无机纳米填料对植入硅橡胶生物相容性的影响北大核心

背景:硅橡胶是人体组织、器官外科修复重建的常用生物材料,但其自身存在生物相容性缺陷,无机纳米填料为植入硅橡胶的生物相容性改良和构建具有特定功能的复合材料提供了新契机。目的:综述植入硅橡胶添加无机纳米填料改性在生物相容改良研究方面已取得的成果及不足。方法:在PubMed、Web of Science和Medline等英文生物医学数据库,输入“siloxane,silicone rubber,inorganic nano-filler,metal nano-filler,metal oxide nano-filler,carbon nanoparticles”关键词,在万方、CNKI和维普等中文数据库输入“硅橡胶、无机纳米填料、纳米金属、纳米金属氧化物、纳米碳”关键词,分别检索出与无机纳米填料改性硅橡胶的相关文献,时间跨度从2014年1月至2020年10月。结果与结论:利用纳米金属及其氧化物和纳米新碳填料对植入硅橡胶本体或表面进行改性,增进了硅橡胶的生物相容性,可在细胞生长、抗凝血、表面特性、力学性能、耐久性、抗感染功能化等方面产生积极影响。未来需研究不同纳米填料对硅橡胶表面性质(如拓扑结构、电荷、湿润性)造成的细胞增殖移行机制、纳米金属杀菌剂在硅橡胶表面控释阳离子的细菌-纳米粒子相互作用调节策略,以及植入后潜在的纳米毒性。     

改善生物医用纤维材料表面血液相容性研究进展

随着医用合成纤维材料在生物医学领域的广泛应用,对其性能的要求也不断提高,近年来许多学者对医用合成纤维材料的表面改性进行了深入的研究,并取得了一定的进展。该文主要从等离子体改性、材料表面内皮化和表面接枝改性三方面论述了医用合成纤维材料血液相容性的表面改性研究。     

医用聚氨醋材料研究新进展

聚氨酯具有良好的生物相容性和机械强度并且易于加工成型,是最具价值的生物医学合成材料之一,可分为惰性聚氨酯和降解性聚氨醋两类.医用惰性聚氨酯材料稳定、耐磨、力学性能好,广泛用于医用装置及人工器官.文中从采用新型抗氧剂,减少醚键,与硅烷嵌段共聚改性以提高其生物稳定性、生物相容性及抗菌性等三个方面,综述了惰性聚氨酯材料的研究重点;医用降解性聚氨酯材料有利于人体健康和环保、安全、便捷,可作为人体修复材料和智能药物缓释材料,文中从提高降解性及力学性能两个方面,讨论了降解性聚氨酯材料的研究热点.解决医用惰性聚氨酯材料环境污染问题,降低医用降解性聚氨酯材料降解产物毒性,研发聚氨酯复合材料,加强临床试验将成为新的课题.     

医用聚氨酯生物相容性研究新进展

聚氨酯因有良好的生物相容性和机械性能，而被广泛用于生物医学领域，但聚氨酯长期植入人体内，也会引起机体的炎症反应，使材料发生老化降解现象。因而要进一步提高医用聚氨酯的生物相容性，使其与机体生理环境更加相容，不诱发或少诱发炎症反应，就要使材料表面更加生物化，可以维持蛋白的正常构象。本文综述了以仿生化为基础提高医用聚氨酯生物相容性的两种主要途径－表面内皮细胞化及仿生物膜结构（表面膦脂化），并总结了其实施方法及存在的问题。     

多孔聚合物材料的应用及其生物相容性

以隔离膜材料、引导组织再生材料和杂化的人造器官材料为代表,介绍了多孔聚合物材料在生物医学领域中的应用。从植入高分子材料诱发肿瘤、囊性增和和长期炎症反应等方面讨论了材料的表面微观拓扑结构对生物相容性的影响,指出了材料结构相容性的重要性。     

硅橡胶材料对血浆蛋白及血小板粘附作用的半体内试验

本文是研究三种血浆蛋白(γ—球蛋白、纤维蛋白原、白蛋白)在医用硅橡胶材料表面吸附的半体内同位素标记评价方法,同时由扫描电镜观察材料表面血小板粘附的数量和形态变化,从而评价国内外三种医用热硫化甲基乙烯基硅橡胶材料的血液相容性。研究结果表明:CHGB和DCGBE二种材料血液相容性相近,而STGB材料血液相容性较差。     

目前生物医用材料领域的研究热点

<正>1生物材料表面改性改进和发展生物医用材料的血液相容性和组织相容性以及生物材料分子相容性评价新方法研究。今后对材料生物相容性的研究主要集中在以下3个方面:①生物医用材料对组织、器官的     

血液相容性抗凝血生物医用高分子材料的制备及其机制

背景:由于生物医用材料要接触人体内环境,甚至必须植入生物体内,因此要求具有无毒性、优良的生物相容性、高化学稳定性、合适的物理机械性能以及易加工成型性。 目的：从生物惰性材料、生物活性表面和白蛋白的结构及其在抗凝血上的应用几个方面分析血液相容性抗凝血生物医用高分子材料的制备及其机制。 方法：由第一作者检索1969/2010 PubMed数据及万方数据库有关血液相容性抗凝血生物医用高分子材料的制备及其机制等方面的文献。 结果与结论：目前抗凝血材料的制备基本上只是采用单独的生物惰性表面或生物活性表面,虽然都获得了较好效果,但不能长期保持其生物相容性尤其是血液相容性,如果能将惰性表面与活性表面结合起来,使材料同时具备两者的长处,并能充分利用人体血液中的天然组分白蛋白或许会是抗凝血材料的一个发展趋势。今后希望通过采用高生物惰性的PEU和具有生物活性的白蛋白识别因子cibacron blue复合,合成具有优良性质的活性改性物,并以此对聚氨酯进行改性。     

用于心血管医疗装置的聚合物表面构建与生物相容性研究Ⅲ——聚合物生物材料表面的凝血及抗凝血涂层改性（英文）

背景:用于心血管医疗的生物材料在血液接触性条件下必须具有抗血栓性、对抗生物降解性与抗感染性。目的:研制用于心血管组织工程的新型植(介)入型聚合物材料(表面),从聚合物生物材料表面的凝血及抗凝血涂层改性方面考察各种相应改性表面的生物相容性、血液相容性和细胞相容性。方法:检索1983至2014年PubMed数据库及万方数据库。英文检索词为"biocompatibility,blood compatibility,biomedical materials,biomedical polymer materials",中文检索词为"生物相容性材料;血液相容性材料;生物医用材料;医用高分子材料"。排除与研究目的相关性差及内容陈旧、重复的文献,保留与生物医用高分子材料的血液相容性研究,进行归纳总结。结果与结论:通过对血液与植入物间的相互作用和生物材料表面的抗凝血涂层改性两个方面的归纳分析,从聚合物生物材料表面的凝血及抗凝血涂层改性方面考察了各种相应改性表面的生物相容性、血液相容性和细胞相容性。研制用于心血管组织工程的新型植(介)入型聚合物材料(表面)关键在于对聚合物生物材料表面的凝血及抗凝血涂层改性以及对其相应生物相容性与内皮细胞相容性的研究。通过对心血管医疗用聚合物生物材料的种类与应用及其心血管医疗器件和可植入性软组织替代物的深入研究可以发现表面与本体的差别则将体现在从表面向本体延伸的很多层分子上,而2种主要因素决定了其包括本体/表面差异及表面相分离在内的本体/表面行为,即表面能和分子运动性。如果考虑到对本体-表面的组成差异的理解,则还必须追加另以附加决定因素,即各组分的结晶行为。     

外科植入硅橡胶材料钙化及抗钙化研究进展

硅橡胶钙化是材料植入体内后其表面或基质内出现病理性矿化的现象,尚无有效防治方法.钙化的重要过程是材料表面的磷酸根离子与钙离子结合启动成核聚集,缓慢增大、融合,逐渐形成较大的羟基磷灰石钙盐堆积.其研究已发展到细胞和基因水平,如基质Gla蛋白质簇是一种硅橡胶假体周围组织钙化的抑制因子.钙化过程中有机模板对无机晶体的调制作用需理论上的突破.硅橡胶自身局部抗钙化性能受到重视.揭示硅橡胶钙化和钙化抑制的机理,可为构建新型抗钙化功能材料提供依据.     

Biocompatibility of platinum-metallized silicone rubber: in vivo and in vitro evaluation

Silicone rubber is commonly used for biomedical applications, including implanted cuff electrodes for both recording and stimulation of peripheral nerves. This study was undertaken to evaluate the consequences of a new platinum metallization method on the biocompatibility of silicone rubber cuff electrodes. This method was introduced in order to allow the manufacture of spiral nerve cuff electrodes with a large number of contacts. The metallization process, implying silicone coating with poly(methyl methacrylate) (PMMA), its activation by an excimer laser and subsequent electroless metal deposition, led to a new surface microtexture. The neutral red cytotoxicity assay procedure was first applied in vitro on BALB/c 3T3 fibroblasts in order to analyze the cellular response elicited by the studied material. An in vivo assay was then performed to investigate the tissue reaction after chronic subcutaneous implantation of the metallized material. Results demonstrate that silicone rubber biocompatibility is not altered by the new platinum metallization method.     

Biocompatibility of platinum-metallized silicone rubber: in vivo and in vitro evaluation

Silicone rubber is commonly used for biomedical applications, including implanted cuff electrodes for both recording and stimulation of peripheral nerves. This study was undertaken to evaluate the consequences of a new platinum metallization method on the biocompatibility of silicone rubber cuff electrodes. This method was introduced in order to allow the manufacture of spiral nerve cuff electrodes with a large number of contacts. The metallization process, implying silicone coating with poly(methyl methacrylate) (PMMA), its activation by an excimer laser and subsequent electroless metal deposition, led to a new surface microtexture. The neutral red cytotoxicity assay procedure was first applied in vitro on BALB/c 3T3 fibroblasts in order to analyze the cellular response elicited by the studied material. An in vivo assay was then performed to investigate the tissue reaction after chronic subcutaneous implantation of the metallized material. Results demonstrate that silicone rubber biocompatibility is not altered by the new platinum metallization method.     

Comparison of corneal epithelial cellular growth on synthetic cornea materials.

The application of artificial corneas for severely wounded ocular surfaces has always encountered the problem of biocompatibility with corneal epithelial cells (CECs). For the eye to stay healthy, it must continually have a complete sheet of CECs across the artificial corneal surface. Various surface modifications of different polymeric materials have been examined to determine which have the best cellular growth rates. A mathematical model of corneal cell growth profiles on synthetic materials was formulated based upon a linear mitotic growth rate. Experimental data reported for the CEC growth on modified poly(vinyl alcohol), silicone rubber, polystyrene, and polycarbonate was analyzed using the model to estimate the linear mitotic rate constant (k). The model proved to be useful in comparing data from different investigators. Plasma-induced graft copolymerized poly(hydroxyethyl methacrylate) (pHEMA) on silicone rubber provided the best growth rate from this particular set of data.     

Biocompatibility of standard and silica-free silicone rubber membrane oxygenators.

Spiral coil membrane oxygenators made from either standard silicone rubber or silica-free silicone rubber were compared using three priming techniques. Standard priming, carbon dioxide priming, and denucleation priming were employed with each type of device. Four-hour venovenous membrane oxygenator perfusions were carried out on awake sheep anticoagulated with heparin. Virtually no differences were observed in any parameters measured between standard silicone rubber and filler-free silicone rubber membranes. Significantly greater platelet losses occurred during the first hour of perfusion with standard priming and with carbon dioxide priming than with denucleation priming, using either type of membrane. These experiments demonstrate that denucleation priming reduces platelet losses during extracorporeal membrane oxygenator perfusion, but that the use of filler-free silicone rubber does not improve the biocompatibility of the membrane.     

硅橡胶膜细胞载体的应力分析及生物相容性

目的 报道一种自制的硅橡胶膜细胞载体,通过三维有限元方法计算其表面应变分布情况,并作细胞生物相容性分析,对材料进行全面评价,为细胞的应力刺激实验提供理论依据。方法 将硅橡胶材料制作成0.1 cm厚的透明薄膜,结合硅橡胶材料的泊松比以及弹性模量,应用三维有限元分析软件对数据进行处理,模拟硅橡胶受到牵张应变后产生的形变;通过MTT方法比较细胞在硅橡胶和标准培养板上的生长情况,并采取体外皮下包埋实验验证硅橡胶材料是否具有生物学毒性。结果 在对材料加载0.5%~20%的过程中,有效应变范围集中在硅橡胶膜的中心区域,约占总面积的90%;同时,硅橡胶材料虽然在生物相容性方面与标准培养板存在一定差异,但其本身无生物学毒性。结论 这种自制的硅橡胶细胞载体表面应力分布良好,生物相容性尚可满足细胞培养,但表面需进一步改善,可满足细胞的牵张应变实验。     

Histological biocompatibility of new, non-absorbable glaucoma deep sclerectomy implant

We performed this study to compare the intrascleral biocompatibility of three materials: non-absorbable hydrogel contact lens polymer, non-absorbable silicone rubber, and absorbable cross-linked sodium hyaluronate. Intrascleral implantation of three different materials was performed in 13 healthy, pigmented rabbits. Implants of methacrylic hydrogel, silicone rubber, and cross-linked sodium hyaluronate were implanted in 10, 8, and 8 eyes, respectively. The animals were euthanized at 7, 30, 180, and 360 days post implantation. The eyes were enucleated and immediately fixed in 10% buffered formalin. Semithin sections were cut and stained with hematoxylin-eosin. Light microscope analysis of the specimens was performed. The least severe inflammatory reaction was observed with cross-linked sodium hyaluronate implants. The number of inflammatory cells in proximity to methacrylic hydrogel and silicone implants at all periods of follow up was similar. The thickest fibrous capsule was observed with silicone implants (average, 28.38 +/- 11.17 microm). This area was thinner with methacrylic hydrogel implants (average, 14.90 +/- 5.57 microm) and was thinnest around sodium hyaluronate implants (average, 7.21 +/- 2.33 microm). For each type of implant, the wall on the conjunctival side of the fibrous capsule was significantly thicker than the wall on the choiroidal side. The space between the implant, scleral flap, and bed was filled soon after surgery with connective tissue rich in vessels. In our study, cross-linked sodium hyaluronate had the highest intrascleral biocompatibility. Although the inflammatory responses of the sclera to methacrylic hydrogel and silicone rubber were similar in nature, a thicker fibrous capsule was generated around silicone implants.     

Microporous flow surface variation and short term thrombogenicity in dogs

This study was designed to evaluate the effect of three luminal surface coatings on short-term thrombogenicity in 4 mm internal diameter vascular prostheses. Microporous replamineform grafts (20–30 μm pore size) composed of silicone rubber were coated with medical grade biomaterials: Biolite^®, TEDMAC-heparin, and Biomer^®.These grafts were compared to each other and to control grafts of silicone rubber and Biomer that did not have coatings. Following three hours of implantation in the canine femoral artery, the prostheses were removed, opened longitudinally and evaluated for quantity of thrombus, % thrombus free surface, and type of thrombus. Silicone rubber grafts coated with Biolite carbon had the least thrombogenic flow surface followed by the control Biomer grafts, Biomer-coated silicone rubber grafts, TEDMAC-heparin coated silicone rubber grafts, and the control silicone rubber grafts. Due to the small number of samples, no statistical analysis was performed. Hence, the conclusions drawn are tentative.     

Surface modification of an experimental silicone rubber aimed at reducing initial candidal adhesion

Silicone rubber, which is a widely used biomaterial, is often used to make soft liners for permanent denture. Colonization of denture soft lining materials by Candida albicans can result in clinical problems. The aim of this study was to chemically modify the surface of an experimental silicone rubber in order to produce a silicone that was less susceptible to candidal colonization. Surface modification was carried out with the use of argon-plasma bombardment followed by silane treatment, which caused the incorporation of either hydrophilic or hydrophobic functional groups onto the surface. Changes in water contact angles and chemical analysis of the materials with scanning ion mass spectroscopy confirmed surface changes. In vitro assays were carried out using C. albicans to measure levels of adherence to the surface-modified silicone after 1 h. C. albicans exhibited very low adherence to all silane-treated surfaces, whether hydrophobic or hydrophilic. This led to the conclusion that incorporated long-chain functional groups were inhibiting the adherence of the yeast, possibly by the formation of a barrier between the surface of the material and the yeast. In conclusion, silane surface treatment of an experimental silicone rubber has been successful in reducing candidal adherence.     

空气介质阻挡辉光放电增强硅橡胶/铁质纳米复合材料的表面亲水性

背景：医用硅橡胶的固有缺点是X射线显影性能欠佳和表面疏水性。添加显影标记物铁质纳米微粒可赋予硅橡胶X射线影像可视性的功能,铁质纳米微粒本体改性硅橡胶表面湿润性的变化尚不清楚,设想表面处理以提高硅橡胶/铁质纳米微粒复合材料的亲水性。 目的：观察硅橡胶/铁质纳米微粒复合材料表面湿润性、亲水改性及表征。 方法：使用空气介质阻挡辉光放电分别对前期制备出的配方比为95∶5,90∶10,85∶15的硅橡胶/纳米铁(INESR)和硅橡胶/碳包铁(Fe/CESR)复合材料表面进行改性,对照组为甲基乙烯基硅橡胶(MVSR)。 结果与结论：INESR和Fe/CESR与MVSR相比,表面水接触角减小幅度不大,疏水性未获得明显改善。经空气介质阻挡辉光放电对硅橡胶/铁质纳米微粒复合材料处理后,表面的亲水性得到较大提高,不同配方比INESR和Fe/CESR的水接触角均降低(P < 0.05);扫描电镜显示改性使试件表面受到刻蚀,粗糙度增加,但无空洞或裂隙;X射线光电子能谱分析表明材料表面的化学成分均发生变化,含氧基团大幅增加,含碳基团则明显减少,含硅基团小幅增加,出现含氮基团,说明改性使氮元素被结合到试件的表面,空气介质阻挡辉光放电处理硅橡胶/铁质纳米微粒复合材料的表面可实现亲水改性。     

Silicone rubber temporomandibular joint (TMJ) meniscal replacements: postimplant histopathologic and material evaluation

Medical grade silicone rubber has long been considered a suitable meniscal replacement, but there has been increasing concern about migration of this material into adjacent tissues. The objectives of this study were to determine the definitive composition of tissue-incorporated material which is presumed by light microscopy to be silicone and to identify long term histopathologic sequelae of meniscal replacements. Adult female patients underwent meniscectomy and replacement with silicone rubber (Silastic) implants. After 12 to 18 months, recurrence of symptoms in 8% of these cases led to implant removal with excision of peri-implant fibrous pseudocapsules. Excised tissues, including one preauricular lymph node and implants were submitted for light microscopy, SEM, and energy dispersive x-ray microanalysis (EDX) for the identification of elemental composition, critical surface tension measurement, and internal reflection infrared spectroscopy. EDX revealed prominent peaks for silicon in both pseudocapsular and nodal tissues. Morphologic findings surrounding the long-term implants included foreign body reaction, synovitis, dystrophic calcification, fibrocartilaginous metaplasia, hyalinization, and scarring. Particulate silicone debris induced a pathologic response in the tissues and migrated to nodes. These findings suggest that periodic evaluation be performed over the life of such implants to rule out breakdown under function. These findings should intensify the search for improvements or replacements for silicone rubber as an interpositional material in the temporomandibular joint.