BETA HAIRPIN PEPTIDE HYDROGELS FOR LIVER REGENERATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We are developing a hydrogelation strategy, based on the triggered self-assembly of peptides, to aid in liver regeneration after cancer resection surgery. We will design hydrogels that can encapsulate cells in vitro that can be subsequently injected in vivo. We have designed peptides that, when dissolved in aqueous solutions, form an ensemble of random coil conformations rendering them fully soluble. However, when we add an exogenous stimulus, such as cell culture media, the peptides fold into a ¿-hairpin conformation. These folded peptides undergo rapid self-assembly forming a highly crosslinked hydrogel. When the selfassembly mechanism triggers hydrogelation in the presence of hepatocytes, gels become impregnated with cells. A unique characteristic of these gels is that when an appropriate shear stress is applied, the gel will shear-thin, becoming a viscous gel. However, after the application of shear has stopped, the viscous gel quickly self-heals producing a gel with mechanical rigidity nearly identical to the original hydrogel before shear-thinning. The gels' material properties, such as the gelation kinetics, mechanical rigidity and recovery kinetics after shear-thinning, will be tuned via peptide design to enable them to be delivered via syringe. With syringe delivery, the resulting gel/cell constructs can be shear-thin-delivered to targeted tissue where they quickly recover, adopting a shape that compliments the wound site. After delivery, the gels remain localized at the point of application (e.g. they do not run). We will investigate the cytocompatibility and biocompatibility of the gels, as well as the ability of the gel/cell constructs to be delivered in a spatially localized manner to rat liver tissue. We will test their ability to aid in the regeneration of resected rat liver. We have assembled the following team to address the aims of this proposal: Cindy Farach-Carson, a cell and molecular biologist, Dr. Joe Bennett M.D., a liver cancer surgeon, Darrin Pochan, an expert in hydrogel materials, and Joel Schneider, an expert in peptide design, synthesis and materials. Collectively, the expertise of the team spans material design, characterization, in vitro cell compatibility, and in vivo biocompatibility.