Polyurethane Calcification:Mechanism and Inhibition

Summary

Principal Investigator: R J Levy
Abstract: Polyurethane calcification and associated thrombosis remain major obstacles hindering the long term use of polyurethanes in prosthetic valves and ventricular assist systems. Progress in the past three years of this Program has successfully addressed the initial goals of this Program by elucidating the mechanisms of polyurethane calcification and creating synthetic methodology involving hard segment activation to modify (either in bulk or on the surface) already polymerized polyurethanes. Thus, we have created polyurethanes with covalently attached bisphosphonates as effective anticalcification agents. In the Program Continuation, we will address inhibiting thrombus deposition on polyurethane, and thrombus related calcification Aim 1. To derivatize polyurethane with heparin in order to confer relative thrombo-resistance. It is hypothesized that this modification will both reduce platelet-fibrin thrombus build up and retard the development of thrombus associated calcification. Aim 2. Polyurethanes modified with tethered gene vectors to provide local fibrinolysis. This aim will be concerned with modifying the polyurethane surfaces to enable gene transfer of an antibody immobilize gene vector encoding for tissue plasminogen activator (tPA), in order to bring about local fibrinolysis. It is hypothesized that fibrinolysis will help to reduce thrombus buildup. Aim 3. Semilunar cusp replacements combining bisphosphonate, heparin, and local gene therapy to over-express tPA. It is hypothesized that our combined therapeutic modifications to prevent polyurethane cuspal calcification and retard thrombosis, will provide optimal pharmacologic synergy in a sheep pulmonary cusp implant model of polyurethane calcification.
Funding Period: 1997-08-01 - 2008-07-31
more information: NIH RePORT

Top Publications

  1. ncbi Cholesterol-derivatized polyurethane: characterization and endothelial cell adhesion
    Stanley J Stachelek
    Division of Cardiology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 4318, USA
    J Biomed Mater Res A 72:200-12. 2005
  2. ncbi Site specific gene delivery in the cardiovascular system
    Ilia Fishbein
    Cardiology Research Laboratories, Children s Hospital of Philadelphia, Abramson Research Center, PA 19104, USA
    J Control Release 109:37-48. 2005
  3. ncbi Cholesterol-modified polyurethane valve cusps demonstrate blood outgrowth endothelial cell adhesion post-seeding in vitro and in vivo
    Stanley J Stachelek
    Department of Pediatrics, The Children s Hospital of Philadelphia, Pennsylvania 19104 4318, USA
    Ann Thorac Surg 81:47-55. 2006
  4. ncbi Surface heparinization of polyurethane via bromoalkylation of hard segment nitrogens
    Ivan S Alferiev
    Children s Hospital of Philadelphia, Divisions of Cardiology and Hematology, Abramson Research Center, Suite 702, 3516 Civic Center Blvd, Philadelphia, PA 19104 4318, USA
    Biomacromolecules 7:317-22. 2006
  5. ncbi Prevention of oxidative degradation of polyurethane by covalent attachment of di-tert-butylphenol residues
    Stanley J Stachelek
    Division of Cardiology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 4318, USA
    J Biomed Mater Res A 78:653-61. 2006
  6. ncbi Biological stability of polyurethane modified with covalent attachment of di-tert-butyl-phenol
    Stanley J Stachelek
    Division of Cardiology, The Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Abramson Research Bldg, Suite 702, Philadelphia, Pennsylvania 19104 4318, USA
    J Biomed Mater Res A 82:1004-11. 2007

Detail Information

Publications6

  1. ncbi Cholesterol-derivatized polyurethane: characterization and endothelial cell adhesion
    Stanley J Stachelek
    Division of Cardiology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 4318, USA
    J Biomed Mater Res A 72:200-12. 2005
    ..56 +/- 0.85% (p < 0.001). It is concluded that covalently linking cholesterol to polyurethane results in improved material properties that permit increased endothelial cell retention compared with unmodified polyurethane...
  2. ncbi Site specific gene delivery in the cardiovascular system
    Ilia Fishbein
    Cardiology Research Laboratories, Children s Hospital of Philadelphia, Abramson Research Center, PA 19104, USA
    J Control Release 109:37-48. 2005
    ..Our group has successfully investigated in animal studies localized gene therapy using an ion channel mutation to treat atrial arrhythmias...
  3. ncbi Cholesterol-modified polyurethane valve cusps demonstrate blood outgrowth endothelial cell adhesion post-seeding in vitro and in vivo
    Stanley J Stachelek
    Department of Pediatrics, The Children s Hospital of Philadelphia, Pennsylvania 19104 4318, USA
    Ann Thorac Surg 81:47-55. 2006
    ....
  4. ncbi Surface heparinization of polyurethane via bromoalkylation of hard segment nitrogens
    Ivan S Alferiev
    Children s Hospital of Philadelphia, Divisions of Cardiology and Hematology, Abramson Research Center, Suite 702, 3516 Civic Center Blvd, Philadelphia, PA 19104 4318, USA
    Biomacromolecules 7:317-22. 2006
    ....
  5. ncbi Prevention of oxidative degradation of polyurethane by covalent attachment of di-tert-butylphenol residues
    Stanley J Stachelek
    Division of Cardiology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 4318, USA
    J Biomed Mater Res A 78:653-61. 2006
    ..In conclusion, these results demonstrate that derivatizing PU with DBP confers significant resistance to oxidative degradation compared with unmodified PU...
  6. ncbi Biological stability of polyurethane modified with covalent attachment of di-tert-butyl-phenol
    Stanley J Stachelek
    Division of Cardiology, The Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Abramson Research Bldg, Suite 702, Philadelphia, Pennsylvania 19104 4318, USA
    J Biomed Mater Res A 82:1004-11. 2007
    ....