acid)Microsphere-Based Composite Scaffolds on Repair of Bone Defects:Evaluating the Role of Nano-hydroxyapatite Content.Artif Organs.2016;40(7):E128-E135.
[7]赵小妹,袁卫军.青少年期下颌骨缺损患者行Ⅱ期修复重建的观察与护理[J].上海护理,2017,17(1):56-58.
[8]彭祥,王文军.纳米羟基磷灰石/聚酰胺66复合材料在脊柱修复重建中的研究与应用[J].中国矫形外科杂志,2016,24(10):911-914.
[9]Cao S,Li H,Li K,et al.In vitro mineralization of MC3T3‐E1osteoblast‐like cells on collagen/nano‐hydroxyapatite scaffolds coated carbon/carbon composites.J Biomed Mater Res A.2016;104(2):533-543.
[10]高宁,刘颖蒙,付坤,等.折叠腓骨瓣修复下颌骨缺损后种植修复的疗效观察[J].中华口腔医学杂志,2018,53(1):26.
[11]Dau M,K?mmerer PW,Henkel KO,et al.Bone formation in mono cortical mandibular critical size defects after augmentation with two synthetic nanostructured and one xenogenous hydroxyapatite bone substitute-in vivo animal study.Clin Oral Implants Res.2016;27(5):597-603.
[12]周莉,吴凤群,罗仲宽,等.多孔载药纳米羟基磷灰石/聚酰胺/壳聚糖复合材料的制备与性能[J].化学研究与应用,2017,29(1):89-93.
[13]王延伟,张雅琪,于翔,等.PHA/纳米羟基磷灰石复合材料的结晶性能和力学性能研究[J].塑料科技,2017,45(3):61-65.
[14]Pripatnanont P,Praserttham P,Suttapreyasri S,et al.Bone Regeneration Potential of Biphasic Nanocalcium Phosphate with High Hydroxyapatite/Tricalcium Phosphate Ratios in Rabbit Calvarial Defects.Int J Oral Maxillofac Implants.2016;31(2):294.
[15]丁姗姗,禹怡君,刘超,等.超顺磁性支架材料修复兔下颌骨缺损的实验研究[J].医学研究生学报,2017,30(3):251-256.
[16]陈婷婷,崔海坡,宋成利,等.不同含量纳米羟基磷灰石/聚乳酸复合材料的性能[J].机械工程材料,2017,41(8):40-43.
[17]罗睿,王银龙.灰度比评价奥邦骨修复材料对下颌骨缺损修复的有效性[J].中国美容医学杂志,2018,27(3):114-117.
[18]车鸿泽,车彦海,卢晴,等.PLGA涂层处理的nHA-Mg多孔复合材料对兔颌骨缺损的修复作用[J].吉林大学学报(医学版),2017,43(2):276-280.
[19]Gravvanis A,Kakagia D,Katsikeris N,et al.Dermal Matrix for Intraoral Lining Following Composite Mandibular Defect Reconstruction With Chimeric Fibular Osseocutaneous Flap.JCraniofac Surg.2016;27(7):1711-1714.
[20]李元,吴迪,王天珏,等.磷酸钙复合材料构建模式对颌骨缺损修复效率的影响[J].实用口腔医学杂志,2017,33(3):297-301.
[21]张广德,靳霞,李荣亮,等.BMP-9/EPO双基因共转染ADSCs复合nHAC/PLA支架修复兔下颌骨缺损的实验研究[J].中国口腔颌面外科杂志,2017,15(3):202-208.
[22]Shao H,Sun M,Zhang F,et al.Custom Repair of Mandibular Bone Defects with 3D Printed Bioceramic Scaffolds.J Dent Res.2018;97(1):22034517734846.
[23]王希乾,彭立伟,王永功.快速原型技术在下颌骨缺损重建中的临床应用[J].河南医学研究,2016,25(10):1784-1785.
[24]Shen SY,Yu Y,Zhang WB,et al.Angle-to-Angle Mandibular Defect Reconstruction With Fibula Flap by Using a Mandibular Fixation Device and Surgical Navigation.JCraniofac Surg.2017;28(6):1486.
[25]孙莲莲,王志兴.同步辐射显微断层成像监测口腔骨植入材料置入体内后的生物相容性及定量分析:随机对照动物实验方案[J].中国组织工程研究,2017,21(6):952-956.
[26]陈贵征,孙玥,刘显,等.负载BMP-2的形状记忆支架修复兔下颌骨缺损的研究[J].口腔颌面外科杂志,2017,27(1):19-24.
[27]Bucci T,Nocini PF.Functional Reconstruction of Nonsegmental Mandibular Defect With Fresh Frozen Bone Graft and Delayed Implants Placement.J Craniofac Surg.2017;28(3):810.
[28]Cruz-Neves S,Ribeiro N,Gra?a I,et al.Behavior of prostate cancer cells in a nanohydroxyapatite/collagen bone scaffold.JBiomed Mater Res A.2017;105(7):2035-2046.
[29]郭佳丽,韩颖超,徐磊,等.纳米羟基磷灰石复合材料作为污水处理吸附剂的研究进展[J].硅酸盐通报,2016,35(8):2466-2475.
[30]Meimandiparizi A,Oryan A,Gholipour H.Healing potential of nanohydroxyapatite,gelatin and fibrin-platelet glue combination as tissue engineered scaffolds in radial bone defects of rats.Connect Tissue Res.2017;(2):1.
[31]罗有福,高金鉴,高浩然,等.负载重组人骨形态发生蛋白2的α型半水硫酸钙/纳米羟基磷灰石复合植骨材料的成骨性能研究[J].中国脊柱脊髓杂志,2016,26(4):348-353.
[32]吕春堂,张庆福.计算机辅助设计和3D打印技术与下颌骨缺损的个体化重建[J].口腔颌面外科杂志,2017,27(1):1-7.
[33]Salgado CL,Grenho L,Fernandes MH,et al.Biodegradation,biocompatibility,and osteoconduction evaluation of collagen-nanohydroxyapatite cryogels for bone tissue regeneration.J Biomed Mater Res A.2016;104(1):55-68.
[34]王彦夫,王程越,王绍刚,等.两种配比纳米羟基磷灰石复合胶原材料对犬拔牙窝骨缺损修复效果的比较[J].中华口腔医学杂志,2016,51(2):98-103.
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