Inherently Antimicrobial Hydrogels Altering Activity via Tryptophan/Arginine Interactions
Date
2010-05
Authors
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Publisher
University of Delaware
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.