Self‐Assembled Peptide Hydrogel for Accelerated Wound Healing: Impact of N‐Terminal and C‐Terminal Modifications

Wound dressings are required to provide a moist environment for wounds, protect against invading infections, expedite tissue regeneration, and improve wound healing efficiency. Developing biomaterials with all aforesaid properties is still a big challenge. However, peptide‐based hydrogels have the potential to overcome these challenges as they are biocompatible, biodegradable as well as have the ability to mimic the extracellular matrix and provide an appropriate moist environment which is important for wound healing. With this in mind, we report the preparation and comparison of three hexapeptide‐based hydrogels, LIVAGD, with the aim to understand the importance of the N‐terminal protecting group as well as the C‐terminal amino acid substitution on its various biological efficacies. Fmoc and acetyl groups were used for N‐terminal peptide protection, while aspartic acid was substituted with lysine at the C‐terminus. The resulting peptide‐based hydrogels were compared. Fmoc peptide‐based hydrogels exhibited efficient anti‐inflammatory action along with improved biocompatibility while lysine provided enhanced antibacterial effect to the hydrogel. Additionally, in vivo efficacy was examined using a mouse model, and Fmoc hydrogels demonstrated an improved wound healing ability with ∼40 % faster healing rate in comparison to the reported acetylated peptide hydrogels. Impact of N‐ and C‐terminal modifications on the self‐assembly of peptides (LIVAGD) was investigated for wound healing. Fmoc protecting groups at the N terminus provided additional π‐π interactions, which improved structural stability, supported 3‐D cell culture, provided anti‐inflammatory properties to the self‐assemblies and enhanced wound healing ability. The C‐terminus modified with lysine additionally contributed to the antimicrobial property.