EAGER: Interfacial Design of Modular, Multifunction Peptide Amphiphile Hydrogels for Tissue Engineering

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1253913/ KokkoliIntellectual Merit: In many cases, a single bioactive ligand or protein is used to functionalize a biomaterial, and as a result, it fails to accurately mimic the complexity necessary to support or promote desired biological phenomena such as long term celladhesion, survival and phenotype maintenance. The ability to design multifunctional interfaces is therefore becoming increasingly important as many biomaterials require the presence of different ligands and chemical cues. Thus far, there is no study that has investigated whether the benefits of scaffold functionalization with multiple classes of ligands are significant or additive. In this exploratory EAGER proposal, the PI proposes to design peptide amphiphiles that will mimic various cell binding domains (fibronectin and type I and type III collagen), growth factors, such as the basic fibroblast growth factor (bFGF), and a growth factor binding peptide, to be combined in a modular fashion and produce defined, multicomponent hydrogel interfaces, optimized to support the culture of different cells. This novel extracellular matrix (ECM)-mimetic peptide amphiphile hydrogel scaffold, capable of reproducing sufficient biochemical complexity via modular combinations of peptide mimetics from multiple classes of signaling biomolecules will give rise to emergent properties. The different peptide amphiphiles will be evaluated as hydrogels individually, in pairs and in mixtures at different concentrations. All gels will be characterized with rheology measurements to evaluate their modulus and scanning electron microscope (SEM) images. Primary human hepatocytes will be used as the model cell system and will be seeded on the interface of the hydrogels as well as within the hydrogels (2D and 3D evaluation). Cell proliferation, cell viability as well as hepatocyte function will be evaluated using different assays at different time points.Broader Impact: Design of interfaces capable of presenting more complex signals will ultimately allow for exploration of approaches which could, in turn, significantly contribute to advances in the field of functional biomaterials with potential applications in biosensors, tissue engineering and regenerative medicine. The educational plan is strongly integrated with the research plan. Educational activities will focus on training of graduate and undergraduate students though lab exposure, participation in group meetings and national meetings as well as publishing in scientific journals. The goal of the PI is to attract and retain women and other underrepresented groups to science and engineering. The PI has a strong record in this area.