The development of biomaterials through desirable biocompatibility has presented a difficult challenge for tissue engineering researchers. Biomaterials tend to be hydrophobic and/or thrombogenic in nature, and thus face compatibility problems upon implantation. To mediate this problem, researchers have attempted to graft proteins or protein fragments onto biomaterial surfaces to promote endothelial cell attachment and minimize thrombosis. However, methods to attachment these proteins to surfaces are usually non-specific, with little control of density, structural stability, and orientation of presentation of the bioactive entity. The investigators envision a novel approach for creating biomaterials with endothelial cell-adhesive, non- thrombogenic properties. This involves the direct incorporation of lipophilic molecules into synthetic peptides by solid-phase methodology. The self-assembly of the lipophilic molecules then facilitates peptide alignment and structure initiation and propagation. The lipophilic entities themselves associate to form monolayers on hydrophobic approaches for biomaterial incompatibility, the peptide-amphophil (PA) method can be used to create a variety of multifunctional surfaces by simply mixing different PAs. The initial work has resulted in the synthesis of PAs which incorporate along chain dialkyl ester lipid """"""""tail"""""""" onto a collagen-model, triple-helical peptide head group. These triple-helical PAs form stable monolayers on a variety of surfaces that specifically promote melanoma and endothelial cell adhesion and spreading. This work will be expanded to allow for the incorporation of monoalkyl ester tails, dialkyl amide tails, phospholipids, fluorescent phospholipids, and unsaturated lipids. Peptide motifs, I.E. collagen-like triple-helices, alpha-helical coiled coils, or turns. The secondary and tertiary structure of the peptide head groups will be investigated by D and NMR spectroscopies. The investigators will used a Langmuir-Blodgett rough to measure monolayer isotherms of PAs. PA assembly on a variety of surfaces will be characterized by AFM, XPS, and AAA. The investigators will study the ability of PAs to promote endothelial cell adhesion, spreading, and activation in vitro. An in vivo swine restonosis model will be used to study the effectiveness of peptide- amphophil coated stents for promoting endothelialization and inhibiting thrombosis. For building materials with molecular and cellular recognition capacity, these PAs may provide an important approach for producing characteristic structures at surfaces and interfaces.
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