Degradation of biomaterials by phagocyte-derived oxidants.

Polymers used in implantable devices, although relatively unreactive, may degrade in vivo through unknown mechanisms. For example, polyetherurethane elastomers used as cardiac pacemaker lead insulation have developed surface defects after implantation. This phenomenon, termed "environmental stress cracking," requires intimate contact between polymer and host phagocytic cells, suggesting that phagocyte-generated oxidants might be involved. Indeed, brief exposure of polyetherurethane to activated human neutrophils, hypochlorous acid, or peroxynitrite produces modifications of the polymer similar to those found in vivo. Damage to the polymer appears to arise predominantly from oxidation of the urethane-aliphatic ester and aliphatic ether groups. There are substantial increases in the solid phase surface oxygen content of samples treated with hypochlorous acid, peroxynitrite or activated human neutrophils, resembling those observed in explanted polyetherurethane. Furthermore, both explanted and hypochlorous acid-treated polyetherurethane show marked reductions in polymer molecular weight. Interestingly, hypochlorous acid and peroxynitrite appear to attack polyetherurethane at different sites. Hypochlorous acid or activated neutrophils cause decreases in the urethane-aliphatic ester stretch peak relative to the aliphatic ether stretch peak (as determined by infrared spectroscopy) whereas peroxynitrite causes selective loss of the aliphatic ether. In vivo degradation may involve both hypohalous and nitric oxide-based oxidants because, after long-term implantation, both stretch peaks are diminished. These results suggest that in vivo destruction of implanted polyetherurethane involves attack by phagocyte-derived oxidants.

Thrombus deposition on polyurethanes designed for biomedical applications.

Thrombogenicity was assessed by measuring the amount of 111In-platelets and 125I-fibrinogen deposited on the inner luminal surface of six polyurethanes for up to 60 min of blood contact in a canine ex-vivo shunt model. Commercial and laboratory synthesized polymers were examined. Two of the commercially synthesized polyurethanes (Biostable PURs) do not contain ether linkages in the polymer backbone and have previously shown resistance to oxidative and hydrolytic degradation. Static contact angle measurements, dynamic contact angle measurements, and ESCA were used to characterize the surfaces of these polyurethanes. The effectiveness of an acetone extraction used to remove extrusion waxes from Pellethane 2363-80A was similarly studied. Both Pellethane 2363-80A and the ether-free materials had relatively nonthrombogenic surfaces, as indicated by low platelet and fibrinogen deposition, making them potentially good candidates for biomedical applications.

Effect of soft segment chemistry on the biostability of segmented polyurethanes. II. In vitro hydrolytic degradation and lipid sorption.

A series of segmented polyurethanes (SPUs) with various polyol soft segments was prepared and their hydrolytic degradation and degradation due to lipid sorption was investigated. The hydrolytic degradation of the SPUs was investigated in a papain solution, where it was shown that the SPU based on poly(ethyleneoxide) (PEO) soft segment was susceptible to hydrolytic degradation. X-ray photoelectron spectroscopic (XPS) data suggest dissociation of the urethane linkage by enzymatic degradation. Degradation by lipid sorption was observed for the SPU based on a poly(dimethylsiloxane) (PDMS) soft segment. This is ascribed to the high solubility of lipid in the PDMS segment of the SPU.

Effect of surface hydrophilicity on ex vivo blood compatibility of segmented polyurethanes.

The relationship between surface, bulk and ex vivo blood-contacting properties of segmented polyurethanes with various polyol soft segment was investigated. The polyols used in this study were poly(ethylene oxide), poly(tetramethylene oxide), hydrogenated poly(butadiene), poly(butadiene) and poly(dimethylsiloxane). The hard segment of these segmented polyurethanes was composed of 4,4' diphenylmethane diisocyanate and 1,4 butanediol, present at 50 wt%. An experimental polyurethane, Biostable PUR, which has shown excellent biostability, was used in this study. The segmented polyurethanes based on the hydrophobic polyols such as poly(dimethylsiloxane) and hydrogenated poly(butadiene) showed distinct microphase separation between hard and soft segments. X-ray photoelectron spectroscopy revealed the surface enrichment of the hydrophobic component at the air-solid interface. Dynamic contact angle measurements indicated that the poly(dimethylsiloxane)-based segmented polyurethane possessed a hydrophobic surface in water. The poly(dimethylsiloxane)-based segmented polyurethane had the lowest platelet adhesion among the segmented polyurethanes investigated in this study, whilst the platelet deposition on the poly(ethylene oxide)-based polymer increased with time.

Effect of soft segment chemistry on the biostability of segmented polyurethanes. I. In vitro oxidation.

A series of segmented polyurethanes (SPUs) containing various polyol soft segments was prepared and their resistance to oxidative degradation was investigated after aging in AgNO3 solution. The SPU with the polyether soft segment showed a large reduction in mechanical strength after exposure to the oxidative environment. Surface cracking was often observed for these specimens. XPS measurements revealed that scission of the ether linkage occurs upon oxidation. The oxidative resistance of SPUs containing aliphatic hydrocarbon soft segments was significantly improved over the poly(tetramethylene oxide) (PTMO) based polyurethane.

Factors and interactions affecting the performance of polyurethane elastomers in medical devices.

Polyurethanes offer the greatest versatility in compositions and properties of any family of polymers. For implantable medical devices, a few specific elastomeric polyurethane compositions have demonstrated a combination of toughness, durability, biocompatibility and biostability not achieved by any other available material. Because of the complex behavior of implantable polyurethanes in the body environment, designers and fabricators of polyurethane-containing devices must pay particular attention to the choice of composition and design of components. Subsequent treatment during qualification, fabrication, sterilization, storage, implantation, in vivo operation and explantation also determine the performance and provide the means for assessing the efficacy of the polyurethane in the implanted device.

Biostability considerations for implantable polyurethanes.

Polyurethanes have become the most valuable implantable elastomers for uses requiring toughness, durability, biocompatibility and biostability. They are inherently stable in the body environment. However, physical and chemical changes may be effected by conditions of processing, fabrication, use or interactions with other device components. Most prominent modes of polyurethane degradation include mineralization, environmental stress-cracking and oxidation. While the mechanisms of these forms of degradation are not fully understood, an awareness of their causes and effects can lead to procedures that provide all of the long-term functionality required for the sophisticated polyurethane-based devices of today and tomorrow.

Development of a screening system for cystic fibrosis.

We have developed a simple method for detecting high concentrations of chloride in sweat from ambulatory subjects, a measurement useful in the detection of cystic fibrosis. The method is based on the standard approach of stimulating sweat generation through iontophoresis of pilocarpine nitrate into the skin, followed by collection and analysis of the sweat for chloride concentration. The sweat-stimulating reagents are contained in polymeric gel pads, which are used in conjunction with a small battery-powered stimulator. The chloride analysis is subsequently done on the stimulated site by use of a thin test patch that picks up a fixed amount of sweat and changes color if the chloride concentration is higher than a predetermined value. The successful completion of a test is indicated by a fill tab, which changes color when the appropriate amount of sweat has been picked up by the chloride test patch.