Hierarchical structures based on self-assembling beta-hairpin peptides and their application as biomaterials and hybrid materials

Self-assembly represents a robust and powerful paradigm for the bottom-up construction of nanostructures. Self-assembled peptide hydrogels are emerging as promising routes to novel multifunctional materials.;The 20 amino acid MAX1and MAX8 peptides self-assemble into a three dimensional network of entangled, branched fibrils rich in beta-sheet secondary structure with a high density of lysine groups exposed on the fibril-surfaces. These hydrogels form self-supporting structures that shear thin upon application of shear and then immediately recover to a solid hydrogel upon cessation of shear which facilitates the local delivery of the hydrogel into a site in vivo.;Templated condensation of silica precursors on self-assembled nanoscale peptide fibrils with various surface functionalities can be used to mimic biosilicification. This template-defined approach towards biomineralization was utilized for the controlled fabrication of 3D hybrid nanostructures. We report a study on the structure-property relationship of self-assembled peptide hydrogels where mineralization of individual fibrils through sol-gel chemistry was achieved. The nanostructure and consequent mechanical characteristics of these hybrid networks can be modulated by changing the stoichiometric parameters of the sol-gel process. Construction of such organic-inorganic hybrid networks by sol-gel processing of self-assembled peptide hydrogels has improved mechanical properties and resulted in materials with ∼ 3 orders of magnitude higher stiffness. The physical characterization of the hybrid networks via electron microscopy and small angle scattering is detailed and correlated with changes in the network mechanical behavior. The resultant high fidelity templating process suggests that the peptide substrate can be used to template the coating of other functional inorganic materials.;Self-assembling peptide hydrogels encapsulating an anti-tumorigenic drug, curcumin, have been prepared and demonstrated to be an effective vehicle for the localized delivery of curcumin over sustained periods of time in vitro. The curcumin-hydrogel is prepared in-situ where curcumin encapsulation within the hydrogel network is accomplished concurrently with peptide self-assembly. Physical characterization methods and in vitro biological studies were used to demonstrate the effectiveness of curcumin-loaded beta-hairpin hydrogels as injectable agents for localized curcumin delivery. Notably, rheological characterization of the curcumin loaded hydrogel before and after shear flow have indicated solid-like properties even at high curcumin payloads. In vitro experiments with a medulloblastoma cell line confirm that the encapsulation of the curcumin within the hydrogel does not have an adverse effect on its bioactivity. Most importantly, the rate of curcumin release and its consequent therapeutic efficacy can be conveniently modulated by changing the morphological characteristics of the peptide hydrogel network.;Lastly, MAX8 hydrogel cytocompatibility and biocompatibility was assessed with the future aim of utilizing this hydrogel as a scaffold in liver regeneration studies in rats.;MAX8 hydrogel cytotoxity was evaluated using MC3T3-E1 and MG63 cell lines. Encapsulation, syringe delivery and subsequent viability of MG63 cells in hydrogels was also assessed to study the feasibility of using hydrogel/cell constructs as minimally invasive cell delivery vehicles. Biocompatibility was evaluated by monitoring inflammatory response induced by the MAX8 hydrogel via a subcutaneous mice model. Biocompatibility of MAX8 hydrogels at sites other than the subcutaneous region was also investigated using a cylindrical punch resection model in rat liver. The preliminary biocompatibility studies provide an elemental understanding of MAX8 hydrogel behavior in vivo.