The long-term goal of this research is to engineer peptide-based viscoelastic biomaterials (hydrogels) that can be used as encapsulated matrices for drug delivery and tissue repair applications. The focus of this proposal is on design principles, characterization and biocompatibility of these materials so that a foundation can be laid for future rational design of peptide-based viscoelastic biomaterials. This project has five specific design goals: 1). The materials can self-assemble in a combinatorial fashion from oligopeptide modules via non-covalent interactions at physiologically compatible conditions. 2). The materials possess tunable viscoelastic properties. 3). The materials can effectively retard solute diffusion and control solute release. 4). The materials contain appropriate magnetic signals for non-invasive imaging. 5). The materials are biocompatible. Various design strategies will be evaluated for their effectiveness in achieving the design goals. Interactions between hydrogels and encapsulated molecules (solutes) will be investigated. The impact of solutes on the viscoelastic properties of the hydrogels and the ability of the hydrogels to retard solute diffusion and control solute released will both be determined. The purpose is to evaluate the suitability of these hydrogels as encapsulation matrices for drug delivery applications. Biocompatibility of the materials at the molecular and cellular levels will be investigated. At the molecular level, the effect of hydrogel encapsulation on protein folding and phosphorylation will be evaluated. A high-resolution non-invasive molecular biocompatibility testing method based on magnetic resonance spectroscopy will be developed. At the cellular level, viability of various cell lines cultured in the hydrogels will be determined. The purpose is to evaluate the suitability of these hydrogels as scaffolds for tissue engineering applications.