Abstract
Polymeric heart valves (PHVs) hold the promise to be more durable than bioprosthetic heart valves and less thrombogenic than mechanical heart valves. We introduce a new framework to manufacture hemocompatible polymeric leaflets for HV (PHV) applications using a novel material comprised of interpenetrating networks (IPNs) of hyaluronan (HA) and linear low density polyethylene (LLDPE). We establish and characterize the feasibility of the material as a substitute leaflet material through basic hemodynamic measurements in a trileaflet configuration, in addition to demonstrating superior platelet response and clotting characteristics. Plain LLDPE sheets were swollen in a solution of silylated-HA, the silylated-HA was then crosslinked to itself before it was reverted back to native HA via hydrolysis. Leaflets were characterized with respect to (1) bending stiffness, (2) hydrophilicity, (3) whole blood clotting, and (4) cell (platelet and leukocyte) adhesion under static conditions using fresh human blood. In vitro hemodynamic testing of prototype HA/LLDPE IPN PHVs was used to assess feasibility as functional HVs. Bending stiffness was not significantly different from natural fresh leaflets. HA/LLDPE IPNs were more hydrophilic than LLDPE controls. HA/LLDPE IPNs caused less whole blood clotting and reduced cell adhesion compared to the plain LLDPE control. Prototype PHVs made with HA/LLDPE IPNs demonstrated an acceptable regurgitation fraction of 4.77 ± 0.42%, and effective orifice area in the range 2.34 ± 0.5 cm2. These results demonstrate strong potential for IPNs between HA and polymers as future hemocompatible HV leaflets. Further studies are necessary to assess durability and calcification resistance.
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References
ASTM. Standard Test Method for Stiffness of Fabrics. D1388-08. ASTM International, West Conshohocken, PA, 2012.
ASTM. Standard Test Method for Tensile Properties of Thin Plastic Sheeting. D882-12 ASTM International, West Conshohocken, PA, 2012.
ASTM. Standard Test Method for Transition Temperatures and Enthalpies of Fusion and Crystallization of Polymers by Differential Scanning Calorimetry. D3418-12. ASTM International, West Conshohocken, PA, 2012.
Baudet, E. M., V. Puel, et al. Long-term results of valve replacement with the St-Jude Medical Prosthesis. J. Thorac. Cardiovasc. Surg. 109(5):858–870, 1995.
Bjorck, C. G., D. Bergqvist, C. O. Esquivel, R. Larsson, and Y. Rudsvik. In vitro evaluation of a biologic graft surface—effect of treatment with conventional and low-molecular weight (LMW) heparin. Thromb. Res. 35(6):653–663, 1984.
Black, M. M., and P. J. Drury. Mechanical and Other Problems of Artificial Valves. Springer-Verlag Berlin Heidelberg: Current Topics in Pathology, 1994.
Boddohi, S., and M. J. Kipper. Engineering Nanoassemblies of Polysaccharides. Adv. Mater. 22(28):2998–3016, 2010.
Butany, J., M. S. Ahluwalia, C. Munroe, C. Fayet, C. Ahn, P. Blit, C. Kepron, R. J. Cusimano, and R. L. Leask. Mechanical heart valve prostheses: identification and evaluation (erratum). Cardiovasc. Pathol. 12(6):322–344, 2003.
Daebritz, S. H., B. Fausten, B. Hermanns, J. Schroeder, J. Groetzner, R. Autschbach, B. J. Messmer, and J. S. Sachweh. Introduction of a flexible polymeric heart valve prosthesis with special design for aortic position. Eur. J. Cardiothorac. Surg. 25(6):946–952, 2004.
Daebritz, S. H., J. S. Sachweh, B. Hermanns, B. Fausten, A. Franke, J. Groetzner, B. Klosterhalfen, and B. J. Messmer. Introduction of a flexible polymeric heart valve prosthesis with special design for mitral position. Circulation 108(10):134–139, 2003.
Dasi, L. P., H. A. Simon, P. Sucosky, and A. P. Yoganathan. FLUID MECHANICS OF ARTIFICIAL HEART VALVES. Clin. Exp. Pharmacol. Physiol. 36(2):225–237, 2009.
Dean, H. C. Development of a Biopoly™ Micro-composite For Use In Prosthetic Heart Valve Replacements. Fort Collins: Colorado State University, Master of Science, 2011.
Ellis, J. T., T. M. Healy, et al. Velocity measurements and flow patterns within the hinge region of a Medtronic Parallel(TM) bileaflet mechanical valve with clear housing. J. Heart Valve Dis. 5(6):591–599, 1996.
Forleo, M., and L. Dasi. Effect of hypertension on the closing dynamics and lagrangian blood damage index measure of the B-Datum Regurgitant Jet in a bileaflet mechanical heart valve. Ann. Biomed. Eng. 1–13, 2013. doi:10.1007/s10439-013-0896-1.
Ghanbari, H., A. G. Kidane, G. Burriesci, B. Ramesh, A. Darbyshire, and A. M. Seifalian. The anti-calcification potential of a silsesquioxane nanocomposite polymer under in vitro conditions: potential material for synthetic leaflet heart valve. Acta Biomater. 6(11):4249–4260, 2010.
Ghanbari, H., H. Viatge, A. G. Kidane, G. Burriesci, M. Tavakoli, and A. M. Seifalian. Polymeric heart valves: new materials, emerging hopes. Trends Biotechnol. 27(6):359–367, 2009.
Goodman, S. L. Sheep, pig, and human platelet-material interactions with model cardiovascular biomaterials. J. Biomed. Mater. Res. 45(3):240–250, 1999.
Grande-Allen, K. J., A. Calabro, V. Gupta, T. N. Wight, V. C. Hascall, and I. Vesely. Glycosaminoglycans and proteoglycans in normal mitral valve leaflets and chordae: association with regions of tensile and compressive loading. Glycobiology 14(7):621–633, 2004.
Han, D. K., K. Park, K. D. Park, K. D. Ahn, and Y. H. Kim. In vivo biocompatibility of sulfonated PEO-grafted polyurethanes for polymer heart valve and vascular graft. Artif. Organs 30(12):955–959, 2006.
James, S. P., H. Dean IV, L. P. Dasi, M. H. Forleo, K. C. Popat, and N. R. Lewis. Glycosaminoglycan and Synthetic Polymer Materials for Blood-contacting Applications. WIPO# WO/2013/138240-A1, Sept 19, 2013.
James, S. P., R. K. Oldinski, M. Zhang, and H. Schwartz. Chapter 18: UHMWPE/hyaluronan microcomposite biomaterials. In: UHMWPE Handbook, 2nd ed., edited by S. Kurtz. New York: Elsevier, 2009.
Kidane, A. G., G. Burriesci, M. Edirisinghe, H. Ghanbari, P. Bonhoeffer, and A. M. Seifalian. A novel nanocomposite polymer for development of synthetic heart valve leaflets. Acta Biomater. 5(7):2409–2417, 2009.
Kito, H., and T. Matsuda. Biocompatible coatings for luminal and outer surfaces of small-caliber artificial grafts. J. Biomed. Mater. Res. 30(3):321–330, 1996.
Lee, J. H., and H. B. Lee. Platelet adhesion onto wettability gradient surfaces in the absence and presence of plasma proteins. J. Biomed. Mater. Res. 41(2):304–311, 1998.
Leo, H. L., L. P. Dasi, J. Carberry, H. A. Simon, and A. P. Yoganathan. Fluid dynamic assessment of three polymeric heart valves using particle image velocimetry. Ann. Biomed. Eng. 34(6):936–952, 2006.
MatWeb. Material Property Data. Retrieved from http://www.matweb.com/, (n.d.).
Mohammadi, H., and K. Mequanint. Prosthetic aortic heart valves: modeling and design. Med. Eng. Phys. 33(2):131–147, 2011.
Oosthuysen, A., P. P. Zilla, P. A. Human, C. A. P. Schmidt, and D. Bezuidenhout. Bioprosthetic tissue preservation by filling with a poly(acrylamide) hydrogel. Biomaterials 27(9):2123–2130, 2006.
Sacks, M. S., and A. P. Yoganathan. Heart valve function: a biomechanical perspective. Philos. Trans. R. Soc. B Biol. Sci. 362(1484):1369–1391, 2007.
Simon, H. A., L. P. Dasi, H. L. Leo, and A. P. Yoganathan. Spatio-temporal flow analysis in bileaflet heart valve hinge regions: potential analysis for blood element damage. Ann. Biomed. Eng. 35(8):1333–1346, 2007.
Smith, B. S., S. Yoriya, L. Grissom, C. A. Grimes, and K. C. Popat. Hemocompatibility of titania nanotube arrays. J. Biomed. Mater. Res., Part A 95A(2):350–360, 2010.
Tan, Q. G., J. Ji, M. A. Barbosa, C. Fonseca, and J. C. Shen. Constructing thromboresistant surface on biomedical stainless steel via layer-by-layer deposition anticoagulant. Biomaterials 24(25):4699–4705, 2003.
Thorslund, S., J. Sanchez, R. Larsson, F. Nikolajeff, and J. Bergquist. Bioactive heparin immobilized onto microfluidic channels in poly(dimethylsiloxane) results in hydrophilic surface properties. Colloids Surf. B Biointerfaces 46(4):240–247, 2005.
Tsai, C. C., Y. Chang, H. W. Sung, J. C. Hsu, and C. N. Chen. Effects of heparin immobilization on the surface characteristics of a biological tissue fixed with a naturally occurring crosslinking agent (genipin): an in vitro study. Biomaterials 22(6):523–533, 2001.
Unger, F., and P. Ghosh. International cardiac surgery. Semin. Thorac. Cardiovasc. Surg. 14(4):321–323, 2002.
Vesely, I., and D. Boughner. Analysis of the bending behavior of porcine xenograft leaflets and of natural aortic-valve material—bending stiffness, neutral axis and shear measurements. J. Biomech. 22(6–7):655–671, 1989.
Wang, Y.-X., J. L. Robertson, W. B. Spillman, and R. O. Claus. Effects of the Chemical Structure and the Surface Properties of Polymeric Biomaterials on Their Biocompatibility. Pharm. Res. 21(8):1362–1373, 2004.
Werner, C., M. F. Maitz, and C. Sperling. Current strategies towards hemocompatible coatings. J. Mater. Chem. 17(32):3376–3384, 2007.
Wu, K. K., and P. Thiagarajan. Role of endothelium in thrombosis and hemostasis. Annu. Rev. Med. 47:315–331, 1996.
Yacoub, M., and J. Takkenberg. Will heart valve tissue engineering change the world? Nat. Clin. Pract. Cardiovasc. Med. 2(2):60–61, 2005.
Yoganathan, A. P., Z. M. He, and S. C. Jones. Fluid mechanics of heart valves. Annu. Rev. Biomed. Eng. 6:331–362, 2004.
Zhang, M., S. P. James, and E. Rentfrow. The effect of IPN treatment on the mechanical properties of UHMWPE. Biomed. Sci. Instrum. 37:7–12, 2001.
Zhang, M., R. King, M. Hanes, and S.P. James. A novel ultra high molecular weight polyethylene–hyaluronan microcomposite for use in total joint replacements. I. Synthesis and physical/chemical characterization. J. Biomed. Mater. Res. A 78A(1):86–96, 2006.
Zhang, M., R. King, M. Hanes, and S. P. James. A novel ultra high molecular weight polyethylene–hyaluronan microcomposite for use in total joint replacements. II. Mechanical and tribological property weight composite for evaluation. J. Biomed. Mater. Res. A 82A(1):18–26, 2007.
Zilla, P., J. Brink, P. Human, and D. Bezuidenhout. Prosthetic heart valves: catering for the few. Biomaterials 29(4):385–406, 2008.
Acknowledgments
Research reported in this publication was supported by the Colorado Office of Economic Development and International Trade, Bioscience Discovery Evaluation Grant Program, and by the National Institutes of Health National Heart, Lung and Blood Institute under Award Number R01HL119824. The content is solely the responsibility of the authors and does not necessarily represent the official views of the State of Colorado or the National Institutes of Health.
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Authors David A. Prawel, Harold (Casey) Dean, Marcio Forleo, Nicole Lewis, Justin Gangwish, Ketul C. Popat, Lakshmi Prasad Dasi, and Susan P. James declare that they have no conflict of interest.
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Associate Editor Ajit P. Yoganathan oversaw the review of this article.
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Prawel, D.A., Dean, H., Forleo, M. et al. Hemocompatibility and Hemodynamics of Novel Hyaluronan–Polyethylene Materials for Flexible Heart Valve Leaflets. Cardiovasc Eng Tech 5, 70–81 (2014). https://doi.org/10.1007/s13239-013-0171-5
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DOI: https://doi.org/10.1007/s13239-013-0171-5