Current effort in the engineering of synthetic extracellular matrixes has focused on installing molecular features (peptides, proteins and bio-interactive polymers) within insoluble scaffolds, either by self-assembly or through covalent modifications of polymer or biopolymer networks. Apart from their direct role in cell interaction, bioactive molecules or peptide sequences affect the hierarchical structural organization and mechanical properties of the resulting material, thus indirectly affecting the cellular response. The overall aim of the proposed research is to develop a fundamental understanding of the structure-mechanical properties-function relations of multicomponent polysaccharide hydrogels used in tissue engineering applications and to apply this understanding in the development of engineering principles that can serve as a generic guide for the design of polysaccharide-based materials for biological applications. Three specific aims will be addressed: 1) Characterization of the interrelations between the chemical compositions of the building blocks (both polymers and peptides) and the resulting structure of the bioactive gels; 2) Systematic investigation of the effect of the different structures on the physical properties of the hydrogel constructs; and 3) Evaluation of the cellular response of the synthesized hydrogels. A methodical study correlating the effect of the bioactive molecules on the resulting hierarchical structure (explored by small angle scattering) and consequent properties will be performed to elucidate the synergetic interactions among the components that determine scaffold effectiveness. A systematic exploration of the polysaccharide type, method of peptide incorporation and gelling parameters will reveal the key factors involved in structure-function relations of the synthetic ECMs. These factors will be employed to create general guidelines for the design of multi-component polysaccharide hydrogels for desired applications.
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