Animal derived materials have been widely used in biomedical products owing to their good biocompatibility and appropriate mechanical properties. It is crucial to evaluate the immunotoxicity of such materials in preclinical testing to prevent severe immune responses in patients. In this study, a pipeline of immunotoxicity tests was established to evaluate animal-derived materials before de-cellularization and final products. This pipeline contains a serial of animal tests on BALB/c mice and an in vitro quantification test for a-Gal antigen. It is well-recognized that the interaction between materials and patients profoundly alters immune responses, thus, a comprehensive dataset including body weight, immune organ coefficient, histopathology, peripheral hematology, serum immunoglobulin level, spleen lymphocyte proliferation rate, and their subpopulation was created and analyzed using the SPSS tool. These results clearly suggested that the de-cellularized materials possessed better biocompatibility, in addition, the a-Gal antigen content was effectively decreased by 96.0 % after decellularization. Thus, this study confirmed that this multi-step enzymatic de-cellularization treatment is a potent method to reduce the immunotoxicity of animal-derived biomaterials. Moreover, the experimental pipeline will likely be transferable to other biomedical materials and products.

The treatment and reconstruction of large or critical size bone defects is a challenging clinical problem. Additive manufacturing breaks the technical difficulties of preparing complex conformation and anatomically matched personalized porous tantalum implants, but the ideal pore structure for 3D-printed porous tantalum in critical bone defect repair applications remains unclear. Guiding appropriate bone tissue regeneration by regulating proper pore size-pore distribution-pore geometry-porosity is a challenge for its fabrication and application. We fabricated porous tantalum (PTa) scaffolds with six different combinations of pore structures using powder bed laser melting (L-PBF) technology. In vitro biological experiments were conducted to systematically investigate the effects of pore structure characteristics on osteoblast behaviors, showing that the bionic trabecular structure with both large and small poress facilitated cell permeation, proliferation and differentiation compared to the cubic structure with uniform pore sizes. The osteogenesis of PTa with different porosity of trabecular structures was further investigated by a rabbit condyle critical bone defect model. Synthetically, T70% up-regulated the expression of osteogenesis-related genes (ALP, COLI, OCN, RUNX-2) and showed the highest bone ingrowth area and bone contact rate in vivo after 16 weeks, with the best potential for critical bone defect repair. Our results suggested that the bionic trabecular structure with a pore size distribution of 200-1200 μm, an average pore size of 700 μm, and a porosity of 70 % is the best choice for repairing critical bone defects, which is expected to guide the clinical application of clinical 3D-printed PTa scaffolds.

The lung is an important organ in systemic toxicity test of medical devices and is significant in safety evaluation. Based on the authors' understanding of medical devices, this study provides a brief analysis of the lung examination and common problems in systemic toxicity, so as to provide references for the pre-clinical safety evaluation of medical devices. It should be noted that a reasonable risk assessment should be made after comprehensive assessment for specific medical device products.

在骨缺损治疗中通常使用生物相容性和机械性能较好的钛合金骨科医疗器械进行替换,但是传统的加工制造工艺不能满足对复杂外形医疗器械的加工要求.近年来流行的3D打印技术具有传统材料制造技术不具有的优点,其性能优良的生物医用材料结合先进的材料制造技术,在骨科医疗器械领域具有很大的发展潜力.在计算机软件的帮助下,可以按照患者的需求制造特殊外形和结构的骨科医疗器械,从而实现个性化医疗.近几年出现了很多3D打印的骨科植入物,都表现出了优良的生物学性能.但是也存在一些问题,例如钛合金材料在力学性能上不能很好地匹配人骨,产生"应力屏蔽"现象,研究者们通过3D打印制造多孔结构的钛合金来降低钛合金人体植入物的弹性模量,也有研究者通过3D打印制造低模量的新型β型钛合金,这两种途径都有效地减小了应力屏蔽现象.此外,3D打印制造的钛合金零件往往会产生空隙和未熔化的粉末缺陷,从而导致表面光滑度下降和金属离子过度析出,影响骨科植入物的生物安全性.研究者们通过对3D打印钛合金骨科植入物进行表面处理,提高了生物安全性.通过创新三维结构和改进钛合金材料的成分使骨科钛合金医疗器械的力学性能得到了较好的优化,通过一些表面处理技术提高了 3D打印钛合金骨科医疗器械的表面质量,进一步提高了其生物安全性和有效性.因此近年来出现了很多临床上使用3D打印钛合金骨科医疗器械修复骨缺损的案例,取得了良好的效果.在未来,3D打印技术将成为定制化骨科医疗器械的主流制造方法,会有更多的3D打印新工艺和新材料出现.本文主要就3D打印骨科钛合金医疗器械产品的研究进展做出简要评述.

背景:作为与循环血液大面积、长时间接触的医疗器械,血液灌流器的血液相容性检测非常重要.目的:检测供试血液灌流器的血液相容性.方法:取供试血液灌流器与已经上市血液灌流器(对照)中的树脂微粒,分别与人抗凝血混合,置于37℃的旋转培养器上,进行体外血液学、血小板、凝血、补体检测.将两种树脂微粒分别与半抗凝兔血接触,通过检测血浆中剩余纤维蛋白原的含量来比较两者血栓形成的程度.将两种树脂微粒置入生理盐水中,再加入稀释抗凝兔血,进行溶血实验.动物实验经中国食品药品检定研究院伦理委员会批准.结果 与结论:①供试血液灌流器树脂微粒组的活化部分凝血活酶时间、血小板数量大于对照灌流器树脂微粒组(P＜0.01),总补体活性小于对照灌流器树脂微粒组(P＜0.01);两组的凝血酶原时间、纤维蛋白原、白细胞及红细胞数量比较差异无显著性意义(P＞0.05);②血栓形成实验中,两组的纤维蛋白原浓度比较差异无显著性意义(P＞0.05);③供试血液灌流器树脂微粒的溶血率为0.2％;④结果表明与对照灌流器中的树脂微粒相比,供试血液灌流器中的树脂微粒对补体和凝血系统的激活相对较为严重(与对照的相对百分比在85％-115％之间),但对血小板数量的影响相对较小,供试血液灌流器中树脂微粒的溶血率较小,其血液相容性可被接受.

医疗器械材料对血小板的激活与其表面性质、接触面积、接触时间和血小板的浓度等因素有关.首先使用家兔血液分别与不同的医疗器械材料进行接触反应,然后检测医疗器械材料接触血液后其血小板数量和形态学指标的变化,并在显微镜下观察分析血小板的数量和形态以对检测结果作进一步的确认和验证.最后统计分析血小板数量的变化和形态学的变化并且进行关联,从而建立一种医疗器械材料体外激活血小板的新方法,可以更科学、更准确地反映出医疗器械材料激活血小板的情况.

目的 评价3D打印骨科钛合金的亚慢性全身毒性.方法 40只SD大鼠随机分为2组,以尾静脉注射途径进行亚慢性全身毒性试验.通过对大鼠体质量、血液学、临床生化、脏器系数、组织病理学检测等指标,综合分析3D打印骨科钛合金的亚慢性全身毒性.结果 两组大鼠均未观察到有生物学意义的异常指标.结论 本研究评价的3D打印骨科钛合金未观察到亚慢性全身毒性.

目的:通过对一个冠脉支架系统血液相容性的全面检测,介绍所用的血液相容性测试方法.方法:以上市的金属药物洗脱支架为产品对照进行体外凝血试验、体内比格犬颈静脉短期血栓形成试验,不用产品对照进行冠脉支架原位植入血栓形成试验和直接光学法溶血试验,对一个聚乳酸基全降解雷帕霉素洗脱冠脉支架系统的血液相容性进行全面检测.结果:供试输送系统和支架的凝血及输送系统的短期血栓形成与产品对照无明显差异,供试冠脉支架的血栓形成及溶血性能、输送系统的溶血性能均可被接受.结论:供试冠脉支架系统的血液相容性可被接受.目前的冠脉支架系统血液相容性试验方法基本可满足需要,但有待于进一步优化并形成标准化的试验方法.

Bioactive bone-inducing material (BBIM) is a collagen-based scaffold composed of demineralized bone matrix and collagen-binding domain bone morphogenetic protein 2 (BMP-2). BBIM is regarded as a promising bone-inducing scaffold to repair bone defects. In this work, we evaluated the biocompatibility and osteogenecity of BBIM. Using enzyme-linked immunosorbent assay, the level of BMP-2 on BBIM was detected and considered adequate. Kunming mice were used as the animal model to investigate the acute systemic toxicity, long-term bone regeneration, ectopic bone formation, and chronic systemic toxicity. Results show that BBIM induced no serious inflammatory reaction or acute and chronic systemic toxicity. Our analyses also demonstrated significant homogeneous ectopic bone formation as well as significantly high numbers of erythrocytes in the BBIM groups in the chronic systemic toxicity study, a phenomenon which may provide indirect proof of the bone regeneration capacity of BBIM, which may be considered as a bioactivity indicator in future studies.

In China, the evaluation of hemocompatibility of biomaterials is limited to hemolysis, coagulation time,and the number and morphology of platelets adhered on biomaterials. The present research, however, is aimed to establish a method for evaluating the function of sheet biomaterials in platelet activation. Platelet activation caused by glass, polyvinyl chloride or polymethylvinylsiloxane sheets was evaluated by measuring alpha-granule membrane protein (GMP-140) in platelet poor plasma, using a reasonable blood-material contact model vibrating at different speed. The result showed that the difference in platelet activation was not significantly different among the three above-mentioned materials at 140r/m or 200r/m. However, when it comes to 230r/m, significant difference was observed among these three groups, with glass > polyvinyl chloride > polymethylvinylsiloxane. But the order was reversed at 270r/m, which may be due to the different interfacial tension of different materials. Therefore, the method is suitable to evaluate platelet activation caused by sheet biomaterials, but an appropriate vibrating speed should be chosen. The interfacial tension plays an important role in the model and should be considered for results assessment.

OBJECTIVE: To study the subchronic dermal toxicity of sodium lactate in rats,and analyze the target organ damage and its reversibility. METHODS:Sodium lactate was given to rats by transdermal administration at th th dose of 2 000,1 000 and 500 mg/kg for 90 days. Some rats from each group were sacrificed at 7 ,13 week and 4 weeks after recovery,blood count and biochemistry were tested,ophthalmic and urinalysis tests were performed,wet weight of individual organs and the coefficient values were determined,and anatomic pathology were observed. RESULTS:With +-+ 2+ all treatment doses,K ,Cl decreased and Na ,Ca increased,protein precipitation was found in the bladder lumen. High dose group showed urinary protein and bilirubin concentration increased,specific gravity reduced. The above had + dose-response relationship. Na values in high dose group remained elevated in the recovery stage. CONCLUSION: Sodium lactate showed significant toxic effects in rats as determined by mild disturbance of electrolyte and abnormal urinary protein.

Objective: To evaluate the biocompatibility of drug eluting stents coated with anti-CD34 antibody using both in vitro test and animal experiment,so as to provide a reference for clinical application of the stents.Methods: Using extracts of drug eluting stents coated with anti-CD34 antibody,series of biocompatibility evaluation experiment was performed,including cytotoxic test,hemolysis test,intracutaneous irritation test,skin sensitization test,acute systematic toxicity test and pyrogen test.Results: Cytotoxicity of the stents was grade 0.There was no obvious intracutaneous irritation and acute systematic toxic reaction as well as skin sensitization reaction.The hemolysis rate of stents materials was 0,showing that the stents had no hemolysis.Pyrogen reaction was not found in three experimental rabbits,and the temperature increase of each rabbit was less than 0.6 ℃(0.1 ℃,0.1 ℃,and 0.1 ℃),and the total temperature increase was 0.3 ℃,less than 1.3 ℃.Conclusion: It shows that when referring to GB / T 16886 standard,drug eluting stents coated with anti-CD34 antibody are biocompatible.

Objective:To observe the corrosion behavior of pure magnesium in different corrosive media,and explore the possible degradation mechanism.Methods:According to ASTM-G31-72 standard used simulated body fluid(SBF) and Dulbecco's modify Eagle medium(DMEM)for immersion media to immerse pure magnesium.Measured calcium,magnesium ion concentration and system pH changes in the different time point.The changes of material surface morphology were investigated by scanning electron microscopy,EDS and XRD.Results: After immersing 8 days,the samples in SBF could not observe the complete shape,while the samples' shape were completed in DMEM.The magnesium ion release quantity and calcium consumption in SBF solution are obviously higher than that of the DMEM solution.The changes of pH in two kinds of corrosion medium did not present too big difference,and the pH was maintained at about 10.0 finally.The product of pure magnesium which soaked in the two kinds of corrosion medium presented big difference.Samples' surface in the SBF system generated magnesium hydroxide,and emerged a small amount of magnesium phosphate precipitation.While in DMEM,there has been a lot of magnesium monohydrogen phosphate,magnesium phosphate,and a small amount of magnesium hydroxide crystals.Conclusion:The SBF system of the corrosion rate was significantly higher than DMEM.Pure magnesium corrosion products generated differently at different time points in the SBF system and DMEM.

BACKGROUND:The bilirubin adsorbent column is used to reduce the high concentration of bilirubin in the blood of patients.During the healing process,the resin particle in the column has a large-scale and long-time contact with the blood of patients.Therefore,the evaluation of blood compatibility of bilirubin adsorbent column is very important.OBJECTIVE:To assess the blood compatibility of a bilirubin adsorbent column.METHODS:Commercially available bilirubin adsorbent column was used as product control.The resin particles in test and control bilirubin adsorbent column were put into silicified glass tubes,respectively.The empty silicified glass tubes were used as blank control.The fresh human plasma was put into silicified glass tubes in three groups and cultured on the rotary incubator in impermeable incubator at the rate of 30 r/min under 37 ℃.After 3 minutes,the plasma was taken out to detect the prothrombin time,activated partial thromboplastin time,fibrinogen and complement hemolysis CH50.The whole process was repeated three times.RESULTS AND CONCLUSION:Compared with the blank control group,prothrombin time and activated partial thromboplastin time in the control group and experimental group were prolonged;concentration of fibrinogen and complement hemolysis CH50 in the control group and experimental group were decreased,but the difference was reducing with the increasing plasma-resin particle contact processes.Compared with control group,values of prothrombin time,activated partial thromboplastin time,fibrinogen in the experimental group were closer to those in the blank control group in three determinations.In three determinations,complement hemolysis CH50 concentration in the experimental group was larger than that in the control group at first,then insignificantly different from the control group and at last smaller than that in the control group.Results indicated that:①The blood compatibility of the resin particles was improved with increasing plasma-resin particle contact processes.②The resin particle in the test bilirubin adsorbent column has fewer effect on the coagulation system than the control product.In first adsorption,the influence of the test resin particle on the complement system was smaller than the control product,but the control product had a faster increase in comparison with complement in later two adsorption processes.

Objective:To investigate the short-term local reaction of α-cyanoacrylate adhesive on a rat liver wound model.Methods: The SD male rat was applied in this study.Testing medical adhesive was sprayed on the liver trauma surface,while,liver trauma surface of control group did not make any treatments.Rats were sacrificed humanely 5 minutes,1 day and 3 days post-operation.The local reaction was observed macroscopically and microscopically.Results: Gross appearance: There was no abnormal appearance in the operation area.Microscopic appearance: Inflammatory response was observed in both testing and control group after 1 day,accompanied by exudation of neutrophils,lymphocytes and phagocytes,and fibrous cell proliferation;but necrosis was not found.The medical adhesive group displayed minor inflammation and better wound healing than control group after 3 days.Conclusion: α-cyanoacrylate adhesive could not cause local liver tissue necrosis.Only minor inflammation was found.The wound healing of testing group was better than that of control group.

For the problem of the near-far unfairness in cognitive radio system, an improved power control algorithm(GLNPC) was proposed by designing a logarithm utility function based on SNR and adding channel gain factor to pricing function, then the existence and uniqueness of the Nash equilibrium were proved. The simulation results show that GLNPC can not only meets the requirement of user's SIR, but also effectively solves the near-far unfairness, therefore realized sharing spectrum resources.

目的 研究不同浓度的银纳米颗粒对神经元毒性的剂量-效应关系,探索银纳米颗粒对神经元的毒性机理.方法 首先培养一种活性好、生长状态优良的原代神经元,将不同浓度(2.5～500μg/mL)的银纳米颗粒加入神经元中作用24h后,通过MTT法计算细胞增殖率,并分析不同浓度的银纳米颗粒对神经元毒性的剂量-效应关系.结果 在25～250μg/mL范围内,细胞数量与形态呈现不同的变化,银纳米颗粒浓度与细胞增殖率呈负相关.结论 在25～250μg/mL的浓度范围内,银纳米颗粒对神经元细胞的毒性呈剂量-效应关系.

BACKGROUND: The hollow fiber in hemodialyzer has a large-scale and long-time contact with the blood of the renal dialysis patients. The evaluation of the hollow fiber's hemocompatibility is very important. OBJECTIVE: The evaluation method of in vitro hemocompatibility of the hemodialyzer was primarily established by twice evaluating hollow fiber's hemocompatibility in a hemodialyzer. METHODS: The hollow fiber of the sample hemodialyzer was cut into 3-cm length, and 100 hollow fibers were put into the silicified glass tube as a sample. In this experiment, the sample hemodialyzer was tested twice with two different commercially available hemodialyzers as controls. The similar surface-area hollow fiber of the control hemodialyzers was disposed in the same way. 1.2 mL fresh human blood was added into every silicified glass tube, then all tubes was put onto the slightly sloping rotary incubator at 37 °C and rotated at the speed of 30 r/min for 30 minutes. Finally, the blood in all silicified glass tubes was detected for blood cell analysis, coagulation analysis and serum total complements activity determination respectively. RESULTS AND CONCLUSION: Different parameters exhibited significant differences between the sample hollow fiber and two control hollow fibers. But the remarkable consume of fibrinogen and platelet was similar in the two tests, and the "{pipe}(parameter of sample-parameter of control){pipe}/parameter of control ×100%" was far greater than 15%.So the difference on the hemocompatibility between the sample hollow fiber and control hollow fibers is not acceptable, which indicates that the in vitro hemocompatibility evaluation method has a good reproducibility.

Objective:Assess cytotoxicity of medical device with silver nanoparticles and assay the reason of the cytotoxicity.Method:The nine kinds of silver nanoparticle samples in three types were tested by MTT cytotoxicity method.Result:The test showed that the cytotoxic ity in 9 final samples all were grade 3 to 4;the gels and dressings which are semi-finished products without silver nanoparticles,were grade 1 of cytotoxicity;patches were grade 4 of cytotoxicity;patches without adhesive were grade 1 of cytotoxicity.Conclusion:Silver nanoparticle medical devices in the present test showed moderate or severe cytotoxicity.Gels or dressings only which without silver nanoparticle showed slightly cytotoxicity.Patches only which without silver nanoparticle showed severe cytotoxicity,and adhesive is the main reason of the cytotoxicity.Whether the severe cytotoxicity will induce persist cell damage,and the detail mechanisms of silver nanoparticle or adhesive-induced cytotoxicity need further investigation.

Objective To evaluate the hemocompatibility of a new inferior vena cava filter (X filter) and the Cordis inferior vena cava filter(C filter). Methods Eight male pigs, (30 ± 5) kg wt were adopted as the experimental animal. The X and C filters were implanted into animal’s vena cava inferior(at the margin of renal vein opening) without using any anticoagulants and followed-up 14 days. Then withdrew the filters and observed thrombosis on them. The filter transmission system was observed by scanning electron microscopy(SEM). Before implanting and withdrawing the filter, cavography was performed respectively, WBC and platelet count were detected. Results The results showed that the X and C filters didn’t significantly affect the WBC and platelet count. The average change of WBC was (0.575 ± 4.333) × 109 in X filters and(3.375 ± 9.411) × 109 in C filters,and the average change of PLT was(-0.500 ± 57.190) × 109 in X filters and (-33.000 ± 57.860) × 109 in C filters. No thrombosis was found in both filter transmission systems by SEM study. The result of cavography showed that the blood flow in X filters was blocked in different intensities but the blood flow was not affected in C filters. Thrombosis was serious in the X filters, but was not found in C filters. Conclusion It is demonstrated that the hemocompatibility of C filter is superior to X filter.