Current Development of Polyurethane Heart Valves - Essay Example

Introduction Prosthetic heart valves are either mechanical or bioprosthetic. However, both these type of valves have limitations. Although mechanical heart valves are very durable, they require lifetime anticoagulation. Tissue valves do not need anticoagulation but often develop calcification and tissue tearing, leading to failure. Synthetic polymers like polyurethanes have high tensile strength and have excellent resistance to cyclic fatigue; therefore, this class of materials has been widely studied as a potential prosthetic heart valve. Polyurethane Heart Valves: Design and Evaluation Polyurethanes belong to a large family of materials, having in common, a characteristic of urethane linkage. Recently, a polyurethane tri-leaflet valve has been developed. This valve has three, thin polyurethane leaflets of approximately 100µm thickness, which are suspended from the inside of a flexible polyurethane frame. In the closed position, the valve is elliptical in the radial direction and hyperbolic in the circumferential direction. Hydrodynamic tests have shown that the polyurethane valve exhibits pressure gradients similar to those for a bioprosthetic valve, and lesser regurgitation and leakage than a bileaflet mechanical valve or the bioprosthetic valve. Accelerated fatigue tests have shown six consecutively manufactured polyurethane valves to have exceeded the equivalent of 10 years function without failure, and three valves have reached 527 million cycles (approximately 13 years equivalent). The only failure occurred after the equivalent of approximately 12 years cycling (González, et al., 2003). A new family of polymers, called the segmented polyurethane elastomers display high flexure endurance, strength, and inherent non-thrombogenic characteristics (González, et al., 2003). Bernacca, Straub and Wheatley (2002) used two biostable siloxane-based polyurethanes, EV3.34 and EV3.35, to manufacture a flexible trileaflet heart valve. This valve was implanted in 12 young adult (18 month) sheep in the mitral position. At 6 months, six valves were electively explanted while the remaining six valves were explanted at 9 months follow-up. Surface Fourier transform infrared spectrometry (ATR/FTIR) and scanning electron microscopy (SEM) were used to examine the leaflet material. The leaflet was also put through cyclic mechanical testing and was compared with non-implanted control material, to see if there was any change in mechanical properties during implantation. There was no degradation of functional groups. The study also observed that EV3.35 might have superior long-term fatigue properties. Polyether urethane Elasthane is a polyether urethane with a chemical structure similar to that of polyurethane. This material has excellent smooth surfaces, high strength, stability and good biocompatibility. It has a two-phase microstructure of hard and soft segments. One characteristic feature of this material is that its tensile stress increases as the percentage of elongation increases, up to a certain point, which is the proportional limit (Borrero et al., 2003). Elasthane valves have reduced degree of calcification. Chemical modification of Elasthane with polyethylene oxide (P) and sulfonate (SO) lowers surface platelet adhesion and thrombus formation, leading to better biocompatibility (González, et al., 2003). Hemodynamics ADIAM high performance valves are very durable and blood compatible. The hemodynamics of such a valve mimics that of natural valves without blood flow turbulence, blood cell destruction or clotting (ADIAM, n.d). These valves are made of asymmetric polycarbonate-urethane (PCU). Since these valves are synthetic like a mechanical valve, but flexible like a bioprosthesis, they are called ‘biomechanical’. This valve supposedly has long-term durability and does not require permanent anticoagulation. In one study (Daebritz et al., 2004) 7 aortic valves underwent long-term in vitro testing and in vivo testing in a growing calve animal model (20 weeks) and was compared to two different commercial bioprostheses. The results indicated good in vitro and in vivo hemodynamics. In vitro fatigue testing demonstrated valve durability of up to 300 million cycles. The mean systolic gradient across the size 21 PCU valves was 40–90 mmHg in echocardiography and 41–88 mmHg when invasively measured; CO was 12.2–12.9 l/min. The systolic gradients across the size 19 PCU aortic valves were 145 and 170 mmHg, respectively, at a CO of 11 l/min. The PCU valves demonstrated increased in vivo durability without thromboembolic complications or permanent anticoagulation. Although polyurethanes have relatively low thrombogenicity and good biocompatibility, long-term biostability has been a problem. A new family of polyurethanes, Elast-Eon, has been shown to be biostable. Bernacca, O’Connor, Williams and Wheatley (2002) examined the hydrodynamic behaviour of biostable polyurethane valves, with varying Young ’s modulus (5 to 63.6Mpa) and varying leaflet thickness (48–238 mm). The various parameters, which were studied included: mean pressure gradient, energy losses and regurgitation over 5 equivalent cardiac outputs (3.6, 4.9, 6.4, 8.0 and 9.6 l min_1). The results showed that at low cardiac output, there was insignificant correlation of the modulus with any valve opening parameter. At 9.6 l min_1, the modulus significantly influenced mean pressure gradient (p ¼ 0:033). At all cardiac outputs (p50:001) the mean leaflet thickness significantly correlated with mean pressure gradient and energy losses during forward flow. The conclusion that can be drawn from this study is that over a wide range of moduli, the hydrodynamic function of the valve is not affected to a great degree by the material modulus. The leaflet thickness is a highly significant factor. High modulus elastomers (range up to 32.5Mpa) will retain good hydrodynamic function and potentially extend the longevity of the valve. One study (Dohmen et al., 2002) compared the hydrodynamic performances of a decellularized pulmonary porcine valve (group I), glutaraldehyde fixated stentless porcine bioprosthesis (group II) and a polyurethane three leaflet valve prostheses (group III). The results revealed significantly different measured closing time (p < 0.001) between group I and II (24.333 and 53.600 ms, respectively) and group II and III (53.600 and 24.000, respectively). The closing volume showed significant difference (p < 0.05) between groups II and I (3.67 and 0.68 ms respectively) and group II and III (3.67 and 0.71 respectively). Systolic mean pressure gradient was 18.25 +/- 1.04 mm Hg in group II, which was significantly different (p < 0.001) from groups I and III (10.65 +/- 0.29 mm Hg and 7.70 +/- 0.30 mm Hg, respectively). From this, it was concluded that polyurethane valve prosthesis and decellularized pulmonary porcine valves had similar parameters and were superior to the glutaraldehyde fixated stentless porcine bioprosthesis. Biocompatibility One disadvantage of polyether-based polyurethane is the absorption of proteins, which can lead to thrombosis and bacterial infection. A better biocompatibility can be achieved if a polymer alloy consisting of polyurethane along with a phospholipid polymer can be synthesized. Currently, 2-methacryloyloxethylphosphorylcholine (PMEH) with segmented polyurethane has demonstrated lesser protein absorption at the blood-surface interface. Other polyurethane alloys, which have been synthesized includes: phospholipids polymer alloy, PEU-G and PEU-N. PEU-N consists of polyurethane with the addition of poly (tetramethylammonium) oxide and methylene diphenylene diisocyanate along with chain extenders of 3-trinethylammonium-1,2-propanedioliodide (TMPI) and 3-dimethylamino-1,2-propanedioliodide (DMP). Although PEU-N had a higher attachment constant (.00059 cm/min) than the other polyurethane alloys, it had a lower adhesion constant than pure polyurethane (PEU-B) (González et al., 2003). One major problem with polyurethane heart valves is the formation of calcified thrombus and subsequent thrombosis. This has been attributed partly to the lack of an intact endothelium on the implant surfaces. Stachelek et al (2006) seeded autologous sheep blood outgrowth endothelial cells (BOECs) onto cholesterol-modified polyurethane (PUChol) valves. In vitro shear flow studies were carried out comparing BOEC retention on control surfaces against that on PU-Chol. The results showed an endothelial monolayer on PU-Chol surfaces and a higher BOEC adhesion under 75-dyne/cm2 shear force, in vitro, than control polyurethane. The findings support the hypothesis that PU-Chol has significantly greater BOEC adhesion properties than plain polyurethane. BOEC seeding of PU-Chol can result in an intact, shear-resistant endothelium that prevents thrombosis and calcification. Durability The leaflet thickness of a flexible trileaflet polyurethane valve determines its durability and hydrodynamic function. Bernacca et al (1997) conducted an accelerated fatigue test at 37ºC on polyetherurethane (PEU) valve leaflets and polyetherurethane urea (PEUE) valve leaflets of varying thickness (60 to 200µm). The results revealed that the PEU valve durability was less than 400 million cycles, whereas PEUE valves exceeded 800 million cycles. This better durability in the PEUE valves was directly related to leaflet thickness (r = .93, p < 0.001), with median leaflet thickness of approximately 150 µm. Modification of PEUE valves with aminosilane also increases durability (González, et al., 2003). Bernacca et al (1997) subjected six PEUE flexible-leaflet prosthetic heart valves to long-term fatigue and calcification testing. The results showed that three valves exceeded 800 million cycles without failure. Three valves failed at 775, 460, and 544 million cycles, respectively. Calcification was observed in regions of high strain. They concluded that PEUE leaflets are vulnerable to calcification due to high strain in the same area. However, this is a long-term phenomenon and is unlikely to cause early valve failure. These valves show a lesser degree of calcification than bioprosthetic valves. Bisphosphonates are agents that are effective in modulating bone mineralisation, and are widely used for preventing and controlling osteoporosis, and in the prevention of pathologic calcification. Alferiev et al., (2001) have reported the first successful formulation and characterization of bisphosphonate-derivatized polyurethanes, which demonstrate stable and irreversible binding of bisphosphonate. Studies on rat subdermal implants, and sheep circulation have shown that these bisphosphonate-derivatized polyurethanes resist calcification without any adverse effects on growth. However, it was found that the surface polar anionic bisphosphonate groups on the polyurethane valves attracted sodium counter ion adsorption, which increased the valve’s water absorption. In order to address this issue, Alferiev et al., (2003) studied whether covalent attachment of diethylamino and bisphosphonate groups (DBP) to the bisphosphonate-modified polyurethane will reduce water absorption. The findings showed that DPB polyurethane showed a reduction in water absorption and calcification. Conclusion Various studies have revealed some important benefits of polyurethane valves. They exhibit lesser regurgitation and leakage than a bileaflet mechanical valve or the bioprosthetic valve. Segmented polyurethane elastomers have high flexure endurance, strength, and non-thrombogenicity. Elasthane has high strength, stability and biocompatibility. ADIAM valves have good in vitro and in vivo hemodynamics. A new family of polymers, Elast-Eon has been shown to be biostable. PMEH, PEU-G and PEU-N demonstrated lesser protein absorption at the blood-surface interface. A lesser degree of calcification is seen with PEUE valves when compared to bioprosthetic valves. Bisphosphonate-derivatized polyurethanes have been shown to resist calcification. However, more studies in the future and better refinement of technology may see polyurethane valves being used more frequently. References ADIAM, n.d. Biomechanical valves. Retrieved from Alferiev, I, Vyavahare, N, Song, C, Connolly, J, Travis, J, Hinson, Lu, Z, Tallapragada, S, Bianco, R, Levy, R (2001). Bisphosphonate derivatized polyurethanes resist calcification. Biomaterials. 2001 Oct; 22(19): 2683-93. Alferiev, I. Stachelek, SJ, Lu, Z, Fu, AL, Sellaro, TL, Connolly, JM, Bianco ,RW, Sacks, MS, Levy RJ (2003). Prevention of polyurethane valve cusp calcification with covalently attached bisphosphonate diethylamino moieties. J Biomed Mater Res A. 2003 Aug 1;66(2):385-95. Borrero, JR, Cure, J, Fabre, NJ and Rosado, E (2003). Mechanics of prosthetic heart valves. Applications of Engineering Mechanics in Medicine, GED - University of Puerto Rico, Mayaguez. December 2003. Bernacca GM, MacKay, TG, Gulbransen, MJ, Donn, AW and Wheatley, DJ (1997). Polyurethane heart valve durability: Effects of leaflet thickness and material. Int.J. Artif. Organs. 20:327–331, 1997. Bernacca GM, Mackay TG, Wilkinson R, Wheatley DJ (1997). Polyurethane heart valves: fatigue failure, calcification, and polyurethane structure. J Biomed Mater Res 1997;34:371– 9. Bernacca GM. Straub I, Wheatley DJ (2002). Mechanical and morphological study of biostable polyurethane heart valve leaflets explanted from sheep. J Biomed Mater Res. 2002 Jul;61(1):138-45. Bernacca, GM, O’Connor, B, Williams, DF, Wheatley, DJ (2002). Hydrodynamic function of polyurethane prosthetic heart valves: influences of Young’s modulus and leaflet thickness. Biomaterials. 2002 Jan;23(1):45-50. Daebritz, SH. Fausten, B, Hermanns, B, Schroeder, J, Groetzner, J, Autschbach, R, Messmer, BJ, Sachweh, JS (2004). Introduction of a flexible polymeric heart valve prosthesis with special design for aortic position. Eur J Cardiothorac Surg. 2004 Jun;25(6):946-52. Dohmen, PM. Scheckel, M, Stein-Konertz, M, Erdbruegger, W, Affeld, K. Konertz, W (2002). In vitro hydrodynamics of a decellularized pulmonary porcine valve, compared with a glutaraldehyde and polyurethane heart valve. Int J Artif Organs. 2002 Nov;25(11):1089-94. González, B, Benítez, H, Rufino, K, Fernández M and Echevarría, W (2003). Biomechanics of mechanical heart valve. Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez. December 2003. Stachelek, SJ. Alfeniev, I, Connolly, JM. Sacks, M, Hebbel, RP, Bianco, R and Levy, RJ (2006). Cholesterol-modified polyurethane valve cusps demonstrate blood outgrowth endothelial cell adhesion post-seeding in vitro and in vivo. Ann Thorac Surg. 2006 Jan;81(1):47-55. Read More