Bernacca Gm

New polyurethane heart valve prosthesis: design, manufacture and evaluation

In light of the thrombogenicity of mechanical valves and the limited durability of bioprosthetic valves, alternative designs and materials are being considered for prosthetic heart valves. A new tri-leaflet valve, made entirely from polyurethane, has been developed. The valve comprises three thin polyurethane leaflets (approximately 100 microns thick) suspended from the inside of a flexible polyurethane frame. The closed leaflet geometry is elliptical in the radial direction and hyperbolic in the circumferential direction. Valve leaflets are formed and integrated with their support frame in a single dip coating operation. The dipping process consistently gives rise to tolerably uniform leaflet thickness distributions. In hydrodynamic tests, the polyurethane valve exhibits pressure gradients similar to those for a bioprosthetic valve (St Jude Bioimplant), and levels of regurgitation and leakage are considerably less than those for either a bi-leaflet mechanical valve (St Jude Medical) or the bioprosthetic valve. Six out of six consecutively manufactured polyurethane valves have exceeded the equivalent of 10 years function without failure in accelerated fatigue tests. The only failure to date occurred after the equivalent of approximately 12 years cycling, and three valves have reached 527 million cycles (approximately 13 years equivalent). The simplicity of valve manufacture, combined with promising results from in vitro testing, indicate that further evaluation is warranted.

In vitro blood compatibility of surface-modified polyurethanes

Polyurethanes have proven durable materials for the manufacture of flexible trileaflet heart valves, during in vitro tests. The response of two polyurethanes of differing primary structure to parameters of blood compatibility has now been investigated, using an in vitro test cell. Platelet (beta-thromboglobulin) release, complement (C3a) activation, the activation of free plasma and surface-bound factor XII were studied using fresh, human blood (no anticoagulant) or citrated plasma in control and surface-modified polyurethane. Surface modifications were designed to affect material thrombogenicity and included covalent attachment of heparin, taurine, a platelet membrane glycoprotein fragment, polyethylene oxide (PEO), 3-aminopropyltriethoxysilane, and glucose or glucosamine. Unmodified control polyurethanes caused platelet release and complement activation. High molecular weight (2000 D) polyethylene oxide reduced platelet release slightly but only glucose attachment to the surface produced a significant reduction in platelet activation. All modifications reduced C3 activation compared with controls, but the greatest reduction was achieved with polyethylene oxide attachment or glycosylation. Most surface modifications were more activating of factor XII, both in plasma and on the material surfaces, than the control polyurethanes. Heparin and high molecular weight PEO produced the greatest activation of factor XII in the free plasma form, but low molecular weight PEO and glucosamine produced the greatest activation of surface-bound factor XIIa. The least activating surfaces, affecting both free plasma and surface-bound factor XIIa, were those treated with platelet membrane glycoprotein fragment and glucose. PEO surfaces performed relatively well, compared with controls and most surface modifications. The best overall surface, however, was the glucose-modified surface which was least activating considering all parameters of blood compatibility.

Polyurethane heart valves: Fatigue failure, calcification, and polyurethane structure

Six flexible-leaflet prosthetic heart valves, fabricated from a polyetherurethaneurea (PEUE), underwent long-term fatigue and calcification testing. Three valves exceeded 800 million cycles without failure. Three valves failed at 775, 460, and 544 million cycles, respectively. Calcification was observed with and without associated failure in regions of high strain. Comparison with similar valves fabricated from a polyetherurethane (PEU) suggests that the PEU is likely to fail sooner as a valve leaflet. Localized calcification developed in PEUE leaflets at the primary failure site of PEU leaflets, close to the coaptation region of the three leaflets. The failure mode in PEU valves had the appearance of abrasion wear associated with calcification. High strains in the same area may render the PEUE leaflets vulnerable to calcification. Intrinsic calcification of this type, however, is a long-term phenomenon unlikely to cause early valve failure. Both polymers performed similarly during static in vitro and in vivo calcification testing and demonstrated a much lesser degree of calcification than bioprosthetic types of valve materials. Polyurethane valves can achieve the durabilities required of an implantable prosthetic valve, equaling the fatigue life of currently available bioprosthetic valves.

Polyurethane heart valve durability: effects of leaflet thickness and material.

A flexible trileaflet polyurethane valve has been made by dip-moulding leaflets directly onto an injection-moulded frame. The durability of this valve is, in part, determined by the thickness of its leaflets. Leaflet thickness is also a major determinant of hydrodynamic function. This study examines valves (n=31) with leaflets made of a polyetherurethane (PEU, n = 22) or a polyetherurethaneurea (PEUE, n = 9), of varying thickness distributions. The valves were subjected to accelerated fatigue test at 37°C and failure monitored. Leaflet thicknesses ranged from 60 to 200 μm. PEU leaflet thickness bore no relationship to durability, which was less than 400 million cycles. PEUE valves, in contrast, exceeded 800 million cycles. Durability in PEUE valves was directly related to leaflet thickness (r = 0.93, p < 0.001), with good durability achieved with median leaflet thicknesses of approximately 150μm. Thus polyurethane valves can be made with good hydrodynamic properties and with sufficient durability to consider potential clinical use.

Surface modification of polyurethane heart valves: effects on fatigue life and calcification.

Polyurethane heart valves can be functionally durable with minimal calcification, in vitro. In vivo, these characteristics will depend on the resistance of the polyurethane to thrombogenesis and biodegradation. Surface modification may improve the polyurethane in these respects, but may adversely affect calcification and durability. This study investigates the effects of surface modifications of two polyurethane heart valves (PEU and PEUE) on their in vitro fatigue and calcification behaviour. Modifications included heparin, taurine, 3-aminopropyltriethoxysilane and polyethylene oxide (PEO). Neither hydrodynamic function nor leaflet thickness distribution was significantly altered by surface modification. PEO-modification was detrimental to valve fatigue durability and calcification. Heparin, taurine or aminosilane modifications of PEU valves increased durability. Aminosilane modification of PEUE valves increased durability compared with PEO modification. Appropriate surface modification may be useful to improve blood compatibility of implantable polyurethanes, and may also be advantageous as regards fatigue durability of flexing materials in long-term applications.

Calcification Modelling in Artificial Heart Valves

This study has examined a range of methods of studying the calcification process in bovine pericardial and polyurethane biomaterials. The calcification methods include static and dynamic, in vitro and in vivo tests. The analytical methods include measurement of depletion rates of calcium and phosphate from in vitro calcifying solutions, analysis of tissue contents of calcium, histological staining of tissue sections for calcium, X-ray elemental analysis, by scanning electron microscopy, of calcium and phosphorus distributions over valve leaflets calcified in vitro under dynamic conditions. Bovine pericardium, in all test settings, calcified to a much greater degree than polyurethane biomaterials. Polyurethane extracts calcified to a greater degree than bulk polyurethanes. The test protocol used allows progress through increasily demanding calcification tests, with the possibility of eliminating unsuitable materials with tests of limited complexity and expense.

Laser profiling of bovine pericardial heart valves.

Laser profiling techniques have been used to examine the 2-dimensional and 3-dimensional patterns of leaflet motion in functioning bovine pericardial heart valves (1 normal valve and 1 fatigued/calcified). In the normal valve the general patterns of opening and closing were similar for all leaflets; however, localised variations such as areas of high curvature, retarded motion and high speed motion were identified. In the fatigued/calcified valve significant differences from the normal leaflet motion were observed e.g. increased crimping, gross leaflet lag and irregular deformation. The laser profiling technique was able to reveal changes in the functional dynamics of pericardial valve leaflets not otherwise detectable by conventional hydrodynamic measurements of valve performance.