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, maleimide-modified 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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Cryogels/chemistry , Staphylococcal Infections/drug therapy , Anti-Bacterial Agents/chemistry , Antimicrobial Cationic Peptides/chemistry , Cryogels/chemical synthesis , Cryogels/radiation effects , Cycloaddition Reaction , Drug Liberation , Escherichia coli/drug effects , Furans/chemical synthesis , Furans/chemistry , Furans/radiation effects , HeLa Cells , Heating , Humans , Infrared Rays , Methacrylates/chemical synthesis , Methacrylates/chemistry , Methacrylates/radiation effects , Microbial Sensitivity Tests , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/chemistry , Polyethylene Glycols/radiation effects , Staphylococcus aureus/drug effectsABSTRACT
A precise and thorough methodology is presented for the design and fabrication of bimodal phantoms to be used in medical microwave and ultrasound applications. Dielectric and acoustic properties of human soft tissues were simultaneously mimicked. The phantoms were fabricated using polyvinyl alcohol cryogel (PVA-C) as gelling agent at a 10% concentration. Sucrose was employed to control the dielectric properties in the microwave spectrum, whereas cellulose was used as acoustic scatterer for ultrasound. For the dielectric properties at microwaves, a mathematical model was extracted to calculate the complex permittivity of the desired mimicked tissues in the frequency range from 500 MHz to 20 GHz. This model, dependent on frequency and sucrose concentration, was in good agreement with the reference Cole-Cole model. Regarding the acoustic properties, the speed of sound and attenuation coefficient were employed for validation. In both cases, the experimental data were consistent with the corresponding theoretical values for soft tissues. The characterization of these PVA-C phantoms demonstrated a significant performance for simultaneous microwave and ultrasound operation. In conclusion, PVA-C has been validated as gelling agent for the fabrication of complex multimodal phantoms that mimic soft tissues providing a unique tool to be used in a range of clinical applications.