Mechanical heart valve failure is primarily due to thrombosis and thromboembolic complications. Titanium (Ti) has advantageous bulk and surface properties but is still susceptible to surface thrombus formation. Our hypothesis is the layer of chemisorbed oxygen or oxide layer established on the Ti surface can be utilized to form Ti-O-Si bonds on Ti implants using the coupling agent (3-aminopropyl) triethoxysilane (Silane). Silane covalently bonded to the Ti surface will result in pendant amine functional groups to which the antithrombin agent recombinant hirudin (rHir) can be covalently attached using specific crosslinkers.
The specific aims of this proposal are to: optimize the application conditions of Silane to Ti plates (Ti-Silane), characterize the chemical and physical properties of the Ti- Silane surface, optimize reaction conditions for covalent linkage of rHir to the Ti-Silane surface, determine surface bound antithrombin properties and assess the biostability of immobilized rHir under simulated arterial flow conditions. This technology, if applied only to mechanical heart valves, could have an annual market in excess of $100 million and can be applied to other Ti implants such as left ventricular assist devices, dental implants and bone replacements to which biologic agents such as growth factors or adhesion molecules could be covalently bound.
Development of a coating for titanium implants to which protein binding can occur would have a significant role in medical devices such as heart valves, bone prostheses, artificial heart systems and dental implants. Potentially, application of this technology to mechanical hearts could have an annual market of over $100 million.
