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Short-term in vitro and in vivo biocompatibility of a biodegradable polyurethane foam based on 1,4-butanediisocyanate.

In this study short-term in vitro and in vivo biocompatibility apects of a biodegradable polyurethane (PU) foam were evaluated. The PU consists of hard urethane segments and amorphous soft segments based on a copolyester of dl-lactide and epsilon-caprolactone. The urethane segments are of uniform length and synthesized with 1,4-butanediisocyanate. The foam has good mechanical properties and will be used for tissue regeneration applications. Degradation tests were carried out in a buffer solution for twelve weeks. Cytotoxicity was determined using extract and direct contact test methods with incubation periods varying form 24 to 72 h. The foam was implanted subcutaneously for one, four and twelve weeks and the tissue response to the material was histologically evaluated. In vitro, the mass loss was 3.4% after twelve weeks. In the cytotoxicity tests the PU caused no abnormal growth behaviour, nor morphological changes or inhibition in metabolic activity. The in vivo studies showed no toxic tissue response to the PU. Connective tissue ingrowth, accompanied by vascular ingrowth was complete at twelve weeks. In vivo degradation had started within four to twelve weeks. In conclusion, the PU shows a good in vitro and in vivo biocompatibility in these short-term experiments.

Absorbable Implants↗

Silicone based polyurethane materials: a promising biocompatible elastomeric formulation for cardiovascular applications.

The biocompatibility of a new material for cardiovascular applications constituted by a poly(ether)urethane (PEtU) and a silicone [polydimethylsiloxane (PDMS)] was evaluated. The achieved material shows properties similar to both polyurethanes and silicones. The material was transformed into porous membranes by a spray-deposition technique. Since any material preparation and manufacturing procedure may introduce some toxicity, in vitro cytotoxicity screening tests were carried out. Human umbilical vein endothelial cells (HUVECs) and a mouse fibroblasts cell line (L929) were cultivated with extracts obtained from materials containing 10, 40 and 100% (w/w) of PDMS. The commercially available Estane 5714-F1 and Cardiothane 51 were used as controls. Extracts were incubated up to 72 hours with HUVECs and L929 cells. The cytotoxic effect was evaluated by light microscopy, cell viability (MTT reduction and neutral red uptake) and proliferation (5-bromo-2'-deoxyuridine incorporation) tests. In vivo studies were carried out using materials containing the same PDMS percentages as for in vitro experiments. The same commercial controls were used. Results obtained with cell culture studies agreed with those obtained in the in vivo experiments and showed that the material preparation and manufacturing procedure do not introduce any toxicity in the products at each PDMS concentration investigated.

Animals↗

Development of the polyurethane sponge as a delivery system for aryl 4-guanidinobenzoates.

The Today Contraceptive Sponge was evaluated as a vehicle for the delivery of aryl 4-guanidinobenzoates (AGs) which are highly active sperm acrosin inhibitors. Studies in animals have shown that several AGs are more potent vaginal contraceptives and less irritating to the vagina than nonoxynol-9 (N-9), the most frequently used active ingredient in commercial vaginal contraceptive formulations. Neither nonoxynol-9 nor the material that could be solubilized from the sponge matrix altered the enzyme-inhibitory activity of 4'-acetamidophenyl 4-guanidinobenzoate HCl (AGB), 4'-carboxyphenyl 4-guanidinobenzoate HCl (EGB) or 4'-carbomethoxyphenyl 4-guanidinobenzoate HCl (MSGB). Besides being acrosin inhibitors, all three AGs exhibited antimotility activity towards human spermatozoa, EGB being as potent as N-9. The antimotility effects of the AGs and N-9 were additive. For subsequent studies, AGB was used as the model compound. Manufacture of the AGB-containing sponges did not affect the chemical structure of AGB. Good release rates of AGB were obtained from the sponges over a 7-day period. The release rates were 20-50% higher when the sponges also contained N-9. These results indicate that certain AGs exert a dual contraceptive action on spermatozoa by inhibiting both the sperm enzyme acrosin and sperm motility. Furthermore, the polyurethane sponge appears to be a convenient and satisfactory long-term delivery system for the AGs. A mixture of N-9 and AG can be used clinically because these compounds have no adverse effects on each other.

Benzoates↗

Vas deferens occlusion by percutaneous injection of polyurethane elastomer plugs: clinical experience and reversibility.

A non-incision method of vas occlusion based on the percutaneous injection of polyurethane elastomer solution to form plugs is described. The results are based on clinical experience in 12,000 men in which only 56 cases of minor complications were recorded. Follow-up of 500 men for up to 3 years demonstrated an azoospermia rate of 98%. Plugs have been removed from 86 men and, to date, 51 have made their wives pregnant. In those from which the plugs have been removed for more than 1 year (n = 31), the pregnancy rate is 100%.

Adult↗

Modified technique for preparing a polyurethane lining for facial prostheses.

A simplified technique for preparing, under a vacuum, a polyurethane lining for a facial prosthesis is described. A previously presented technique strengthened the prosthesis and allowed it to be attached with a water-based adhesive. This technique eliminates wrinkling, simplifies bonding, allows multiple linings to be made at the same time, conserves time and cost, and improves predictability of the results.

Ear, External↗

Application of polyurethane foam for sampling volatile mutagens from ambient air.

This paper reports the use of polyurethane foam (PUF) in the sampling of airborne mutagens too volatile to be retained by glass fibre filters. Air was sampled simultaneously with a glass fibre filter and PUF plugs, and the two extracts of the samples were tested for mutagenicity and analysed for polycyclic aromatic hydrocarbons (PAH). As PUF itself was found to contain mutagens, it was thoroughly rinsed, and a blank extract of the same PUF used for sampling was tested as a control. The resulting blank extracts were not mutagenic. In the first series of experiments, in which methanol was used as the extraction solvent, sampling induced clear-cut mutagenic effects in the PUF extracts. As the mutagenicity of the PUF itself appeared only with the use of methanol or other alcohols as extraction solvents, a second series of experiments was carried out in which acetone was used as the extraction solvent. In these experiments sampling induced no mutagenicity in the extracts. The discrepancy between the two series of experiments may be due to the absence of volatile mutagens in the second series, but another explanation may be an artefact induced by the solvent in the first series. Additional experiments suggest that sampling induces the formation, from PUF, of compounds mutagenic upon extraction with methanol. The study leads to the provisional conclusion that no volatile mutagens could be demonstrated in ambient air sampled by the use of PUF as an absorbent, notwithstanding the clear-cut effects of the filter extracts and the presence of volatile PAH in the PUF extracts.

Air Pollutants, Occupational↗

Visualization and analysis of mural thrombogenesis on collagen, polyurethane and nylon.

Visualization and analysis of mural thrombogenesis on collagen-coated glass, polyurethane and nylon was discussed. Epi-fluorescent video microscopy was used to visualize thrombotic events at a protein or polymer surface in contact with flowing whole blood. Digital image processing was used to analyse the real-time microscopic images obtained, resulting in measurements of morphological features and the number of platelets that compose each thrombus. The three-dimensional structures of the thrombi were also estimated. A photodiode was used to measure integrated end-point platelet accumulation at different axial positions along the surface. Additionally, the convection-diffusion equations were solved to estimate the concentrations of adenosine diphosphate, thromboxane A2, and thrombin generated by activated platelets at the blood-contacting surface.

Adenosine Diphosphate↗

Microporous hydrophilic polyurethane vascular grafts as substitutes in the abdominal aorta of dogs.

Polyurethanes are emerging as promising biomaterials. A microporous vascular graft fabricated from Mitrathane, a new polyetherurethane urea, appeared to be particularly interesting according to in vitro evaluation and was tested in vivo as an infrarenal aortic substitute (i.d. 5 mm) in 24 dogs. After implantation for scheduled periods ranging from 4 h to 6 mnth, morphology evaluation and healing analysis of the grafts were performed. At harvesting, 18 grafts were patent and 6 were thrombosed. The thrombosed grafts had been implanted for 4 h (1 graft), 1 mnth (2 grafts) and 6 mnth (3 grafts). No macroscopic deposits other than red mural thrombi were observed. At 1 mnth complete external encapsulation was observed in 2 grafts. The capsule then contracted and became thinner; over the long term it shrank, became translucent and incomplete at 6 mnth. Yellow and brown stains appeared on many of the grafts. Characterization of the brown stains showed them to be iron (Fe3+) and the yellow stains were associated with the deposition of a bile pigment (bilirubin).

Animals↗

An X-ray photoelectron spectroscopy study of the external surface of explanted microporous polyurethane vascular prostheses.

XPS has been used to examine the external surfaces of microporous polyurethane vascular prostheses implanted for up to 6 months in dogs. The phenomena of bilirubin absorption and physical degradation were investigated, using three different chemical washes to clean the prostheses. Very little evidence for chemical change was found, indicating a predominant role for the mechanical or biochemical ablation of degraded material.

Animals↗

Synthesis and physicochemical characterization of a new material (PUPA) based on polyurethane and poly(amido-amine) components capable of strongly adsorbing quantities of heparin.

The synthesis of new materials (PUPAs) based on a commercial polyurethane and a heparin-complexing polymer, poly(amido-amine), was studied. PUPAs are capable of adsorbing heparin because the basic nitrogens of poly(amido-amine), once protonated, interact with the negative charges carried by the heparin molecule. Six different samples of PUPA were synthesized having a varied ratio of the components. The quantity of basic nitrogen on the surface and the bound heparin for each sample was determined. Two different kinds of heparin are present on a PUPA surface: one is strongly bound but can be detached by 0.1 M NaOH solution, the other is physically adsorbed and is slowly released by a stream of saline solution. A relationship between the quantity of strongly bound heparin and basic nitrogen was found. SEM and FTIR-ATR analysis were performed on all the PUPA samples. The mechanical characteristics change according to chemical composition.

Adsorption↗

Polyurethane elastomer with PEO-PTMO-PEO soft segment for sustained release of drugs.

Blood-compatible segmented polyurethanes and polyurethaneureas were evaluated as drug delivery matrices using crystal violet and benzethonium chloride as model drugs. These polymers were synthesized from ABA-type triblock copolyether as a prepolymer, where A stands for poly(ethylene oxide) and B for poly(tetramethylene oxide). Microphase separation was observed in segmented polyurethaneureas, including drug-doped films. Crystal violet dissolved more in the hard segment domain than in the soft segment matrix, whereas benzethonium chloride was easily dissolved in the soft segment matrix. The drug release behaviours from these films were analysed by the exponent relation Mt/M infinity = ktn, where k and n are constants and Mt/M infinity is the fraction of drug released until time, t. The constant k grew with increasing poly(ethylene oxide) content in the prepolymer, i.e. increased swelling. The constant n was found to be close to 0.5 in many samples, which suggests the release of drug from these polymers is explained by the Fickian diffusion model. However, the mechanism became non-Fickian with increased swelling of the devices.

Benzethonium↗

Tantalum-loaded polyurethane microspheres for particulate embolization: preparation and properties.

Polyurethane microspheres having diameters in the range 150-1500 microns were prepared by condensation polymerization of toluene diisocyanate (TDI) with poly(tetramethylene glycol) (PTMG) of average mol wt 990 in an aqueous dispersion medium containing dioctyl sulphosuccinate (DOS) as the suspension stabilizer and 1,4-diazabicyclo[2.2.2]octane (DABCO) as the catalyst for polymerization. Incorporation of tantalum powder in the polymerizing phase led to the formation of Ta-loaded microspheres with good radiopacity. Microspheres were surface-modified by grafting methacrylic acid (MA) on to them using gamma-radiation from a Co60 source. Conversion of the grafted MA into its sodium salt imparted hydrophilicity and slipperiness to the microspheres enabling them to pass through Teflon catheters without obstructing the catheter lumen. These microspheres may find application as radiopaque embolization agents.

Biocompatible Materials↗

Synthesis and physicochemical characterization of a hydrophilic polyurethane able to bind heparin.

The synthesis of a new segmented polyurethane containing quaternary ammonium groups in the side-chain is reported. The quaternization was carried out both on the polymer dissolved in an organic solvent and on polymer films. Polymeric films quaternized by both techniques were heparinized. The amount of bonded heparin, determined by spectrophotometry, was remarkably higher than previously described. Polymer quaternized in solution bonded more heparin than that heparinized directly on film. In vitro evaluations of antithrombogenicity by activated partial thromboplastin time (APTT) carried out on the films confirmed these data. The polymers were also characterized by chemical, i.r., n.m.r., differential scanning calorimetry and viscometric techniques.

Binding Sites↗

Polyurethane surface modification by graft polymerization of acrylamide for reduced protein adsorption and platelet adhesion.

Surface modification of polyurethane by glow-discharge treatment and subsequent graft polymerization of acrylamide was studied. The modified hydrophilic surfaces were characterized by the measurements of dynamic contact angle and zeta potentials and examined for protein adsorption behaviour and platelet adhesion. Data from in vitro and ex vivo experiments indicated a reduction of protein adsorption and platelet adhesion for the hydrophillic graft polymers, the extent of which was correlated to polymer graft density.

Acrylamides↗

Morphological, physical and chemical evaluation of the Vascugraft arterial prosthesis: comparison of a novel polyurethane device with other microporous structures.

In this study the morphology, physical properties, surface chemical characteristics and microstructure of the Vascugraft arterial prosthesis have been investigated. This is a novel microporous polyurethane device, recently developed by the company Braun-Melsungen AG in Germany for use as a small calibre arterial substitute. This comparative study included two other synthetic grafts: the Mitrathane prosthesis, a hydrophilic prototype polyetherurethane urea graft with closed internal pores, and the commercially successful expanded polytetrafluoroethylene reinforced Goretex prosthesis with an open microporous structure. The Vascugraft prosthesis contains a network of fused microfibres of varying thickness and orientation which provide open and communicating pores similar in size to those in the Goretex material. In addition, they extend from one side of the graft wall to the other. As well as having superior longitudinal and radial compliance to the reinforced Goretex device, the Vascugraft prosthesis has more than adequate bursting and suture retention strengths. Through the use of contact angle measurements, electron spectroscopy for chemical analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry and molecular weight analysis by size exclusion chromatography, the surface of the Vascugraft prosthesis has been shown to be uniquely hydrophobic, as well as containing carbonate groups within an aliphatic polyesterurethane polymer. In addition, variations in micro-phase separation structure of hard and soft segment domains between different sizes and batches of product are marginal. Because of the interesting physical and chemical properties, it is recommended that in vitro biocompatibility and biostability studies be undertaken prior to using the prosthesis in animal or clinical trials.

Animals↗

Quantitative analysis of the surface morphology and textile structure of the polyurethane Vascugraft arterial prosthesis using image and statistical analyses.

The surface morphology and textile structure of the Vascugraft polyurethane arterial prosthesis were investigated. Novel methods of image analysis and the presentation of statistical data were used to obtain quantitative results of the surface morphology of the non-woven microfibrous structure of prostheses of three different sizes. These techniques have identified apparent differences in the distributions of thickness and orientation of the microfibres between the internal and external surfaces and between the three prostheses investigated.

Biocompatible Materials↗

In vitro biocompatibility evaluation of a heparinizable material (PUPA), based on polyurethane and poly(amido-amine) components.

The biocompatibility of a new heparinizable material based on polyurethane and poly(amido-amine) (PUPA) was evaluated both in the heparinized and non-heparinized forms. The quantity of heparin present on the material was measured using radiolabelled heparin and biological tests. Heparin release in plasma from heparinized PUPA was investigated using in vitro methods. The behaviour of PUPA towards cellular and plasmatic blood components was studied. The influence of sterilization on the cytocompatibility response of both heparinized and non-heparinized PUPA was investigated; gamma-rays were found to be a suitable method of sterilization as no toxic response was noticed.

Animals↗