Potential of Chrysin‐loaded PCL/gelatin nanofibers for modulation of macrophage functional polarity towards anti-inflammatory/pro-regenerative phenotype

Abstract

Recent reports imply that drug delivery approaches aimed to modulate the phenotypic and functional switching of macrophages towards anti-inflammatory (M2) phenotypes have a great regenerative potential in wound healing. Therefore, the present work was designed to reveal the effectiveness of a nanofiber (NF)-based drug delivery system incorporated with a natural immunomodulatory agent, Chrysin (CHR) to repolarize RAW264.7 macrophage cells from M1 to M2 phenotype. In this regard, CHR-polycaprolactone (PCL)/gelatin (GEL) NFs were obtained by electrospinning and characterized for morphology, chemical configuration, mechanical properties, and drug release profile. Through MTT assay, it was revealed noticeably higher cell survival on 15% (wt:wt%) CHR-NFs compared to neat PCL/GEL and 5% CHR-PCL/GEL mat (p < 0.05) after 3 days of incubation. According to the Western blotting and qPCR assay, A decrease in iNOS-2 and an increment in Arg-1 expression were observed in the cells cultured on CHR-PCL/GEL NFs, signifying the significant repolarization of the M1 cells toward M2 state. Besides, it was found a major reduction in the expression of pro-inflammatory mediators while the levels of growth factors associated with M2 phenotype were significantly upregulated. Conclusively, CHR-loaded PCL/GEL NFs may have an advantageous potential for efficient modulation of the macrophage polarity toward a pro-regenerative/anti-inflammatory M2 phenotype.