ZYNPEPTIDES AS MODULATORS OF RESPONSES TO BIOMATERIALS

INTRAVASCULAR STENTS ARE SPRING-LIKE DEVICES WHICH ARE PLACED IN ATHEROSCLEROTIC HUMAN CORONARY AND ILIAC ARTERIES TO KEEP THEM FROM COLLAPSING AFTER BALLOON ANGIOPLASTY. A NECESSARY ADJUNCT TO STENT IMPLANTATION IS SYSTEMIC ANTIPLATELET AND ANTICOAGULANT THERAPY TO PREVENT ACUTE THROMBOSIS WITH THE ATTENDANT RISK OF UNWANTED BLEEDING. ZYNAXIS CELL LINKERS, WHICH BIND TIGHTLY TO PERIPHERAL BLOOD CELLS AND OTHER BIOLOGICAL CELL-TYPES, ALSO ADHERE TO ARTIFICIAL SURFACES. WE WILL CREATE A BIOADHESIVE ANTITHROMBOTIC USING OUR CELL-LINKER TECHNOLOGY BY CHEMICALLY ATTACHING AN ANTITHROMBOTIC FRAGMENT OF THE LEECH ANTICOAGULANT PEPTIDE, HIRUDIN, TO A ZYNLINKER. THE ANTITHROMBOTIC ACTIVITY OF THIS ZYNPEPTIDE WILL BE ASSESSED IN VITRO IN PLASMA AND WHOLE BLOOD AND AFTER COATING TO ARTIFICIAL SURFACES. IT IS OUR HYPOTHESIS THAT ZYNPEPTIDE COATING OF A STENT SHOULD PROVIDE SUSTAINED LOCAL ANTITHROMBOSIS AND THUS AVOID THE NECESSITY FOR SYSTEMIC ANTICOAGULATION. DEMONSTRATION OF THE VALIDITY OF THIS HYPOTHESIS WOULD ALSO SUPPORT A GENERAL APPROACH TO SITE-SPECIFIC MODIFICATION OF BIOLOGICAL RESPONSES TO IMPLANTABLE BIOMATERIALS.