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A novel formulation for controlled release of heparin-DOCA conjugate dispersed as nanoparticles in polyurethane film.

Heparin is a potent anticoagulant agent that interacts strongly with antithrombin III to prevent the formation of fibrin clot. In this study, we propose a new method for preparing a heparin-releasing system using a simple solvent casting. The heparin-DOCA conjugate, having an amphiphilic property, was homogeneously mixed with polyurethane in the co-solvent of dioxane, propanol and water. After casting the film, heparin-DOCA was homogeneously dispersed as nanoparticles in a polyurethane film. As the loading amount of heparin-DOCA in the film was increased, nanoparticle size, water uptake, and release rate were increased. Moreover, the percentage of released amount of heparin-DOCA was increased with the increase in the loading amount of heparin-DOCA. This was because the size of heparin-DOCA particles increases with the increase in the loading amount of heparin-DOCA, thereby decreasing the distance between particles and the total diffusion length to the surface. The release rate of heparin-DOCA can be controlled by the amount of the drug being loaded and the film thickness. When the heparin-DOCA loaded on the polyurethane films was above 7.5%, the released heparin-DOCA prevented the formation of fibrin clot and the platelet adhesion on the film surface.

Desoxycorticosterone↗

Hydrodynamic function of polyurethane prosthetic heart valves: influences of Young's modulus and leaflet thickness.

The development of flexible polyurethane heart valves has been hindered by material degradation in vivo. Low modulus polyurethane leaflets are regarded as desirable to achieve good hydrodynamic function. However, low modulus materials may suffer high strain accumulation, hence poor durability. Higher modulus materials may improve durability, but may have poor hydrodynamic function. This study examines the hydrodynamic behaviour of biostable polyurethane valves, varying Young's modulus from 5 to 63.6 MPa and mean leaflet thickness from 48-238 microm. Parameters studied included mean pressure gradient, energy losses and regurgitation over 5 equivalent cardiac outputs (3.6, 4.9, 6.4, 8.0 and 9.61 min(-1)) At low cardiac output, modulus was not significantly correlated with any parameter of valve opening. At 9.61 min(-1), modulus significantly influenced mean pressure gradient (p = 0.033). Mean leaflet thickness significantly correlated with mean pressure gradient and energy losses during forward flow at all cardiac outputs (p<0.001). This study demonstrates that, over a wide range of moduli, valve hydrodynamic function is not affected significantly by the material modulus. Leaflet thickness is a highly significant factor. Higher modulus elastomers in a range up to 32.5 MPa may be useful in prosthetic heart valve leaflet manufacture, retaining good hydrodynamic function while potentially extending the lifetime of the valve.

Heart Valve Prosthesis↗

Synthesis, characterization and platelet adhesion of segmented polyurethanes grafted phospholipid analogous vinyl monomer on surface.

New segmented polyurethanes (SPUs) grafted phospholipid analogous vinyl monomer, 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) on surface were synthesized. The soft segment of these polyurethanes was hydroxylated poly(isoprene) diol and the hard segments were 4,4'-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BD). SPUs were hydroxylated by potassium peroxodisulfate and MPC was grafted on the surface of hydroxylated SPUs using di-ammonium cerium (IV) nitrate (ceric ammonium nitrate, CAN) as a radical initiator. The bulk characterization of synthesized SPUs was investigated by infrared spectroscopy (IR) and gel-permeation chromatography (GPC). The existence of phospholipid analogous groups on the surface of these SPUs was revealed by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The surfaces of MPC-grafted SPUs showed decreased water contact angles compared to non-grafted SPU and the presence of phosphorylcholine groups. The blood compatibilities of the new polymers were evaluated by platelet rich plasma (PRP) contact studies and viewed by scanning electron microscopy (SEM) using BioSpan and non-grafted polyurethane as references. We found that fewer platelets adhered to the MPC-grafted surfaces and that they showed less shape variation than the references. These results suggest that these grafted polymers may have the possibility of the usage for biomaterials.

Biocompatible Materials↗

Activated polyurethane modified with latent thiol groups.

A novel type of modified polyurethane with pendant acetylthio groups (as a latent form of thiol groups) has been proposed for the use in surface modifications with various biomolecules. The polymer was prepared via a modified variant of low-temperature bromoalkylation of urethane hard segments followed by the reaction of pendant bromoalkyl groups with thiolacetic acid in mild conditions. The extent of modification with acetylthio groups can be made as high as 0.45 mmol/g. After deprotection of acetylthio groups and reaction of the resulting thiol groups with an excess of Ellman's reagent, 0.1 nmol/cm(2) of thiol-reactive 3-carboxy-4-nitrophenyldithio groups were detected on the surface of films cast from the modified polymer. A sensitive fluorescent probe--dansyl-L-cysteine was used for the quantification of thiol-reactive groups bound to the surface. The acetylthio-modified polyurethane is sufficiently stable to withstand conditions typical for the high-temperature processing (molding, extrusion) of polyurethanes.

Cysteine↗

The use of biodegradable polyurethane scaffolds for cartilage tissue engineering: potential and limitations.

The aim of the present study was to evaluate the capability of novel biodegradable polyurethane scaffolds to support attachment, growth and maintenance of differentiated chondrocytes in vitro for up to 42 days. After an initial decrease, although not significant, the DNA content of the constructs remained constant over the culture time. A progressive increase in glycosaminoglycans and collagen was observed during the culture period. However, a significant release of matrix molecules into the culture medium was also noticeable. At the transcriptional level, a decrease in aggrecan and procollagen II mRNA expression was noticeable, whereas procollagen I expression was increased. To conclude, the present data demonstrate that biodegradable polyurethane porous scaffolds seeded with articular chondrocytes support cell attachment and the production of extracellular matrix proteins. The limitations of the system are the diffusion of large amounts of matrix molecules into the culture medium and the dedifferentiation of the chondrocytes with prolonged time in culture. However, due to the favourable mechanical properties of the polyurethane scaffold, stimulation of chondrocytes by mechanical loading can be considered in order to improve the formation of a functional cartilage-like extracellular matrix.

Absorbable Implants↗

Controlled delivery of therapeutics from microporous membranes. I. Fabrication and characterization of microporous polyurethane membranes containing polymeric microspheres.

This paper describes a process for the inclusion of polymer microspheres in microporous polyurethane tubes and membranes. These composites were fabricated via a spray, phase-inversion technique using Cardiothane 51, a medical grade polyurethane, and either spray-dried poly(D,L-lactide-co-glycolide 50:50) microspheres or commercially available fluorescent polystyrene-latex microspheres. Characterization of the polyurethane membranes was performed using Fouriertransform infrared spectroscopy, differential scanning calorimetry, dynamic mechanical analysis, hydraulic permeability testing, scanning electron microscopy, and visible and fluorescence light microscopy. The results indicated the feasibility of layering microspheres throughout the microporous membrane or wall of the microporous tube, and the potential of such composite structures for local delivery of bioactive substances.

Blood Vessel Prosthesis↗

Photoimmobilisation of poly(N-vinylpyrrolidinone) as a means to improve haemocompatibility of polyurethane biomaterials.

A novel method to improve the haemocompatibility of polymeric biomaterials (in particular: polyurethane elastomers) is reported. The new approach essentially rests upon photochemical immobilisation of the highly biocompatible polymer poly(N-vinylpyrrolidinone) (poly(NVP)) onto the biomaterial's surface. One of the key steps in the surface modification procedure is the preparation of a copolymer of NVP and the photoreactive building block 4-[4'-azidobenzoyl]-oxo-n-butylmethacrylate (1). This copolymer is first dissolved in a volatile solvent, then sprayed onto the biomaterial's surface, and subsequently immobilised via irradiation with ultraviolet light. The paper describes: (i) preparation of 1, (ii) preparation of the copolymer (NVP + 1), (iii) physico-chemical characterisation of the modified surfaces, and (iv) results of two in vitro haemocompatibility assays (i.e. thrombin generation and adhesion of blood platelets from recalcified human platelet-rich plasma). Furthermore, the surface modification was performed with a microporous polyurethane vascular graft (Chronoflex), which is already in clinical use. The in vitro experiments revealed that significant improvement of the haemocompatibility of polyurethanes can be achieved through this method.

Biocompatible Materials↗

Clinical efficacy of the polyurethane stent without fluoroscopic guidance in the treatment of nasolacrimal duct obstruction.

PURPOSE: To evaluate the clinical efficacy of the polyurethane (Song) stent in the treatment of nasolacrimal duct obstruction without fluoroscopic guidance, especially at the junction between the lacrimal sac and nasolacrimal duct or at the nasolacrimal duct. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: This study evaluated 59 cases of nasolacrimal duct obstruction in 53 patients, with mean epiphora of 36 months (range, 2 months-17 years). METHODS: Without the assistance of a radiologist, a polyurethane nasolacrimal stent was placed by introducing a guidewire through the superior or inferior punctum into the canaliculus and advancing it across the obstruction into the opening of the inferior meatus of the nasal cavity. The mean follow-up period was 22 months (range, 12 months-48 months). MAIN OUTCOME MEASURES: Patency of the lacrimal passage to irrigation and the duration of this procedure. RESULTS: Complete resolution of epiphora was accomplished in 55 (93.2%) of the 59 eyes. There was recurrence of epiphora in four cases because of obstruction of the stent in three cases and obstruction of the common canaliculus by recurrent dacryocystitis in one case. CONCLUSIONS: Polyurethane stenting without fluoroscopic guidance seems to be a valuable technique for primary management of nasolacrimal duct obstruction before dacryocystorhinostomy.

Adult↗

A comparative study of polyurethane and silicone cuffed-catheters in long-term home total parenteral nutrition patients.

AIM: The purpose of this study was to report our compared experience of long-term complications with polyurethane (LeaderCuff) and silicone (Lifevac) tunnelled, cuffed catheters in home adult TPN patients. METHODS: All catheters were inserted by a percutaneous technique under local anaesthesia. RESULTS: Forty silicone catheters were inserted in 31 patients and 13 polyurethane catheters were inserted in 11 patients totaling a total experience of 480 months and 175 months respectively. Mean catheter life span was 12 months (range: 0.25-47) and 13 months (range: 3-44) for Lifevac and LeaderCuff catheters, respectively. Complication rates (expressed as patient-year of TPN) were no significantly different for Lifevac and LeaderCuff catheters: sepsis (0.15 vs 0.14), obstruction (0.05 vs 0), dislodgement (0.13 vs 0.07) and thrombosis (0 vs 0.14). The fracture rate was 20 times lower for Lifevac than for LeaderCuff (P << 0.01): in all cases, this mechanical problem was due to the dysfunction of the detachable flow-control device. CONCLUSION: Both Lifevac and LeaderCuff catheters enable safe, long-term, venous access and prevent, in most cases, inadvertent catheter dislodgement. There is little evidence, from our study, to support the hypothesis that polyurethane catheters offer more security than silicone catheters in home TPN adult patients.

Adolescent↗

The effect of hydrogen ion concentration on the force-degradation rate of orthodontic polyurethane chain elastics.

The effect of pH on the force-degradation rates of seven commercial orthodontic polyurethane chain elastics was evaluated in an in vitro study. The pH values of 4.95 and 7.26 were selected for testing because they represent values close to the reported extremes of plaque and saliva pH. Seven test elastic products were extended to (1) equal distances and (2) equal initial force levels, and the force-degradation rates were recorded over 4 weeks. All the test products yielded a significantly greater force-decay rate in the basic (pH 7.26) solution than in the acidic (pH 4.95) solution over 4 weeks. A hypothesis is presented that the decay rate of orthodontic polyurethane chain elastics is inversely proportional to the oral pH, with a corollary that basic pH levels are most hostile to polyurethane chain elastics.

Analysis of Variance↗

Biocompatibility of the polyurethane resin of the castor bean inserted into the alveolar bone of the dog.

The biocompability of the polyurethane resin of the castor bean (Ricinus vulgaris) was studied following its insertion into the alveolar bone of dogs, after extraction of their premolar teeth. The resin was left to polymerise in the dental alveolus. Excess of material due to polymerisation was removed and polishing was employed to smooth and adapt the occlusal surface to the margins of the alveolar bone. This allowed a perfect suture of the mucosa together with the periosteum. The resin remained in the dental alveolus for 90 days. It was observed that the polyurethane was replaced by osteoid and bone tissues and no immune or inflammatory reactions were detected. There has been work on and discussion about the use of the polyurethane in grafts, prostheses and orthoses. Attention was paid to all the surgical steps, in particular the preservation of the periosteal integrity. Further research is being followed in our Department in order to test the biocompatibility of the material presented in this paper when used together with metallic or ceramic implants.

Animals↗

New prostheses for use in bypass grafts with special emphasis on polyurethanes.

Vascular bypass procedures using traditional prosthetic grafts such as polytetrafluoroethylen (PTFE) and polyethylene tetraphthlate (Dacron) are prone to failure when used in low flow states such as in below knee bypass and when the diameter of the graft is less than 6 mm. A major factor in this is compliance mismatch between the graft and the diseased vessel, which may cause intimal hyperplasia at the distal anastomosis. PTFE and Dacron are rigid grafts with poor compliance. By improving the compliance of the prosthetic graft it is hoped that patency will improve. Recent advances in polyurethane chemistry have developed materials that do not degrade and which allow compliance matching of the graft to the patient's vasculature. It is now possible to manufacture biologically and haemodynamically compatible grafts with small diameter from these polyurethane graft materials. This review will focus on the lack of compliance in current vascular bypass grafts and the promise of the new polyurethane polymers in a new generation of small-bore bypass grafts.

Biocompatible Materials↗

Biologic fixation of polyester- versus polyurethane-covered stents in a porcine model.

PURPOSE: Migration of endoprostheses remains a concern in endovascular aneurysm treatment. Biologic fixation is supposed to enhance anchorage, but the diseased atherosclerotic aorta in humans has demonstrated a limited capacity to incorporate an endoprosthesis by cellular proliferation. The biologic response of two different types of endoprostheses was evaluated in the porcine aorta. MATERIALS AND METHODS: Two types of endoprostheses--four polyurethane-covered (PUC) stents with a macroporous polyurethane covering and four polyester-covered (PEC) stents with a woven polyester covering--were implanted in eight infrarenal porcine aortas for 6 weeks. Electron microscopy and qualitative and quantitative microscopy were performed on serial cross sections. RESULTS: The PUC stents demonstrated an increase in diameter (from 8 mm +/- 1 to 10 mm +/- 1, 12.5%; P = .009), whereas the PEC stents persisted in their original dimensions (8 mm +/- 1, 0%). PUC and PEC stents were covered by continuous thrombus-free neointima (269 microm +/- 51 vs 575 microm +/- 113, respectively; P < .01). The PUC stents demonstrated firm attachment to the aorta as a consequence of a granulation tissue with ingrowth into the pores of the polyurethane covering. The PEC stents remained in loose contact with the aorta in the absence of tissue ingrowth. CONCLUSIONS: Enhanced biologic fixation was achieved by extensive granulation tissue invading the pores of PUC endoprostheses. This finding can modify the design of future devices.

Animals↗

Stability of the offset V osteotomy: effects of fixation, orientation, and surgical translocation in polyurethane foam models and preserved cadaveric specimens.

Polyurethane foam models and cadaver specimens were used to examine the stability of the offset V first metatarsal osteotomy. Uniform osteotomies were performed in all specimens by using a specially designed jig. Specimens in the polyurethane foam model series (n = 10) varied with respect to fixation type, fixation orientation, and degree of lateral translocation of the osteotomy. All specimens were loaded to failure in an Instron testing machine (Instron, Canton, MA). The plantar wing-pin (Kirschner wire) osteotomy group showed statistically significantly greater stiffness (P =.0119) and load at failure (P =.0027) than the dorsal wing-pin group. Cadaveric offset V specimens received the same amount of capital fragment lateral translocation but had different fixation types and orientations. Using the identical protocol as the models, the cadaveric dorsal wing-screw group showed statistically significantly less displacement at failure than the plantar wing-screw, plantar wing-pin, and dorsal wing-pin groups (P =.0262). The dorsal wing-pin group with a synthetic tension band showed a statistically significant greater stiffness (P =.0054) and peak load at failure (P =.0004) compared with the dorsal wing-pin group without the tension band. The most stable offset V construct in the polyurethane foam model was the plantar wing-pin group. The preserved cadaveric specimens yielded different results. The cadaveric dorsal wing-pin group with the synthetic tension band showed superior stability compared with all other non-tension-band groups. These results indicate the importance of tension band effects provided by capsular and ligamentous structures, which are typically ignored in surgical optimization research.

Biomechanical Phenomena↗

Water makes it hydrophobic: contraphilic wetting for polyurethanes with soft blocks having semifluorinated and 5,5-dimethylhydantoin side chains.

A series of polyurethanes with novel copolymer soft blocks display a new surface phenomenon, contraphilic wetting, in which the dry surface is hydrophilic and the wetted surface is hydrophobic. A precursor polymer was prepared with copolymer soft blocks containing semifluorinated (trifluoroethoxy, 3FOx, or pentafluoropropoxy, 5FOx) and bromomethyl functional pendant groups with 2:1, 1:1, and 1:2 semifluorinated/bromomethyl ratios. The hard block consists of isophorone diisocyanate (IPDI) and 1,4-butanediol (BD). 5,5-Dimethylhydantoin was introduced by the substitution of Br via reaction-on-polymer. The composition, structure, and percent of 5,5-dimethylhydantoin substitution for both the precursor and the 5,5-dimethylhydantoin-substituted polyurethanes were analyzed by 1H NMR. The difference between the advancing contact angle on the wetted surface and that on the dry surface (deltaC) is highest (38 degrees ) for the polyurethane with the highest ratio of semifluorinated/hydantoin soft block side chains. A model is proposed according to which contraphilic wetting is driven enthalpically by hydrogen bonding. For the dry surface, hydrogen bonding of 5,5-dimethylhydantoin amide carbonyl groups to methylene hydrogens of semifluorinated groups disrupts the normal surface concentration of semifluorinated groups, whereas the geometric arrangement of hydantoin N-H results in availability for hydrogen bonding with water. Upon exposure to water, amide groups switch from hydrogen bonding to -CH2CF2CF3 to stronger hydrogen bonding with water. As a result, semifluorinated groups are "released", and the surface becomes hydrophobic. Drying the coating (50 degrees C) reversibly restores hydrophilic character. Coatings stored at ambient temperature and humidity have deltaC values intermediate between dry and wet states.

Fluorocarbon Polymers↗

Safety, functionality and acceptability of a prototype polyurethane condom.

Male condoms made from synthetic materials offer an alternative to latex condoms that may be more acceptable to users, thereby potentially resulting in more protected acts of intercourse. A prospective, noncomparative clinical study was conducted to evaluate the safety of using certain polyurethane materials to make condoms. Fifty-one healthy, contracepting, mutually monogamous couples were recruited between June 30 and November 24, 1993 to use a prototype roll-on polyurethane condom developed by Family Health International. Couples were to use the condoms for 10 consecutive acts of vaginal intercourse over a 4-week period. Baseline and postexposure genital examinations, including colposcopy for female participants, were performed. Fifty couples completed the study requirements and 517 acts of intercourse occurred using the condoms. Two adverse events were reported: irritation of introitus in a female participant and a small irritated erythematous lesion on a male participant's penis. Neither event was considered to be serious and both were resolved without treatment. Breakage and slippage rates were similar to those reported for latex condoms. These results suggest that polyurethane condoms represent a safe, functional and acceptable alternative to latex condoms.

Adult↗

Blood compatibility of polyurethane immobilized with acrylic acid and plasma grafting sulfonic acid.

Sulfonic and carboxyl groups can effectively improve the blood compatibility of polyurethane. But it is difficult to obtain an optimum ratio of the two groups. In this article, polyurethane (PU) was dissolved with acrylic acid in a tetrahydrofuran solution and then spread on the glass plate to produce a film. At the same time, acrylic acid partly polymerized and immobilized with the PU films. The films (PU-AA) were exposed to sulfur dioxide plasma to graft sulfonic acid group on its surfaces. Through adjusting the quantity of acrylic acid and the plasma reaction condition, the antithrombin of polyurethane can be improved. The surface-modified PUs were characterized by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscope (XPS) and a contact angle goniometer. The blood compatibility of the films was examined by using thrombin time (TT), activated partial thromboplastin time (APTT) and prothrombin time (PT). The TT and APTT were significantly prolonged for the surface-modified films of PU-AA by sulfur dioxide plasma and only APTT was elongated for PU-AA. The results suggest that sulfonic acid and acrylic acid have the different effect on the blood compatibility of surface-modified PUs.

Acrylates↗

Long-term structural failure of coaxial polyurethane implantable cardioverter defibrillator leads.

Transvene models 6936/6966, a coaxial polyurethane ICD lead, may be prone to structural failure. These models comprise 54% of ICD lead failures in the authors' Multicenter Registry database. Because ICD leads perform a vital function, the clinical features, causes, and probability of Transvene 6936/6966 lead failure were determined. The Registry and United States Food and Drug Administration databases were queried for the clinical features and structural causes of the Transvene 6936/6966 lead failure, and a five-center substudy estimated the survival probability for 521 Transvene 6936/6966 implants. The mean time to failure was 4.8 +/- 2.1 years, and the estimated survival at 60 and 84 months after implant were 92% and 84%, respectively. Oversensing was the most common sign of failure (76%), and 24 patients experienced inappropriate shocks. The manufacturer's reports indicated that high voltage coil fracture and 80A polyurethane defects were the predominant causes of lead failure. Transvene models 6936 and 6966 coaxial polyurethane ICD leads are prone to failure over time. Patients who have these leads should be evaluated frequently. Additional studies are needed to identify safe management strategies.

Death, Sudden, Cardiac↗