聚乳酸-乙醇酸复合中药自然铜活性骨修复支架生物学评价

目的评价新型骨修复材料聚乳酸-乙醇酸复合中药自然铜活性骨修复支架的生物安全性。方法根据医疗器械生物学评价标准的要求,选取了溶血试验、细胞毒性试验、遗传毒性试验、刺激与致敏试验、全身毒性试验、植入试验等,全方位评价该新型材料的生物安全性。结果聚乳酸-乙醇酸复合中药自然铜活性骨修复支架的血液相容性良好,无全身毒性和细胞毒性,未发现短期遗传毒性,无皮肤刺激和致敏作用,材料植入骨后周围组织反应正常,骨修复情况良好。结论聚乳酸-乙醇酸复合中药自然铜活性骨修复支架是一种生物相容性好的骨修复材料,可安全应用于临床。     

纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥的生物相容性与体内降解研究

对制备的纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥的生物相容性及体内降解情况进行研究,为临床提供实验依据.参照GB/T16886医疗器械生物学评价标准和要求,对纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥进行急性细胞毒性试验、溶血试验、热源试验、急性全身毒性试验及体内植入试验等系列体内外生物学试验研究,以进行有效的生物相容性和安全性评价.纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥的溶血率小于国家规定的5％,在体外不引起溶血反应;浸提液注入动物体内后无死亡,活动进食正常;无细胞毒性反应;热原试验动物体温升高均在0.7℃以下,3只兔体温升高值的总数＜1.5℃,无致热作用;材料植入体内初期有轻度炎症反应,随植入时间延长逐渐减轻,材料也逐渐降解吸收.纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥具有良好的生物相容性和降解性能,具有临床开发应用前景.     

纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥的生物相容性与体内降解研究

对制备的纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥的生物相容性及体内降解情况进行研究,为临床提供实验依据。参照GB/T16886医疗器械生物学评价标准和要求,对纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥进行急性细胞毒性试验、溶血试验、热源试验、急性全身毒性试验及体内植入试验等系列体内外生物学试验研究,以进行有效的生物相容性和安全性评价。纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥的溶血率小于国家规定的5%,在体外不引起溶血反应;浸提液注入动物体内后无死亡,活动进食正常;无细胞毒性反应;热原试验动物体温升高均在0.7℃以下,3只兔体温升高值的总数〈1.5℃,无致热作用;材料植入体内初期有轻度炎症反应,随植入时间延长逐渐减轻,材料也逐渐降解吸收。纳米羟基磷灰石/羧甲基壳聚糖-海藻酸钠复合骨水泥具有良好的生物相容性和降解性能,具有临床开发应用前景。     

生物衍生组织工程骨支架材料生物学评价

采用基本评价和补充评价的生物学评价试验 ,比较全面地评价了生物衍生组织工程骨支架材料的生物相容性。结果显示 :该材料细胞评级为 1级 ,无致敏作用 ,热原试验合格 ,遗传毒性试验未见异常 ,骨植入试验未见异常 ,溶血率为 0 6 1 % ,慢性毒性试验未见异常。故可以认为生物衍生组织工程骨支架材料是一种理想的骨生物材料     

碳纳米管/聚氨酯复合材料的制备及生物相容性评价

目的 制备和评价碳纳米管/聚氨酯复合材料的生物相容性。方法 通过溶胶-凝胶方法制备碳纳米管/聚氨酯复合材料,对其力学性能进行测试;根据ISO10993指南,选取溶血实验、动态凝血实验、血小板黏附实验、血小板活化实验、细胞毒性实验和材料局部植入方法对复合材料的生物相容性进行评价。结果 复合材料无明显细胞毒性,并表现出比聚氨酯材料更好的抗溶血性能、动态凝血性能、抑制血小板黏附性能以及组织相容性。结论 碳纳米管－聚氨酯复合材料具有优良的生物相容性,可以作为制备组织工程细胞生长支架、人工血管、药物载体的基础材料。     

己内酯-碳酸亚乙酯共聚物力学性能及初步生物相容性研究

研究新型可降解高分子材料己内酯（CL）/碳酸亚乙酯（EC）共聚物的力学性能和生物相容性。利用Nd（DBMP）3催化合成可降解共聚物Poly（CL-co-EC）,对不同CL/EC共聚比例的Poly（CL-co-EC）进行力学性能和表面特征的测试;并对Poly（CL-co-EC）薄膜和浸提液进行生物相容性测试：细胞粘附试验、细胞增殖实验、溶血试验、乳酸脱氢酶（LDH）释放实验、四唑氮盐（MTS）细胞毒性试验和肌肉植入试验。结果表明随不同的CL/EC共聚比例可调控Poly（CL-co-EC）力学性能;细胞粘附试验,L929细胞在Poly（CL-co-EC）薄膜粘附较聚苯乙烯慢;MTS细胞毒性试验,共聚物组吸光度较阴性对照组无明显升高（P〈0.05）;LDH释放试验,各实验组LDH相对释放率〈10%;溶血反应,共聚物浸提液溶血率〈6%;肌肉植入试验,Poly（CL-co-EC）柱状物周围组织炎症反应轻微。Poly（CL-co-EC）共聚物具有可调控的力学性能和熔点,并具有良好的生物相容性,可作为医用材料和组织工程材料。     

羊膜基质/聚丙烯复合补片的制备及其生物相容性评价

制备脱细胞羊膜基质, 运用物理方法将其复合于临床用聚丙烯补片, 以形成具有更好组织相容性的生物补片。通过细胞培养, 以聚丙烯膜为对照, 评价复合生物补片的细胞相容性;通过动物皮下植入实验, 以评价复合补片的组织相容性。结果表明, 复合补片羊膜基质表面上的成纤维细胞生长和形态均好于聚丙烯表面, 细胞增殖较快, 增殖率超过聚丙烯表面的50%。动物实验显示, 复合补片周围增生少, 无明显纤维包膜形成, 初期在植入周围有淋巴细胞等炎性细胞浸润, 随着羊膜逐渐降解, 4周时可见毛细血管新生;而对于聚丙烯材料, 植入处纤维包囊明显, 炎性情况也较严重。经羊膜基质复合的聚丙烯补片具有良好的细胞和组织相容性。     

新型生物可吸收房间隔缺损封堵器的生物相容性研究

目的评价自主研究的新型房间隔封堵器的生物相容性,为动物实验提供依据。方法封堵器框架由生物可吸收聚左旋乳酸(poly-L-lactic acid,PLLA)单丝网编织成型。通过对PLLA单丝进行体外细胞毒性测试、体外溶血测试、全身急性毒性测试、肌肉植入实验,评价新型房间隔封堵器的生物相容性。结果 PLLA房间隔缺损封堵器无体外细胞毒性,体外溶血率0.9%,无急性全身毒性反应。通过分析样品植入肌肉1个月、3个月和6个月后组织病理,观察样品与组织之间的反应,未发现明显的组织损伤和组织增生。结论生物可吸收PLLA房间隔封堵器的生物相容性良好,可进行下一步的动物实验研究。     

髓内钉及骨科植入材料的研究进展

髓内钉是一类优点突出的骨科植入器械,这类产品对生物相容性和耐摩擦磨损性能的高要求促进了新型骨科植入材料的开发和研制。我们综述了多种骨科植入材料尤其是碳纤维增强聚醚醚酮复合材料（CF /PEEK）在植入器械领域的广泛应用。     

β型钛合金材料的生物相容性评价

背景:前期大量研究证实钛及钛合金具有良好的生物相容性和较强的耐腐蚀性,β钛合金以其高机械强度、低弹性模量,使其成为目前最具有吸引力的金属生物医学应用材料。目的:评价两种新型β型钛合金材料TLE(Ti-(3～6)Zr-(2～4)Mo-(24～27)Nb),TLM2(Ti-(1.5～4.5)Zr-(0.5～5.5)Sn-(1.5～4.4)Mo-(23.5～26.5)Nb)的生物相容性。方法:取健康成年新西兰兔30只,随机抽签法分为皮下植入组和肌肉植入组。将2种新型钛合金TLE、TLM2加工成圆柱形实验试件,分别植入家兔大腿皮下和背侧肌肉内。对照材料(Ti-6Al-4V)同法植入同一动物的对侧相同部位。依据GB/T16886.6-1997标准,在1,2,6,12,24周取标本大体观察纤维包膜的形态,光学显微镜下观察皮下和肌肉组试件与周围组织界面反应情况,苏木精-伊红染色进行组织学观察。结果与结论:植入2,6,12,24周后,试件周围均形成了血管化的包膜,随着植入时间的延长包膜逐渐变薄、透明度增高,包膜内毛细血管的数量增加。肌肉植入组包膜厚度在6,12周时比皮下植入组薄,炎细胞主要是中性粒细胞、巨噬细胞、多核巨细胞、淋巴细胞和浆细胞,随着时间的延长,各类炎细胞的数量逐渐减少,12周后中性粒细胞数量明显减少,淋巴细胞和浆细胞随时间延长数量逐渐变少,24周时均未见中性粒细胞。说明TLE,TLM2新型医用钛合金生物相容性好,具有良好的临床应用前景。     

强的松龙纳米微球缓释膜的生物安全性

背景：如何用药物去抑制神经修复后瘢痕的生长成为周围神经损伤后功能恢复的关键。课题组以往研究借鉴广泛应用于抗肿瘤药物局部释放的纳米微球缓释技术设计了一种强的松龙纳米微球缓释膜,取得了良好的体外药物缓释效果。 目的：制备强的松龙纳米微球缓释膜,观察该膜的生物相容性及安全性。 方法：采用反胶束乳化溶剂挥发法和球膜结合的方法制备强的松龙纳米微球缓释膜,用细胞毒性实验、溶血实验、急慢性全身毒性实验对药膜的生物安全性进行初步评价。 结果与结论：培养第7天,L929小鼠成纤维细胞相对增殖率为92.6%,证实此膜无细胞毒性;该膜对新鲜的抗凝兔血溶血率为0.59%,无明显的溶血作用;此缓释膜的浸提液腹腔注射小鼠未见明显的生物学行为的异常,对大鼠肝肾功能无明显影响。结果证实,强的松龙纳米微球缓释膜具有良好的生物相容性,安全无毒性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

牙科氧化锆氧化铝陶瓷复合材料的生物相容性

BACKGROUND: The physiological environment of oral cavity is very complex. Dental restoration materials exposed to the weakly acidic body fluids in the long term, and were in the complex influences including physical, chemical, biological and mechanical and other factors. Therefore, the evaluation of biocompatibility for dental materials is the focus of research before entering the clinical trials, and also the important technical indicators to  ensure the clinical safety. OBJECTIVE: To preliminarily evaluate the biocompatibility of ZrO2 and Al2O3 ceramic composites. METHODS: The experiment was divided into six groups: ZrO2 and Al2O3 (1:1) 100% extract group, ZrO2 and Al2O3 (1:1) 50% extract group, ZrO2 and Al2O3 ( 4:1) 100% extract group, ZrO2 and Al2O3 (4:1) 50% extract group, and the volume fraction of 0.64% phenol positive control group and 100% fresh medium of negative control group. Acute hemolysis and in vitro cytotoxicity experiments were conducted according to the biological evaluation standards and requirements of GB-T16886 15-2003 medical devices. The effects of the above six groups of extracts on rabbit blood cells and L-929 mouse fibroblast cells were tested respectively. RESULTS AND CONCLUSION: There was no significant difference in the absorbance values between different concentrations of experimental groups and negative control group (P > 0.05). The cytotoxicity rating of all experimental groups was 0-1 grade. The hemolysis rates in the ZrO2 and Al2O3 (1:1) 100% extract and ZrO2 and Al2O3 (4:1) 100% extract groups were 1.27% and 2.4% respectively, less than the accepted safety standards of 5%. These results demonstrate that the acute hemolytic experiment and in vitro cytotoxicity experiment of (1:1), (4:1) ZrO2 and Al2O3 ceramic composites are all negative, and all have good cytocompatibility and blood compatibility.       

新型纳米拓扑结构的生物相容性**◆

背景：国内外对纳米拓扑结构生物效应的探讨比较多,而缺乏对纳米拓扑结构的安全性评估。 目的：评价新型纳米拓扑结构的生物相容性。 方法：依据GB/T_16886中相关规定,采用纳米拓扑结构材料对昆明小鼠、新西兰大白兔、人行全身毒性试验、刺激与致敏试验及急性溶血试验。分离培养兔骨髓间充质干细胞复合培养于纳米拓扑结构,观察细胞的形态及增殖情况。 结果与结论：全身毒性试验结果显示,所有试验动物均无死亡,试验前后体质量无明显差异;刺激与致敏试验中,所有试验动物局部皮肤均无红斑、溃烂等反应,阳性对照组与试验组之间差异有显著性意义;急性溶血试验结果显示,试验组无明显溶血反应,吸光光度计检测吸光度,溶血率符合小于5%的标准。体外细胞试验结果显示,骨髓间充质干细胞在此纳米坑上表现出良好的黏附、细胞形态,并且复合培养3 d较1 d细胞增殖明显。提示此纳米坑结构无生物学毒性,具有良好的生物相容性,可以作为骨科替代植入物试用于临床,但长期生物相容性仍需要全面的评测。 关键词：纳米拓扑结构;纳米生物材料;生物相容性;急性毒性试验;刺激与致敏试验;急性溶血试验;体外细胞试验 doi:10.3969/j.issn.1673-8225.2012.03.019     

可降解血管支架材料的表面性能及生物相容性

BACKGROUND: Biodegradable stent implantation is a commonly used method in the clinical treatment of a variety of cardiovascular diseases. Importantly, the corresponding stent should have good surface properties and biocompatibility. OBJECTIVE: To observe the surface properties of the biodegradable vascular stent material, and to analyze its biocompatibility. METHODS: Artificial plasma was prepared for soaking the biodegradable magnesium alloy stent, and the corrosion of the material was observed by scanning electron microscope. Stent extraction solution was prepared and cytotoxicity test was carried out to observe the toxicity level of human umbilical vein endothelial cells cultured in the culture medium. Platelet adhesion test and hemolysis test were performed to detect cell and blood compatibility of the material. RESULTS AND CONCLUSION: After the 10-day immersion in artificial plasma, the material was scanned and a uniform corrosion layer was found on the surface of the material. During the drying of the material, some cracks appeared on the corrosion layer. After the corrosion products were removed, there were corrosion pits uniformly distributed on the corrosion surface of the material. In the cytotoxicity test, there were no absorbance values in the positive control group, and almost all of the cells died. After cultured in the material extraction, the toxicity level of human umbilical vein endothelial cells was graded 0 or 1. In the adhesion test, platelets on the stent surface were mostly disk-shaped under scanning electron microscope, some of which were deformed and extended pseudopodia, but no platelet aggregation occurred. The hemolysis rate of the material was 3.15%, in accordance with the requirement of the hemolytic rate < 5%. These experimental results show that the biodegradable magnesium alloy stent material has good corrosion resistance and good cell and blood compatibility, which can meet the demand of clinical application.      

镍钛形状记忆合金表面改性后的血液相容性

背景：镍钛形状记忆合金植入人体内必需要有很好的生物相容性和生物安全性。 目的：观察分析镍钛形状记忆合金表面改性后对其生物相容性的影响。 方法：将镍钛形状记忆合金随机分为两组,经阴极电沉积法处理的材料为实验组,未经处理的为空白组,通过扫描电镜观察实验组材料表面的变化,并测定材料的溶血率和动态凝血时间。体外培养骨髓基质干细胞,与两组材料复合培养,通过MTT法检测两组材料中细胞存活数量。 结果与结论：镍钛形状记忆合金表面改性后,表面出现由很多的纳米级颗粒紧密聚集形成的Ti-O膜,实验组材料的溶血率下降,凝血时间延长,两组材料与骨髓基质干细胞复合培养第2,4,6天,实验组吸光度比空白组明显增高(P < 0.05)。说明镍钛形状记忆合金经阴极电沉积法表面改性后具有较好的生物相容性和生物安全性。     

地塞米松复合聚己内酯胶原支架材料的构建及性能评价

BACKGROUND: Tissue engineering scaffold materials have been widely used in all kinds of tissue and nerve repair, but there are many limitations and the effect is not good. OBJECTIVE: To construct a kind of tissue engineering scaffold material for the regeneration and repair of spinal cord injury. METHODS: The dexamethasonemicrospheres were prepared by emulsification-solvent evaporation. The comprehensive scores of encapsulation efficiency, drug-loading rate and yield were taken as the indexes. The effect of dosage of dexamethasone and polylactic acid-glycolic acid copolymer and mass fraction of polyvinyl alcohol on formulation process of dexamethasone sustained-release microsphere was inspected by orthogonal experiment. The characterization of microspheres was observed by scanning electron microscope. The nanofiber scaffold of compound dexamethasone microspheres was prepared by taking collagen protein and polycaprolactone as raw materials using electrospinning technology. The mouse bone marrow mesenchymal stem cells were co-cultured with the scaffold for 3 days. Cell morphology was observed by scanning electron microscope. Composite material was implanted into the defect of spinal cord in rats. RESULTS AND CONCLUSION: The optimal preparation process of dexamethasone sustained-release microspheres: dosage of dexamethasone was 10 mg, dosage of poly lactic acid-glycolic acid copolymer was 80%, mass fraction of polyvinyl alcohol was 0.5%. Appearance of dexamethasone microspheres was smooth, with a round surface. The encapsulation efficiency, drug-loading rate and yield of microspheres were (2.26±0.03)%, (83.62±0.21)% and (90.87±2.45)% respectively. The growth of mouse bone marrow mesenchymal stem cells was good on the surface of compound dexamethasone microspheres. There was no immunological reaction between the implant material and host, and the material was degraded gradually with time. These results demonstrate that the compound dexamethasone microsphere scaffold has good biocompatibility, which is a favorable kind of biological scaffold material.        

The influence of implantation site on the biocompatibility and survival of alginate encapsulated pig islets in rats

This work investigated the impact of implantation sites on the biocompatibility of alginate encapsulated pig islets. Non-diabetic rats were implanted with adult pig islets encapsulated in alginate either intraperitoneally (IP; n=25), subcutaneously (SC; n=37) or under the kidney capsule (KC; n=34). Capsule biocompatibility (retrieval rate, capsule diameter, degree of capsule broken and cellular overgrowth, CD68/CD3 staining) as well as islets viability and functionality were assessed until 30 days after transplantation. Implantation site did not significantly influence the biocompatibility of empty alginate capsules after transplantation (n=48). Most of the empty capsules (>90%) were retrieved after harvesting and were free of cellular overgrowth until day 30 post-transplantation. Three days after implantation, no significant difference for encapsulated pig islets was observed in terms of capsule biocompatibility and islet functionality in peritoneum, KC or subcutaneously. However, between days 5 and 30 after transplantation, explanted capsules from IP demonstrated a higher degree of broken capsules (>13%) and capsules with severe cellular overgrowth (>50%, CD68+ infiltration) than capsules removed from SC and KC (p<0.05). This was associated with a significant reduction of islet viability, insulin content and insulin secretion. In rats, the peritoneum site seems not appropriate for promoting the engraftment of encapsulated pig islets. Kidney subcapsular and subcutaneous spaces represent an interesting alternative.     

纯镁及两种不同涂层纯镁的溶血现象

背景：尽管作为植入材料镁具有良好的生物相容性及可降解吸收等优点,但镁腐蚀过快,它的快速腐蚀将引起其机械性能在骨组织康复之前就显著下降。 目的：检测纯镁及微弧氧化、二水磷酸氢钙涂层后的纯镁的血液相容性。 方法：将纯镁及微弧氧化、二水磷酸氢钙两种涂层后的纯镁浸提液与抗凝稀释兔血接触,阴性对照组用为生理盐水,阳性对照为蒸馏水。混匀后离心,用分光光度计测定其上清液的A值,计算溶血率。 结果与结论：未经处理的纯镁浸提液组溶血率为52.34%,微弧氧化涂层后的纯镁浸提液组溶血率为0.32%,二水磷酸氢钙涂层后的纯镁浸提液组溶血率为0.14%,阴性对照组溶血率为0,阳性对照组溶血率为100%。提示未经处理的纯镁出现了较严重的溶血现象,涂层后的纯镁血液相容性良好,溶血率小于5%,符合国家标准。     

Differential degradation rates in vivo and in vitro of biocompatible poly(lactic acid) and poly(glycolic acid) homo- and co-polymers for a polymeric drug-delivery microchip

The biocompatibility and biodegradation rate of component materials are critical when designing a drug-delivery device. The degradation products and rate of degradation may play important roles in determining the local cellular response to the implanted material. In this study, we investigated the biocompatibility and relative biodegradation rates of PLA, PGA and two poly(lactic-co-glycolic acid) (PLGA) polymers of 50 : 50 mol ratio, thin-film component materials of a drug-delivery microchip developed in our laboratory. The in vivo biocompatibility and both in vivo and in vitro degradation of these materials were characterized using several techniques. Total leukocyte concentration measurements showed normal acute and chronic inflammatory responses to the PGA and low-molecular-weight PLGA that resolved by 21 days, while the normal inflammatory responses to the PLA and high-molecular-weight PLGA were resolved but at slower rates up to 21 days. These results were paralleled by thickness measurements of fibrous capsules surrounding the implants, which showed greater maturation of the capsules for the more rapidly degrading materials after 21 days, but less mature capsules of sustained thicknesses for the PLA and high-molecular-weight PLGA up to 49 days. Gel-permeation chromatography of residual polymer samples confirmed classification of the materials as rapidly or slowly degrading. These materials showed thinner fibrous capsules than have been reported for other materials by our laboratory and have suitable biocompatibility and biodegradation rates for an implantable drug-delivery device.     

可塑性钛钢板置入治疗有移位的跟骨关节内骨折

背景：切开复位金属植入物置入内固定的方法和内固定材料很多,如特异性钢板、“U”型或者4脚钉直接固定、张力带固定等。由于跟骨形态复杂,切开复位必须是解剖复位及坚强的内固定,那么选择什么样的内固定材料方可避免远期并发创伤性关节炎和行走疼痛等症状呢？ 目的：探讨可塑性钛钢板在治疗有移位跟骨关节内骨折的临床应用价值及生物相容性。 方法：纳入对30例(34足)SandersⅡ~Ⅳ型跟骨骨折患者,采用外侧L型及斜型切口入路、开放复位,置入可塑性钛钢板内固定,全部患者均自体髂骨植骨。X射线片评估钢板置入后疗效,按照Maryland足部功能评分,综合观察患者对疼痛主观感觉、功能恢复、运动情况等方面,同时观察两种切口能否一期愈合。 结果与结论：30例中26例获得随访,时间为9~18个月,与内固定置入前相比,跟骨Bohler、Gissane角均得到很好的恢复(P < 0.001)。按照Maryland足部功能评分,优良率为88.5%,并且外侧斜型切口具备良好的优势。提示可塑性钛钢板是治疗有移位跟骨关节内骨折的可靠方法,内固定前充分有效的准备和医生对跟骨的解剖熟悉以及内固定技巧和时机的掌握是手术成功的关键。