Peptide Supramolecular Hydrogels with Sustained Release Ability for Combating Multidrug-Resistant Bacteria

• Published in: ACS applied materials & interfaces Vol. 15; no. 22; pp. 26273 - 26284
• Main Authors: Shang, Lu, Liu, Jing, Wu, Yuting, Wang, Mi, Fei, Chenzhong, Liu, Yingchun, Xue, Feiqun, Zhang, Lifang, Gu, Feng
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.06.2023
• Subjects: Animals; Anti-Bacterial Agents - chemistry; antimicrobial peptides; antimicrobial properties; arginine; biocompatible materials; biofilm; Biological and Medical Applications of Materials and Interfaces; cell proliferation; collagen; crosslinking; Delayed-Action Preparations - pharmacology; drugs; hydrogels; Hydrogels - chemistry; inflammation; Methicillin-Resistant Staphylococcus aureus; Mice; mortality; multiple drug resistance; muscles; nanofibers; Peptides - pharmacology; Peptides - therapeutic use; therapeutics; Wound Infection - drug therapy; chronic wound healing; antimicrobial hydrogel; arginine end-tagging peptides; supramolecular biomaterial; sustained release
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.3c01453

Chronic wound infection caused by multidrug-resistant bacteria is a major threat globally, leading to high mortality rates and a considerable economic burden. To address it, an innovative supramolecular nanofiber hydrogel (Hydrogel-RL) harboring antimicrobial peptides was developed based on the novel arginine end-tagging peptide (Pep 6) from our recent study, triggering cross-linking. In vitro results demonstrated that Hydrogel-RL can sustain the release of Pep 6 up to 120 h profiles, which is biocompatible and exhibits superior activity for methicillin-resistant Staphylococcus aureus (MRSA) biofilm inhibition and elimination. A single treatment of supramolecular Hydrogel-RL on an MRSA skin infection model revealed formidable antimicrobial activity and therapeutic effects in vivo. In the chronic wound infection model, Hydrogel-RL promoted mouse skin cell proliferation, reduced inflammation, accelerated re-epithelialization, and regulated muscle and collagen fiber formation, rapidly healing full-thickness skin wounds. To show its vehicle property for wound infection combined therapy, etamsylate, an antihemorrhagic drug, was loaded into the porous network of Hydrogel-RL, which demonstrated improved hemostatic activity. Collectively, Hydrogel-RL is a promising clinical candidate agent for functional supramolecular biomaterials designed for combating multidrug-resistant bacteria and rescuing stalled healing in chronic wound infections.