Synergistic berberine chloride and Curcumin-Loaded nanofiber therapies against Methicillin-Resistant Staphylococcus aureus Infection: Augmented immune and inflammatory responses in zebrafish wound healing.

ABSTRACT

BACKGROUND: Wound healing pivots on a finely orchestrated inflammatory cascade, critical for tissue repair. Chronic wounds, compounded by persistent inflammation and susceptibility to infection, pose formidable clinical challenges. Nanofiber dressings offer promising avenues for wound care, yet their interaction with inflammation and infection remains elusive. We aim to delineate the inflammatory cascade preceding wound closure and assess Cu@Bbc nanofibers' therapeutic efficacy in mitigating inflammation and combating infection. Their unique attributes suggest promise in modulating inflammation, fostering tissue regeneration, and preventing microbial colonization. Investigating the intricate interplay between nanofiber scaffolds, inflammation, and infection may unveil mechanisms of enhanced wound healing. Our findings could stimulate the development of tailored dressings, urgently needed for effective wound management amidst immune dysregulation, infection, and inflammation. METHODS: In this investigation, we synthesized Cu@Bbc nanofibers, incorporating curcumin and berberine chloride, for wound healing applications. We evaluated their individual and combined antibacterial, anti-biofilm, and antioxidant activities, alongside binding affinity with pro-inflammatory cytokines through molecular docking. Morphological characterization was conducted via SEM, FTIR assessed functional groups, and wettability contact angle measured hydrophobic properties. The physical properties, including tensile strength, swelling behavior, and thermal stability, were evaluated using tensile testing, saline immersion method and thermogravimetric analysis. Biodegradability of the nanofibers was assessed through a soil burial test. Biocompatibility was determined via MTT assay, while wound healing efficacy was assessed with in vitro scratch assays. Controlled drug release and antibacterial activity against MRSA were examined, with in vivo assessment in a zebrafish model elucidating inflammatory responses and tissue remodeling. RESULTS: In this study, the synergistic action of curcumin and berberine chloride exhibited potent antibacterial efficacy against MRSA, with significant anti-mature biofilm disruption. Additionally, the combination demonstrated heightened antioxidant potential. Molecular docking studies revealed strong binding affinity with pro-inflammatory cytokines, suggesting a role in expediting the inflammatory response crucial for wound healing. Morphological analysis confirmed nanofiber quality, with drug presence verified via FTIR spectroscopy. Cu@Bbc demonstrated higher tensile strength, optimal swelling behavior, and robust thermal stability as evaluated through tensile testing and thermogravimetric analysis. Additionally, the Cu@Bbc nanofiber showed enhanced biodegradability, as confirmed by the soil burial test. Biocompatibility assessments showed favorable compatibility, while in vitro studies demonstrated potent antibacterial activity. In vivo zebrafish experiments revealed accelerated wound closure, re-epithelialization, and heightened immune response, indicative of enhanced wound healing. CONCLUSION: In summary, our investigation highlights the efficacy of Cu@Bbc nanofibers, laden with curcumin and berberine chloride, in displaying robust antibacterial and antioxidant attributes while also modulating immune responses and inflammatory cascades essential for wound healing. These results signify their potential as multifaceted wound dressings for clinical implementation.