A Homochiral Diphenylalanine Analog Based Mechanoresponsive Hydrogel: An Insight Towards Its Wound Healing Efficacy

Abstract

Deciphering the most promising strategy for the evolution of potential wound‐healing therapeutics is one of the greatest challenging affairs to date. The development of peptide‐based smart scaffolds with innate antimicrobial, anti‐inflammatory, and antioxidant properties is an appealing way out. Aligned to the goal a set of Hydrogelators I – IV were developed utilizing the concept of chiral orchestration in diphenylalanine fragment, such that the most potent construct with all the bench marks namely mechanoresponsiveness, biocompatibility, consistent antimicrobial and antioxidant properties, could be fished out from the design. Interestingly, our invitro Antifungal and Lipid peroxidation analysis identified the homochiral isomer (Hydrogelator I), as an ideal candidate for the wound healing experiment. So we proceeded for the invivo measurements in Wister rats. Indeed the wound images demonstrated that with increased recovery time, hydrogelator I displayed a significant reduction in the lesion diameter compared to the marketed drug, and negative control. Even the histopathological measurements using H & E staining demonstrated diminished tissue destruction, neutrophil infiltration necrosis, and lymphatic proliferation in the hydrogelators, incomparison to others, backed by invivo lipid peroxidation data. Overall our investigation certifies hydrogelator I as an effective therapeutic for managing the wound healing complication.

Stereogenic Harmony Fabricated Mechanoresponsive Homochiral Triphenylalanine Analogues with Synergistic Antibacterial Performances: A Potential Weapon for Dermal Wound Management

“…The lipid peroxidation (LPO) assay is an experiment that gives a measure of the antioxidant property of a molecule by the release of malonaldehyde from the unsaturated lipids by snatching electrons . The more consistent the antioxidant behavior is, the better it functions as a wound-healing material . Our experiments illustrated that until 20 mM concentration (much higher than the MGC of the hydrogelators; MGC of hydrogelators I , II , IV , and V – VII: 4.5 mmol; hydrogelator III : 7.6 mmol), hydrogelators I – VII showed a significant decrease in LPO values (Table S7, Figure , Figure S38) as compared to the control group.…”

“…Based on the results of antimicrobial and antioxidant properties, the therapeutic efficacy of hydrogelator IV was deciphered using full-thickness excisional wounds in Wister rats as described . Here, four different groups of animals, i.e., groups 1 to 4, were considered, and each set contained six animals.…”

“…779/Po/Ere/S/03/ CPCSEA) (Table S8). The wound creation and entire healing assay was done as described . Details are available in the Supporting Information.…”

“…57 The more consistent the antioxidant behavior is, the better it functions as a wound-healing material. 49 Our experiments illustrated that until 20 mM concentration (much higher than the MGC of the hydrogelators; MGC of hydrogelators I, II, IV, and V−VII: 4.5 mmol; hydrogelator III: 7.6 mmol), hydrogelators I−VII showed a significant decrease in LPO values (Table S7, Figure 6, Figure S38) as compared to the control group. But the maximum consistency was noticed for hydrogelator IV, so we used this molecule for our in vivo experiment 3.7.…”

“…Simple replacement of a single stereogenic center with its isomer in a peptide magnificently alters the self-assembled architectures and, consequently, the hydrogelation properties. ,− Using this concept in one of our previous reports, we have fished out the most potent hydrogelator ( I ) from a set of four and investigated its wound-healing efficacy. Although the hydrogelator showed good anti-inflammatory and antimicrobial activities, it indicated a moderate recovery behavior, which might be due to the proteolytic instability and insufficient antimicrobial potency, inevitable for a good wound dressing material …”