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Biocompatibility of poly(carbonate urethane)s with various degrees of nanophase separation.

Nanophase separation has been suggested to influence the biological performance of polyurethane. In a previous work, six different 4,4'-diphenylmethane diisocyanate (MDI)-based poly(carbonate urethane)s (PCUs) that exhibited various degrees of nanophase separation were synthesized and characterized. In the present work, these PCUs were used as a model system to study the effect of nanometric structures on the biocompatibility of polyurethane. Human blood platelet activation, monocyte activation, protein adsorption, and bacterial adhesion on PCU were investigated in vitro. It was found that human blood platelets as well as monocytes were less activated on the PCU surfaces with a greater degree of nanophase separation in general. This phenomenon was closely associated with the lower ratio of human fibrinogen/albumin competitively adsorbed on these surfaces. Bacterial adhesion was also inhibited in some nanophase-separated PCUs. [diagram in text].

Bacillus subtilis↗

Biocompatibility of nanofilm-encapsulated silicone and silicone-hydrogel contact lenses.

A material placed in or in contact with a biological system, that causes the minimum perturbation that can be tolerated by the host biological system, can be considered to be biocompatible. The major effects caused by a contact lens can be considered to be 1) the blocking of the natural supply of oxygen to the epithelium cells of the cornea, 2) interference with the normal evaporation of water from the tear fluid layer, and 3) hindrance of the normal functions of blinking for replenishing oxygen-saturated tear fluid and removing dead epithelium cells, which result from apoptosis. The encapsulation of a highly oxygen-permeable contact lens by a nanofilm with an imperturbable surface state minimizes all these terms. The encapsulated contact lens can be worn safely in extended wear.

Biocompatible Materials↗

Development of biocompatible oxygen-permeable films holding paramagnetic carbon particles: evaluation of their performance and stability in EPR oximetry.

EPR oximetry using paramagnetic particles relies on the measurement of the EPR linewidth, which is directly related to the pO2. It was previously found that some of the paramagnetic materials with optimal EPR spectroscopic properties in vitro may lose their responsiveness to oxygen in tissues (change of the calibration curve of the EPR linewidth as a function of the pO2). We hypothesized that coating paramagnetic particle materials could improve the stability of response, as well as the biocompatibility. In this study, very thin films holding paramagnetic materials were prepared with different biopolymers (cellulose acetate, cellulose triacetate, cellulose nitrate, silicone, and polyurethane) that already are accepted for clinical applications. Their performance was evaluated in EPR oximetry by measuring the stability of the calibration curves (EPR linewidth as a function of pO2) after a prolonged period in an aqueous environment (1 week in saline) or in vivo (implantation for 3 weeks under the skin of mice). We found that one type of silicone film was able to stabilize the responsiveness of an intrinsically unstable carbon material (a wood char).

Animals↗

Biocompatibility of cardiovascular gene delivery catheters with adenovirus vectors: an important determinant of the efficiency of cardiovascular gene transfer.

Gene therapy approaches hold promise for the treatment of a wide variety of cardiovascular diseases. Many strategies for cardiovascular gene therapy involve catheter-mediated vector delivery via intramyocardial injection, intracoronary infusion, or direct gene transfer into the vessel wall. Several different gene delivery catheters have been developed and utilized in preclinical and clinical studies of cardiovascular gene therapy. However, rigorous studies of the biocompatibility of these catheters with gene therapy vectors have not yet been reported. In this report, we have examined the compatibility of cardiovascular gene therapy catheters and catheter constituents with first-generation E1/E3-deleted adenovirus vectors. We show that (i) currently available catheters rapidly and efficiently inactivate adenovirus vector infectivity; (ii) this inactivation is mediated by a variety of commonly used catheter constituents including stainless steel, nitinol, and polycarbonate; (iii) catheter-mediated inactivation of adenovirus vectors can be prevented by preflushing catheters with solutions of serum albumin; and (iv) it is possible to identify a set of catheter materials that are compatible with current adenovirus vectors. These results underscore the importance of catheter/vector compatibility and suggest methods for increasing the efficiency of catheter-mediated cardiovascular gene therapy.

Adenoviridae↗

Perfluorinated organic liquids and emulsions as biocompatible NMR imaging agents for 19F and dissolved oxygen.

Emulsions of fluorocarbons are finding considerable use in physiology for intravascular oxygen transport. Their wide clinical application as blood substitutes, anti-shock, and anti-ischemic agents seems imminent. Whole body NMR imaging is rapidly gaining clinical application and may one day almost completely supplant X-ray imaging. All of the 19F compounds used in biocompatible fluorocarbon emulsions give 19F signals identical to those in the corresponding neat liquid. In concentrations of 10% w/v they are readily imaged. The paramagnetic oxygen molecule reduces T1 in such a way as to make possible whole body imaging of oxygen. T1 typically decreases from 1-4 to 0.3-0.5 seconds and is an inverse linear function of oxygen tension. Spin-lattice relaxation times versus oxygen tensions from 0 to 600 torr have been obtained for F-decalin, F-tributylamine, and F-44E. The usefulness of these 19F effects in clinical NMR imaging depends upon the sensitivity of the method and the tolerable dose. The 19F signal may find use in monitoring 19F compounds as vapors or gases dissolved in plasma or in perfluorocarbons in neat liquid or particle form.

Animals↗

Needs, problems, and opportunities in biomaterials and biocompatibility.

There are four topics related to biomaterials and biocompatibility which I feel are key problems, are often unrecognized, and are therefore rich opportunities for work in the near future: (i) the covalent instability of proteins, (ii) the concept of statistical specificity and statistical heterogeneity, (iii) the issue of solid surface dynamics and surface relaxation, and (iv) the growing concern with the costs of health care and of medical research. Each is briefly discussed in this paper.

Biocompatible Materials↗

Characterization of endosteal osteoblasts isolated from human maxilla and mandible: an experimental system for biocompatibility tests.

Fragments of cancellous and cortical bone from human maxilla and mandible were cultured by the explant technique. Cells isolated by trypsinization of primary cultures were characterized as osteoblasts on the basis of intracellular alkaline phosphatase activity, the constituents of the extracellular matrix, and response to human parathormone (PTH). In culture, the osteoblasts often gave rise to superposed clumps of large cells whose cytoplasm contained endoplasmic reticulum, numerous mitochondria, vacuoles, and a dense network of intermediate filaments, often at the level of the plasma membrane. In the presence of vitamin C and 1,25-dihydroxyvitamin D3, the osteoblasts produced an extracellular matrix composed of collagen type I and various non-collagenous proteins, including osteocalcin. Biochemical test results were comparable to those reported for osteoblasts of other origins (rat calvaria, human iliac crest), and namely elevated intracellular alkaline phosphatase activity and cAMP accumulation in response to stimulation by human PTH (1-34). Osteoblasts isolated in this manner were cultured in the presence of pure titanium disks to determine the effects of exposure to this metal. Electron microscopy revealed few significant differences in cell growth and specific enzyme activity compared to control osteoblasts grown on plastic dishes, reflecting the excellent biologic and biochemical relationship between the osteoblasts and pure titanium. This experimental system thus appears suitable for biocompatibility studies, and in particular, evaluation of dental implants.

Alkaline Phosphatase↗

Biocompatibility of biodegradable and nonbiodegradable polymer-coated stents implanted in porcine peripheral arteries.

PURPOSE: To investigate the neointimal response to poly(organo)phosphazene- and amphiphilic polyurethane-coated, oversized, stainless steel stents implanted in porcine peripheral arteries. METHODS: Nonarticulated, stainless steel, slotted-tube stents were coated with 1) a biodegradable poly-(organo)phosphazene with aminoacid ester side groups and 2) a biostable polyurethane prepared from an amphiphilic polyether, diphenyl methane-4,4'-diisocyanate and butane diol as chain extender. The stents were deployed in porcine peripheral arteries using an oversized balloon. RESULTS: The neonintimal response to amphiphilic polyurethane-coated stents was similar to the uncoated metallic stents. Poly(organo)phosphazene-coated stents, however, induced a severe histiolymphocytic and fibromuscular reaction resembling a foreign body reaction. CONCLUSIONS: Amphiphilic polyurethane is very promising as a biocompatible stent coating. Poly-(organo)phosphazene, however, appears unsuitable for this purpose.

Angioplasty, Balloon↗

[Problems of biocompatibility in hemodialysis treatment].

Although hemodialysis is one of the best examined, and clinically best established, methods of patient treatment with artificial organs, a number of biocompatibility problems remain. This review discusses the problem of water quality. Recently, much concern has been focused on potential longterm risks from patients exposure to subthreshold concentrations of endotoxin in dialysate. Further problems comprise inorganic and organic contaminants, some of which with potential carcinogenetic hazards. Complement activation by, and thrombogenicity of, dialysis membranes have not been eliminated. Presumably, the hazards of complement activation are less acute shortterm reactions (which according to more recent studies appear to be ETO-related anaphylactoid reactions) but rather potential longterm hazards, e.g. beta 2 m related amyloid. However, the issue is not settled since we have recently found cell activation by dialysis membranes even in the absence of complement. Apart from membranes, dialysis tubing presents hazards, e.g. leakage of plasticizers and release of oligomers or radicals. The recognition of ETO as a potent immunogen, inducing antibodies detectable in approximately 40% of the dialysis population, will require to replace ETO as a sterilisant for dialysis devices. This demand is even more urgent in view of the recognized carcinogenicity of this alkylating agent.

Biocompatible Materials↗

Generation of leukotriene B4 by hemodialyzer membranes: a novel index of biocompatibility.

Leukotriene B4 (LTB4) plays an important role in acute and chronic inflammatory and hypersensitive reactions. We studied the time course of LTB4 biosynthesis in whole blood in 18 patients with end-stage renal failure maintained on regular hemodialysis with two different membranes, cuprophane and polyacrylonitrile (AN 69). The basal levels of LTB4 from dialysis patients did not differ significantly from a normal control group. Compared to predialytic values, the cuprophane membrane caused a maximal release of LTB4 by a factor of about 4.5 (p less than 0.01) within the first 10 to 20 minutes. Thereafter the level fell and returned to baseline range at the end of the hemodialysis session. With the use of the AN 69 membrane no significant increase of LTB4 could be demonstrated. The changes in LTB4 concentration showed a close temporal correlation to the alterations in white blood cell count. We conclude that (1) LTB4 is a biologically important mediator of neutrophil activation during hemodialysis, and (2) LTB4 may be a sensitive marker of biocompatibility in vivo.

Acrylic Resins↗

Development of biocompatible implants of fusinite for in vivo EPR oximetry.

The development of oxygen-sensitive paramagnetic materials is being actively pursued because of their potential applications for in vivo electron paramagnetic resonance (EPR) oximetry. Among these materials, fusinite is of particular interest because of the high sensitivity of the EPR linewidth to the partial pressure pO2. Although this material has led to a number of very useful results in experimental systems, its potential use in humans is limited by the need to prove that it will not cause deleterious effects. The strategy used in this study to optimize the biocompatibility of the oxygen-sensitive materials was to prepare small silicon implants containing the fusinite. The use of silicon permits the diffusion of oxygen inside the implant while the material does not have contact with the biological environment. Radiosterilization did not affect the pO2 sensitivity of the material. The feasibility of performing pO2 measurement was verified in vivo by periodically inducing ischemia in the gastrocnemius muscle of mice over a period of 6 weeks.

Animals↗

The chick chorioallantoic membrane as test system for biocompatible materials.

Biologic and non-biologic materials clinically used as hemostyptica, as vascular prostheses, or as temporary skin substitutes were implanted to the chick chorioallantoic membrane (CAM) during days 9-14 of incubation. The histological study revealed an intact CAM after application of cellulose gauze (Tabotamp). The fibrin tissue adhesive (Tissucol), the collagen sponge (Tachotop), or the gelatin sponge (Gelfoam) induced different amounts of connective tissue. Some fibroblasts were about to grow into the fibrin adhesive. Fibroblasts and capillaries filled the interstices of the collagen sponge poorly, and in the case of the gelatin sponge markedly. Neutrophils and giant cells of the foreign body type occurred more often in the gelatin sponge than in the collagen sponge. With regard to the non-biologic materials, expanded polytetrafluorethylene induced squamous metaplasia of the chorionic epithelium. Dacron caused ulceration with the onset of connective tissue ingrowth, based on a reaction of giant cells of the foreign body type. Polyurethane foam (SYSpur-derm) showed bleeding into the implant due to spikes of the material. Eosinophilic granulocytes were absent in all materials studied. The results are related to different clinical findings. The correlation allows consideration of the CAM as an in vivo model in screening materials for their biocompatibility and their connective tissue reaction.

Allantois↗

[Neon-colored plastics for orthodontic appliances. Biocompatibility studies].

Public concern and issues of liability have made product safety a major concern throughout the medical field including orthodontics. The purpose of this study was to test the biocompatibility of the new neon colored plastic materials to be used for removable orthodontic appliances before they reach the market and are used in patient treatment. In addition, eight modifications of this synthetic material, which has been used in appliances for many years, were examined without neon color. The procedures established tested for: 1. mutagenicity, 2. toxicity, and 3. irritation of the mucous membrane. As alternatives to using animals the Ames Test, the Agar Overlay Assay, and the HET-CAM Test were employed to test for these properties. The tests revealed that, when the manufacturer's instructions are followed, neither the polymerized materials as used in patient appliances nor the shavings resulting from the orthodontist or the technician grinding the appliance exhibit mutagenic, toxic, or irritating properties.

Animals↗

Biocompatibility of latex and silicone T tubes in the porcine common bile duct: an experimental study.

Toxicity of materials used in indwelling drains or catheters has the potential to damage surrounding tissues. The biocompatibility of biliary T-tubes was investigated using in groups of piglets (total 30 animals). In group 1 (n=16) a choledochotomy was performed with insertion of a latex T-tube (n=6) or a silicone T-tube (n=8), or without a T-tube (n=2). In group 2 (n=14) the common bile duct (CBD) was 3/4-transected, and the lesion was sutured over a latex T-tube (n=4) or a silicone T-tube (n=5), or without a T-tube (n=5). The groups were reoperated upon after 2 and 6 weeks respectively, and the CBD was harvested for scanning electron microscopy and light microscopy. The T-tubes were examined for cell culture toxicity with a DNA synthesis inhibition test. According to the cell culture tests, latex T-tubes were toxic and silicone T-tubes nontoxic. T-tubes induced moderate to pronounced fibrosis and epithelial damage in the CBD wall, but did not induce excessive fibrosis or scarring at the site of CBD suture. In the 6-week study period, however, the grade of tissue reactions in the CBD did not correlate with the toxicity of the T-tube materials, but rather reflected a foreign body reaction and mechanical pressure. Although gross anatomical changes did not occur, neither material seemed to be completely harmless for porcine CBD wall.

Animals↗

The biocompatibility of compressed collagen foam plugs.

The tissue reaction to reexpanded, purified bovine collagen sponge placed percutaneously into the lung, pleural space, liver, kidney, and muscle was studied in dogs and rabbits. In addition, the biocompatibility and radiopacity of tantalum-treated collagen foam plugs was examined. No adverse effects were found. We believe that collagen plugs may be of use in occluding needle tracts from biopsy sites to prevent complications such as bleeding or pneumothoraces.

Animals↗

Plastics from bacteria and for bacteria: poly(beta-hydroxyalkanoates) as natural, biocompatible, and biodegradable polyesters.

Hence, PHB belongs to the family of poly(beta-hydroxyalkanoates), PHA, all of which are usually formed as intracellular inclusions under unbalanced growth conditions. Recently, it became of industrial interest to evaluate PHA polyesters as natural, biodegradable, and biocompatible plastics for a wide range of possible applications such as surgical sutures or packaging containers. For industrial applications, the controlled incorporation of repeating units with different chain lengths into a series of copolymers is desirable in order to produce polyesters with a range of material properties because physical and chemical characteristics depend strongly on the polymer composition. Such "tailormade" copolymers can be produced under controlled growth conditions, in that if a defined mixture of substrates for a certain type of microorganisms is supplied, a well defined and reproducible copolymer is formed.

Bacteria↗

Biocompatible channels for field-flow fractionation of biological samples: correlation between surface composition and operating performance.

Biocompatible methods capable of rapid purification and fractionation of analytes from complex natural matrices are increasingly in demand, particularly at the forefront of biotechnological applications. Field-flow fractionation is a separation technique suitable for nano-sized and micro-sized analytes among which bioanalytes are an important family. The objective of this preliminary study is to start a more general approach to field-flow fractionation for bio-samples by investigation of the correlation between channel surface composition and biosample adhesion. For the first time we report on the use of X-ray photoelectron spectroscopy (XPS) to study the surface properties of channels of known performance. By XPS, a polar hydrophobic environment was found on PVC material commonly used as accumulation wall in gravitational field-flow fractionation (GrFFF), which explains the low recovery obtained when GrFFF was used to fractionate a biological sample such as Staphylococcus aureus. An increase in separation performance was obtained first by conditioning the accumulation wall with bovine serum albumin and then by using the ion-beam sputtering technique to cover the GrFFF channel surface with a controlled inert film. XPS analysis was also employed to determine the composition of membranes used in hollow-fiber flow field-flow fractionation (HF FlFFF). The results obtained revealed homogeneous composition along the HF FlFFF channel both before and after its use for fractionation of an intact protein such as ferritin.

Animals↗

Biocompatibility of silicon carbide in colony formation test in vitro. A promising new ceramic THR implant coating material.

We studied the possible use of silicon carbide (SiC) as a ceramic coating material of titanium-based total hip replacement (THR) implants. The idea is to prevent wear debris formation from the soft titanium surface. SiC is a hard and tightly bonding ceramic surface material, and because of these physical properties it is not easily degradable, as is the case with hydroxyapatite. Our previous in vivo and in vitro studies have indicated that SiC and hydroxyapatite are equally biocompatible regarding particle size for phagocytosis. The present cytotoxicity test using JCRB0603 cells showed that 5 microns SiC particles inhibited colony outgrowth by one-third (67% + 10% vs control), while SiC-coated pins did not cause any inhibition and acted similarly to uncoated titanium pins. The results support the hypothesis that SiC is a promising ceramic THR implant coating material.

Carbon Compounds, Inorganic↗