In the previous application, we have made significant progress and have been successful in the synthesis of multiblock (hydrophobic-hydrophilic) copolymers and triblocks containing hydrophobic (HPB), hydrophilic (HPL) and heparin (HEP) components and the characterization and evaluation of their blood compatibility in vitro and in vivo. Proposed hypothesis for the use of triblocks has also been proven with various promising data. In this renewal application, the hypothesis will be extended for tailoring phase separated interpenetrating network (IPN) polymers to create distinct phases consisting of HPB and HPL segments. It is expected that these phases of HPB and HPL (plus HEP) will greatly improve blood compatibility due to the HPB and HPL balance, favorable reorientation of HPL-HEP molecules toward blood flow and high dynamic motion of the HPL phase. Two main approaches include: 1) temperature sensitive IPN surfaces for effective loading of HEP and predetermined HEP release and 2) HPB-HPL IPN which contains chemically bound HEP to the HPL phase. Both HEP releasing and HEP chemically bound systems applied to blood contacting materials are effective in reducing surface induced thrombosis. The proposed HEP releasing IPN system will allow a minimal effective dose of heparin (minimal side effects) to be released at the blood polymer interface, effective for short time applications (up to 3 months). The HEP chemically bound IPN system will be useful for long term application since the drug will not be released into the systemic blood circulation and the bound agent will interact only at the blood/polymer interface. This grant will apply the concept of HEP releasing and HEP chemically bound IPN and investigate these new systems in in vitro assay, ex vivo, add in vivo experiments. Systematic surface characterization, in vitro assay, ex vivo and in vivo evaluation of newly designed surfaces are proposed in this application. The obtained results will not only provide mechanistic concepts, but practical design of surfaces using commercial polymers for the enhancement of blood compatibility.
