Regioisomer-specific, self-healing, and moldable supramolecular hydrogel fabrication: chiroptical tuning, biocompatibility, cell attachment, and bacteria-infected wound healing topical applications

Herein, we 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 moieties (shortened as 2ClCA and 4ClCA) were attached to the N-terminal of EA to fabricate the gelators 2ClCA-EA and 4ClCA-EA. Only 2ClCA-EA formed a stable translucent hydrogel, suggesting its remarkable regioisomer-specific hydrogelation phenomena. The hydrogels of 2ClCA-EA, comprising 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 of 2ClCA-EA 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, <i>in vivo</i> experiments on bacteria-infected mice demonstrated the remarkable topical wound-healing potential of the drug-loaded hydrogel.