pH-Switchable Antimicrobial Nanofiber Networks of Hydrogel Eradicate Biofilm and Rescue Stalled Healing in Chronic Wound.

Biofilm infections can induce chronic inflammation and stall normal orchestrated course of wound healing cascades. Herein pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wound is reported based on the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber networks destabilization and activated release of IKFQFHFD which is antimicrobial only at acidic pH due to the antimicrobial peptides-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. In vitro experiments show that loaded drugs exhibit acidic pH (pH ~5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascades activation of cells proliferation is achieved based on the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enables in vivo complete healing of MRSA biofilm-infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.