Amyloid-Inspired Engineered Multidomain Amphiphilic Injectable Peptide Hydrogel─An Excellent Antibacterial, Angiogenic, and Biocompatible Wound Healing Material

Abstract

The ingrained mechanical robustness of amyloids in association with their fine-tunable physicochemical properties results in the rational design and synthesis of tailor-made biomaterials for specific applications. However, the incredible antimicrobial efficacy of these ensembles has largely been overlooked. This research work provides an insight into the interplay between selfassembly and antimicrobial activity of amyloid-derived peptide amphiphiles and thereby establishes a newfangled design principle toward the development of potent antimicrobial materials with superior wound healing efficacy. Apart from the relationship with many neurodegenerative diseases, amyloids are now considered as an important cornerstone of our innate immune response against pathogenic microbes. Impelled by this observation, a class of amphiphilic antimicrobial peptide-based biomaterial has been designed by taking Aβ42 as a template. The designed AMP due to its amphipathic nature undergoes rapid self-assembly to form a biocompatible supramolecular hydrogel network having significant antibacterial as well as wound healing effectivity on both Gramnegative P. aeruginosa and MRSA-infected diabetic wounds via reduced inflammatory response and enhanced angiogenesis. Results suggest that disease-forming amyloids can be used as a blueprint for the fabrication of biomaterial-based antimicrobial therapeutics by fine-tuning both the hydrophobicity of the β-aggregation prone zone as well as membrane interacting cationic residues.

Multi-Faceted Antimicrobial Efficacy of a Quinoline-Derived Bidentate Copper(II) Ligand Complex and Its Hydrogel Encapsulated Formulation in Methicillin-Resistant Staphylococcus aureus Inhibition and Wound Management

“…The resolution of wound healing is closely linked to the presence of balanced collagen deposition at the wound site. The Masson trichrome staining technique was utilized to assess the quantity of collagen that had accumulated in the surroundings of the wound . On the basis of the analysis of Figure B of the 10-day excised skin samples, it was evident that the group treated with SG-Cu-PA-NV hydrogel showed a substantial increase in collagen deposition (stained blue) on the 10th day, closely followed by the PA-NV treated sections.…”

Preparation of an injectable zinc-containing hydrogel with double dynamic bond and its potential application in the treatment of periodontitis

“…The microbial proliferation was assessed by colony assay. 34 The images of the spread plates of F. nucleatum and S. aureus disclosed a lower bacterial count in the hydrogel groups compared to the control group, and the bactericidal effect was signicantly enhanced with increasing zinc ion concentration (p < 0.05). In the time kill assay (Fig.…”

Self-Assembly and Antimicrobial Activity of Lipopeptides Containing Lysine-Rich Tripeptides

“…Later, the antimicrobial activity of C 16 -KKFF in a hybrid material with alginate and graphene oxide was examined, and significant antimicrobial activity specific to the Gram-positive bacterium Listeria monocytogenes was noted . Another recent study reports a very thorough investigation of the self-assembly, antibacterial, and wound-healing properties of lysine-rich lipopeptides incorporating amyloid sequences to drive β-sheet fibril formation . Laverty and co-workers developed antimicrobial lipopeptides of the form C n -OOWW ( n = 6–16, and O denotes ornithine, the analogue of lysine with one less methyl group in the side chain) .…”

“… 35 Another recent study reports a very thorough investigation of the self-assembly, antibacterial, and wound-healing properties of lysine-rich lipopeptides incorporating amyloid sequences to drive β-sheet fibril formation. 36 Laverty and co-workers developed antimicrobial lipopeptides of the form C n -OOWW ( n = 6–16, and O denotes ornithine, the analogue of lysine with one less methyl group in the side chain). 37 Most closely related to the study here, Makovitzki et al reported lipopeptides comprising palmitic acid conjugated to cationic di- and tri-peptides containing all l -amino acids or mixed d , l -sequences and observed significant antimicrobial activity, although the conjugates containing d -amino acid did not display any enhanced activity compared to those based on l -amino acids.…”