Nanocurcumin-enhanced zein nanofibers: Advancing macrophage polarization and accelerating wound healing.

Introduction: Chronic wounds continue to pose a significant global challenge, incurring substantial costs and necessitating extensive research in wound healing. Our previous work involved synthesizing zein nanofibers embedded with 5 %, 10 %, and 15 % nano-curcumin (Zein/nCUR 5, 10, and 15 % NFs), and examining their physicochemical and biological properties. This study aims to explore the potential of these nanofibers in macrophage (MØ) polarization and wound healing. Methods: We assessed the survival of RAW264.7 cells cultured on Zein/nCUR 5, 10, and 15 % NFs using the MTT assay. To evaluate MØ polarization, we measured the expression of iNOS and Arg-1 genes in MØs cultured on Zein/nCUR 10 % NFs through real-time PCR. Furthermore, we examined the nanofibers' impact on pro-inflammatory cytokine expression (IL-1β, IL-6, TNF-α) in MØs via real-time PCR. The wound healing efficacy of Zein/nCUR 10 % NFs was tested on 54 male rats with full-thickness wounds, with assessments conducted on days 3, 7, and 14. Wound closure, re-epithelialization, and collagen secretion were evaluated through photographic analysis and tissue staining. Statistical analyses were performed using GraphPad Prism 6, with significance set at Results: Zein/nCUR 10 % NFs significantly enhanced the survival of RAW264.7 cells compared to other groups. They also markedly reduced iNOS expression and increased Arg-1 expression, indicating successful polarization of M1 to M2 MØs. Additionally, these nanofibers decreased the expression of IL-1β, IL-6, and TNF-α, and significantly improved wound closure, re-epithelialization, and collagen deposition compared to control and Zein groups. Conclusions: This study demonstrates that Zein/nCUR 10 % NFs effectively polarize MØs from M1 to M2, significantly enhancing wound healing, thus offering a promising therapeutic approach for improved wound care.