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

Abstract

Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an 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 network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-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 cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable 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.

<p>Potential Applications of Nanomaterials and Technology for Diabetic Wound Healing</p>

“… [ 91 ] Proline IKFQFHFD hydrogel Eradicate MRSA biofilm. [ 85 ] Spider silk fusion proteins Nanofibrous mats of AaSF Efficient matrix remodelling of wounds. [ 93 ] Heparin or bemiparin CS hydrogels Improved diabetes-associated impaired wound healing.…”

pH-Responsive “Smart” Hydrogel for Controlled Delivery of Silver Nanoparticles to Infected Wounds

“…The infiltration of the wound by a pathogen would trigger a burst of AgNPs to rapidly control infection and prevent further colonization, while in the absence of pathogenic bacteria, the hydrogel system would produce minimal therapeutic release. Indeed, the usefulness of such responsive systems has been reflected by several recent studies for the controlled delivery of antibacterial therapeutics for topical wound applications including antibiotics [23,24] and antimicrobial peptides [25,26].…”

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

“…Using pH as a stimulus is another effective way to create smart supramolecular hydrogels since pH could significantly adjust the intensity and strength of hydrogen bonds as well as the ionic forms of amphiphilic gelators only with a small shift. As an example, Wang et al [76] reported a pH-switchable supramolecular hydrogel from a designed octapeptide Ac-IKFQFHFD-NH 2 . The peptide self-assembled into nanofibers at neutral pH (pH 7.4) and disassembles at acidic pH (pH 5.5) due to the protonation of carboxylate group of aspartic acid (D), making pH-controlled release of the peptide hydrogelator in acidic wound environment and generate antimicrobial effect.…”