Regioisomer Specific Self-Healing, and Moldable Supramolecular Hydrogel Fabrication: Chiroptical Tuning, Biocompatibility, Cell Attachment, and Bacteria Infected Wound Healing Topical Applications

Abstract

Herein, we have demonstrated the formation of a biocompatible hydrogel using a novel dipeptide H-Glu-Ala-OH (or EA) for the first time. The isomeric chloro-cinnamoyl (short as 2ClCA and 4ClCA) moiety was attached to the N-terminal of EA to fabricate the gelators 2ClCA-EA and 4ClCA-EA. Only 2ClCA-EA forms a stable translucent hydrogel, suggesting remarkable regioisomer-specific hydrogelation phenomena. The hydrogels of 2ClCA-EA, comprised of high aspect ratio nanofibers, displayed self-healing, injectable, and moldable properties. Spectroscopic data suggested concentration-triggered chiroptical alteration in the hierarchical aggregates of 2ClCA-EA and 4ClCA-EA. X-ray diffraction and computational studies revealed the formation of a highly ordered tilted lamellar organization of both 2ClCA-EA and 4ClCA-EA during self-assembly. Being biocompatible, the hydrogel was utilized for the efficient attachment of WI38 cells. Meanwhile, streptomycin, an aminoglycoside antibiotic, was encapsulated in the hydrogel matrix. Surprisingly, the antibiotic-loaded hydrogel showed superior mechanical properties due to the enhanced physical cross-linking between the gelator and streptomycin. The drug-loaded hydrogel showed efficient antibacterial properties. Finally, in vivo experiments on bacteria-infected mice demonstrated the remarkable topical wound-healing potential of the drug-loaded hydrogel.