Advertisement

Hemocompatibility and Hemodynamics of Novel Hyaluronan–Polyethylene Materials for Flexible Heart Valve Leaflets

  • David A. Prawel
  • Harold Dean
  • Marcio Forleo
  • Nicole Lewis
  • Justin Gangwish
  • Ketul C. Popat
  • Lakshmi Prasad Dasi
  • Susan P. James
Article

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.

Keywords

Interpenetrating polymer network Hemocompatible Thrombus Blood-contacting materials Hemodynamics Platelet Bending stiffness 

Notes

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.

Conflict of interest

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.

References

  1. 1.
    ASTM. Standard Test Method for Stiffness of Fabrics. D1388-08. ASTM International, West Conshohocken, PA, 2012.Google Scholar
  2. 2.
    ASTM. Standard Test Method for Tensile Properties of Thin Plastic Sheeting. D882-12 ASTM International, West Conshohocken, PA, 2012.Google Scholar
  3. 3.
    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.Google Scholar
  4. 4.
    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.CrossRefGoogle Scholar
  5. 5.
    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.CrossRefGoogle Scholar
  6. 6.
    Black, M. M., and P. J. Drury. Mechanical and Other Problems of Artificial Valves. Springer-Verlag Berlin Heidelberg: Current Topics in Pathology, 1994.Google Scholar
  7. 7.
    Boddohi, S., and M. J. Kipper. Engineering Nanoassemblies of Polysaccharides. Adv. Mater. 22(28):2998–3016, 2010.CrossRefGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    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.CrossRefGoogle Scholar
  10. 10.
    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.Google Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    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.Google Scholar
  13. 13.
    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.Google Scholar
  14. 14.
    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.
  15. 15.
    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.CrossRefGoogle Scholar
  16. 16.
    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.CrossRefGoogle Scholar
  17. 17.
    Goodman, S. L. Sheep, pig, and human platelet-material interactions with model cardiovascular biomaterials. J. Biomed. Mater. Res. 45(3):240–250, 1999.CrossRefGoogle Scholar
  18. 18.
    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.CrossRefGoogle Scholar
  19. 19.
    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.CrossRefGoogle Scholar
  20. 20.
    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.Google Scholar
  21. 21.
    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.Google Scholar
  22. 22.
    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.CrossRefGoogle Scholar
  23. 23.
    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.CrossRefGoogle Scholar
  24. 24.
    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.CrossRefGoogle Scholar
  25. 25.
    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.CrossRefGoogle Scholar
  26. 26.
    MatWeb. Material Property Data. Retrieved from http://www.matweb.com/, (n.d.).
  27. 27.
    Mohammadi, H., and K. Mequanint. Prosthetic aortic heart valves: modeling and design. Med. Eng. Phys. 33(2):131–147, 2011.CrossRefGoogle Scholar
  28. 28.
    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.CrossRefGoogle Scholar
  29. 29.
    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.CrossRefGoogle Scholar
  30. 30.
    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.CrossRefGoogle Scholar
  31. 31.
    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.CrossRefGoogle Scholar
  32. 32.
    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.CrossRefGoogle Scholar
  33. 33.
    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.CrossRefGoogle Scholar
  34. 34.
    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.CrossRefGoogle Scholar
  35. 35.
    Unger, F., and P. Ghosh. International cardiac surgery. Semin. Thorac. Cardiovasc. Surg. 14(4):321–323, 2002.CrossRefGoogle Scholar
  36. 36.
    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.CrossRefGoogle Scholar
  37. 37.
    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.CrossRefGoogle Scholar
  38. 38.
    Werner, C., M. F. Maitz, and C. Sperling. Current strategies towards hemocompatible coatings. J. Mater. Chem. 17(32):3376–3384, 2007.CrossRefGoogle Scholar
  39. 39.
    Wu, K. K., and P. Thiagarajan. Role of endothelium in thrombosis and hemostasis. Annu. Rev. Med. 47:315–331, 1996.CrossRefGoogle Scholar
  40. 40.
    Yacoub, M., and J. Takkenberg. Will heart valve tissue engineering change the world? Nat. Clin. Pract. Cardiovasc. Med. 2(2):60–61, 2005.CrossRefGoogle Scholar
  41. 41.
    Yoganathan, A. P., Z. M. He, and S. C. Jones. Fluid mechanics of heart valves. Annu. Rev. Biomed. Eng. 6:331–362, 2004.CrossRefGoogle Scholar
  42. 42.
    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.Google Scholar
  43. 43.
    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.Google Scholar
  44. 44.
    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.Google Scholar
  45. 45.
    Zilla, P., J. Brink, P. Human, and D. Bezuidenhout. Prosthetic heart valves: catering for the few. Biomaterials 29(4):385–406, 2008.CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2013

Authors and Affiliations

  • David A. Prawel
    • 1
    • 2
  • Harold Dean
    • 1
  • Marcio Forleo
    • 2
  • Nicole Lewis
    • 2
  • Justin Gangwish
    • 3
  • Ketul C. Popat
    • 1
    • 2
  • Lakshmi Prasad Dasi
    • 1
    • 2
  • Susan P. James
    • 1
    • 2
  1. 1.Department of Mechanical EngineeringColorado State UniversityFort CollinsUSA
  2. 2.School of Biomedical EngineeringColorado State UniversityFort CollinsUSA
  3. 3.Department of Chemical and Biological EngineeringColorado State UniversityFort CollinsUSA

Personalised recommendations