Mxene-Based Supramolecular Composite Hydrogels for Antioxidant and Photothermal Antibacterial Activities.

Bacterial infections and oxidative damage caused by various reactive oxygen species (ROS) pose a significant threat to human health. It is highly desirable to find an ideal biomaterial system with broad spectrum antibacterial and antioxidant capabilities. A new supramolecular antibacterial and antioxidant composite hydrogel made of chiral L-phenylalanine-derivative (LPFEG) as matrix and Mxene (Ti3 C2 Tx ) as filler material is presented. The noncovalent interactions (H-bonding and π-π interactions) in between LPFEG and Mxene and the inversion of LPFEG chirality are verified by Fourier transform infrared and circular dichroism spectroscopy. The composite hydrogels show improved mechanical properties revealed by rheological analysis. The composite hydrogel system exhibits photothermal conversion efficiency (40.79%), which enables effective photothermal broad-spectrum antibacterial activities against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. Furthermore, the Mxene also enables the composite hydrogel to exhibit excellent antioxidant activity by efficiently scavenging free radicals like DPPH•, ABTS•+, and •OH. These results indicate that the Mxene-based chiral supramolecular composite hydrogel, with improved rheological, antibacterial, and antioxidant properties has a great potential for biomedical applications.

Infected Diabetic Wound Regeneration Using Peptide-Modified Chiral Dressing to Target Revascularization.

Revascularization plays a critical role in the healing of diabetic wounds. Accumulation of advanced glycation end products (AGEs) and refractory multidrug resistant bacterial infection are the two major barriers to revascularization, directly leading to impaired healing of diabetic wounds. Here, an artfully designed chiral gel dressing is fabricated (named as HA-LM2-RMR), which consists of l-phenylalanine and cationic hexapeptide coassembled helical nanofibers cross-linked with hyaluronic acid via hydrogen bonding. This chiral gel possesses abundant chiral and cationic sites, not only effectively reducing AGEs via stereoselective interaction but also specifically killing multidrug resistant bacteria rather than host cells since cationic hexapeptides selectively interact with negatively charged microbial membrane. Surprisingly, the HA-LM2-RMR fibers present an attractive ability to activate sprouted angiogenesis of Human Umbilical Vein Endothelial Cells by upregulating VEGF and OPA1 expression. In comparison with clinical Prontosan Wound Gel, the HA-LM2-RMR gel presents superior healing efficiency in the infected diabetic wound with respect to angiogenesis and re-epithelialization, shortening the healing period from 21 days to 14 days. These findings for chiral wound dressing provide insights for the design and construction of diabetic wound dressings that target revascularization, which holds great potential to be utilized in tissue regenerative medicine.

Assembly of Helical Nanostructures: Solvent-Induced Morphology Transition and Its Effect on Cell Adhesion.

Being able to precisely manipulate both the morphology and chiroptical signals of supramolecular assemblies will help to better understand the natural biological self-assembly mechanism. Two simple l/d-phenylalanine-based derivatives (L/DPFM) have been designed, and their solvent-dependent morphology evolutions are illustrated. It was found that, as the content of H2 O in aqueous ethanol solutions was increased, LPFM self-assembles first into right-handed nanofibers, then flat fibrous structures, and finally inversed left-handed nanofibers. Assemblies in ethanol and H2 O exhibit opposite conformations and circular dichroism (CD) signals even though they are constructed from the same molecules. Thus, the morphology-dependent cell adhesion and proliferation behaviors are further characterized. Left-handed nanofibers are found to be more favorable for cell adhesion than right-handed nanostructures. Quantitative AFM analysis showed that the L929 cell adhesion force on left-handed LPFM fibers is much higher than that on structures with inversed handedness. Moreover, the value of cell Young's modulus is lower for left-handed nanofibrous films, which indicates better flexibility. The difference in cell-substrate interactions might lead to different effects on cell behavior.

Chirality-influenced antibacterial activity of methylthiazole- and thiadiazole-based supramolecular biocompatible hydrogels.

Chiral stereochemistry is a unique and fundamental strategy that determines the interaction of bacteria cells with chiral biomolecules and stereochemical surfaces. The interaction between bacteria and material surface (molecular chirality or supramolecular chirality) plays a significant role in modulating antibacterial performance. Herein, we developed inherent chiral antibacterial hydrogels by modifying the carboxyl groups of our previously reported supramolecular gelator (LPF-left handed phenylalanine gelator and DPF- right handed phenylalanine gelator) with 2-amino-5-methylthiazole (MTZ) and 5-amino-1,3,4-thiadiazole-2- thiol (TDZ). The new L/D-gelator molecules initiate self-assembly to form hydrogels through non-covalent interactions (Hydrogen bonding and π-π interactions) verified by FTIR and CD spectroscopy. Morphological studies of the xerogels revealed left and right-handed chiral nanofibers for the gelators' L-form and D-form, respectively. The resulting hydrogels exhibited inherent antibacterial activity against Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria, with TDZ hydrogels showing more significant antibacterial activity than MTZ hydrogels. Interestingly, the D-form (having right-handed nanofibers) of both hydrogels (MTZ and TDZ) exhibited higher antibacterial activities compared with the left-handed nanofibrous hydrogels (L-form) attributed to the stereoselective interaction of the chiral helical nanofiber. Moreover, the amplification of chirality moving from a molecular to a supramolecular level essentially improved the antibacterial action. Our results provide deep insight into the development of unique supramolecular chiral antimicrobial agents and hint at the potentiality of right-handed nanofibers (D-form) having enhanced antibacterial activity. STATEMENT OF SIGNIFICANCE: Chiral stereochemistry plays a significant role in many biological processes, which determines the interaction of bacteria cells with chiral biomolecules. The interaction between bacteria and material surface (molecular chirality or supramolecular chirality) plays a significant role in modulating antibacterial performance. Here, we deigned and synthesized unique inherent biocompatible supramolecular chiral hydrogel. From this study we concluded that the D-form (having right-handed nanofibers) of hydrogels exhibited higher antibacterial activities compared with the left-handed nanofibrous hydrogels (L-form) attributed to the stereoselective interaction of the chiral helical nanofiber. Additionally, this study also explored the amplification of chirality moving from a molecular to a supramolecular level essentially improved the antibacterial action.

Combined Experimental and Computational Study of the Gelation of Cyclohexane-Based Bis(acyl-semicarbazides) and the Multi-Stimuli-Responsive Properties of Their Gels.

The current study reports the one-step synthesis and gelation properties of cyclohexane-based bis(acyl-semicarbazide) gelators with an additional -NH group incorporated into urea moieties and carrying hydrophobic chains of varying length (C8-C18). The gels exhibited thermoreversibility and could be tuned in the presence of anions at different concentrations in addition their the ultrasound-responsive nature, thus making them multi-stimuli-responsive. The combined experimental and computational study on these gels reveals that the balance between two noncovalent interactions, viz., hydrogen bonding between the amide groups in acyl-semicarbazide moieties and van der Waals forces between long hydrocarbon tails, is found to be the determining factor in the process of organogelation. A systematic increase in alkyl chain length leads to equilibrium between these two types of noncovalent forces that is manifested in the spectral and thermal properties of the gels. The H-bonding interactions dominated up to a certain chain length, and further increases in the alkyl chain length led to increased van der Waals interactions as observed by IR, XRD, and thermal studies. Computational calculations were carried out on dimer structures of C8-C18 to understand the variation in noncovalent forces responsible for aggregate formation in the gel state as a function of the alkyl chain length. The results indicate that both intermolecular and intramolecular hydrogen bonding stabilize the aggregate structures. Supramolecular aggregation in the gel state led to the viscoelastic nature of the gels, and the addition of anions led to the disruption of self-assembly, which was studied by rheology.