Inherently Antimicrobial Hydrogels Altering Activity via Tryptophan/Arginine Interactions
| Author(s) | Larsen, Tyler | |
| Date Accessioned | 2013-07-29T22:10:10Z | |
| Date Available | 2013-07-29T22:10:10Z | |
| Publication Date | 2010-05 | |
| Abstract | Hydrogels are heavily hydrated, viscoelastic, porous materials that show promise as artificial extracellular matrices for use in tissue regenerative therapies. Unfortunately, not only can injected hydrogels make a wound site into an ideal environment for cell proliferation, but for opportunistic bacteria as well. To combat the threat of infection, hydrogels are often modified to display antibacterial activity, usually by impregnating the gel with antibiotic agents or covalently attaching them to the gel surface. The development of hydrogels that are inherently antibacterial has been of great interest to the hydrogel research community. We have developed MAX1, a self-assembling, twenty amino acid peptide hydrogel whose surface exhibits inherent antibacterial activity against several gram-negative and gram-positive bacteria prevalent in hospital settings. Under physiological conditions, MAX1 folds into an amphiphilic β-hairpin and subsequently self-assembles into a highly-crosslinked hydrogel network composed of fibrils rich in β-sheet, but the process is too slow to homogenously encapsulate cells for delivery . Previous attempts to speed self-assembly by reducing the peptide’s cationic charge led to a loss of antibacterial activity. This study aims to design, synthesize, and characterize a peptide hydrogel with favorable folding and self-assembly kinetics and potent antibacterial activity through incorporation of cation-β interactions, which are common in antibacterial peptides found in nature. A new peptide sequence (RWMAX1) was designed and synthesized, incorporating a crossstrand Tryptophan/Arginine pair into the MAX1 sequence. The folding and selfassembly properties were assessed using circular dichroism and rheology and the antibacterial activity was investigated against representative gram-positive and gramnegative bacterial strains Staphylococcus aureus and Escherichia coli, respectively. RWMAX1 hydrogels were found to possess both rapid folding and self-assembly and potent antimicrobial activity against both bacterial strains, suggesting that Tryptophan/Arginine substitution may be a viable strategy for the development of injectable hydrogel therapies. | en_US |
| Advisor | Joel P. Schneider | |
| Program | Biological Sciences | |
| URL | http://udspace.udel.edu/handle/19716/12604 | |
| Publisher | University of Delaware | en_US |
| Title | Inherently Antimicrobial Hydrogels Altering Activity via Tryptophan/Arginine Interactions | en_US |
| Type | Thesis | en_US |