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Fabrication and surface modification of poly lactic acid (PLA) scaffolds with epidermal growth factor for neural tissue engineering. 用表皮生长因子制造和修饰聚乳酸(PLA)支架,用于神经组织工程。
Pub Date : 2016-01-01 Epub Date: 2016-10-14 DOI: 10.1080/21592535.2016.1231276
Tanit Haddad, Samantha Noel, Benoît Liberelle, Rouwayda El Ayoubi, Abdellah Ajji, Gregory De Crescenzo

In an effort to design biomaterials that may promote repair of the central nervous system, 3-dimensional scaffolds made of electrospun poly lactic acid nanofibers with interconnected pores were fabricated. These scaffolds were functionalized with polyallylamine to introduce amine groups by wet chemistry. Experimental conditions of the amination protocol were thoroughly studied and selected to introduce a high amount of amine group while preserving the mechanical and structural properties of the scaffold. Subsequent covalent grafting of epidermal growth factor was then performed to further tailor these aminated structures. The scaffolds were then tested for their ability to support Neural Stem-Like Cells (NSLCs) culture. Of interest, NSLCs were able to proliferate on these EGF-grafted substrates and remained viable up to 14 d even in the absence of soluble growth factors in the medium.

为了设计可促进中枢神经系统修复的生物材料,我们制作了由电纺聚乳酸纳米纤维制成的具有相互连接孔隙的三维支架。通过湿化学方法,这些支架被聚烯丙基胺功能化,从而引入胺基团。对胺化方案的实验条件进行了深入研究和选择,以引入大量胺基,同时保持支架的机械和结构特性。随后进行了表皮生长因子的共价接枝,以进一步定制这些胺化结构。然后测试了这些支架支持神经干样细胞(NSLCs)培养的能力。令人感兴趣的是,NSLCs 能够在这些表皮生长因子接枝的基底上增殖,即使在培养基中没有可溶性生长因子的情况下也能存活长达 14 天。
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引用次数: 0
Enhanced bioactivity of glass ionomer cement by incorporating calcium silicates 通过掺入硅酸钙提高玻璃离子水门合剂的生物活性
Pub Date : 2016-01-01 DOI: 10.1080/21592535.2015.1123842
Song Chen, Yixiao Cai, H. Engqvist, W. Xia
ABSTRACT Glass ionomer cements (GIC) are known as a non-bioactive dental cement. During setting the GIC have an acidic pH, driven by the acrylic acid component. It is a challenge to make GIC alkaline without disturbing its mechanical properties. One strategy was to add slowly reacting systems with an alkaline pH. The aim of the present study is to investigate the possibility of forming a bioactive dental material based on the combination of glass ionomer cement and calcium silicates. Two types of GIC were used as control. Wollastonite (CS also denoted β-CaSiO3) or Mineral Trioxide Aggregate (MTA) was incorporated into the 2 types of GIC. The material formulations’ setting time, compressive strength, pH and bioactivity were compared between modified GIC and GIC control. Apatite crystals were found on the surfaces of the modified cements but not on the control GIC. The compressive strength of the cement remained with the addition of 20% calcium silicate or 20% MTA after one day immersion. In addition, the compressive strength of GIC modified with 20% MTA had been increased during the 14 d immersion (p < 0 .05).
玻璃离子水门剂(GIC)是一种非生物活性的牙科水门剂。在凝固过程中,受丙烯酸组分的驱动,GIC的pH值呈酸性。在不影响其力学性能的情况下使GIC碱性是一个挑战。一种策略是添加具有碱性的缓慢反应系统。本研究的目的是研究形成基于玻璃离子水门合剂和硅酸钙组合的生物活性牙科材料的可能性。两种类型的GIC作为对照。硅灰石(CS也表示β-CaSiO3)或矿物三氧化骨料(MTA)被加入到两种类型的GIC中。比较了改性GIC与对照GIC对材料配方的凝固时间、抗压强度、pH值和生物活性的影响。在改性水泥表面发现了磷灰石晶体,而在对照水泥表面没有发现磷灰石晶体。掺入20%硅酸钙或20% MTA后,水泥的抗压强度保持不变。此外,经20% MTA改性的GIC抗压强度在浸泡14 d期间有所提高(p < 0.05)。
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引用次数: 18
Effect of grain sizes on mechanical properties and biodegradation behavior of pure iron for cardiovascular stent application. 晶粒尺寸对心血管支架用纯铁力学性能和生物降解行为的影响。
Pub Date : 2016-01-01 DOI: 10.4161/21592527.2014.959874
Camillus Sunday Obayi, Ranna Tolouei, Afghany Mostavan, Carlo Paternoster, Stephane Turgeon, Boniface Adeleh Okorie, Daniel Oray Obikwelu, Diego Mantovani

Pure iron has been demonstrated as a potential candidate for biodegradable metal stents due to its appropriate biocompatibility, suitable mechanical properties and uniform biodegradation behavior. The competing parameters that control the safety and the performance of BMS include proper strength-ductility combination, biocompatibility along with matching rate of corrosion with healing rate of arteries. Being a micrometre-scale biomedical device, the mentioned variables have been found to be governed by the average grain size of the bulk material. Thermo-mechanical processing techniques of the cold rolling and annealing were used to grain-refine the pure iron. Pure Fe samples were unidirectionally cold rolled and then isochronally annealed at different temperatures with the intention of inducing different ranges of grain size. The effect of thermo-mechanical treatment on mechanical properties and corrosion rates of the samples were investigated, correspondingly. Mechanical properties of pure Fe samples improved significantly with decrease in grain size while the corrosion rate decreased marginally with decrease in the average grain sizes. These findings could lead to the optimization of the properties to attain an adequate biodegradation-strength-ductility balance.

纯铁具有良好的生物相容性、良好的力学性能和均匀的生物降解性能,是生物可降解金属支架的潜在候选材料。适当的强度-延性组合、生物相容性、动脉腐蚀速率与愈合速率的匹配率是影响BMS安全性和性能的竞争参数。作为一种微米尺度的生物医学设备,上述变量已被发现由块材料的平均晶粒尺寸控制。采用冷轧和退火的热机械加工技术使纯铁晶粒细化。对纯铁试样进行单向冷轧,然后在不同温度下进行等时退火,以诱导不同范围的晶粒尺寸。研究了热处理对试样力学性能和腐蚀速率的影响。纯铁试样的力学性能随着晶粒尺寸的减小而显著提高,而腐蚀速率随着平均晶粒尺寸的减小而略有下降。这些发现可能导致性能的优化,以达到适当的生物降解-强度-延性平衡。
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引用次数: 62
The effect of oligo(trimethylene carbonate) addition on the stiffness of acrylic bone cement 低聚碳酸三亚甲基对丙烯酸骨水泥刚度的影响
Pub Date : 2016-01-01 DOI: 10.1080/21592535.2015.1133394
C. Persson, Alejandro López, H. Fathali, A. Hoess, R. Rojas, M. Ott, J. Hilborn, H. Engqvist
ABSTRACT With the increasing elderly population an increase in the number of bony fractures associated to age-related diseases such as osteoporosis also follows. The relatively high stiffness of the acrylic bone cements used in these patients has been suggested to give raise to a suboptimal load distribution surrounding the cement in vivo, and hence contribute to clinical complications, such as additional fractures. The aim of this study was to develop a low-modulus bone cement, based on currently used, commercially available poly(methyl methacrylate) (PMMA) cements for vertebroplasty. To this end, acrylate end-functionalized oligo(trimethylene carbonate) (oTMC) was incorporated into the cements, and the resulting compressive mechanical properties were evaluated, as well as the cytotoxic and handling properties of selected formulations. Sixteen wt%oTMC was needed in the vertebroplastic cement Osteopal V to achieve an elastic modulus of 1063 MPa (SD 74), which gave a corresponding compressive strength of 46.1 MPa (SD 1.9). Cement extracts taken at 1 and 12 hours gave a reduced MG-63 cell viability in most cases, while extracts taken at 24 hours had no significant effect on cell behavior. The modification also gave an increase in setting time, from 14.7 min (SD 1.7) to 18.0 min (SD 0.9), and a decrease in maximum polymerization temperature, from 41.5°C (SD 3.4) to 30.7°C (SD 1.4). While further evaluation of other relevant properties, such as injectability and in vivo biocompatibility, remains to be done, the results presented herein are promising in terms of approaching clinically applicable bone cements with a lower stiffness.
随着老年人口的增加,骨质疏松症等与年龄相关疾病相关的骨折数量也随之增加。在这些患者中使用的丙烯酸骨水泥相对较高的刚度被认为会导致体内骨水泥周围的负荷分布不理想,从而导致临床并发症,例如额外的骨折。本研究的目的是开发一种低模量骨水泥,基于目前使用的,市售的用于椎体成形术的聚甲基丙烯酸甲酯(PMMA)水泥。为此,将丙烯酸酯端功能化低聚(三亚甲基碳酸酯)(oTMC)掺入水泥中,并评估了所选配方的压缩力学性能,以及细胞毒性和处理性能。椎体成形性骨水泥V需要16%的oTMC才能达到1063 MPa (SD 74)的弹性模量,相应的抗压强度为46.1 MPa (SD 1.9)。在大多数情况下,1小时和12小时服用的水泥提取物会降低MG-63细胞的活力,而24小时服用的提取物对细胞行为没有显著影响。改性还使固化时间从14.7 min (SD 1.7)增加到18.0 min (SD 0.9),最大聚合温度从41.5℃(SD 3.4)降低到30.7℃(SD 1.4)。虽然其他相关性能的进一步评估,如可注射性和体内生物相容性,仍有待完成,但本文提出的结果在接近临床应用的低刚度骨水泥方面是有希望的。
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引用次数: 6
Small-sized granules of biphasic bone substitutes support fast implant bed vascularization. 小颗粒双相骨替代物支持快速种植床血管化。
Pub Date : 2015-01-01 DOI: 10.1080/21592535.2015.1056943
M Barbeck, M Dard, M Kokkinopoulou, J Markl, P Booms, R A Sader, C J Kirkpatrick, S Ghanaati

The present study investigated the influence of granule size of 2 biphasic bone substitutes (BoneCeramic® 400-700 μm and 500-1000 μm) on the induction of multinucleated giant cells (MNGCs) and implant bed vascularization in a subcutaneous implantation model in rats. Furthermore, degradation mechanisms and particle phagocytosis of both materials were examined by transmission electron microscopy (TEM). Both granule types induced tissue reactions involving primarily mononuclear cells and only small numbers of MNGCs. Higher numbers of MNGCs were detected in the group with small granules starting on day 30, while higher vascularization was observed only at day 10 in this group. TEM analysis revealed that both mono- and multinucleated cells were involved in the phagocytosis of the materials. Additionally, the results allowed recognition of the MNGCs as the foreign body giant cell phenotype. Histomorphometrical analysis of the size of phagocytosed particles showed no differences between the 2 granule types. The results indicate that granule size seems to have impact on early implant bed vascularization and also on the induction of MNGCs in the late phase of the tissue reaction. Furthermore, the results revealed that a synthetic bone substitute material can induce tissue reactions similar to those of some xenogeneic materials, thus pointing to a need to elucidate their "ideal" physical characteristics. The results also show that granule size in the range studied did not alter phagocytosis by mononuclear cells. Finally, the investigation substantiates the differentiation of material-induced MNGCs, which are of the foreign body giant cell type.

本研究在大鼠皮下植入模型中研究了两种双相骨替代物(BoneCeramic®400-700 μm和500-1000 μm)颗粒大小对诱导多核巨细胞(MNGCs)和植入床血管形成的影响。通过透射电子显微镜(TEM)研究了两种材料的降解机制和颗粒吞噬作用。两种颗粒类型均诱导主要涉及单个核细胞和少量MNGCs的组织反应。小颗粒组在第30天开始检测到较多的MNGCs,而在第10天仅观察到较高的血管化。透射电镜分析表明,单核细胞和多核细胞都参与了物质的吞噬。此外,结果允许将MNGCs识别为异物巨细胞表型。吞噬颗粒的组织形态学分析显示,两种颗粒类型之间没有差异。结果表明,颗粒大小似乎对早期植入床血管化有影响,也对组织反应后期MNGCs的诱导有影响。此外,研究结果表明,合成骨替代材料可以诱导类似于某些异种材料的组织反应,因此需要阐明其“理想”的物理特性。结果还表明,颗粒大小在研究范围内不改变单核细胞的吞噬作用。最后,研究证实了材料诱导的MNGCs的分化,属于异物巨细胞类型。
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引用次数: 44
Cell infiltration into a 3D electrospun fiber and hydrogel hybrid scaffold implanted in the brain. 细胞浸润到3D电纺丝纤维和水凝胶混合支架植入大脑。
Pub Date : 2015-01-01 DOI: 10.1080/21592535.2015.1005527
Christopher J Rivet, Kun Zhou, Ryan J Gilbert, David I Finkelstein, John S Forsythe

Tissue engineering scaffolds are often designed without appropriate consideration for the translational potential of the material. Solid scaffolds implanted into central nervous system (CNS) tissue to promote regeneration may require tissue resection to accommodate implantation. Or alternatively, the solid scaffold may be cut or shaped to better fit an irregular injury geometry, but some features of the augmented scaffold may fail to integreate with surrounding tissue reducing regeneration potential. To create a biomaterial able to completely fill the irregular geometry of CNS injury and yet still provide sufficient cell migratory cues, an injectable, hybrid scaffold was created to present the physical architecture of electrospun fibers in an agarose/methylcellulose hydrogel. When injected into the rat striatum, infiltrating macrophages/microglia and resident astrocytes are able to locate the fibers and utilize their cues for migration into the hybrid matrix. Thus, hydrogels containing electrospun fibers may be an appropriate platform to encourage regeneration of the injured brain.

组织工程支架的设计往往没有适当考虑材料的转化潜力。固体支架植入中枢神经系统(CNS)组织促进再生可能需要组织切除以适应植入。或者,实体支架可以被切割或塑造,以更好地适应不规则的损伤几何形状,但增强支架的某些特征可能无法与周围组织融合,从而降低再生潜力。为了创造一种能够完全填补中枢神经系统损伤的不规则几何形状,同时仍能提供足够的细胞迁移线索的生物材料,一种可注射的混合支架被创造出来,在琼脂糖/甲基纤维素水凝胶中呈现电纺丝纤维的物理结构。当注入大鼠纹状体时,浸润的巨噬细胞/小胶质细胞和驻留的星形胶质细胞能够定位纤维并利用它们的线索迁移到混合基质中。因此,含有电纺丝纤维的水凝胶可能是促进受伤大脑再生的合适平台。
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引用次数: 49
Strontium ranelate improves the interaction of osteoblastic cells with titanium substrates: Increase in cell proliferation, differentiation and matrix mineralization. 雷奈酸锶改善成骨细胞与钛基质的相互作用:增加细胞增殖、分化和基质矿化。
Pub Date : 2015-01-01 DOI: 10.1080/21592535.2015.1027847
William Querido, Marcos Farina, Karine Anselme

We describe direct effects of strontium ranelate on the interaction of osteoblastic cells with different titanium substrates. Our goal was to better understand the potential of this drug for improving the efficacy of bone implants. Treatment was done with 0.12 and 0.5 mM Sr(2+) of strontium ranelate in cell culture. We analyzed cell response to the drug on titanium substrates with surface topographies obtained using acid etching, electro-erosion processing, sandblasting, and machine-tooling. Treatment preserved the initial cell adhesion to the substrates, cell shape parameters (area, aspect ratio, circularity, and solidity), and the orientation of cells on grooved surfaces. However, both concentrations of the drug increased cell proliferation in all substrates. Moreover, a dose-dependent increase in alkaline phosphatase activity and in the production of mineralized matrix with typical features of bone tissue was shown. The observed effects were similar in the different substrates. In conclusion, strontium ranelate improved the interaction of osteoblastic cells with titanium substrates, increasing cell proliferation and differentiation into mature osteoblasts and the production of bone-like mineralized matrix for all substrates. This study highlights a promising role of strontium ranelate on enhancing the clinical success of bone implants, particularly in patients with osteoporosis.

我们描述了雷奈酸锶对成骨细胞与不同钛基质相互作用的直接影响。我们的目标是更好地了解这种药物在提高骨植入物疗效方面的潜力。在细胞培养中分别用0.12和0.5 mM Sr(2+)的雷奈酸锶处理。我们分析了细胞对药物在钛基板上的反应,这些钛基板的表面形貌是通过酸蚀刻、电侵蚀、喷砂和机械加工获得的。处理保留了细胞与基质的初始粘附、细胞形状参数(面积、长宽比、圆度和固体度)以及细胞在凹槽表面上的方向。然而,两种浓度的药物都增加了所有底物中的细胞增殖。此外,碱性磷酸酶活性和矿化基质的产生呈剂量依赖性增加,具有骨组织的典型特征。在不同基质中观察到的效果是相似的。综上所述,雷奈酸锶改善了成骨细胞与钛基质的相互作用,促进了成骨细胞的增殖和向成熟成骨细胞的分化,并促进了所有基质的骨样矿化基质的产生。这项研究强调了雷奈酸锶在提高骨植入物临床成功率方面的重要作用,特别是在骨质疏松症患者中。
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引用次数: 14
Development of a novel carrier optimized for cell sheet transplantation. 细胞片移植优化载体的研制。
Pub Date : 2015-01-01 DOI: 10.1080/21592535.2015.1027846
Yosuke Amagai, Kaoru Karasawa, Jung Kyungsook, Akira Matsuda, Masanori Kojima, Jun Watanabe, Toyoji Hibi, Hiroshi Matsuda, Akane Tanaka

Tissue engineering is a rapidly advancing technology in the field of regenerative medicine. For the transplantation of cell sheets, a carrier must maintain the shape of a cell sheet from a culture dish to affected sites as well as release the sheet easily onto the lesion. In this study, we examined the utility of a novel, poly(lactic acid)-based carrier for cell sheets transplantation to the cornea of dogs and the skin of rats. The poly(lactic acid)-based carrier easily picked a cell sheet up from the dish, fit to the shape of the transplantation sites, and saved time for cell sheets detachment comparing to a conventional carrier. Thus, the poly(lactic acid)-based carrier would be useful for easy cell sheet transplantations.

组织工程是再生医学领域中一项快速发展的技术。对于细胞片的移植,载体必须保持细胞片从培养皿到受影响部位的形状,并且很容易将细胞片释放到病变部位。在这项研究中,我们研究了一种新型的、基于聚乳酸的细胞片载体移植到狗的角膜和大鼠的皮肤上的效用。聚乳酸基载体很容易从培养皿中取出细胞片,适合移植部位的形状,与传统载体相比,节省了细胞片剥离的时间。因此,以聚乳酸为基础的载体可用于细胞片移植。
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引用次数: 8
On the potential for fibronectin/phosphorylcholine coatings on PTFE substrates to jointly modulate endothelial cell adhesion and hemocompatibility properties. 聚四氟乙烯基纤维连接蛋白/磷胆碱涂层联合调节内皮细胞粘附和血液相容性的潜力。
Pub Date : 2015-01-01 DOI: 10.4161/21592535.2014.979679
Vanessa Montaño-Machado, Pascale Chevallier, Diego Mantovani, Emmanuel Pauthe

The use of biomolecules as coatings on biomaterials is recognized to constitute a promising approach to modulate the biological response of the host. In this work, we propose a coating composed by 2 biomolecules susceptible to provide complementary properties for cardiovascular applications: fibronectin (FN) to enhance endothelialization, and phosphorylcholine (PRC) for its non thrombogenic properties. Polytetrafluoroethylene (PTFE) was selected as model substrate mainly because it is largely used in cardiovascular applications. Two approaches were investigated: 1) a sequential adsorption of the 2 biomolecules and 2) an adsorption of the protein followed by the grafting of phosphorylcholine via chemical activation. All coatings were characterized by immunofluorescence staining, X-Ray Photoelectron Spectroscopy and Scanning Electron Microscopy analyses. Assays with endothelial cells showed improvement on cell adhesion, spreading and metabolic activity on FN-PRC coatings compared with the uncoated PTFE. Platelets adhesion and activation were both reduced on the coated surfaces when compared with uncoated PTFE. Moreover, clotting time tests exhibited better hemocompatibility properties of the surfaces after a sequential adsorption of FN and PRC. In conclusion, FN-PRC coating improves cell adhesion and non-thrombogenic properties, thus revealing a certain potential for the development of this combined deposition strategy in cardiovascular applications.

利用生物分子作为生物材料的涂层被认为是一种有前途的方法来调节宿主的生物反应。在这项工作中,我们提出了一种由两种生物分子组成的涂层,它们易于为心血管应用提供互补特性:纤维连接蛋白(FN)增强内皮化,磷酰胆碱(PRC)具有非血栓形成特性。选择聚四氟乙烯(PTFE)作为模型基材主要是因为它在心血管领域有广泛的应用。研究了两种方法:1)2个生物分子的顺序吸附和2)蛋白质的吸附,然后通过化学活化接枝磷胆碱。采用免疫荧光染色、x射线光电子能谱和扫描电镜对涂层进行表征。内皮细胞实验显示,与未涂覆PTFE相比,涂覆FN-PRC的细胞粘附、扩散和代谢活性均有改善。与未涂覆的PTFE相比,涂覆表面的血小板粘附和活化都降低了。此外,凝血时间测试显示,连续吸附FN和PRC后,表面具有更好的血液相容性。综上所述,FN-PRC涂层改善了细胞粘附性和非血栓形成性,从而揭示了这种联合沉积策略在心血管应用中的发展潜力。
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引用次数: 31
Platinum metallization for MEMS application MEMS应用的铂金属化
Pub Date : 2014-04-17 DOI: 10.4161/biom.28822
V. Guarnieri, L. Biazi, R. Marchiori, A. Lago
The adherence of Platinum thin film on Si/SiO2 wafer was studies using Chromium, Titanium or Alumina (Cr, Ti, Al2O3) as interlayer. The adhesion of Pt is a fundamental property in different areas, for example in MEMS devices, which operate at high temperature conditions, as well as in biomedical applications, where the problem of adhesion of a Pt film to the substrate is known as a major challenge in several industrial applications health and in biomedical devices, such as for example in the stents.1-4 We investigated the properties of Chromium, Titanium, and Alumina (Cr, Ti, and Al2O3) used as adhesion layers of Platinum (Pt) electrode. Thin films of Chromium, Titanium and Alumina were deposited on Silicon/Silicon dioxide (Si/SiO2) wafer by electron beam. We introduced Al2O3 as a new adhesion layer to test the behavior of the Pt film at higher temperature using a ceramic adhesion thin film. Electric behaviors were measured for different annealing temperatures to know the performance for Cr/Pt, Ti/Pt, and Al2O3/Pt metallic film in the gas sensor application. All these metal layers showed a good adhesion onto Si/SiO2 and also good Au wire bondability at room temperature, but for higher temperature than 400 °C the thin Cr/Pt and Ti/Pt films showed poor adhesion due to the atomic inter-diffusion between Platinum and the metal adhesion layers.5 The proposed Al2O3/Pt ceramic-metal layers confirmed a better adherence for the higher temperatures tested.
采用铬、钛或氧化铝(Cr、Ti、Al2O3)作为中间层,研究了铂薄膜在Si/SiO2硅片上的粘附性。Pt的粘附性是不同领域的基本特性,例如在高温条件下工作的MEMS器件,以及在生物医学应用中,Pt薄膜粘附到衬底的问题被认为是几个工业应用中健康和生物医学设备(例如支架)的主要挑战。我们研究了铬、钛和氧化铝(Cr、Ti和Al2O3)作为铂(Pt)电极粘附层的性能。利用电子束在硅/二氧化硅(Si/SiO2)薄片上沉积了铬、钛和氧化铝薄膜。我们引入Al2O3作为新的粘附层,使用陶瓷粘附薄膜测试Pt薄膜在高温下的行为。测定了不同退火温度下Cr/Pt、Ti/Pt和Al2O3/Pt金属薄膜在气体传感器中的性能。在室温下,这些金属层对Si/SiO2和Au线均具有良好的粘附性,但当温度高于400℃时,由于铂与金属粘附层之间的原子互扩散,Cr/Pt和Ti/Pt薄膜的粘附性较差所提出的Al2O3/Pt陶瓷-金属层在高温测试中具有更好的粘附性。
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引用次数: 24
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