The use of implantable blood-contacting medical devices is always associated with the substantial risks of thrombosis and microbial infection, which greatly influence patient outcomes and health costs. The objective of this application is to create novel biomaterials through synthesis and development of new polyphosphazene polymers combined with surface texturing approach to improve hemocompatibility of biomaterials. The central hypothesis of the work states that The fluorinated organic side groups linked to polyphosphazene backbone produce specific chemical functionalities leading to unique biological properties. Further, a textured surface modification approach additively or synergistically increases the efficiency in reducing platelet adhesion/activation, plasma protein activation, and bacterial adhesion/biofilm formation, thereby reducing thrombosis and microbial infections. To test this hypothesis, we propose three specific aims that involve development of new polyphosphazene materials, fabrication of the textured surface, and characterization of biological responses to materials. The new biostable elastomer, poly[bis(octafluoropentoxy) phosphazene] (OFP), is synthesized and a series of crosslinkable OFPs (X-OFP) will be further developed to improve the mechanical properties of materials. The materials will be fabricated as textured films bearing ordered arrays of pillars on surface. We will characterize surface properties of the materials by state-of-the-art surface analysis techniques (e.g., XPS, AFM, SEM, and TEM), and utilize a series of in-vitro tests to assess biological responses to the materials, related to thrombosis and microbial infection, including platelet adhesion/activation, plasma protein adsorption/activation, plasma coagulation, and pathogenic bacterial adhesion and biofilm formation, as well as the cytocompatibility. These studies will demonstrate the feasibility of new polyphosphazene biomaterials for the use in blood-contacting medical devices and explore the molecular mechanisms underlying the biological responses to surface with the physical modification, thereby providing the route to design and fabricate new biomaterials with improved biological responses. Ultimately the application will optimize the synthesized polyphosphazene biomaterials bearing the surface topography at >99% efficiency in pillar yield. We expect that the reductions of platelet and bacterial adhesions will be larger than 90% and 99%, respectively, and the long term prevention of biofilm formation will be at least 28 d under shear, largely increasing the resistance to thrombosis and microbial infection compared to widely used polyurethane biomaterials. The successful completion of this application will provide a practical approach to improve the hemocompatibility of current biomaterials, eventually for clinical use to improve patient care and incur cost-savings.
Biomaterial induced thrombosis and infection cause serious problems in blood-contacting medical devices. The project proposes new polyphosphazene biomaterials with combination of physical surface modification to increase the efficiency in controlling plasma protein adsorption and activation, platelet adhesion and activation, bacterial adhesion and biofilm formation, thereby reducing the thrombosis and infection induced by biomaterials. The application focuses on synthesis of new polyphosphazene polymers, optimization of surface texturing of polyphosphazene materials, the study of biological responses on surfaces, and exploration of molecular mechanisms behind the phenomena occurring on biomaterial surfaces.
|Xu, Li-Chong; Meyerhoff, Mark E; Siedlecki, Christopher A (2018) Blood coagulation response and bacterial adhesion to biomimetic polyurethane biomaterials prepared with surface texturing and nitric oxide release. Acta Biomater :|