Recent Advances in Smart Self-Assembled Bioinspired Hydrogels: A Bridging Weapon for Emerging Health Care Applications from Bench to Bedside.

Stimuli-responsive low molecular weight hydrogel interventions for Biomedical challenges are a rapidly evolving paradigm in the bottom-up approach recently. Peptide-based self-assembled nano biomaterials present safer alternatives to their non-degradable counterparts as demanded for today's most urged clinical needs.Although a plethora of work has already been accomplished, programming hydrogelators with appropriate functionalities requires a better understanding as the impact of the macromolecular structure of the peptides and subsequently, their self-assembled nanostructures remain unidentified. Henceforth this review focuses on two aspects: Firstly, the underlying guidelines for building biomimetic strategies to tailor scaffolds leading to hydrogelation along with the role of non-covalent interactions that are the key components of various self-assembly processes. In the second section, it is aimed to bring together the recent achievements with designer assembly concerning their self-aggregation behaviour and applications mainly in the biomedical arena like drug delivery carrier design, antimicrobial, anti-inflammatory as well as wound healing materials. Furthermore, it is anticipated that this article will provide a conceptual demonstration of the different approaches taken towards the construction of these task-specific designer hydrogels. Finally, a collective effort among the material scientists is required to pave the path for the entrance of these intelligent materials into medicine from bench to bedside.

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

The wound recovery phenomenon remains as one of the long challenging concerns worldwide. In search of user-friendly dressing materials, in this report, we fabricated a rational combinatorial strategy utilizing stereogenic harmony in a triphenylalanine fragment and appending it to δ-amino valeric acid at the N-terminus (hydrogelators I-VII) such that a potential scaffold could be fished out from the design. Our investigations revealed that all the hydrogelators displayed not only excellent self-healing performance as well as high mechanical strength at physiological pH but also mechanical stress-triggered gel-sol-gel transition properties. The structural and morphological investigation confirmed the presence of ß-sheet-like assemblies stabilized by intermolecular H-bonding and π-π interactions. Moreover, these scaffolds showed substantial antibacterial as well as antifungal efficacy against common wound pathogens, i.e, four Gram-positive bacteria (Staphylococcus aureus, Streptococcus mutans, B. subtilis, E. fecalis), four Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, P. aerugonosa, Proteus spp.), and two fungal strains (C. albicans and A. niger). The manifestation of consistent antioxidant properties might be due to the enhancement of amphiphilicity in hydrogelators, which has led to the generation of reactive oxygen species (ROS) in a facile manner, a probable mechanism to damage the microbial membrane, the driving force behind the antimicrobial efficacy. Also, the constructs exhibited proteolytic resistance and remarkable biocompatibility toward mammalian cells. Thus, based on the above benchmarks, the homochiral hydrogelator IV was seived out from a pool of seven, and we proceeded toward its in vivo evaluation using full-thickness excisional wounds in Wister rats. The scaffolds also accentuated the re-epithelialization as well in comparison to the negative control, thereby facilitating the wound closure process in a very short span of time (10 days). Overall, our in vitro and in vivo analysis certifies hydrogelator IV as an ideal dressing material that might hold immense promise for future wound care management.

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

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 in vitro Antifungal and Lipid peroxidation analysis identified the homochiral isomer Boc-δ-Ava-L-Phe-L-Phe-OH (Hydrogelator I), as an ideal candidate for the wound healing experiment, so we proceeded for the in vivo histopathological and antioxidant measurements in Wister rats. Indeed the wound images obtained from the different sets of animals on the 14th day of treatment 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, in comparison to others, backed by in vivo lipid peroxidation data. Overall our investigation certifies hydrogelator I as an effective therapeutic for managing the wound healing complication.