Murthy, Ranjini (2009-05). Enhancing Protein-Resistance of PEO-Modified Biomaterials. Doctoral Dissertation. Thesis uri icon

abstract

  • The ultimate goal of this dissertation research is to enhance the protein resistant nature of poly(ethylene oxide) (PEO) or poly(ethylene glycol) by introduction of a siloxane linker and to subsequently prepare coatings which prevent surface-induced thrombosis. The hydrophobicity and flexibility of the siloxane tether should impart both amphiphilicity and conformational mobility to the PEO chain to further decrease protein adhesion. Because adsorption of plasma (blood) proteins initiates the clotting process, coating surfaces based on these new PEO-silanes should prevent or significantly diminish thrombosis. Thus, these coatings would be extremely useful for bloodcontacting medical devices such as stents, grafts, arteriorintravenous shunts, and biosensors. Novel amphiphilic PEO-silanes were prepared with systematic variations to several key structural features, including: siloxane tether length, PEO segment length, and PEO architecture. Thus, PEO-silanes were prepared having the general formulas: a-(EtO)3Si(CH2)2-oligodimethylsiloxanen-block-[PEO8-OCH3] (n = 0, 4, and 13; linear architecture) and a-(EtO)3Si(CH2)2-oligodimethylsiloxanen-block-[PEOm-OCH3]2 (n = 0, 4, and 13; m = 6 and 12 branched architecture). The reactive triethoxysilane [(EtO)3Si-] group serves as the crosslinking or grafting moiety. The PEO segment is distanced from the (EtO)3Si- group by an oligodimethylsiloxane tether which is both hydrophobic and exhibits a high degree of chain flexibility. Crosslinked silicone coatings and surfacegrafted coatings were prepared with amphiphilic linear PEO-silanes (a-c). Crosslinked silicone coatings were also prepared with branched PEO-silanes (1a-3a and 1b-3b). All coatings showed improved resistance to common plasma proteins compared to silicone coatings. Furthermore, protein adsorption generally decreased with siloxane tether length. For crosslinked PEO-modified silicone coating systems based on linear (a-c) and branched PEO-silanes (1a-3a and 1b-3b), longer tethers enhanced PEO reorganization to the film-water interface to enhance protein resistance. In the absence of surface reorganization for surface grafted coatings prepared with linear PEO-silanes, longer siloxane tethers better inhibited protein adsorption despite a moderate decrease in graft density (sigma) and decrease in surface hydrophilicity. This indicates that longer siloxane tethers enhance the configurational mobility of the PEO segments to better repel proteins.
  • The ultimate goal of this dissertation research is to enhance the protein resistant
    nature of poly(ethylene oxide) (PEO) or poly(ethylene glycol) by introduction of a
    siloxane linker and to subsequently prepare coatings which prevent surface-induced
    thrombosis. The hydrophobicity and flexibility of the siloxane tether should impart both
    amphiphilicity and conformational mobility to the PEO chain to further decrease protein
    adhesion. Because adsorption of plasma (blood) proteins initiates the clotting process,
    coating surfaces based on these new PEO-silanes should prevent or significantly
    diminish thrombosis. Thus, these coatings would be extremely useful for bloodcontacting
    medical devices such as stents, grafts, arteriorintravenous shunts, and
    biosensors.
    Novel amphiphilic PEO-silanes were prepared with systematic variations to
    several key structural features, including: siloxane tether length, PEO segment length,
    and PEO architecture. Thus, PEO-silanes were prepared having the general formulas:
    a-(EtO)3Si(CH2)2-oligodimethylsiloxanen-block-[PEO8-OCH3] (n = 0, 4, and 13; linear
    architecture) and a-(EtO)3Si(CH2)2-oligodimethylsiloxanen-block-[PEOm-OCH3]2 (n = 0, 4, and 13; m = 6 and 12 branched architecture). The reactive triethoxysilane [(EtO)3Si-]
    group serves as the crosslinking or grafting moiety. The PEO segment is distanced from
    the (EtO)3Si- group by an oligodimethylsiloxane tether which is both hydrophobic and
    exhibits a high degree of chain flexibility. Crosslinked silicone coatings and surfacegrafted
    coatings were prepared with amphiphilic linear PEO-silanes (a-c). Crosslinked
    silicone coatings were also prepared with branched PEO-silanes (1a-3a and 1b-3b). All
    coatings showed improved resistance to common plasma proteins compared to silicone
    coatings. Furthermore, protein adsorption generally decreased with siloxane tether
    length.
    For crosslinked PEO-modified silicone coating systems based on linear (a-c) and
    branched PEO-silanes (1a-3a and 1b-3b), longer tethers enhanced PEO reorganization
    to the film-water interface to enhance protein resistance. In the absence of surface
    reorganization for surface grafted coatings prepared with linear PEO-silanes, longer
    siloxane tethers better inhibited protein adsorption despite a moderate decrease in graft
    density (sigma) and decrease in surface hydrophilicity. This indicates that longer siloxane
    tethers enhance the configurational mobility of the PEO segments to better repel
    proteins.

publication date

  • May 2009