Antibacterial hydrogels of aromatic tripeptides

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Peptide hydrogels are promising for drug delivery and wound healing.
• Antibacterial peptide hydrogels are underexplored but highly needed.
• Conventional antimicrobial strategies face challenges like resistance.

Purpose of the Study:

• To design and evaluate novel ultrashort peptide hydrogels with inherent antibacterial activity.
• To investigate the structure-property relationships influencing hydrogel mechanical strength and antibacterial efficacy.
• To explore the mechanisms underlying the antibacterial action of these peptide hydrogels.

Main Methods:

• Synthesis of three ultrashort peptide hydrogels: Fmoc-FFH-CONH2, Fmoc-FHF-CONH2, and Fmoc-HFF-CONH2.
• Rheological studies to assess mechanical properties (storage modulus).
• In vitro antibacterial assays against Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria.
• Mechanism studies including reactive oxygen species (ROS) generation and outer membrane permeabilization assays.

Main Results:

• Fmoc-FFH-CONH2 exhibited significantly higher storage modulus (30.43 kPa) compared to Fmoc-FHF-CONH2 and Fmoc-HFF-CONH2, attributed to enhanced aromatic interactions.
• Antibacterial activity followed the order: Fmoc-FFH-CONH2 > Fmoc-FHF-CONH2 > Fmoc-HFF-CONH2.
• Antibacterial effects were mediated by osmotic stress and membrane disruption, evidenced by ROS generation and outer membrane permeabilization.

Conclusions:

• The designed ultrashort peptide hydrogels, particularly Fmoc-FFH-CONH2, demonstrate potent antibacterial properties and favorable mechanical characteristics.
• Enhanced aromatic interactions in Fmoc-FFH-CONH2 contribute to its superior mechanical rigidity and antibacterial efficacy.
• These peptide hydrogels show significant potential as novel agents for topical antimicrobial applications.