The Design of Molecular Systems: Implications for Regenerative Medicine
Wednesday, February 27, 2008
Organizers: Jin Montclare, Polytechnic University; Isaac Carrico, Stony Brook University
Artificial protein- and peptide-based materials represent a new class of materials with precisely controlled length, sequence, stereochemistry, and functionality, offering major advantages over natural and synthetic molecules. As such, these biologically inspired materials are finding widespread application especially in the arena of regenerative medicine and therapeutics. In particular, they have great potential in medicine as artificial tissue scaffolds, stimuli-responsive therapeutic-delivery agents, and engineered protein drugs. Our three speakers, Joel Schneider, Vince Conticello, and Dave Tirrell will present cutting edge developments in the translational power of tailored protein and peptide-derived molecules.
Program
4:30-5:00
Arrivals/Registration
4:55–5:00
Welcome and Introduction
Jin Montclare and Isaac Carrico, Program Organizers
5:00–5:45
Design of Peptide Hydrogels for Use in Tissue Regenerative Therapies
Joel Schneider, University of Delaware
5:45–6:30
Bioengineering of Elastin-Mimetic Materials
Vincent P. Conticello, Emory University
6:30–7:15
Non-Canonical Amino Acids in Protein Design, Evolution and Analysis
David A. Tirrell, California Institute of Technology
7:15–7:30
Questions and Answers/Open Discussions
Design of Peptide Hydrogels for Use in Tissue Regenerative Therapies
Joel Schneider, University of Delaware
We are developing peptide-based hydrogels, heavily hydrated materials that are finding use as extracellular matrix substitutes and in the delivery of therapeutics (e.g. small molecules, biomolecules, and cells). Specifically, we have designed "smart" peptides that undergo sol-gel phase transitions in response to biological media enabling minimally invasive delivery of the material in-vivo. When dissolved in aqueous solutions, these peptides exist in an ensemble of random coil conformations rendering them fully soluble. The addition of an exogenous stimulus results in peptide folding into ƒÒ-hairpin conformation. This folded structure undergoes rapid assembly into a highly crosslinked hydrogel network whose nanostructure is defined and controllable. This mechanism, which links intramolecular peptide folding to self-assembly, allows temporally resolved material formation. Peptides can be designed to fold and assemble affording hydrogel in response to changes in pH or ionic strength, the addition of heat or even light. In addition to these stimuli, DMEM cell culture media is able to initiate folding and consequent self-assembly. DMEM-induced gels are cytocompatible towards NIH 3T3 murine fibroblasts, mesenchymal stem cells, hepatocytes, osteoblasts and chondrocytes. As an added bonus, many of these hydrogels possess broad spectrum antibacterial activity suggesting that adventitious bacterial infections that may occur during surgical manipulations and after implantation can be greatly reduced. Lastly, when hydrogelation is triggered in the presence of a therapeutic, gels become impregnated and can serve as a delivery vehicle. A unique characteristic of these gels is that when an appropriate shear stress is applied, the gel will shear-thin, becoming an injectable low viscosity gel. However, after the application of shear has stopped, the material quickly self-heals producing a gel with mechanical rigidity nearly identical to the original hydrogel. This attribute allows therapeutic-impregnated gels to be delivered to target tissues via syringe where they quickly recover complementing the shape of the tissue defect. If cells have been impregnated into the gel, this shear-thin delivery method is a convenient way to introduce cells to wound sites.