Peptidoglycan-inspired peptide-modified injectable hydrogels with enhanced elimination capability of bacterial biofilm for chronic wound healing

Abstract

Majority of human infectious diseases is related to bacterial biofilm formation, especially the wound infection and delayed healing. Herein, recognizing peptide-modified polysaccharide based injectable hydrogel has been synthesized for effective anti-biofilm and infected wound healing. Inspiration from similar compatibility principle, the peptide (Alanine-glutamate-lysine-alanine), which is a part of the peptidoglycan, is grafted into the quaternized carboxymethyl chitosan （HTCC）for the first time. Afterwards, the quaternary ammonium salt groups in the synthetic injectable hydrogel cross-linked by the peptide modified quaternized carboxymethyl chitosan (HTCC-P) and oxidized dextran (OD), which can penetrate the bacterial cell wall and membrane under the recognition of peptide. Furthermore, the synergistic effect of quaternary ammonium salt groups and the peptide significantly enhance the anti-biofilm property of the hydrogels. In addition, the injectable hydrogel (HTCC-P/OD) cross-linked by Schiff base exhibits an excellent self-healing property and can completely cover the irregular wound shape. The cytotoxicity and in vivo wound healing also confirm the biocompatibility and capacity to accelerate tissue reconstruction of the hydrogels. Therefore, the hydrogels are expected to become competitive multifunctional dressings in biomedical field, including chronic wound infection and other bacterial biofilm related tissue repair.