Shubham Kanaujiya

Cyclodextrins (CDs) have emerged as versatile building blocks for regenerative biomaterials owing to their unique host–guest chemistry, biocompatibility, and structural tunability.

Infected wound healing is delayed due to compromised immunity and antimicrobial resistance. Antibiotic resistance is an emerging threat due to the unnecessary use of antibiotics. Current wound dressings that promote chronic wound healing either require additional processes, such as photothermal irradiation, or leave behind large amounts of undesirable residues. Gramicidin D (GCN), a mixture of gramicidin A, B, and C derived from Bacillus brevis, is a linear antimicrobial peptide that has been shown to exhibit wound healing properties in recent studies. In silico molecular docking simulations of GCN were conducted to preliminarily explore its potential interactions with proteins associated with the wound-healing process. The analysis suggested possible binding interactions with MMP3 and MMP7, indicating a hypothetical mechanism that may warrant further experimental validation, rather than establishing a direct role in the observed wound-healing effects. Therefore, in this study, we report a dual-functionality chitosan (CS) hydrogel dressing enriched with GCN and a multifunctional, non-reducing carbohydrate moiety called trehalose (TH) for combating antimicrobial resistance and accelerating infected wound healing. The GCN- and TH-enriched hydrogel matrix was successfully developed using an ionic-crosslinking method and optimised with the Box-Behnken Design (BBD) approach using Design Expert Software. The developed hydrogel formulation demonstrated controlled GCN release, suitable physicochemical properties, and excellent antibacterial and antibiofilm potential. Moreover, the in vitro cell line data on HaCaT cells indicated suitable biocompatibility, non-toxic behaviour and enhanced cell migration. Additionally, an in vivo chronic infectious wound healing study confirmed that the GCN and TH dual-functional hydrogel promotes accelerated healing in rats. This approach represents a potential therapeutic strategy for the rapid healing of chronically infected wounds in a multifunctional manner.

Background: The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodelling to rebuild the skin and subcutaneous tissue integrity. Recent advancements in nanomaterials, especially nanofibers, have opened a new way for efficient healing of wounds due to burning or other injuries. Methods: This study aims to develop and characterize collagen-decorated, bilayered electrospun nanofibrous mats composed of PVP and PVA loaded with Resveratrol (RSV) and Ampicillin (AMP) to accelerate burn wound healing and tissue repair. Results: Nanofibers with smooth surfaces and web-like structures with diameters ranging from 200 to 400 nm were successfully produced by electrospinning. These fibres exhibited excellent in vitro properties, including the ability to absorb wound exudates and undergo biodegradation over a two-week period. Additionally, these nanofibers demonstrated sustained and controlled release of encapsulated Resveratrol (RSV) and Ampicillin (AMP) through in vitro release studies. The zone of inhibition (ZOI) of PVP-PVA-RSV-AMP nanofibers against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was found 31± 0.09 mm and 12± 0.03, respectively, which was significantly higher as compared to positive control. Similarly, the biofilm study confirmed the significant reduction in the formation of biofilms in nanofiber-treated group against both S. aureus and E. coli. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis proved the encapsulation of RSV and AMP successfully into nanofibers and their compatibility. Haemolysis assay (%) showed no significant haemolysis (less than 5%) in nanofiber-treated groups, confirmed their cytocompatibility with red blood cells (RBCs). Cell viability assay and cell adhesion on HaCaT cells showed increased cell proliferation, indicating its biocompatibility as well as non-toxic properties. Results of the in-vivo experiments on a burn wound model demonstrated potential burn wound healing in rats confirmed by H&E-stained images and also improved the collagen synthesis in nanofibers-treated groups evidenced by Masson-trichrome staining. The ELISA assay clearly indicated the efficient downregulation of TNF-alpha and IL-6 inflammatory biomarkers after treatment with nanofibers on day 10. Conclusion: The RSV and AMP-loaded nanofiber mats, developed in this study, expedite burn wound healing through their multifaceted approach.