In vitro and in vivo assessment of orange waste-derived flavonoid-incorporated poly(ε-caprolactone)/gelatin nanofiber dressings for wound healing

This study explores the development and characterization of poly(ϵ-caprolactone)/gelatine nanofibers enriched with orange waste-derived flavonoids (PCL/GT/FL) for wound healing applications. Flavonoid incorporation enhanced the antioxidant activity of the nanofibers, potentially reducing oxidative stress in wound environments. Moreover, the incorporation of flavonoids into the nanofibers resulted in an enhanced inhibition rate of 15.7–77.1 % against various pathogens. However, the antibacterial activity against S. pyogenes and S. aureus ATCC 6538 was not influenced. Chemical, thermal, mechanical, and physical characterizations confirmed the suitability of the nanofibers as wound dressings. In vitro assays showed that increased flavonoid concentration significantly promoted cellular growth and the treated cells demonstrated a closure rate of 81.2 % on the PCL/GT/FL30 nanofibers after 24 h, compared to 59.8 ± 17.06 % for the PCL/GT control. In vivo studies using a rat wound model demonstrated that flavonoid-incorporated nanofibers accelerated wound closure compared to untreated controls. Histological analysis indicated improved re-epithelialization, enhanced collagen deposition, and reduced inflammatory cytokines (IL-6, TNF-α), suggesting a favorable healing response. Among all formulations, PCL/GT/FL30 nanofibers with 30 % of flavonoids concentration displayed the best combination of mechanical strength, biological activity, and sustained flavonoid release, positioning them as promising wound dressing candidates. This study highlights the upcycling of food waste into a bioactive medical product, showing that orange waste flavonoids can be repurposed to improve wound healing. The findings underscore the potential of sustainable, waste-derived biomaterials to unite environmental benefits with clinical efficacy.