In vitro and in vivo antimicrobial activity of covalently coupled quaternary ammonium silane coatings on silicone rubber

Biomaterial-centered infection is a dreaded complication associated with the use of biomedical implants. In this paper, the antimicrobial activity of silicone rubber with a covalently coupled 3-(trimethoxysilyl)-propyldimethyloctadecylammonium chloride (QAS) coating was studied in vitro and in vivo. Gram-positive Staphylococcus aureus ATCC 12600, Staphylococcus epidermidis HBH, 102, and Gram-negative Esherichia coli O2K2 and Pseudomonas aeruginos AK1 were seeded on silicone rubber with and without QAS-coating, in the absence or presence of adsorbed human plasma proteins. The viability of the adherent bacteria was determined using a live/dead fluorescent stain and a confocal laser scanning microscope. The coating reduced the viability of adherent staphylococci from 90% to 0%), and of Gram-negative bacteria from 90% to 25% while the presencc of adsorbed plasma proteins had little influence. The biomaterials were also subcutaneously implanted in rats for 3 or 7 days, while pre- or postoperatively seeded with S. aureus ATCC 12600. Preoperative seeding resulted in infection of 7 out of 8 silicone rubber implants against 1 out of 8 QAS-coated silicone rubber implants. Postoperative seeding resulted in similar infection incidences on both implant types, but the numbers of adhering bacteria were 70% lower on QAS-coated silicone rubber. In conclusion, QAS-coated silicone rubber shows antimicrobial properties against adhering bacteria, both in vitro and in vivo.     

Review Physicochemical and immunological basis of silicone pathophysiology

Silicones, model biomaterials with almost ubiquitous applications, are the focus of a contentious debate. In this review, we will consider both established physicochemical phenomena and immunological phenomena; and then consider the human clinical phenomena that relate directly to them. We will explore the two competing theories of the biological activity of silicones, and we will discuss the weaknesses in the various arguments that silicone is inert. We conclude that from a pathophysiological perspective, silicones should be expected to be bioactive materials and that the physicochemical and immunological data at the experimental level are compelling.     

Silicone granulomas: report of three cases and review of the literature

Since silicone is rapidly becoming one of the most commonly used biomaterials in modern medicine, pathologists will be observing increasing numbers of cases of silicone-related disease. Although numerous case reports have established that silicone elicits a characteristic response in tissues, the varying tissue reactions to silicone gels, liquids, and elastomers (rubber) have not been emphasized. Three cases are reported, and the literature is reviewed to illustrate the varying features of tissue reaction to silicone in its different forms. The first case is an example of silicone lymphadenopathy in an inguinal lymph node. This case demonstrates exuberant foreign body granuloma formation in response to particles of silicone elastomer. The second case involves a patient who had facial subcutaneous liquid silicone injections, and the third case is that of a woman in whom breast carcinoma developed 13 years after mammary augmentation with liquid silicone injections. These two cases illustrate the characteristic reaction to silicone liquid, with numerous cystic spaces and vacuoles in the soft tissues but minimal or no foreign body giant cell reaction. Scanning electron microscopy and energy dispersive x-ray analysis were performed in the first two cases, confirming the presence of silicon. Silicone migration and the clinical significance of various silicone-induced lesions are discussed.     

In vivo degradation of polymers. II. Change of mechanical properties and cross-link density in silicone rubber pacemaker lead insulations during long-term implantation in the human body

The results of mechanical testing, microscopic examinations and swelling of the explanted clinically used silicone rubber pacemaker lead insulations are presented. An experimental set of 100 lead insulations implanted for times ranging from 3 d to 11 yr were evaluated for change of mechanical properties and cross-link density during clinical use. The results show that the silicone rubber tubing suffers a gradual structural change due to its exposure to the physiological environment of the human body. A spiral deformation pattern due to the permanent set of the silicone rubber tubing in contact with the electrode leading wire was observed.     

Utilization of the platelet release reaction in the blood compatibility assessment of polymers

The release reaction is directly associated with platelet adhesion and aggregation, which are primary events leading to thrombus formation following contact of blood with artificial surfaces. This investigation examined the release reaction from the alpha granules of platelets after blood-polymer interaction, and utilized the measurement of beta-thromboglobulin (BTG), a platelet-specific protein, in the assessment of the in vitro blood compatibility of polymers. A radioimmunoassay was used, to determine the release of BTG following contact of blood with tubes of siliconized glass and polypropylene and flat sheets of poly(vinyl chloride) and silicone rubber. Polypropylene tubes caused less release of BTG than those of siliconized glass and silicone rubber induced less BTG release than poly(vinyl chloride). The investigation indicates a role for BTG measurement in blood compatibility assessment.     

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.     

Silicone rubber and natural rubber as biomaterials

The roles of silicone rubber and natural rubber as biomaterials are contrasted, with silicone rubber being widely used and natural rubber having, as yet, found limited application. Relevant properties of both elastomers are described, applications are discussed and possible future developments are considered.     

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.     

医用硅橡胶的生物相容性缺点及现代改良

硅橡胶具有性能稳定、易于塑形、产品效益可观的优点,已广泛应用于生物医学工程领域和医疗卫生行业.尽管如此,硅橡胶在生物医学领域中的应用仍然受到其自身缺陷的挑战.表面疏水性、自身影像相容性欠佳、长期植入体内后发生钙化乃是医用硅橡胶制品在生物相容性方面亟待克服的缺点.近几年来国内外专家针对以上缺点进行了诸多改良研究,热点主要集中于硅橡胶的表面湿润性增加、X-线阻射功能增强、防钙化预处理等方面.取得了阶段性成果,但尚未使医用硅橡胶的生物相容性达到理想的境界.     

The transport of octamethylcyclotetrasiloxane (D4) and polydimethylsiloxane (PDMS) in lightly cross-linked silicone rubber

The transport of octamethylcyclotetrasiloxane (D4), one of the major constituents of silicone fluids and rubbers, and low viscosity polydimethylsiloxane oil into a silica filled cross-linked silicone elastomeric rubber was measured as a function of temperature, cross-link density of the rubber, and concentration of the D4 in methanol solution. A small amount of material, approximately 3 wt%, is extracted from the rubber with hexane. The extraction process has a large effect upon D4 solubility in the rubber, increasing from approximately 160 to 180 wt% after extraction. The heats of solution for both penetrants into the rubber are essentially zero and the activation energies for diffusion are small, approximately 8 and 15 kJ molt(-1) for D4 and PDMS, respectively. The diffusion process is Fickian and the diffusion coefficient of D4 into silicone/silica rubbers is essentially independent of concentration over the concentration investigated, i.e. from 1 to 100 vol% D4 in methanol. The permeability, i.e. the product of the diffusion coefficient and the solubility, decreases rapidly for D4 concentrations less than 50 vol% (0.1 mol fraction). This suggests that the permeation of D4 out of any encapsulation device, such as a silicone breast implant, is linearly dependent upon the concentration of D4 in the prosthesis. Swelling is isotropic and was measured by dimensional changes in rectangular samples and correlates well with the volume of D4 sorbed.     

Improved biocompatibility of silicone rubber by removal of surface entrapped air nuclei

Biomaterials activate the complement system which is important since C3a promotes platelet aggregation and release, and C5a activates neutrophils that may augment coagulation. Tiny air nuclei (microbubbles) are found in the surface roughness of biomaterials on exposure to a liquid, therefore two interfaces exist: (a) a blood/biomaterial, and (b) a blood/air interface. Experiments were carried out that documented that air bubbles activate complement and augment in vitro platelet aggregation in human plasma. The air nuclei were removed from the surface of silicone rubber by a technique termed denucleation to determine if complement activation and platelet aggregation could be reduced. We observed a significant reduction in C3a and C5a in the plasma samples incubated with denucleated silicone rubber as compared to the control samples (p less than 0.001, ANOVA). The plasma incubated with the denucleated silicone caused reduced platelet aggregation as compared to the plasma incubated with the control silicone when added to a platelet suspension (p less than 0.001, ANOVA). Surface chemical analysis by x-ray photo-electron spectroscopy (XPS) showed no change in the silicone rubber surface after the denucleation procedure.     

纳米铁显影增强硅橡胶的制备及影像可视性评价

目的 探讨纳米铁微粒作为显影标记物对医用硅橡胶改性的可行性并评价复合材料的影像可视性.方法 硅油与纯铁粉、碳包铁粉混合,按预定的配方比分别与甲基乙烯基硅橡胶共混、密炼、模压、硫化,得到纳米纯铁粉增强硅橡胶（第1组）、纳米碳包铁粉增强硅橡胶（第2组）,空白对照组为医用硅橡胶.CT扫描体外各组材料试件,获取图像并测得CT值,比较组间CT值均值的差异性;将2组材料试件植入犬皮下,获得标准X-线图像;X射线衍射技术分析材料内铁微粒的组分稳定性.结果 分别制备出铁粉显影增强硅橡胶和碳包铁粉显影增强硅橡胶,新材料在体内外的X-线图像清晰可见,复合材料的CT值随金属纳米粉体量和纳米微粒原子量的增加而增加,2组材料的CT值均值、组间配方比相同的材料的CT值均值差异显著（P＜0.001）;材料放置180 d后,单质铁出现衍射峰的位置基本没有变化,分散在硅橡胶中的纳米纯铁微粒、碳包铁微粒较为稳定.结论 金属纳米铁粉、碳包铁粉可作为硅橡胶显影性改良的标记物.     

Photochemically immobilized polymer coatings: effects on protein adsorption,cell adhesion,and leukocyte activation

Amphiphilic chains of 4-benzoylbenzoic acid moieties and polymer were photochemically immobilized onto silicone rubber to ask whether the covalently coupled polymers would passivate the silicone rubber by inhibiting protein adsorption and subsequent cell adhesion and activation. Three groups of polymers were utilized: the hydrophilic synthetic polymers of polyacrylamide, polyethylene glycol, and polyvinylpyrrolidone; the glycosaminoglycan, hyaluronic acid; and poly(glycine-valine-glycine-valine-proline), a polypeptide derived from the sequence of clastin. Each coating variant decreased the adsorption of fibrinogen and immunoglobulin G compared to uncoated silicone rubber. All except the methoxy-polyethylene glycol coating nearly abolished fibroblast growth, but none of the coating variants inhibited monocyte or polymorphonuclear leukocyte adhesion. Interleukin-1β, interleukin-1 receptor antagonist, and tumor necrosis factor-α secretion by leukocytes were not statistically different between any of the coating variants and uncoated silicone rubber. However, the methoxy-polyethylene glycol and elastin-based polypeptide coatings, which supported the highest numbers of adherent monocytes, also elicited the lowest levels of pro-inflammatory cytokine secretion. When these in vitro data were collectively evaluated, the coating that most effectively passivated silicone rubber was the polypeptide derived from elastin.     

青蒿琥酯硅橡胶埋植剂的制备与体外释放量的测试

制备青蒿琥酯硅橡胶棒埋植剂,进行体外释放量的测试,为动物(小鼠)试验提供样品及参考依据。用青蒿琥酯原料药与硅橡胶基质混炼均匀,分别加入交联剂和催化剂混匀,于手工挤出机上挤出一定直径的药棒,加热硫化,裁成一定长度的药棒。首先,测定含量,然后测定体外释放量。结果表明青蒿琥酯硅橡胶棒埋植剂平均含量为24.025mg/cm,体外(含药24mg/支)释放量:第一天达860ug,第20天为539ug,第30天仍有305ug的药释放。青蒿琥酯硅橡胶棒埋植剂制剂稳定,体外释放较缓慢稳定。     

Photochemically immobilized polymer coatings: effects on protein adsorption, cell adhesion, and leukocyte activation

Amphiphilic chains of 4-benzoylbenzoic acid moieties and polymer were photochemically immobilized onto silicone rubber to ask whether the covalently coupled polymers would passivate the silicone rubber by inhibiting protein adsorption and subsequent cell adhesion and activation. Three groups of polymers were utilized: the hydrophilic synthetic polymers of polyacrylamide, polyethylene glycol, and polyvinylpyrrolidone; the glycosaminoglycan, hyaluronic acid; and poly(glycine-valine-glycine-valine-proline), a polypeptide derived from the sequence of elastin. Each coating variant decreased the adsorption of fibrinogen and immunoglobulin G compared to uncoated silicone rubber. All except the methoxy-polyethylene glycol coating nearly abolished fibroblast growth, but none of the coating variants inhibited monocyte or polymorphonuclear leukocyte adhesion. Interleukin-1beta, interleukin-1 receptor antagonist, and tumor necrosis factor-alpha secretion by leukocytes were not statistically different between any of the coating variants and uncoated silicone rubber. However, the methoxy-polyethylene glycol and elastin-based polypeptide coatings, which supported the highest numbers of adherent monocytes, also elicited the lowest levels of proinflammatory cytokine secretion. When these in vitro data were collectively evaluated, the coating that most effectively passivated silicone rubber was the polypeptide derived from elastin.     

涤纶网加强型医用硅橡胶引流条的研制及临床应用

为解决外科手术中的引流问题 ,研制了一种涤纶网加强型医用硅橡胶引流条。该产品是用医用加成型硅橡胶与涤纶网复合 ,通过模压方式制作的波纹状引流条。经临床应用表明引流效果好 ,使用方便 ,能促进伤口愈合     

引导组织生长硅橡胶人工颅骨的研制及皮下植入试验

为减少颅骨修补术后皮下积液及响颅综合症的发生 ,研制一种新型引导组织生长硅橡胶人工颅骨。通过模压方法制备硅橡胶颅骨 ,采用硅橡胶粘合剂在颅骨的外表面复合聚酯无纺布 ,并进行了物理、化学性能和生物安全性评价。家兔皮下种植实验表明 ,聚酯无纺布具有显著诱生组织细胞爬生作用 ,引导组织生长硅橡胶人工颅骨是一种安全、可靠的颅骨修复用品     

In vivo degradation of silicone rubber poppets in prosthetic heart valves.

Dynamic shear modulus G' was measured throughout the volume of three nonvariant silicone rubber poppets which were recovered from aortic prosthetic heart valves that had been implanted for 4 days, 52 days, and 8 years. Similar measurements were obtained for two unused silicone rubber poppets. Although the recovered poppets exhibited no obvious physical evidence of damage, the silicone rubber had undergone in vivo degradation throughout the poppet volume as indicated by decreases in modulus. The measurements also indicate that the poppet surface degrades at a rate faster than the core. Further, comparison with data reported in the literature suggests that the surfaces of variant poppets degrade at a rate faster than the surfaces of nonvariant poppets.     

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。     

Effect of silicone rubber surface on the calcium balance of human serum

The nature and mechanism of calcium complexation with human serum components in the presence of silicone rubber were assessed in in vitro model experiments. Silicone rubber samples were incubated for 67 h in serum of both physiologic calcium concentrations and induced hypercalcemic levels. Physiologic calcium incubation decreased the intrinsic and nth binding site association constants by factors of 2 and 4, respectively, from initial serum values. Incubation with silicone rubber did not change the association constants. Hypercalcemia incubation lowered the intrinsic and nth binding site association constants by 39 and 61%, respectively. Polymer incubation increased the intrinsic association constant and decreased the number of binding sites by a factor of 2. With initial binding site association constants unperturbed by incubation and Hill coefficients equivalent to 1, complexation was non-cooperative and binding sites were considered to be identical and independent. Both Scatchard and Hill plots show nonlinearity for the polymer incubation case giving two distinct linear regions. This is indicative of cooperative binding for incubation with polymer; the Hill coefficient for the physiologic calcium concentration range was 0.97, while the coefficient for the hypercalcemic calcium range was 6.