The proposed exploratory research focuses on the development of a new class of biomaterials designed to improve blood and tissue biocompatibility- biomimetic materials based on novel self-assembling monomers with peptide nucleic acid (PNA) units attached to their termini. The PNA units will result in the formation of a supramolecular polymer whose the repeat unit sequence will depend on the nature of PNA units attached to the monomer core. Our central hypothesis is that multi-component non-covalent self-assemblies of such bis-PNA monomers will result in spatial orientation of biological components and thus provide biomaterials with enhanced interracial biocompatibility and biological function. The objective is therefore to prepare tailored monomers that self-assemble on biomaterials in a controlled way. We will utilize hydrophobic interactions for surface attachment, and the nucleobase pair interactions, in the form of PNA sequences, for controlled spatial placement of the individual biological components, which will be attached to the monomer core. Guidance in biomimetic designs is focused through two operational paradigms, 'cell surface glycocalyx' and 'extracellular matrix' (ECM), including (i) carbohydrates to provide a biocompatible """"""""glycocalyx-like"""""""" interface, and (ii) integrin binding peptides, derived from fibronectin, designed to facilitate shear stable endothelialization of biomaterials. Overall integration of our three specific aims will provide a foundation for expanding bioengineering design principles in the development of self-assembling biomimetic structures. Our results should lead to greater understanding of interfacial biocompatibility for biomaterials, new insights into biomimetic designs, and ultimately, to a new class of biomaterials with a range of biomedical applications. ? ?
