CAJ | 학술논문

背景:理想的修复材料是既具有良好生物相容性,又具有成骨能力.任何一种生物材料必须具备使用安全性和良好的生物相容性,这是生物材料获准临床使用的前提.目的:探讨载银二氧化钛纳米羟基磷灰石/聚酰胺66(TiO_2-Ag-nHA/PA66)骨修复材料的体内生物相容性及安全性.设计、时间及地点:随机对照,重复测量设计,于2008-07/2009-07在重庆医科大学完成.材料:清洁级3周龄昆明小鼠40只,同窝同系健康成年新西兰大白兔32只,均由重庆医科大学实验动物中心提供.粉末状TiO_2-Ag-nHA/PA66复合材料10 g,直径5 mm×长度25 mm和直径3 mmx长度5 mm的TiO_2-Ag-nHA/PA66复合材料各32根,由四川大学纳米生物材料研究中心提供.方法:①急性全身毒性试验:40只小鼠随机分为实验组和对照组,选择粉末状复合材料制各材料浸提液,将浸提液注入实验组小鼠腹腔内,对照组注入等量生理盐水.②肌内埋植实验:16只兔随机分为实验组和对照组,实验组每只兔左、右竖脊肌各植入2根直径5 mm×长度25 mm复合材料,对照组行相同的手术操作但不植入任何材料.③骨内埋植试验:取剩余16只兔,每只兔左、右外上髁各植入1根直径3 mm×长度5 mm柱状复合材料.④溶血试验:取抗凝兔血8 mL,分别加入复合材料粉末0.1,0.15,0.2 g.主要观察指标:TiO_2-Ag-nHA/PA66的体内生物相容性及安全性.结果:急性全身毒性试验结果表明,两组小鼠活动及进食良好,呼吸正常,无瘫痪、惊厥及死亡发生,小鼠体质量稳定.肌内埋植试验和骨内埋植试验结果显示,植入前及植入后4 d,1周,2周,两组丙氨酸氨基转移酶、天门冬酸氨基转移酶、尿素氮、肌酐水平及白细胞数量均无明显差异(P>0.05),且实验组内各时相点比较亦无明显差异(P>0.05).肌内埋植中,实验组的组织切片示材料周围的包裹组织,材料周围炎性演变转归与对照组基本相似;骨内埋植中,实验组的组织切片示围绕材料出现新骨.溶血试验结果显示,3种浓度梯度的TiO_2-Ag-nHA/PA66复合材料其溶血率均未超过5%,达到标准要求.结论:TiO_2-Ag-nHA/PA66复合材料具有良好的生物相容性及生物安全性. 揹景:理想的脩複材料是既具有良好生物相容性,又具有成骨能力.任何一種生物材料必鬚具備使用安全性和良好的生物相容性,這是生物材料穫準臨床使用的前提.目的:探討載銀二氧化鈦納米羥基燐灰石/聚酰胺66(TiO_2-Ag-nHA/PA66)骨脩複材料的體內生物相容性及安全性.設計、時間及地點:隨機對照,重複測量設計,于2008-07/2009-07在重慶醫科大學完成.材料:清潔級3週齡昆明小鼠40隻,同窩同繫健康成年新西蘭大白兔32隻,均由重慶醫科大學實驗動物中心提供.粉末狀TiO_2-Ag-nHA/PA66複閤材料10 g,直徑5 mm×長度25 mm和直徑3 mmx長度5 mm的TiO_2-Ag-nHA/PA66複閤材料各32根,由四川大學納米生物材料研究中心提供.方法:①急性全身毒性試驗:40隻小鼠隨機分為實驗組和對照組,選擇粉末狀複閤材料製各材料浸提液,將浸提液註入實驗組小鼠腹腔內,對照組註入等量生理鹽水.②肌內埋植實驗:16隻兔隨機分為實驗組和對照組,實驗組每隻兔左、右豎脊肌各植入2根直徑5 mm×長度25 mm複閤材料,對照組行相同的手術操作但不植入任何材料.③骨內埋植試驗:取剩餘16隻兔,每隻兔左、右外上髁各植入1根直徑3 mm×長度5 mm柱狀複閤材料.④溶血試驗:取抗凝兔血8 mL,分彆加入複閤材料粉末0.1,0.15,0.2 g.主要觀察指標:TiO_2-Ag-nHA/PA66的體內生物相容性及安全性.結果:急性全身毒性試驗結果錶明,兩組小鼠活動及進食良好,呼吸正常,無癱瘓、驚厥及死亡髮生,小鼠體質量穩定.肌內埋植試驗和骨內埋植試驗結果顯示,植入前及植入後4 d,1週,2週,兩組丙氨痠氨基轉移酶、天門鼕痠氨基轉移酶、尿素氮、肌酐水平及白細胞數量均無明顯差異(P>0.05),且實驗組內各時相點比較亦無明顯差異(P>0.05).肌內埋植中,實驗組的組織切片示材料週圍的包裹組織,材料週圍炎性縯變轉歸與對照組基本相似;骨內埋植中,實驗組的組織切片示圍繞材料齣現新骨.溶血試驗結果顯示,3種濃度梯度的TiO_2-Ag-nHA/PA66複閤材料其溶血率均未超過5%,達到標準要求.結論:TiO_2-Ag-nHA/PA66複閤材料具有良好的生物相容性及生物安全性.
배경:이상적수복재료시기구유량호생물상용성,우구유성골능력.임하일충생물재료필수구비사용안전성화량호적생물상용성,저시생물재료획준림상사용적전제.목적:탐토재은이양화태납미간기린회석/취선알66(TiO_2-Ag-nHA/PA66)골수복재료적체내생물상용성급안전성.설계、시간급지점:수궤대조,중복측량설계,우2008-07/2009-07재중경의과대학완성.재료:청길급3주령곤명소서40지,동와동계건강성년신서란대백토32지,균유중경의과대학실험동물중심제공.분말상TiO_2-Ag-nHA/PA66복합재료10 g,직경5 mm×장도25 mm화직경3 mmx장도5 mm적TiO_2-Ag-nHA/PA66복합재료각32근,유사천대학납미생물재료연구중심제공.방법:①급성전신독성시험:40지소서수궤분위실험조화대조조,선택분말상복합재료제각재료침제액,장침제액주입실험조소서복강내,대조조주입등량생리염수.②기내매식실험:16지토수궤분위실험조화대조조,실험조매지토좌、우수척기각식입2근직경5 mm×장도25 mm복합재료,대조조행상동적수술조작단불식입임하재료.③골내매식시험:취잉여16지토,매지토좌、우외상과각식입1근직경3 mm×장도5 mm주상복합재료.④용혈시험:취항응토혈8 mL,분별가입복합재료분말0.1,0.15,0.2 g.주요관찰지표:TiO_2-Ag-nHA/PA66적체내생물상용성급안전성.결과:급성전신독성시험결과표명,량조소서활동급진식량호,호흡정상,무탄탄、량궐급사망발생,소서체질량은정.기내매식시험화골내매식시험결과현시,식입전급식입후4 d,1주,2주,량조병안산안기전이매、천문동산안기전이매、뇨소담、기항수평급백세포수량균무명현차이(P>0.05),차실험조내각시상점비교역무명현차이(P>0.05).기내매식중,실험조적조직절편시재료주위적포과조직,재료주위염성연변전귀여대조조기본상사;골내매식중,실험조적조직절편시위요재료출현신골.용혈시험결과현시,3충농도제도적TiO_2-Ag-nHA/PA66복합재료기용혈솔균미초과5%,체도표준요구.결론:TiO_2-Ag-nHA/PA66복합재료구유량호적생물상용성급생물안전성.
BACKGROUND: An ideal repairing material characterizes by both great biocompatibility and osteogenesis ability. Any biomaterials should meet excellent biological security and biocompatibility prior to clinical application.OBJECTIVE: To evaluate the biocompatibility and the biological security of the TiO_2-Ag-nano-hydroxyapatite/polyamide66 (TiO_2-Ag-nHA/PA66) composite.DESIGN, TIME AND SETTING: A randomized controlled duplicated design was performed in Chongqing Medical University from July 2008 to July 2009.MATERIALS: A total of 40 Kunming mice aged 3 weeks and of clean grade and 32 healthy adult New Zealand rabbits were provided by Experimental Animal Center of Chongqing Medical University. TiO_2-Ag-nHA/PA66 composite powder (10 g),TiO_2-Ag-nHA/PA66 composites (n=32, 5 mm ×25 mm), and TiO_2-Ag-nHA/PA66 composites (n=32, 3 mm × 5 mm) were provided by Research Center of Nano-Biomaterials of Sichuan University.METHODS: General toxicity test: Forty mice were randomly divided into experimental and control groups. Composite powder was used to prepare leaching liquor which was treated on experimental mice by an intraperitoneal injection. While, an equal amount saline was inserted into the control mice. Intramuscular implanting test: The 16 rabbits were randomly divided into experimental and control groups. Two TiO_2-Ag-nHA/PA66 composite (5 mm × 25 mm) were implanted into left and right erector spinae, respectively. A similar surgery with the exception of implantation was performed on the control rabbits. Intrabony implanting test: The resting 16 rabbits were implanted one TiO_2-Ag-nHA/PA66 composite (3 mm × 5 mm) into left and right lateral epicondyle, respectively. Hemolytic test: A 8-mL anti-coagulation blood was obtained and added with composite powder (0.1,0.15, and 0.2 g).MAIN OUTCOME MEASURES: Biocompatibility and biological security of TiO_2-Ag-nHA/PA66 composite.RESULTS: General toxicity test demonstrated that mice in the two groups had good activity and eating, normal breathing, stable body mass, no paralysis, convulsion, and death. Intramuscular implanting test and intrabony implanting test showed that there was no significant difference in levels of alanine aminotransferase, aspartate transaminase, urea nitrogen, and creatinine and leukocyte numbers between the two groups before implantation and at day 4,1 week, and 2 weeks after implantation (P> 0.05).In particular, there was no significant difference in the experimental group at varying time points (P> 0.05). Intramuscular implanting test indicated that tissue sections in the experimental group displayed coated tissue of materials. The inflammatory variation in the experimental group was generally similar to that in the control group. Intrabony implanting test indicated that tissue sections in the experimental group displayed new bone formation. Hemolytic test suggested that hemolytic ratio of three varying concentrations of TiOrAg-nHA/PA66 composites was less than 5%, which met the normal criterion.CONCLUSION: TiO_2-Ag-nHA/PA66 composite has a good biocompatibility and biological security.