Photothermally Active Cryogel Devices for Effective Release of Antimicrobial Peptides: On-Demand Treatment of Infections

Abstract

There has been significant interest in the use of peptides as antimicrobial agents, and peptide containing hydrogels have been proposed as biological scaffolds for various applications. Limited stability and rapid clearance of small molecular weight peptides pose challenges to their widespread implementation. As a common approach, antibacterial peptides are physically loaded into hydrogel scaffolds, which leads to continuous release through the passive mode with spatial control but provides limited control over drug dosage. Although utilization of peptide covalent linkage onto hydrogels addresses partially this problem, the peptide release is commonly too slow. To alleviate these challenges, in this work, maleimidemodified antimicrobial peptides are covalently conjugated onto furan-based cryogel (CG) scaffolds via the Diels−Alder cycloaddition at room temperature. The furan group offers a handle for specific loading of the peptides, thus minimizing passive and burst drug release. The porous nature of the CG matrix provides rapid loading and release of therapeutic peptides, apart from high water uptake. Interfacing the peptide adduct containing a CG matrix with a reduced graphene oxide-modified Kapton substrate allows "on-demand" photothermal heating upon near-infrared (NIR) irradiation. A fabricated photothermal device enables tunable and efficient peptide release through NIR exposure to kill bacteria. Apart from spatial confinement offered by this CG-based bandage, the selective ablation of planktonic Staphylococcus aureus is demonstrated. It can be envisioned that this modular "on-demand" peptide-releasing device can be also employed for other topical applications by appropriate choice of therapeutic peptides.

A Review on Hydrogels with Photothermal Effect in Wound Healing and Bone Tissue Engineering

“…Hydrogels can be incorporated with drugs to improve antibacterial properties via π−π stacking, reversible covalent cross-links [ 105 ], and direct encapsulation [ 106 ]. A photothermal trigger or pH trigger can be chosen to control drug release [ 107 ].…”

“…As shown in Figure 2, after the bacteria were incubated with the hydrogel, the cell membranes were damaged to varying degrees [104]. Hydrogels can be incorporated with drugs to improve antibacterial properties via π−π stacking, reversible covalent cross-links [105], and direct encapsulation [106]. A photothermal trigger or pH trigger can be chosen to control drug release [107].…”

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

“…Therapeutic agents may not necessarily be represented solely by drug molecules. Recent examples of other types of therapeutic cargos used for delivery by cryogels include fertilizers for agrochemical applications [ 103 ], peptides [ 104 ], proteins [ 37 ], and growth factors [ 81 , 105 – 106 ]. For example, Lee et al reported the use of a double cryogel structure for the delivery of growth factor for enhanced bone regeneration [ 105 ].…”

Design and Assessment of Biodegradable Macroporous Cryogels as Advanced Tissue Engineering and Drug Carrying Materials

“…Animal experiments have shown that this antibiotic-free cryogel is effective in killing microbes in a wound and accelerating wound healing, and is therefore a promising wound dressing material for clinical use. Photo-thermally active cryogels have been prepared for the release of antimicrobial peptides [ 154 ]. The peptides were covalently conjugated onto furan-based cryogel scaffolds by Diels-Alder cycloaddition and were enabled to release “on-demand” at NIR exposure to kill bacteria.…”