AZ31B生物可降解镁合金植入兔下颌骨生物学行为的实验研究
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摘要
目前,临床上应用于颌面部骨折复位、正颌手术及骨移植手术后固定的材料主要有不锈钢、钛合金和可吸收高分子材料等。由于不锈钢、钛合金弹性模量与骨皮质问的巨大差异,将使两者间存在应力遮挡作用。而且,不锈钢、钛合金作为一种异物,最好术后二期取出。聚乳酸(PLA)、聚乙醇酸(PGA)等可吸收高分子材料也己用于临床,但仍存在不足:亲水性差;细胞吸附力较弱;可引起无菌性炎症;机械强度不够;可引起周围组织的纤维化及免疫反应等。近年来,镁及镁合金作为一种金属基生物材料引起了越来越多学者的关注。镁的化学性质十分活泼,在动物体内可以在短时间内降解。镁与其他常用的金属类植入物相比,更接近天然骨皮质的弹性模量和机械强度,这样的物理特性使镁及其合金在作为内固定材料修复骨折过程中能够最大程度地避免植入材料的应力遮挡作用。当前,研究镁合金的耐腐蚀性及生物相容性的实验方法有很多,主要分为体外实验和体内实验两大类。体外实验可以直观地时时观测合金的腐蚀情况,体内实验则可以在观察镁合金降解过程的同时,观察研究实验动物机体对镁合金降解过程的生物学反应,以此分析镁合金的生物安全性和生物相容性。为了评估将镁合金应用于临床修复颌面部骨损伤的可行性,本文设计将不同形态(条型骨折内固定板和片状多孔板)的AZ31B镁合金内固定系统植入兔下颌骨,并以钛合金内固定系统作对照,通过实验动物血液、尿液生化分析,局部组织及植入物宏观观察、扫描电镜观察、能谱分析、新生骨组织切片、免疫组织化学、RT-PCR等实验手段,研究分析了AZ31B镁合金植入动物下颌骨后的降解行为、镁合金对实验动物的全身影响、及其对颌骨局部的骨诱导作用。具体实验内容分为如下三部分:
实验一:AZ31B镁合金植入兔下颌骨表面的体内降解情况及镁合金体内降解过程对实验动物的生物学影响研究
目的
探讨实验动物全身及下颌骨局部对镁合金降解过程的生物学反应及镁合金在该位置的降解特性。
方法
在实验动物(兔)单侧下颌骨表面分别植入不同型态的镁合金内固定系统(A、B),并用钛合金内固定系统作为对照组(C)。将各组动物平均分成1、2两组,两组的实验操作时间点分别为2周和8周。A1组动物术后2周处死,取下颌骨植入物周围纤维结缔组织,取心脏、肝脏、肾脏、脾脏等组织。将各组织标本制作成病理切片,通过HE染色观察组织形貌。A2组动物术后从第1周开始,至第8周,每周采血、尿样本,生化检测其中镁离子的浓度。术后8周处死,取下颌骨植入物周围骨组织。将标本脱钙后常规石蜡包埋,HE染色,观察新骨生成情况。取心脏、肝脏、肾脏、脾脏等组织,制作病理切片,HE染色观察组织形貌。B型、C型两组实验动物的实验方法同A组。将A、B两组动物局部取出的镁合金内固定系统迅速用酒精冲洗表面,去除血迹及多余动物组织,密闭保存。扫描电子显微镜观察表面降解产物形态结构,利用EDS(能谱分析)功能及相关软件分析表面降解产物构成成分。
结果
术后2周,植入的镁合金内固定系统被一层纤维结缔组织包裹,镜下可见大量纤维成分间分布着骨小梁和毛细血管,局部有明显的钙盐沉积特征,少量成骨细胞散在分布,组织边缘有部分单核细胞及嗜酸性粒细胞浸润。钛合金植入物周围仍包裹一层纤维结缔组织,镜下观察可见大量成纤维细胞平行排列,未见明显的骨小梁、新生毛细血管及钙盐沉积特征。术后8周,植入的镁合金内固定系统边缘处被新生骨组织充填,质地坚硬,与镁合金板结合紧密,镁合金板中未进行螺钉固定的两个孔相对应的位置处,亦有骨组织长入。镜下观察,可见新生骨组织已分化成表层平行排列的骨板和内部的骨松质。钛合金植入物周围仍为纤维结缔组织。各镁合金组实验动物的内脏组织病理切片观察均未见明显异常。实验动物各时间点血中镁离子浓度在0.79～1.05mmol/L小范围内波动(正常值为0.82～2.22mmol/L)。与钛合金相比,镁合金植入后,动物尿中的镁离子浓度升高,且波动较大。在植入手术后的2周及8周取出A型和B型两组镁合金内固定系统,肉眼观察可见镁合金表面失去原有金属光泽,边缘不清晰,干燥后表面出现白色疏松物质。扫描电镜显示,镁合金表面上覆盖一层降解产物,降解产物表面粗糙、强度低,并呈现为不规则的龟裂状。能谱分析表明,这层物质的主要成分为Ca、Mg、P、Al、zn、Mn等。
结论
AZ31B镁合金具有引导动物机体新骨生成的作用。镁合金的植入并未对动物机体的循环、免疫、泌尿系统产生负面影响。镁合金降解产物可经动物的肾脏代谢,而血液中的镁离子含量相对稳定。
目的
观察镁合金在修复兔下颌骨不同类型骨损伤时的降解行为及周围组织的生物学反应。
方法
在实验动物(兔)单侧下颌骨表面分别植入镁合金条型骨折固定系统和片状多孔板内固定系统,分别修复10 mmx2 mm条索状骨缺损及底边15 mm、高15 mm的单层骨皮质缺损模型,并用钛合金作为对照组。实验观察时间点分别为镁合金内固定系统植入后3个月和6个月,植入物周围下颌骨经4%多聚甲醛固定,采用EDTA脱钙制作病理切片。通过HE染色观察新生纤维结缔组织形态和组成成分,分析新骨生成情况。通过免疫组织化学染色病理切片,观察局部骨形态发生蛋白BMP-2表达位置及水平。取植入物与骨组织间的纤维结缔组织,应用RT-PCR技术,分析各组中BMP-2的mRNA表达水平。将已去除软组织的下颌骨用戊二醛固定,利用扫描电镜观察骨表面的新骨生成与溶骨现象。取出的镁合金内固定系统干燥保存,利用扫描电镜观察镁合金表面的降解情况,并采用能谱分析研究降解产物的组成。
植入镁合金条型骨折固定系统3个月后,镁合金的50%左右由新生骨组织所覆盖,条索状骨缺损已经完全愈合。6个月后,镁合金大部分已被新生骨组织覆盖,只可见一颗螺钉头部露出。镁合金与新生骨组织间存在一层纤维结缔组织膜,靠近新生骨组织一侧可见丰富的毛细血管和新生成的骨岛;靠近镁合金一侧可见部分炎性细胞浸润。对照组钛合金周围仅为一薄层新生骨组织覆盖,原有骨缺损也已愈合。钛合金周围的纤维结缔组织膜的厚度不及镁合金组,膜内毛细血管及骨岛少见,新生骨组织形态成熟。植入镁合金片状多孔板3个月后,镁合金被一完整纤维结缔组织囊包裹,可清晰见到囊内有多个氢气气泡存在,植入物下方大面积骨缺损部分修复。钛合金片状多孔板内固定系统未见纤维囊中有任何气泡,植入物下方大面积骨缺损部分修复。6个月后,镁合金下方呈现出不规则的成骨区和溶骨区。不同内固定系统植入3个月后,在各组新生骨组织中均可见细胞浆被染成棕黄色的成骨细胞贴附于新生骨组织表面。其中以镁合金多孔板组染色最为明显,并可见多个核的破骨细胞散于新骨表面。植入6个月后,各组新生骨组织表面BMP-2的表达量均较3个月时的要高。而钛合金植入并未使植入物周围的BMP-2表达量有所不同,两个时间点间表达差异不大。SEM结果显示,镁合金表面覆盖一层降解产物,降解产物表面粗糙、疏松,并呈现出不规则的龟裂状,靠近边缘处有层状崩解的痕迹。在多孔板中央位置,镁合金的局部降解严重,层状崩解现象更为严重。能谱分析结果表明该层物质的主要成分有Ca,Mg,P,Al,C和O等元素。肉眼观发现溶骨区域的下颌骨表面,局部骨组织呈现出不规则的骨吸收形貌,多处可见直径在100μm左右的骨陷窝。在未成骨区与溶骨区的交替处,可见毛细血管与骨陷窝同时存在。
结论
小体积的镁合金在修复小范围骨缺损时表现出良好的骨诱导作用:而与机体接触面积大、修复大范围骨缺损的镁合金植入物,则会引起局部的溶骨反应。镁合金在降解过程中释放的镁离子及其周围形成的碱性环境,可以引起镁合金周围组织中骨形态发生蛋白(BMP-2)的增加,进而引起局部的新骨生成;过量的镁离子浓度及过高的pH值将会引起过量的BMP-2分泌,激活破骨细胞,导致溶骨现象。
目的
观察采用低温化学沉积方法在预处理后镁合金表面制备出B-TCP(B-磷酸三钙)涂层的AZ31B镁合金对兔下颌骨局部成骨的短期影响,从而分析带有B-TCP涂层的AZ31B镁合金体内降解特性及其降解过程对实验动物的影响。
方法
在实验动物(兔)单侧下颌骨植入带有B-TCP涂层的条型镁合金内固定系统,并以未处理镁合金及钛合金内固定系统作为对照组。术后4周观察植入物周围软组织、硬组织改变情况,脱钙骨组织切片的组织学观察,对取出的镁合金植入物应用扫描电子显微镜观察其表面降解产物形态结构,利用EDS、XRD功能及相关软件分析表面降解产物构成成分。
术后4周,带有B-TCP涂层的条型镁合金表面粗糙,失去原有B-TCP涂层的灰黑色外观,植入物下方靠近下颌骨表面处未见明显的新生骨组织。镜下可见少量的新生骨组织,新生骨岛细小,表面有部分成骨细胞单层分布,新生骨组织间可见毛细血管及少量纤维结缔组织分布。钛合金植入物周围同样没有出现明显的新生骨组织。没有B-TCP涂层的条型镁合金内固定夹板周围出现了相对丰富的新生骨组织。镜下可见丰富的新生骨组织,新生骨岛彼此连接,局部骨组织成熟。AZ31B镁合金表面制备B-TCP涂层后,经扫描电子显微镜观察可见,镁合金表面被一层粗糙的不规则结构所覆盖,表层为散在分布的直径在30～50μm颗粒状物质,深层则为一层致密的筛孔样结构。经过4周的体内植入后,B-TCP涂层的条型镁合金内固定夹板表面覆盖一层降解产物,表面呈现出不规则的龟裂状,龟裂间连通性差,整体未见明显的层状崩解现象。没有B-TCP涂层的条型镁合金内固定夹板表面的降解产物可见更明显的不规则的龟裂,镁合金表面呈现层状腐蚀现象。对镁合金取出物表面进行EDS分析,结果可见,两组镁合金表面的降解产物中均含有Ca,Mg,P,Al,C和O等元素,进一步进行XRD分析发现,经过体内4周的降解过程,带有B-TCP涂层的镁合金表面仍残留有部分B-TCP成分,而B组镁合金表面则没有类似产物出现。
结论
B-TCP涂层作为一种生物可降解陶瓷材料,能够通过化学方法与AZ31B镁合金表面结合,在体内植入实验早期,B-TCP涂层可以作为一种屏障结构,起到控制镁合金早期降解速率的作用。
At present,the stainless steel,titanium and absorbable polymeric materials are widely used in clinical application of maxillofacial fracture,orthognathic surgery and bone graft surgery.A limitation of these current materials is the possible release of toxic metallic ions and/or particles through corrosion or wear processes that lead to inflammatory cascades which reduce biocompatibility and cause tissue loss.Moreover, the elastic moduli of the stainless steel and titanium are not well matched with that of natural bone tissue,resulting in stress shielding effects.Current metallic materials are essentially neutral in vivo,remaining as permanent fixtures,which in the case of plates, screws and pins used to secure serious fractures,must be removed by a second surgical procedure after the tissue has healed sufficiently.Polylactic acid(PLA),polyglycolic acid(PGA) and other absorbable polymer materials have also been used in clinic,but there are still inadequate:poor hydrophilicity;cells weak absorption;causation of aseptic inflammation;poor mechanical strength.As a degradable biomaterial for osteosynthesis,magnesium alloys provide potential advantages for patients with bone fractures or defects due to a good biocompatibility and a high primary stability.The elastic modulus and compressive yield strength of magnesium are closer to those of natural bone than is the case for other commonly used metallic implants.There are lots of experimental methods in the study of corrosion resistance of magnesium alloy and biocompatibility,which can be broadly divided into in vitro and in vivo studies.The corrosion of the magnesium alloy can be observed from time to time directly in vitro studies.As a means of analysis of the bio-safety and biocompatibility of the magnesium alloy,the biological response can be observed at the degradation process of magnesium alloy with the in vivo studies.In order to evaluate the feasibility of the clinical application of magnesium alloy in maxillofacial bone injury reparation,AZ31B
magnesium alloy samples with two dimensions(stabilization splint and dictyo-plate) were implanted on the submaxilla surface of New-Zealand rabbits,with comparison of Ti-6A1-4V titanium alloy as a control.Biochemical analysis of the experimental animals blood and urine,tissue and implant macro-observation,scanning electron microscope,energy spectrum analysis,immunohistochemistry,RT-PCR and other experimental means were used to investigate the biodegradation mechanism of AZ31B magnesium alloy and the response of the submaxilla.There are three parts in this study:
To study the biological response of the experimental animals mandibular and body to the degradation process of magnesium alloy and the degradation characteristics of the magnesium alloy at the location.
AZ31B magnesium alloy samples with two dimensions(group A and B) were implanted on the submaxilla surface of New-Zealand rabbits,with comparison of Ti-6A1-4V titanium alloy as a control(group C).The animals in each of the groups are divided into two groups equally,the experimental operation time points are two weeks and eight weeks.The animals in group Al were sacrificed after two weeks,the soft tissue around the implants,heart,liver,kidney and spleen were made into sections for histomorphology analysis.The sample of the blood and urine were collected on each week from the implantation to the eight weeks.The concentration of magnesium ions of every sample was biochemical detected.After eight weeks,the bone tissue around the implants,heart,liver,kidney and spleen were made into sections for histomorphology analysis.The methods of group B and C are the same to group A. After douching with alcohol to remove excess blood and animal tissue,confined preservation,the magnesium alloy implants in group A and B were observed by SEM and analyzed by EDS.
After two weeks of implantation,magnesium alloy implant fixation system was wrapped with a layer of fibrous connective tissue.Micrangium and bone trabecula were found in the fiber composition by optical microscope.Calcium salt deposition, mononuclear cells,eosinophile granulocyte and a small amount of osteoblasts distribution were also observed.There is a layer of fibrous connective tissue around the titanium implants.A large number of fibroblasts can be observed without obvious bone trabecula,new capillaries or calcium salt deposition.After eight weeks of implantation, newly formed hard tissue was observed both on the edge and in the hole of magnesium alloy implants,with the combination of magnesium alloy plate closely.The new bone tissue had differentiated maturity,with the surface of the bone plate and cancellous bone inside.There was still connective tissue fibers around the titanium implants.No obvious abnormalities were observed in histopathological sections of the internal organs of animals in group A and B.The concentration of magnesium an blood on different time points in group A is undulate in a small range(0.79-1.05mmol/L). Compared with the group C,the concentration of magnesium ions in urine was increased and fluctuated intensity after the implantation of magnesium alloy.After two and eight weeks of implantation,the magnesium alloy implants in group A and B has lost metallic luster and clear edge.White loose material can be observed on the surface after exsiccation.The product of the degradation on the surface of magnesium alloy implants is rough and curmbly,and shows irregular-shaped cracks.The main component of the material layer is Ca,Mg,P,Al,Zn,Mn and so on.
AZ31B magnesium alloy implant can be beneficial to the new bone formation. The implantation of the magnesium alloy did not show negative influence on the recirculating,immune and urinary systems of the rabbits.Magnesium ions concentration in the blood was in the range of normal values.
To investigate the biodegradation mechanism of AZ31B magnesium alloy and the response of the surrounding bone as it was used in repairing different types of bone injury in rabbit mandibular.
AZ31B alloy samples with two dimensions(stabilization splint and dictyo-plate) were implanted on the submaxilla surface of New-Zealand rabbits,with comparison of Ti-6A1-4V titanium alloy as a control.Two kinds of bone coloboma were made on the submaxilla surface in order to model the different areas of bone defect.After three and six months,newly formed bone tissues around the implants were made into sections for histomorphology analysis.The BMP-2 was detected by SABC immunohistochemistry. SEM and EDS analysis were used to investigate the layer of degradation product.
After the implantation,all the implants were covered by a fibrous capsule. Hydrogen bubbles appeared frequently in the fibrous capsule of dictyo-plate implants. On the country,hydrogen bubble was not found around stabilization splint implants at all.After three months,over 50%of the stabilization splint body was embedded by the newly formed bone.After six months,only one head of a screw could be seen.The small bone defect(10mmx2mm) under the stabilization splint implant healed very well. While the big bone defect(15mmxl5mm) model showed another scene after 24 weeks, both newly formed bone and osteolysis were found under the dictyo-plate implants. Histomorphology analysis and immunohistochemistry showed higher expression of BMP-2 in newly formed bone,which displayed the osteoblast activity.The degradation product was the magnesium calcium phosphates.
Magnesium alloy implants with small outsize in repairing of small bone defects demonstrated good bone induction,while the bigger implant surface area contacted with body fluid produced more magnesium ion that will lead local osteolytic reaction. Magnesium ions from biodegradation of magnesium alloy and the alkaline environment cause bone morphogenetic protein(BMP-2) increase,thus causing a partial new bone formation.Excessive amount of magnesium ions concentration and the too high pH value will cause excessive levels of BMP-2 secretion,which will activate osteoclasts, resulting in osteolytic situation.
To investigate the effects of AZ31B magnesium alloy with B-TCP coating on rabbit mandibular ossify.To explore the biodegradation mechanism of AZ31B magnesium alloy with 8-TCP coating and the response of the surrounding bone.
AZ31B magnesium alloy implants with and without B-TCP coating(group A and B ) were implanted on the submaxilla surface of New-Zealand rabbits,with comparison of Ti-6A1-4V titanium alloy as a control(group C ).Four weeks after the implantation, the soft tissue and the bone around the implants were made into sections for histomorphology analysis.After douching with alcohol to remove excess blood and animal tissue,confined preservation,the magnesium alloy implants in group A and B were observed by SEM and analyzed by EDS.
After four weeks of implantation,magnesium alloy implants with B-TCP coating (group A) were wrapped with a layer of fibrous connective tissue.There were not much newly formed bone around the implants.Only a small amount of new bone tissue and island of new bone with single-layer distribution of osteoblasts can be observed in sections.Few new bone tissue was found around titanium implants.In group C,newly formed hard tissue was observed around the magnesium alloy without B-TCP coating. The new bone tissue had differentiated maturity,and the new bone islands connected to each other.After four weeks of implantation,the product of the degradation on the surface of magnesium alloy with B-TCP coating implants shows irregular-shaped cracks.Bad connectivity between cracks and no obvious layered collapse were observed.More obvious layered collapse and irregular-shaped cracks were found on the surface of the magnesium alloy without B-TCP coating.The main component of the material layer is Ca,Mg,P,A1,Zn,C,0 and so on.Some residual B-TCP composition is still on the surface of magnesium alloy after four weeks of degradation in vivo (group A).
B-TCP coating,as a biodegradable ceramic materials,can be coated on the surface of AZ31B magnesium alloy by chemical methods.In the early stage of in vivo implantation,B-TCP can be used as a barrier structure to control the biodegradation rate of AZ31B magnesium alloy.
实验一:AZ31B镁合金植入兔下颌骨表面的体内降解情况及镁合金体内降解过程对实验动物的生物学影响研究
目的
探讨实验动物全身及下颌骨局部对镁合金降解过程的生物学反应及镁合金在该位置的降解特性。
方法
在实验动物(兔)单侧下颌骨表面分别植入不同型态的镁合金内固定系统(A、B),并用钛合金内固定系统作为对照组(C)。将各组动物平均分成1、2两组,两组的实验操作时间点分别为2周和8周。A1组动物术后2周处死,取下颌骨植入物周围纤维结缔组织,取心脏、肝脏、肾脏、脾脏等组织。将各组织标本制作成病理切片,通过HE染色观察组织形貌。A2组动物术后从第1周开始,至第8周,每周采血、尿样本,生化检测其中镁离子的浓度。术后8周处死,取下颌骨植入物周围骨组织。将标本脱钙后常规石蜡包埋,HE染色,观察新骨生成情况。取心脏、肝脏、肾脏、脾脏等组织,制作病理切片,HE染色观察组织形貌。B型、C型两组实验动物的实验方法同A组。将A、B两组动物局部取出的镁合金内固定系统迅速用酒精冲洗表面,去除血迹及多余动物组织,密闭保存。扫描电子显微镜观察表面降解产物形态结构,利用EDS(能谱分析)功能及相关软件分析表面降解产物构成成分。
结果
术后2周,植入的镁合金内固定系统被一层纤维结缔组织包裹,镜下可见大量纤维成分间分布着骨小梁和毛细血管,局部有明显的钙盐沉积特征,少量成骨细胞散在分布,组织边缘有部分单核细胞及嗜酸性粒细胞浸润。钛合金植入物周围仍包裹一层纤维结缔组织,镜下观察可见大量成纤维细胞平行排列,未见明显的骨小梁、新生毛细血管及钙盐沉积特征。术后8周,植入的镁合金内固定系统边缘处被新生骨组织充填,质地坚硬,与镁合金板结合紧密,镁合金板中未进行螺钉固定的两个孔相对应的位置处,亦有骨组织长入。镜下观察,可见新生骨组织已分化成表层平行排列的骨板和内部的骨松质。钛合金植入物周围仍为纤维结缔组织。各镁合金组实验动物的内脏组织病理切片观察均未见明显异常。实验动物各时间点血中镁离子浓度在0.79～1.05mmol/L小范围内波动(正常值为0.82～2.22mmol/L)。与钛合金相比,镁合金植入后,动物尿中的镁离子浓度升高,且波动较大。在植入手术后的2周及8周取出A型和B型两组镁合金内固定系统,肉眼观察可见镁合金表面失去原有金属光泽,边缘不清晰,干燥后表面出现白色疏松物质。扫描电镜显示,镁合金表面上覆盖一层降解产物,降解产物表面粗糙、强度低,并呈现为不规则的龟裂状。能谱分析表明,这层物质的主要成分为Ca、Mg、P、Al、zn、Mn等。
结论
AZ31B镁合金具有引导动物机体新骨生成的作用。镁合金的植入并未对动物机体的循环、免疫、泌尿系统产生负面影响。镁合金降解产物可经动物的肾脏代谢,而血液中的镁离子含量相对稳定。
目的
观察镁合金在修复兔下颌骨不同类型骨损伤时的降解行为及周围组织的生物学反应。
方法
在实验动物(兔)单侧下颌骨表面分别植入镁合金条型骨折固定系统和片状多孔板内固定系统,分别修复10 mmx2 mm条索状骨缺损及底边15 mm、高15 mm的单层骨皮质缺损模型,并用钛合金作为对照组。实验观察时间点分别为镁合金内固定系统植入后3个月和6个月,植入物周围下颌骨经4%多聚甲醛固定,采用EDTA脱钙制作病理切片。通过HE染色观察新生纤维结缔组织形态和组成成分,分析新骨生成情况。通过免疫组织化学染色病理切片,观察局部骨形态发生蛋白BMP-2表达位置及水平。取植入物与骨组织间的纤维结缔组织,应用RT-PCR技术,分析各组中BMP-2的mRNA表达水平。将已去除软组织的下颌骨用戊二醛固定,利用扫描电镜观察骨表面的新骨生成与溶骨现象。取出的镁合金内固定系统干燥保存,利用扫描电镜观察镁合金表面的降解情况,并采用能谱分析研究降解产物的组成。
植入镁合金条型骨折固定系统3个月后,镁合金的50%左右由新生骨组织所覆盖,条索状骨缺损已经完全愈合。6个月后,镁合金大部分已被新生骨组织覆盖,只可见一颗螺钉头部露出。镁合金与新生骨组织间存在一层纤维结缔组织膜,靠近新生骨组织一侧可见丰富的毛细血管和新生成的骨岛;靠近镁合金一侧可见部分炎性细胞浸润。对照组钛合金周围仅为一薄层新生骨组织覆盖,原有骨缺损也已愈合。钛合金周围的纤维结缔组织膜的厚度不及镁合金组,膜内毛细血管及骨岛少见,新生骨组织形态成熟。植入镁合金片状多孔板3个月后,镁合金被一完整纤维结缔组织囊包裹,可清晰见到囊内有多个氢气气泡存在,植入物下方大面积骨缺损部分修复。钛合金片状多孔板内固定系统未见纤维囊中有任何气泡,植入物下方大面积骨缺损部分修复。6个月后,镁合金下方呈现出不规则的成骨区和溶骨区。不同内固定系统植入3个月后,在各组新生骨组织中均可见细胞浆被染成棕黄色的成骨细胞贴附于新生骨组织表面。其中以镁合金多孔板组染色最为明显,并可见多个核的破骨细胞散于新骨表面。植入6个月后,各组新生骨组织表面BMP-2的表达量均较3个月时的要高。而钛合金植入并未使植入物周围的BMP-2表达量有所不同,两个时间点间表达差异不大。SEM结果显示,镁合金表面覆盖一层降解产物,降解产物表面粗糙、疏松,并呈现出不规则的龟裂状,靠近边缘处有层状崩解的痕迹。在多孔板中央位置,镁合金的局部降解严重,层状崩解现象更为严重。能谱分析结果表明该层物质的主要成分有Ca,Mg,P,Al,C和O等元素。肉眼观发现溶骨区域的下颌骨表面,局部骨组织呈现出不规则的骨吸收形貌,多处可见直径在100μm左右的骨陷窝。在未成骨区与溶骨区的交替处,可见毛细血管与骨陷窝同时存在。
结论
小体积的镁合金在修复小范围骨缺损时表现出良好的骨诱导作用:而与机体接触面积大、修复大范围骨缺损的镁合金植入物,则会引起局部的溶骨反应。镁合金在降解过程中释放的镁离子及其周围形成的碱性环境,可以引起镁合金周围组织中骨形态发生蛋白(BMP-2)的增加,进而引起局部的新骨生成;过量的镁离子浓度及过高的pH值将会引起过量的BMP-2分泌,激活破骨细胞,导致溶骨现象。
目的
观察采用低温化学沉积方法在预处理后镁合金表面制备出B-TCP(B-磷酸三钙)涂层的AZ31B镁合金对兔下颌骨局部成骨的短期影响,从而分析带有B-TCP涂层的AZ31B镁合金体内降解特性及其降解过程对实验动物的影响。
方法
在实验动物(兔)单侧下颌骨植入带有B-TCP涂层的条型镁合金内固定系统,并以未处理镁合金及钛合金内固定系统作为对照组。术后4周观察植入物周围软组织、硬组织改变情况,脱钙骨组织切片的组织学观察,对取出的镁合金植入物应用扫描电子显微镜观察其表面降解产物形态结构,利用EDS、XRD功能及相关软件分析表面降解产物构成成分。
术后4周,带有B-TCP涂层的条型镁合金表面粗糙,失去原有B-TCP涂层的灰黑色外观,植入物下方靠近下颌骨表面处未见明显的新生骨组织。镜下可见少量的新生骨组织,新生骨岛细小,表面有部分成骨细胞单层分布,新生骨组织间可见毛细血管及少量纤维结缔组织分布。钛合金植入物周围同样没有出现明显的新生骨组织。没有B-TCP涂层的条型镁合金内固定夹板周围出现了相对丰富的新生骨组织。镜下可见丰富的新生骨组织,新生骨岛彼此连接,局部骨组织成熟。AZ31B镁合金表面制备B-TCP涂层后,经扫描电子显微镜观察可见,镁合金表面被一层粗糙的不规则结构所覆盖,表层为散在分布的直径在30～50μm颗粒状物质,深层则为一层致密的筛孔样结构。经过4周的体内植入后,B-TCP涂层的条型镁合金内固定夹板表面覆盖一层降解产物,表面呈现出不规则的龟裂状,龟裂间连通性差,整体未见明显的层状崩解现象。没有B-TCP涂层的条型镁合金内固定夹板表面的降解产物可见更明显的不规则的龟裂,镁合金表面呈现层状腐蚀现象。对镁合金取出物表面进行EDS分析,结果可见,两组镁合金表面的降解产物中均含有Ca,Mg,P,Al,C和O等元素,进一步进行XRD分析发现,经过体内4周的降解过程,带有B-TCP涂层的镁合金表面仍残留有部分B-TCP成分,而B组镁合金表面则没有类似产物出现。
结论
B-TCP涂层作为一种生物可降解陶瓷材料,能够通过化学方法与AZ31B镁合金表面结合,在体内植入实验早期,B-TCP涂层可以作为一种屏障结构,起到控制镁合金早期降解速率的作用。
At present,the stainless steel,titanium and absorbable polymeric materials are widely used in clinical application of maxillofacial fracture,orthognathic surgery and bone graft surgery.A limitation of these current materials is the possible release of toxic metallic ions and/or particles through corrosion or wear processes that lead to inflammatory cascades which reduce biocompatibility and cause tissue loss.Moreover, the elastic moduli of the stainless steel and titanium are not well matched with that of natural bone tissue,resulting in stress shielding effects.Current metallic materials are essentially neutral in vivo,remaining as permanent fixtures,which in the case of plates, screws and pins used to secure serious fractures,must be removed by a second surgical procedure after the tissue has healed sufficiently.Polylactic acid(PLA),polyglycolic acid(PGA) and other absorbable polymer materials have also been used in clinic,but there are still inadequate:poor hydrophilicity;cells weak absorption;causation of aseptic inflammation;poor mechanical strength.As a degradable biomaterial for osteosynthesis,magnesium alloys provide potential advantages for patients with bone fractures or defects due to a good biocompatibility and a high primary stability.The elastic modulus and compressive yield strength of magnesium are closer to those of natural bone than is the case for other commonly used metallic implants.There are lots of experimental methods in the study of corrosion resistance of magnesium alloy and biocompatibility,which can be broadly divided into in vitro and in vivo studies.The corrosion of the magnesium alloy can be observed from time to time directly in vitro studies.As a means of analysis of the bio-safety and biocompatibility of the magnesium alloy,the biological response can be observed at the degradation process of magnesium alloy with the in vivo studies.In order to evaluate the feasibility of the clinical application of magnesium alloy in maxillofacial bone injury reparation,AZ31B
magnesium alloy samples with two dimensions(stabilization splint and dictyo-plate) were implanted on the submaxilla surface of New-Zealand rabbits,with comparison of Ti-6A1-4V titanium alloy as a control.Biochemical analysis of the experimental animals blood and urine,tissue and implant macro-observation,scanning electron microscope,energy spectrum analysis,immunohistochemistry,RT-PCR and other experimental means were used to investigate the biodegradation mechanism of AZ31B magnesium alloy and the response of the submaxilla.There are three parts in this study:
To study the biological response of the experimental animals mandibular and body to the degradation process of magnesium alloy and the degradation characteristics of the magnesium alloy at the location.
AZ31B magnesium alloy samples with two dimensions(group A and B) were implanted on the submaxilla surface of New-Zealand rabbits,with comparison of Ti-6A1-4V titanium alloy as a control(group C).The animals in each of the groups are divided into two groups equally,the experimental operation time points are two weeks and eight weeks.The animals in group Al were sacrificed after two weeks,the soft tissue around the implants,heart,liver,kidney and spleen were made into sections for histomorphology analysis.The sample of the blood and urine were collected on each week from the implantation to the eight weeks.The concentration of magnesium ions of every sample was biochemical detected.After eight weeks,the bone tissue around the implants,heart,liver,kidney and spleen were made into sections for histomorphology analysis.The methods of group B and C are the same to group A. After douching with alcohol to remove excess blood and animal tissue,confined preservation,the magnesium alloy implants in group A and B were observed by SEM and analyzed by EDS.
After two weeks of implantation,magnesium alloy implant fixation system was wrapped with a layer of fibrous connective tissue.Micrangium and bone trabecula were found in the fiber composition by optical microscope.Calcium salt deposition, mononuclear cells,eosinophile granulocyte and a small amount of osteoblasts distribution were also observed.There is a layer of fibrous connective tissue around the titanium implants.A large number of fibroblasts can be observed without obvious bone trabecula,new capillaries or calcium salt deposition.After eight weeks of implantation, newly formed hard tissue was observed both on the edge and in the hole of magnesium alloy implants,with the combination of magnesium alloy plate closely.The new bone tissue had differentiated maturity,with the surface of the bone plate and cancellous bone inside.There was still connective tissue fibers around the titanium implants.No obvious abnormalities were observed in histopathological sections of the internal organs of animals in group A and B.The concentration of magnesium an blood on different time points in group A is undulate in a small range(0.79-1.05mmol/L). Compared with the group C,the concentration of magnesium ions in urine was increased and fluctuated intensity after the implantation of magnesium alloy.After two and eight weeks of implantation,the magnesium alloy implants in group A and B has lost metallic luster and clear edge.White loose material can be observed on the surface after exsiccation.The product of the degradation on the surface of magnesium alloy implants is rough and curmbly,and shows irregular-shaped cracks.The main component of the material layer is Ca,Mg,P,Al,Zn,Mn and so on.
AZ31B magnesium alloy implant can be beneficial to the new bone formation. The implantation of the magnesium alloy did not show negative influence on the recirculating,immune and urinary systems of the rabbits.Magnesium ions concentration in the blood was in the range of normal values.
To investigate the biodegradation mechanism of AZ31B magnesium alloy and the response of the surrounding bone as it was used in repairing different types of bone injury in rabbit mandibular.
AZ31B alloy samples with two dimensions(stabilization splint and dictyo-plate) were implanted on the submaxilla surface of New-Zealand rabbits,with comparison of Ti-6A1-4V titanium alloy as a control.Two kinds of bone coloboma were made on the submaxilla surface in order to model the different areas of bone defect.After three and six months,newly formed bone tissues around the implants were made into sections for histomorphology analysis.The BMP-2 was detected by SABC immunohistochemistry. SEM and EDS analysis were used to investigate the layer of degradation product.
After the implantation,all the implants were covered by a fibrous capsule. Hydrogen bubbles appeared frequently in the fibrous capsule of dictyo-plate implants. On the country,hydrogen bubble was not found around stabilization splint implants at all.After three months,over 50%of the stabilization splint body was embedded by the newly formed bone.After six months,only one head of a screw could be seen.The small bone defect(10mmx2mm) under the stabilization splint implant healed very well. While the big bone defect(15mmxl5mm) model showed another scene after 24 weeks, both newly formed bone and osteolysis were found under the dictyo-plate implants. Histomorphology analysis and immunohistochemistry showed higher expression of BMP-2 in newly formed bone,which displayed the osteoblast activity.The degradation product was the magnesium calcium phosphates.
Magnesium alloy implants with small outsize in repairing of small bone defects demonstrated good bone induction,while the bigger implant surface area contacted with body fluid produced more magnesium ion that will lead local osteolytic reaction. Magnesium ions from biodegradation of magnesium alloy and the alkaline environment cause bone morphogenetic protein(BMP-2) increase,thus causing a partial new bone formation.Excessive amount of magnesium ions concentration and the too high pH value will cause excessive levels of BMP-2 secretion,which will activate osteoclasts, resulting in osteolytic situation.
To investigate the effects of AZ31B magnesium alloy with B-TCP coating on rabbit mandibular ossify.To explore the biodegradation mechanism of AZ31B magnesium alloy with 8-TCP coating and the response of the surrounding bone.
AZ31B magnesium alloy implants with and without B-TCP coating(group A and B ) were implanted on the submaxilla surface of New-Zealand rabbits,with comparison of Ti-6A1-4V titanium alloy as a control(group C ).Four weeks after the implantation, the soft tissue and the bone around the implants were made into sections for histomorphology analysis.After douching with alcohol to remove excess blood and animal tissue,confined preservation,the magnesium alloy implants in group A and B were observed by SEM and analyzed by EDS.
After four weeks of implantation,magnesium alloy implants with B-TCP coating (group A) were wrapped with a layer of fibrous connective tissue.There were not much newly formed bone around the implants.Only a small amount of new bone tissue and island of new bone with single-layer distribution of osteoblasts can be observed in sections.Few new bone tissue was found around titanium implants.In group C,newly formed hard tissue was observed around the magnesium alloy without B-TCP coating. The new bone tissue had differentiated maturity,and the new bone islands connected to each other.After four weeks of implantation,the product of the degradation on the surface of magnesium alloy with B-TCP coating implants shows irregular-shaped cracks.Bad connectivity between cracks and no obvious layered collapse were observed.More obvious layered collapse and irregular-shaped cracks were found on the surface of the magnesium alloy without B-TCP coating.The main component of the material layer is Ca,Mg,P,A1,Zn,C,0 and so on.Some residual B-TCP composition is still on the surface of magnesium alloy after four weeks of degradation in vivo (group A).
B-TCP coating,as a biodegradable ceramic materials,can be coated on the surface of AZ31B magnesium alloy by chemical methods.In the early stage of in vivo implantation,B-TCP can be used as a barrier structure to control the biodegradation rate of AZ31B magnesium alloy.
引文
1 Thamaraiselvi TV,Rajeswari S.Biological evaluation of bioceramic materials-a review. Trends Biomater Artif讧Organs 2004;19:9-17.
2 张益.下颌骨骨折治疗[M].北京:北京医科大学中国协和医科大学联合出版社,1993.76-76
3 Kim YK Kim SG.Treatment of mandible fracture using bioabsorbable plates[J].Plast Reconstr Surg,2002,110:25-31.
4 Turvey TA,Bell RB,Tejera TJ,et al.The use of self_reinforced biodegradable bone plates and screws in onhognathic surgery[J].J Oral Maxillofac surg,2002,60:59-65.
5 Yerit KC,Hainich S,Turhani D,et al StabiliIy of biodegradable implants in treatment of mandible fractures[J].P1ast Reconstr surg,2005,115:1863-1870.
6 曾永光,彭勇,魏世成,等.超高分子量聚D,L乳酸小型接骨板在下颌骨骨折治疗中的应 用[J].中国口腔颌面外科杂志,2004,2:137-139.
7 Water,electrolyte mineral and acid/base metabolism.Section 2.Endocrine＆Metabolic Djsorders.Merk Manual of Diagnosis and Therapy[chapter 12].
8 Saris NEL.Magnesiurn:an update on physiological,clinical and anal),tical aspects.Clin Chim Acta 2000:294:1-26.
9 Vormann J.Magnesium:nutrition and metabolism.Mol Aspects Med 2003;24:27-37.
10 Lambotte A.L'utilisation du magnesium comme materiel perdu dansl'osteosynthe(?)se.Bull Me'm Soc Nat Chir 1932;28:1325-34.
11 troitskii W,Tsitrin DN.The resorbing metallic allOy‘Osteosinthezit'as material for fastening broken bone.Khirurgiia 1944;8:41-4.
12 Witte F'Kaese V,Haferkamp H,Switzer E,Meyer-Lindenberg A,Wirth CJ,et al.In ViVo corrosion of four magllesium allOys and the associated bolle response.Biomaterials 2005;26: 3557-63.
13 Revell PA,Danlien E,Zhang XS,Evans P,Howlett CR.The efiect of mangesiam ions on bone bonding to hydroxyapatite.Key Eng Mater 2004;254-256:447-50.
14 Zreiqat H,Howlett CR,Zannettino A,Evans P,Schulze-Tanzl G,Knabe C,et al.Mechanisms of magnesium-stimulated adhesion Of Osteoblastic cells to commonly used Orthopaedic implants.J Biomed Mater Res 2002;62:175-84.
1 Mark P S,Alexis M P,Jerawala H,George D.Magnesium and its alloys as orthopedic biomaterials:a review.Biomaterials.2006;27:1728.
2 Ren Y B,Huang J J,Yang K,Zhang B C,Yao Z M,Wang H.Study of bio-corrosion of pure magnesium.Acta Metallurgica Sinica.2005;41:1228.
3 Wolf FI,Cittadini A.Chemistry and biochemistry of magnesium.Mol.Aspects Med.2003;24:3.
4 Vormann J.Magnesium:nutrition and metabolism.Mol.Aspects Med.2003;24:27.
5 Yamasaki Y,Yoshida Y,Okazaki M,Shimazu A,Kubo T,Akagawa Y,et al.Action of FGMgCO3Ap-collagen composite in promoting bone formation.Biomaterials 2003;24:4913.
6 Jiao S Q,Kuang Y F.Corrosion behavior and anodization of magnesium and its alloys.Electroplating and Pollution Control.2002;22(3):1.
7 Shaw BA.Corrosion resistance of magnesium alloys.In:Stephen D,editor.ASM handbook volume 13 a:corrosion:fundamentals,testing and protection.UK:ASM Int;2003.
8 Li L,Gao J,Wang Y.Surf.Coat.Technol.2004;185:92.
9 Kuwahara H,Al-Abdullat Y,Mazaki N,Tsutsumi S,Aizawa T.Mater.Trans.2001;42(7):1317.
10 Witte F,Kaese V,Haferkamp H,Switzer E,Meyer-Lindenberg A,Wirth CJ,et al.In vivo corrosion of four magnesium alloys and the associated bone response.Biomaterials.2005;26:3557.
11 Vasudev D V,Ricci J L,Sabatino C,Li P,Parsons J R.In vivo evaluation of a biomimetic apatite coating grown on titanium surfaces.J.Biomed Mater Res.2004;69(4):629-36.
12 Schliephake H,Scharnweber D,Dard M,Robler S,Sweing A,Huttman C.Biological performance of biomimetic calcium phosphate coating of titanium implants in the dog mandible.J Biomed Mater Res A.2003;64(2):225-34.
1 Mark P.S,Alexis M.P,Jerawala H,George D.Magnesium and its alloys as orthopedic biomaterials:a review.Biomaterials,2006;27:1728.
2 Erbel R,Di Mario C,Bartunek J,Bonnier J,de Bruyne B,Eberli F R,Erne P,Haude M,Heublein B,Horrigan M,Ilsley C,Bose D,Koolen J,L(?)scher T F,Weissman N,Waksman R.Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents:a prospective,non-randomised multicentre trial.Lancet,2007;369:1869.
3 Witte F,Fischer J,Nellesen J,Crostack HA,Kaese V,Pisch A,Beckmann F,Windhagen H.In vitro and in vivo corrosion measurements of magnesium alloys.Biomaterials,2006;27:1013.
4 Witte F,Ulrich H,Rudert M,Willbold E.Biodegradable magnesium scaffolds:Part Ⅰ:Appropriate inflammatory response.J Biomed Mater Res,2007;81:748.
5 Witte F,Ulrich H,Palm C,Willbold E.Biodegradable magnesium scaffolds:Part Ⅱ:Peri-implant bone remodeling.J Biomed Mater Res,2007;81:757.
6 Vonder H N,Krause A,Hackenbroich C,Bormann D,Lucas A,Meyer-Lindenberg A.Influence of different surface machining treatments of resorbable implants made from different magnesium-calcium alloys on their degradation-a pilot study in rabbit models.Dtsch Tierarztl Wochenschr,2006;1 13:439.
7 Waselau M,Samii VF,Weisbrode SE,Litsky AS,Bertone AL.Effects of a magnesium adhesive cement on bone stability and healing following a metatarsal osteotomy in horses.Am J Vet Res,2007;68(4):370-8.
8 Agrawal C M,Athanasiou K A.Technique to control pH in vicinity of biodegrading PLA-PGA implants.J Biomed Mater Res,1997;38:105.
9 Kuwahara H,Al-Abdullat Y,Mazaki N,Tsutsumi S,Aizawa T.Mate Trans,2001;42:1317.
10 Zhang G D,Huang J J,Yang K,Zhang B C,Ai H J.Experimental Study of in Vivo Implantation of a Magnesium Alloy at Early Stage.Acta Metall Sin,2007;43:1186.
11 Duque G,Rivas D.Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells.J Bone Miner Res.2007;22(10):1603-11.
12 Lobato JV,Rodrigues JM,Cavaleiro MV,Lobato JM,Xavier L,Santos JD,Maur(?)cio AC.Maxilla osseus sequestre and oral exposure:effects of the treatment of multiple myeloma with bisphosphonates.Acta Med Port.2007;20(2):185-92.
13 Mandelin J,Hukkanen M,Li TF,Korhonen M,Liljestr(?)m M,Sillat T,Hanemaaijer R,Salo J,Santavirta S,Konttinen YT.Human osteoblasts produce cathepsin K.Bone.2006;38(6):769-77.
14 Perez-Amodio S,Beertsen W,Everts V.Pre-osteoclasts induce retraction of osteoblasts before their fusion to osteo-clasts.J Bone Miner Res.2004;19(10):1722-31.
1 张绍渤,钱均琪,黄受方.微波技术在病理学中的应用.国外医学生理病理科学与临床分 册,1992,12(1):15-17.
2 Yeril KC,Hainich S,Turhani D,et al.Stability of biodegradable implants in treatment of mandible fractures[J].Plast Reconstr sug,2005,115:1863-1870.
3 曾永光,彭勇,魏世成,等.超高分子量聚D,L乳酸小型接骨板在下颌骨骨折治疗中的 应用[J].中国口腔颌面外科杂志,2004,2:137-139.
4 Water,electrolyte mineral and acid/base metabolism.Section 2.Endocrine ＆ Metabolic Disorders.Merk Manual of Diagnosis and Therapy[Chapter 12].
5 Saris NEL.Magnesium:an update on physiological,clinical and analytical aspects.Clin Chim Acta 2000:294:1-26.
6 Vormann J.Magnesium:nutrition and metabolism.Mol Aspects Med 2003;24:27-37.
7 Lambotte A.L'utilisation du magnesium comme materiel perdu dansl'osteosynth(?)se.Bull Me'm Soc Nat Chir 1932:28:1325-34.
8 Troitskii VV:Tsitrin DN.The resorbing metallic alloy‘Osteosinthezit'as material for fastening broken bone.Khiruriia 1944;8:41-4.
9 Witte F,Kaese V,Haferkamp H,Switzer E,Meyer-Lindenberg A,Winh CJ,et al.In ViVo Corrrsion of four magnesium alloys and the associated bone response.Biomaterials 2005;26: 3557-63.
10 Revell PA,Damien E,Zhang XS,Evans P,Howlett CR.The effect of mangesium ions on bone bonding to hydroxyapatite.Key Eng Mater 2004;254-256:447-50.
11 Zreiqat H,Howlett CR,Zannettino A,Evans P,Schulze-Tanzll G Knabe C,et al.Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants.J Biomed Mater Res 2002;62:175-84.
1 Palmer RH.Biological osteosynthesis.Vet Clin North Am Small Anim Pract.1999;29(5):1171-85.
2 Staiger MP,Pietak AM,Huadmai J,Dias G.Magnesium and its alloys as orthopedic biomaterials:a review.Biomaterials.2006;27(9):1728-34.
3 Alkan A,Metin M,Ozden B,et al.Biomechanical comparison of plating techniques for fractures of the mandibular condyle.Br J Oral Maxillofac Surg.2007;45(2):145-9.
4 Kulkarni R K,Moore E G,Hegyeli A F,et al.Biodegradablepoly(lacti2cacid) polymers.Biomed Mater Res,1971;5:169.
5 Getter L,Cut right D E,Bhaskar S N,et al.A biogradeable intraosseous appliance in the treatment of mandibular fractures.Oral Surg,1972;30:344.
6 Jukkala Partio K,Pohjonen T,Laitinen O,et al.Biodegradation and st rength retention of poly L lactide screws in vivo.An experimental long term study in sheep.Ann Chir Gynaecol,2001;90(3):219.
7 Bostman O M,Paivarinta U,Partio E,et al.The tissueimplant interface during degradation of absorbable polyglycolide fracture fixation screws in the rabbit femur.Clin Orthop,2002;(285):263.
8 Morgan C D,Gehrmann R M,Jayo MJ,et al.Histologic findings with a bioabsorbable anterior cruciate ligament interference screw explant after 2.5 years in vivo.Arthroscopy,2002;18(9):47.
9 Viljanen J,Kinnunen J,Bondestam S,et al.Bone changes after experimental osteotomies fixed with absorbable self-reinforced poly-L-lactide screws or metallic screws studied by plain radiographs,quantitative computed tomography and magnetic resonance imaging.Biomaterials,1995;16(17):1353.
10 Liu J K,Gottfried O N,Cole C D,et al.Porous polyethylene implant for cranioplasty and skull base reconst ruction.Neurosurg Focus,2004;16(3):ECP1.
11 Rokkanen P,Bostman O,Vainionpaa S,et al.Biodegradable internal fixation for malleolar fractures.A prospective randomised trial.Bone Joint Surg,1987;69:615.
12 Kuklo TR,Rosner MK,Polly DW.Computerized tomography evaluation of a resorbable implant after transforaminal lumbar interbody fusion.Neurosurg Focus.2004;16(3):E10.
13 Piltz S,Steinbauer T,Meyer L,et al.Bioabsorbable expansion bolt fixation in anterior cruciate ligament reconst ruction.Clin Orthop,2004;(418):225.
14 Bohnsack M,Borner C,Schmolke S,et al.Clinical results of arthroscopic meniscal repair using biodegradable screws.Knee Surg Sports Traumatol Arthrosc,2003;11(6):379.
15 Vaccaro AR,Carrino JA,Venger BH,et al.Use of a bioabsorbable anterior cervical plate in the treatment of cervical degenerative and traumatic disc disruption.Neurosurg Spine,2002;97(4):473.
16 Bostman OM,Pihlajamaki H K.Adverse tissue reactions to bioabsorbable fixation devices.Clin Orthop,2000;(371):216.
17 Bostman OM.Osteoarthritis of the ankle after foreignbody reaction to absorbable pins and screws:a three to nine year follow up study.Bone Joint Surg,1998;80(2):333.
18 Zreiqat H,Howlett CR,Zannettino A,et al.Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants.J Biomed Mater Res 2002;62:175-84.
19 Malhan K,Kumar A,Rees D.Tibial cyst formation after anterior cruciate ligament reconst ruction using a new bioabsorbable screw.Knee,2002;9(1):73.
20 Shaw BA.Corrosion resistance of magnesium alloys.In:Stephen D,editor.ASM handbook volume 13a:corrosion:fundamentals,testing and protection.UK:ASM Int.2003.
21 Werner A,Wild A,Ilg A,et al.Secondary intra-articular dislocation of a broken bioabsorbable interference screw after anterior cruciate ligament reconst ruction.Knee Surg Sports Traumatol Arthrosc,2002;10(1):30.
22 Staigera MP,Pietaka AM,Huadmaia J,Dias G Magnesium and its alloys as orthopedic biomaterials:a review.Biomaterials,2006;27:1728-34.
23 Song GL,Andrej A.Corrosion mechanisms of magnesium alloys.Adv Eng Mater 1999;1:11-33.
24 Li L,Gao J,Wang Y.Evaluation of cyto-toxicity and corrosion behavior of alkalieheat-treated magnesium in simulated body fluid.Surf Coat Technol,2004;185:92-8.
25 Heublein B,Rohde R,Kaese V,Niemeyer M,Hartung W,Haverich A.Biocorrosion of magnesium alloys:a new principle in cardiovascular implant technology?Heart,2003;89:651-6.
26 Zartner P,Cesnjevar R,Singer H,Weyand M.First successful implantation of a biodegradable metal stent into the left pulmonary artery of a preterm baby.Catheter Cardiovasc Interv,2005;66:590-4.
27 Schranz D,Zartner P,Michel-Behnke I,Akinturk H.Bioabsorbable metal stents for percutaneous treatment of critical recoarctation of the aorta in a new born.Catheter Cardiovasc Interv,2006;67:671-3.
28 Kuwahara H,Al-Abdullat Y,Mazaki N,Tsutsumi S,Aizawa T.Precipitation of magnesium apatite on pure magnesium surface during immersing in Hank's solution.Mater Trans,2001;42:1317-21.
29 Heublein B,Rohde R,Kaese V.Biocorrosion of magnesium alloys:a new principl in cardiovascular implant technology.Heart,2003;89:651.
30 Domer Reisel A,Nishida Y,Klemm V,et al.Investigation of interfacial interaction between uncoated and coated carbon fibres and the magnesium alloy AZ91.Anal Bioanal Chem,2002;374(4):635-8.
31 Knox J,Chye KY,Duming P.An ex vivo evaluation of resin-modified glass polyalkenoates and polyacid-modified composite resins as orthodontic band cements.J Orthod,2004;31(4):323-8.
32 Kannan MB,Raman Rk In vitro degradation and mechanical integrity of calcium-containing magnesium alloys in modified-simulated body fluid.Biomaterials,2008;29(15):2306-14.
33 Katzer A,Buchhom GH,Hockertz S,Loehr JF.In vitro toxicity and mutagenicity of CoCrMo and TiAl wear particles.Orthopade.2003(8):744-50.German
34 F.Witte,J.Reifenrath,P.P.M(u|¨)ller.et al.Cartilage repair on magnesium scaffolds used as a subchondral bone replacement,Mat-wiss.U.Werkstofftech,2006;37(6):504-508.
35 F.Witte,V Kaese,H.Haferkamp,et al.In vivo corrosion of four magnesium alloys and the associated bone response,Biomaterials,2005;26:3557-3563.
36 F.Witte,J.Fischer,J.Nellesen,et al.ln vitro and in vivo corrosion measurements of magnesium alloys,Biomaterials,2006;27:1013-1018
37 Witte F,Ulrich H,Palm C,Willbold E.Biodegradable magnesium scaffolds:Pan II:peri-implant bone remodeling.J Biomed Mater Res A.2007;81(3):757-65
38 Witte F,Ulrich H,Rudert M,Willbold E.Biodegradable magnesium scaffolds:Part 1:appropriate inflammatory response.J Biomed Mater Res A.2007;81(3):748-56.
39 Witte F,Abeln l,Switzer E,et al.Evaluation of the skin sensitizing potential of biodegradable magnesium alloys.J Biomed Mater Res A.2007 Dec
40 Huang Jingjing,Ren Yibin,Jiang Yue,Zhang Bingchun and Yang Ke.In vivo study of degradable magnesium and magnesium alloy as bone implant.Frontiers of Materials Scieence in China.2007;1(4):405-409.
41 张广道,黄晶晶,杨柯,张炳春,艾红军,动物体内植入镁合金的早期实验研究,金属学报,2007;43(11):1186-1190.
42 Liping Xu,Guoning Yu,Erlin Zhang,Ke Yang,In vivo corrosion behavior of Mg-Mn-Zn alloy for bone implant application,J Biomedical Mater Res.Part A,83A(2007),703-711.
43 Sreedhara A,Cowan JA.Structural and catalytic roles for divalent magnesium in
44 Leeuwenburgh S,Layrolle P,Barrere F,et al.Osteoclastic resorption of biomimetic calcium phosphate coatings in vitro.Biomed Mater Res.2001;56(2):208-15.
45 Deutscher RL,Cathro KJ.Organochlorine formation in magnesium electrowinning cells.Chemosphere.2001;43(2):147-55.
46 Guangling Song,Control of biodegradation of biocompatible magnesium aIloys,Corrosion Science.2007:49:1696-1701.
47 J.C.Gao,L.C.Li,Y.Wang,L.Y.Qiao,Biocompatibility of magnesium after surface modification by heat-organic films-treatment,RARE METAL MATERIALS AND ENGINEERING 2005;34(6):903-906.
48 Vasudev DV,Ricci JL,Sabatino C,et al.In vivo evaluation of a biomimetic apatite coating grown on titanium surfaces.J Biomed Mater Res A.2004;69(4):629-36.
49 Schliephake H,Scharnweber D,Dard M,et al.Biological performance of biomimetic calcium phosphate coating of titanium implants in the dog mandible.J Biomed Mater Res A.2003;64(2):225-34.
50 Vonder H N,Krause A,Hackenbroich C,et al.Dtsch Tierarztl Wochenschr,2006;113(12):439.
51 Kinoshita K,Hibi H,Yamada Y,Ueda M.Promoted new bone formation in maxillary distraction osteogenesis using a tissue-engineered osteogenic material.J Craniofac Surg.2008;19(1):80-7.
52 Related Articles,LinksLerouxel E,Weiss P,et al.Injectable calcium phosphate scaffold and bone marrow graft for bone reconstruction in irradiated areas:an experimental study in rats.Biomaterials.2006 Sep;27(26):4566-72.
53 Beebe KS,Sabharwal S,Behrens F.Femoral shaft fractures:is rigid intramedullary nailing safe for adolescents.Am J Orthop.2006;35(4):172-4.
54 Naot D,Grey A,Reid IR,Cornish J.Lactoferrin--a novel bone growth factor.Clin Med Res.2005;3(2):93-101.
55 Related Articles,LinksAndreev K,Zenkel M,et al.Expression of bone morphogenetic proteins(BMPs),their receptors,and activins in normal and scarred conjunctiva:role of BMP-6 and activin-A in conjunctival scarring.Exp Eye Res.2006;83(5):1162-70.
56 Valimaki VV,Aro HT.Molecular basis for action of bioactive glasses as bone graft substitute.Scand J Surg.2006;95(2):95-102.
57 Thamaraiselvi TV,Rajeswari S.Biological evaluation of bioceramic materials-a review.Trends Biomater Artif Organs 2004;19:9-17.
58 Selvamurugan N,Kwok S,Vasilov A,et al.Effects of BMP-2 and pulsed electromagnetic field(PEMF) on rat primary osteoblastic cell proliferation and gene expression.J Orthop Res.2007;25(9):1213-20.
59 Kim YK,Kim SG.Treatment of mandible fracture using bioabsorbable plates.Plast Reconstr Surg,2002;110:25-31.
60 Turvey TA,Bell RB,Tejera TJ,et al.The use of self-reinforced biodegradable bone plates and screws in orthognathic surgery.J Oral Maxillofac Surg,2002;60:59-65.
61 黄琴,梁惠,杜凤沛,镁的生理与临床应用,微量元素与健康研究,2005；22：61．63．
62 Frank Feyerabend,Frank Witte.Michael Kammal and Regine Willumeit,Unphysiologically
High Magnesium Concentrations Support Chondrocyte Proliferation and Redifferentiation.
Tissue Engineering,2006;12(12):3545-3556.
63 高妍婷,尹爱萍,镁的正常代谢及其调节,广东微量元素科学,2004;10:20-23.
64 Guangling Song,Control of biodegradation of biocompatible magnesium alloys,Corrosion Science,2007;49:1696-1701.
65 Mani G,Feldman Marc D,Patel D,Agrawal M.Coronary stents:a materials perspective.Biomaterials 2007:28:1689-1710.
66 J C Gao,L C Li,Y.Wang,L Y,et al.Biocompatibility of magnesium after surface modification by heat-organic films-treatment,RARE METAL MATERIALS AND ENGINEERING,2005;34(6):903-906.
67 L C Li,J C GaO,Y Wang.Evaluation of cyto-toxicily and corrosion behavior of alkali-heat-treated magnesium in simulated body fluid,SURFACE & COATINGS TECHNOLOGY,2004;185(1):92-98.
68 谭丽丽;耿芳,杨柯,张炳春,一种生物医用可降解镁合金的生物活性表面改性方法,申请号:200710159044.9(发明专利).
69 F.Geng,L.L.Tan,B.C.Zhang,Study of Magnesium Tissue Engineering Scaffolds with B-TCP Coatings,The lst intemational symposium on surface and interface of biomaterials,Sichuan,5-7 Oct,2007.
70 Zhang Er-lin,Yang Ke,Biomimetic coating of calcium phosphate on biometallic materials,Trans.Nonferrous Met.Soc.China,2005;15:1199-1250.
71 Serre CM,Papillard M,Chavassieux P,et al.,Influence of magnesium substitutiOil on a collagen-apatite biomaterial on the production of a calcifying matrix by human osteoblasts,JOURNAL OF BIOMEDICAL MATERIALS RESEARCH,1998;42(4):626-633.
72 Ten Huisen KS,Brown PW,Effects of magnesium on the formation of calcium-deficient hydroxyapatite from CaHPO4 center dot 2H(2) O and Ca-4(Po4)(2) O,JOURNAL OF BIOMEDlCAL MATERIALS RESEARCH,1997;36(3):306-314.
73 R.Z.LeGeros,A.M.Gatti,R.kijkowska,D.Q.Mijares,J.P.LeGeros,Mg-substituted Tricalcium Phosphates:Formation and Properties,Key Engineering Materials,Vols.254-256(2004):127-13 1.
74 Y.Z.Wan,Y.Huang,F.He,Y.L.Wang,Z.G.Zhao,H.F.Ding,Effect Of Mg ion implantation on calcium phosphate formation on titanium,Surface and coating technology,2006;201:2904-9.
2 张益.下颌骨骨折治疗[M].北京:北京医科大学中国协和医科大学联合出版社,1993.76-76
3 Kim YK Kim SG.Treatment of mandible fracture using bioabsorbable plates[J].Plast Reconstr Surg,2002,110:25-31.
4 Turvey TA,Bell RB,Tejera TJ,et al.The use of self_reinforced biodegradable bone plates and screws in onhognathic surgery[J].J Oral Maxillofac surg,2002,60:59-65.
5 Yerit KC,Hainich S,Turhani D,et al StabiliIy of biodegradable implants in treatment of mandible fractures[J].P1ast Reconstr surg,2005,115:1863-1870.
6 曾永光,彭勇,魏世成,等.超高分子量聚D,L乳酸小型接骨板在下颌骨骨折治疗中的应 用[J].中国口腔颌面外科杂志,2004,2:137-139.
7 Water,electrolyte mineral and acid/base metabolism.Section 2.Endocrine＆Metabolic Djsorders.Merk Manual of Diagnosis and Therapy[chapter 12].
8 Saris NEL.Magnesiurn:an update on physiological,clinical and anal),tical aspects.Clin Chim Acta 2000:294:1-26.
9 Vormann J.Magnesium:nutrition and metabolism.Mol Aspects Med 2003;24:27-37.
10 Lambotte A.L'utilisation du magnesium comme materiel perdu dansl'osteosynthe(?)se.Bull Me'm Soc Nat Chir 1932;28:1325-34.
11 troitskii W,Tsitrin DN.The resorbing metallic allOy‘Osteosinthezit'as material for fastening broken bone.Khirurgiia 1944;8:41-4.
12 Witte F'Kaese V,Haferkamp H,Switzer E,Meyer-Lindenberg A,Wirth CJ,et al.In ViVo corrosion of four magllesium allOys and the associated bolle response.Biomaterials 2005;26: 3557-63.
13 Revell PA,Danlien E,Zhang XS,Evans P,Howlett CR.The efiect of mangesiam ions on bone bonding to hydroxyapatite.Key Eng Mater 2004;254-256:447-50.
14 Zreiqat H,Howlett CR,Zannettino A,Evans P,Schulze-Tanzl G,Knabe C,et al.Mechanisms of magnesium-stimulated adhesion Of Osteoblastic cells to commonly used Orthopaedic implants.J Biomed Mater Res 2002;62:175-84.
1 Mark P S,Alexis M P,Jerawala H,George D.Magnesium and its alloys as orthopedic biomaterials:a review.Biomaterials.2006;27:1728.
2 Ren Y B,Huang J J,Yang K,Zhang B C,Yao Z M,Wang H.Study of bio-corrosion of pure magnesium.Acta Metallurgica Sinica.2005;41:1228.
3 Wolf FI,Cittadini A.Chemistry and biochemistry of magnesium.Mol.Aspects Med.2003;24:3.
4 Vormann J.Magnesium:nutrition and metabolism.Mol.Aspects Med.2003;24:27.
5 Yamasaki Y,Yoshida Y,Okazaki M,Shimazu A,Kubo T,Akagawa Y,et al.Action of FGMgCO3Ap-collagen composite in promoting bone formation.Biomaterials 2003;24:4913.
6 Jiao S Q,Kuang Y F.Corrosion behavior and anodization of magnesium and its alloys.Electroplating and Pollution Control.2002;22(3):1.
7 Shaw BA.Corrosion resistance of magnesium alloys.In:Stephen D,editor.ASM handbook volume 13 a:corrosion:fundamentals,testing and protection.UK:ASM Int;2003.
8 Li L,Gao J,Wang Y.Surf.Coat.Technol.2004;185:92.
9 Kuwahara H,Al-Abdullat Y,Mazaki N,Tsutsumi S,Aizawa T.Mater.Trans.2001;42(7):1317.
10 Witte F,Kaese V,Haferkamp H,Switzer E,Meyer-Lindenberg A,Wirth CJ,et al.In vivo corrosion of four magnesium alloys and the associated bone response.Biomaterials.2005;26:3557.
11 Vasudev D V,Ricci J L,Sabatino C,Li P,Parsons J R.In vivo evaluation of a biomimetic apatite coating grown on titanium surfaces.J.Biomed Mater Res.2004;69(4):629-36.
12 Schliephake H,Scharnweber D,Dard M,Robler S,Sweing A,Huttman C.Biological performance of biomimetic calcium phosphate coating of titanium implants in the dog mandible.J Biomed Mater Res A.2003;64(2):225-34.
1 Mark P.S,Alexis M.P,Jerawala H,George D.Magnesium and its alloys as orthopedic biomaterials:a review.Biomaterials,2006;27:1728.
2 Erbel R,Di Mario C,Bartunek J,Bonnier J,de Bruyne B,Eberli F R,Erne P,Haude M,Heublein B,Horrigan M,Ilsley C,Bose D,Koolen J,L(?)scher T F,Weissman N,Waksman R.Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents:a prospective,non-randomised multicentre trial.Lancet,2007;369:1869.
3 Witte F,Fischer J,Nellesen J,Crostack HA,Kaese V,Pisch A,Beckmann F,Windhagen H.In vitro and in vivo corrosion measurements of magnesium alloys.Biomaterials,2006;27:1013.
4 Witte F,Ulrich H,Rudert M,Willbold E.Biodegradable magnesium scaffolds:Part Ⅰ:Appropriate inflammatory response.J Biomed Mater Res,2007;81:748.
5 Witte F,Ulrich H,Palm C,Willbold E.Biodegradable magnesium scaffolds:Part Ⅱ:Peri-implant bone remodeling.J Biomed Mater Res,2007;81:757.
6 Vonder H N,Krause A,Hackenbroich C,Bormann D,Lucas A,Meyer-Lindenberg A.Influence of different surface machining treatments of resorbable implants made from different magnesium-calcium alloys on their degradation-a pilot study in rabbit models.Dtsch Tierarztl Wochenschr,2006;1 13:439.
7 Waselau M,Samii VF,Weisbrode SE,Litsky AS,Bertone AL.Effects of a magnesium adhesive cement on bone stability and healing following a metatarsal osteotomy in horses.Am J Vet Res,2007;68(4):370-8.
8 Agrawal C M,Athanasiou K A.Technique to control pH in vicinity of biodegrading PLA-PGA implants.J Biomed Mater Res,1997;38:105.
9 Kuwahara H,Al-Abdullat Y,Mazaki N,Tsutsumi S,Aizawa T.Mate Trans,2001;42:1317.
10 Zhang G D,Huang J J,Yang K,Zhang B C,Ai H J.Experimental Study of in Vivo Implantation of a Magnesium Alloy at Early Stage.Acta Metall Sin,2007;43:1186.
11 Duque G,Rivas D.Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells.J Bone Miner Res.2007;22(10):1603-11.
12 Lobato JV,Rodrigues JM,Cavaleiro MV,Lobato JM,Xavier L,Santos JD,Maur(?)cio AC.Maxilla osseus sequestre and oral exposure:effects of the treatment of multiple myeloma with bisphosphonates.Acta Med Port.2007;20(2):185-92.
13 Mandelin J,Hukkanen M,Li TF,Korhonen M,Liljestr(?)m M,Sillat T,Hanemaaijer R,Salo J,Santavirta S,Konttinen YT.Human osteoblasts produce cathepsin K.Bone.2006;38(6):769-77.
14 Perez-Amodio S,Beertsen W,Everts V.Pre-osteoclasts induce retraction of osteoblasts before their fusion to osteo-clasts.J Bone Miner Res.2004;19(10):1722-31.
1 张绍渤,钱均琪,黄受方.微波技术在病理学中的应用.国外医学生理病理科学与临床分 册,1992,12(1):15-17.
2 Yeril KC,Hainich S,Turhani D,et al.Stability of biodegradable implants in treatment of mandible fractures[J].Plast Reconstr sug,2005,115:1863-1870.
3 曾永光,彭勇,魏世成,等.超高分子量聚D,L乳酸小型接骨板在下颌骨骨折治疗中的 应用[J].中国口腔颌面外科杂志,2004,2:137-139.
4 Water,electrolyte mineral and acid/base metabolism.Section 2.Endocrine ＆ Metabolic Disorders.Merk Manual of Diagnosis and Therapy[Chapter 12].
5 Saris NEL.Magnesium:an update on physiological,clinical and analytical aspects.Clin Chim Acta 2000:294:1-26.
6 Vormann J.Magnesium:nutrition and metabolism.Mol Aspects Med 2003;24:27-37.
7 Lambotte A.L'utilisation du magnesium comme materiel perdu dansl'osteosynth(?)se.Bull Me'm Soc Nat Chir 1932:28:1325-34.
8 Troitskii VV:Tsitrin DN.The resorbing metallic alloy‘Osteosinthezit'as material for fastening broken bone.Khiruriia 1944;8:41-4.
9 Witte F,Kaese V,Haferkamp H,Switzer E,Meyer-Lindenberg A,Winh CJ,et al.In ViVo Corrrsion of four magnesium alloys and the associated bone response.Biomaterials 2005;26: 3557-63.
10 Revell PA,Damien E,Zhang XS,Evans P,Howlett CR.The effect of mangesium ions on bone bonding to hydroxyapatite.Key Eng Mater 2004;254-256:447-50.
11 Zreiqat H,Howlett CR,Zannettino A,Evans P,Schulze-Tanzll G Knabe C,et al.Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants.J Biomed Mater Res 2002;62:175-84.
1 Palmer RH.Biological osteosynthesis.Vet Clin North Am Small Anim Pract.1999;29(5):1171-85.
2 Staiger MP,Pietak AM,Huadmai J,Dias G.Magnesium and its alloys as orthopedic biomaterials:a review.Biomaterials.2006;27(9):1728-34.
3 Alkan A,Metin M,Ozden B,et al.Biomechanical comparison of plating techniques for fractures of the mandibular condyle.Br J Oral Maxillofac Surg.2007;45(2):145-9.
4 Kulkarni R K,Moore E G,Hegyeli A F,et al.Biodegradablepoly(lacti2cacid) polymers.Biomed Mater Res,1971;5:169.
5 Getter L,Cut right D E,Bhaskar S N,et al.A biogradeable intraosseous appliance in the treatment of mandibular fractures.Oral Surg,1972;30:344.
6 Jukkala Partio K,Pohjonen T,Laitinen O,et al.Biodegradation and st rength retention of poly L lactide screws in vivo.An experimental long term study in sheep.Ann Chir Gynaecol,2001;90(3):219.
7 Bostman O M,Paivarinta U,Partio E,et al.The tissueimplant interface during degradation of absorbable polyglycolide fracture fixation screws in the rabbit femur.Clin Orthop,2002;(285):263.
8 Morgan C D,Gehrmann R M,Jayo MJ,et al.Histologic findings with a bioabsorbable anterior cruciate ligament interference screw explant after 2.5 years in vivo.Arthroscopy,2002;18(9):47.
9 Viljanen J,Kinnunen J,Bondestam S,et al.Bone changes after experimental osteotomies fixed with absorbable self-reinforced poly-L-lactide screws or metallic screws studied by plain radiographs,quantitative computed tomography and magnetic resonance imaging.Biomaterials,1995;16(17):1353.
10 Liu J K,Gottfried O N,Cole C D,et al.Porous polyethylene implant for cranioplasty and skull base reconst ruction.Neurosurg Focus,2004;16(3):ECP1.
11 Rokkanen P,Bostman O,Vainionpaa S,et al.Biodegradable internal fixation for malleolar fractures.A prospective randomised trial.Bone Joint Surg,1987;69:615.
12 Kuklo TR,Rosner MK,Polly DW.Computerized tomography evaluation of a resorbable implant after transforaminal lumbar interbody fusion.Neurosurg Focus.2004;16(3):E10.
13 Piltz S,Steinbauer T,Meyer L,et al.Bioabsorbable expansion bolt fixation in anterior cruciate ligament reconst ruction.Clin Orthop,2004;(418):225.
14 Bohnsack M,Borner C,Schmolke S,et al.Clinical results of arthroscopic meniscal repair using biodegradable screws.Knee Surg Sports Traumatol Arthrosc,2003;11(6):379.
15 Vaccaro AR,Carrino JA,Venger BH,et al.Use of a bioabsorbable anterior cervical plate in the treatment of cervical degenerative and traumatic disc disruption.Neurosurg Spine,2002;97(4):473.
16 Bostman OM,Pihlajamaki H K.Adverse tissue reactions to bioabsorbable fixation devices.Clin Orthop,2000;(371):216.
17 Bostman OM.Osteoarthritis of the ankle after foreignbody reaction to absorbable pins and screws:a three to nine year follow up study.Bone Joint Surg,1998;80(2):333.
18 Zreiqat H,Howlett CR,Zannettino A,et al.Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants.J Biomed Mater Res 2002;62:175-84.
19 Malhan K,Kumar A,Rees D.Tibial cyst formation after anterior cruciate ligament reconst ruction using a new bioabsorbable screw.Knee,2002;9(1):73.
20 Shaw BA.Corrosion resistance of magnesium alloys.In:Stephen D,editor.ASM handbook volume 13a:corrosion:fundamentals,testing and protection.UK:ASM Int.2003.
21 Werner A,Wild A,Ilg A,et al.Secondary intra-articular dislocation of a broken bioabsorbable interference screw after anterior cruciate ligament reconst ruction.Knee Surg Sports Traumatol Arthrosc,2002;10(1):30.
22 Staigera MP,Pietaka AM,Huadmaia J,Dias G Magnesium and its alloys as orthopedic biomaterials:a review.Biomaterials,2006;27:1728-34.
23 Song GL,Andrej A.Corrosion mechanisms of magnesium alloys.Adv Eng Mater 1999;1:11-33.
24 Li L,Gao J,Wang Y.Evaluation of cyto-toxicity and corrosion behavior of alkalieheat-treated magnesium in simulated body fluid.Surf Coat Technol,2004;185:92-8.
25 Heublein B,Rohde R,Kaese V,Niemeyer M,Hartung W,Haverich A.Biocorrosion of magnesium alloys:a new principle in cardiovascular implant technology?Heart,2003;89:651-6.
26 Zartner P,Cesnjevar R,Singer H,Weyand M.First successful implantation of a biodegradable metal stent into the left pulmonary artery of a preterm baby.Catheter Cardiovasc Interv,2005;66:590-4.
27 Schranz D,Zartner P,Michel-Behnke I,Akinturk H.Bioabsorbable metal stents for percutaneous treatment of critical recoarctation of the aorta in a new born.Catheter Cardiovasc Interv,2006;67:671-3.
28 Kuwahara H,Al-Abdullat Y,Mazaki N,Tsutsumi S,Aizawa T.Precipitation of magnesium apatite on pure magnesium surface during immersing in Hank's solution.Mater Trans,2001;42:1317-21.
29 Heublein B,Rohde R,Kaese V.Biocorrosion of magnesium alloys:a new principl in cardiovascular implant technology.Heart,2003;89:651.
30 Domer Reisel A,Nishida Y,Klemm V,et al.Investigation of interfacial interaction between uncoated and coated carbon fibres and the magnesium alloy AZ91.Anal Bioanal Chem,2002;374(4):635-8.
31 Knox J,Chye KY,Duming P.An ex vivo evaluation of resin-modified glass polyalkenoates and polyacid-modified composite resins as orthodontic band cements.J Orthod,2004;31(4):323-8.
32 Kannan MB,Raman Rk In vitro degradation and mechanical integrity of calcium-containing magnesium alloys in modified-simulated body fluid.Biomaterials,2008;29(15):2306-14.
33 Katzer A,Buchhom GH,Hockertz S,Loehr JF.In vitro toxicity and mutagenicity of CoCrMo and TiAl wear particles.Orthopade.2003(8):744-50.German
34 F.Witte,J.Reifenrath,P.P.M(u|¨)ller.et al.Cartilage repair on magnesium scaffolds used as a subchondral bone replacement,Mat-wiss.U.Werkstofftech,2006;37(6):504-508.
35 F.Witte,V Kaese,H.Haferkamp,et al.In vivo corrosion of four magnesium alloys and the associated bone response,Biomaterials,2005;26:3557-3563.
36 F.Witte,J.Fischer,J.Nellesen,et al.ln vitro and in vivo corrosion measurements of magnesium alloys,Biomaterials,2006;27:1013-1018
37 Witte F,Ulrich H,Palm C,Willbold E.Biodegradable magnesium scaffolds:Pan II:peri-implant bone remodeling.J Biomed Mater Res A.2007;81(3):757-65
38 Witte F,Ulrich H,Rudert M,Willbold E.Biodegradable magnesium scaffolds:Part 1:appropriate inflammatory response.J Biomed Mater Res A.2007;81(3):748-56.
39 Witte F,Abeln l,Switzer E,et al.Evaluation of the skin sensitizing potential of biodegradable magnesium alloys.J Biomed Mater Res A.2007 Dec
40 Huang Jingjing,Ren Yibin,Jiang Yue,Zhang Bingchun and Yang Ke.In vivo study of degradable magnesium and magnesium alloy as bone implant.Frontiers of Materials Scieence in China.2007;1(4):405-409.
41 张广道,黄晶晶,杨柯,张炳春,艾红军,动物体内植入镁合金的早期实验研究,金属学报,2007;43(11):1186-1190.
42 Liping Xu,Guoning Yu,Erlin Zhang,Ke Yang,In vivo corrosion behavior of Mg-Mn-Zn alloy for bone implant application,J Biomedical Mater Res.Part A,83A(2007),703-711.
43 Sreedhara A,Cowan JA.Structural and catalytic roles for divalent magnesium in
44 Leeuwenburgh S,Layrolle P,Barrere F,et al.Osteoclastic resorption of biomimetic calcium phosphate coatings in vitro.Biomed Mater Res.2001;56(2):208-15.
45 Deutscher RL,Cathro KJ.Organochlorine formation in magnesium electrowinning cells.Chemosphere.2001;43(2):147-55.
46 Guangling Song,Control of biodegradation of biocompatible magnesium aIloys,Corrosion Science.2007:49:1696-1701.
47 J.C.Gao,L.C.Li,Y.Wang,L.Y.Qiao,Biocompatibility of magnesium after surface modification by heat-organic films-treatment,RARE METAL MATERIALS AND ENGINEERING 2005;34(6):903-906.
48 Vasudev DV,Ricci JL,Sabatino C,et al.In vivo evaluation of a biomimetic apatite coating grown on titanium surfaces.J Biomed Mater Res A.2004;69(4):629-36.
49 Schliephake H,Scharnweber D,Dard M,et al.Biological performance of biomimetic calcium phosphate coating of titanium implants in the dog mandible.J Biomed Mater Res A.2003;64(2):225-34.
50 Vonder H N,Krause A,Hackenbroich C,et al.Dtsch Tierarztl Wochenschr,2006;113(12):439.
51 Kinoshita K,Hibi H,Yamada Y,Ueda M.Promoted new bone formation in maxillary distraction osteogenesis using a tissue-engineered osteogenic material.J Craniofac Surg.2008;19(1):80-7.
52 Related Articles,LinksLerouxel E,Weiss P,et al.Injectable calcium phosphate scaffold and bone marrow graft for bone reconstruction in irradiated areas:an experimental study in rats.Biomaterials.2006 Sep;27(26):4566-72.
53 Beebe KS,Sabharwal S,Behrens F.Femoral shaft fractures:is rigid intramedullary nailing safe for adolescents.Am J Orthop.2006;35(4):172-4.
54 Naot D,Grey A,Reid IR,Cornish J.Lactoferrin--a novel bone growth factor.Clin Med Res.2005;3(2):93-101.
55 Related Articles,LinksAndreev K,Zenkel M,et al.Expression of bone morphogenetic proteins(BMPs),their receptors,and activins in normal and scarred conjunctiva:role of BMP-6 and activin-A in conjunctival scarring.Exp Eye Res.2006;83(5):1162-70.
56 Valimaki VV,Aro HT.Molecular basis for action of bioactive glasses as bone graft substitute.Scand J Surg.2006;95(2):95-102.
57 Thamaraiselvi TV,Rajeswari S.Biological evaluation of bioceramic materials-a review.Trends Biomater Artif Organs 2004;19:9-17.
58 Selvamurugan N,Kwok S,Vasilov A,et al.Effects of BMP-2 and pulsed electromagnetic field(PEMF) on rat primary osteoblastic cell proliferation and gene expression.J Orthop Res.2007;25(9):1213-20.
59 Kim YK,Kim SG.Treatment of mandible fracture using bioabsorbable plates.Plast Reconstr Surg,2002;110:25-31.
60 Turvey TA,Bell RB,Tejera TJ,et al.The use of self-reinforced biodegradable bone plates and screws in orthognathic surgery.J Oral Maxillofac Surg,2002;60:59-65.
61 黄琴,梁惠,杜凤沛,镁的生理与临床应用,微量元素与健康研究,2005；22：61．63．
62 Frank Feyerabend,Frank Witte.Michael Kammal and Regine Willumeit,Unphysiologically
High Magnesium Concentrations Support Chondrocyte Proliferation and Redifferentiation.
Tissue Engineering,2006;12(12):3545-3556.
63 高妍婷,尹爱萍,镁的正常代谢及其调节,广东微量元素科学,2004;10:20-23.
64 Guangling Song,Control of biodegradation of biocompatible magnesium alloys,Corrosion Science,2007;49:1696-1701.
65 Mani G,Feldman Marc D,Patel D,Agrawal M.Coronary stents:a materials perspective.Biomaterials 2007:28:1689-1710.
66 J C Gao,L C Li,Y.Wang,L Y,et al.Biocompatibility of magnesium after surface modification by heat-organic films-treatment,RARE METAL MATERIALS AND ENGINEERING,2005;34(6):903-906.
67 L C Li,J C GaO,Y Wang.Evaluation of cyto-toxicily and corrosion behavior of alkali-heat-treated magnesium in simulated body fluid,SURFACE & COATINGS TECHNOLOGY,2004;185(1):92-98.
68 谭丽丽;耿芳,杨柯,张炳春,一种生物医用可降解镁合金的生物活性表面改性方法,申请号:200710159044.9(发明专利).
69 F.Geng,L.L.Tan,B.C.Zhang,Study of Magnesium Tissue Engineering Scaffolds with B-TCP Coatings,The lst intemational symposium on surface and interface of biomaterials,Sichuan,5-7 Oct,2007.
70 Zhang Er-lin,Yang Ke,Biomimetic coating of calcium phosphate on biometallic materials,Trans.Nonferrous Met.Soc.China,2005;15:1199-1250.
71 Serre CM,Papillard M,Chavassieux P,et al.,Influence of magnesium substitutiOil on a collagen-apatite biomaterial on the production of a calcifying matrix by human osteoblasts,JOURNAL OF BIOMEDICAL MATERIALS RESEARCH,1998;42(4):626-633.
72 Ten Huisen KS,Brown PW,Effects of magnesium on the formation of calcium-deficient hydroxyapatite from CaHPO4 center dot 2H(2) O and Ca-4(Po4)(2) O,JOURNAL OF BIOMEDlCAL MATERIALS RESEARCH,1997;36(3):306-314.
73 R.Z.LeGeros,A.M.Gatti,R.kijkowska,D.Q.Mijares,J.P.LeGeros,Mg-substituted Tricalcium Phosphates:Formation and Properties,Key Engineering Materials,Vols.254-256(2004):127-13 1.
74 Y.Z.Wan,Y.Huang,F.He,Y.L.Wang,Z.G.Zhao,H.F.Ding,Effect Of Mg ion implantation on calcium phosphate formation on titanium,Surface and coating technology,2006;201:2904-9.