This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017716-08
Application #
8168492
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2010-08-01
Project End
2011-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
8
Fiscal Year
2010
Total Cost
$414,646
Indirect Cost
Name
University of Delaware
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
Li, Linqing; Stiadle, Jeanna M; Levendoski, Elizabeth E et al. (2018) Biocompatibility of injectable resilin-based hydrogels. J Biomed Mater Res A 106:2229-2242
Drolen, Claire; Conklin, Eric; Hetterich, Stephen J et al. (2018) pH-Driven Mechanistic Switching from Electron Transfer to Energy Transfer between [Ru(bpy)3]2+ and Ferrocene Derivatives. J Am Chem Soc 140:10169-10178
Potocny, Andrea M; Riley, Rachel S; O'Sullivan, Rachel K et al. (2018) Photochemotherapeutic Properties of a Linear Tetrapyrrole Palladium(II) Complex displaying an Exceptionally High Phototoxicity Index. Inorg Chem 57:10608-10615
Potocny, Andrea M; Pistner, Allen J; Yap, Glenn P A et al. (2017) Electrochemical, Spectroscopic, and 1O2 Sensitization Characteristics of Synthetically Accessible Linear Tetrapyrrole Complexes of Palladium and Platinum. Inorg Chem 56:12703-12711
Li, Linqing; Stiadle, Jeanna M; Lau, Hang K et al. (2016) Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration. Biomaterials 108:91-110
Li, Linqing; Mahara, Atsushi; Tong, Zhixiang et al. (2016) Recombinant Resilin-Based Bioelastomers for Regenerative Medicine Applications. Adv Healthc Mater 5:266-75
Ou, Shu-Ching; Cui, Di; Wezowicz, Matthew et al. (2015) Free energetics of carbon nanotube association in aqueous inorganic NaI salt solutions: Temperature effects using all-atom molecular dynamics simulations. J Comput Chem 36:1196-212
Ooms, Kristopher J; Vega, Alexander J; Polenova, Tatyana et al. (2015) Double and zero quantum filtered (2)H NMR analysis of D2O in intervertebral disc tissue. J Magn Reson 258:6-11
Suiter, Christopher L; Quinn, Caitlin M; Lu, Manman et al. (2015) MAS NMR of HIV-1 protein assemblies. J Magn Reson 253:10-22
Li, Linqing; Luo, Tianzhi; Kiick, Kristi L (2015) Temperature-triggered phase separation of a hydrophilic resilin-like polypeptide. Macromol Rapid Commun 36:90-5

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