Asiaticoside loading into polylactic-co-glycolic acid electrospun nanofibers attenuates host inflammatory response and promotes M2 macrophage polarization.

ABSTRACT

Polylactic-co-glycolic acid (PLGA) is one of the most promising synthetic materials for tissue engineering due to its excellent biocompatibility, good mechanical properties, and tunable biodegradation time. However, the accumulation of PLGA degradative products could cause significant host inflammatory response, a microenvironment favoring tissue fibrosis that is mainly mediated by M1 subtype macrophage. Drug loading is an emerging technology to modify electrospun nanofibers, and asiaticoside (AS) was demonstrated as an anti-inflammatory drug. This study investigated the potential effect of AS incorporating into PLGA electrospun nanofibers on modulating host inflammatory response. The results showed that AS co-electrospun with PLGA nanofibers could significantly reduce the infiltration of inflammatory cells at the implantation site as opposed to the site of regular PLGA nanofibers. In particular, immunohistochemistry demonstrated decreased M1 macrophage infiltration whereas increased M2 macrophage infiltration in the implantation site of AS-PLGA nanofibers when compared to the PLGA implantation site. In vitro study also revealed that culture of human fibroblasts on PLGA nanofibers resulted in significantly enhanced gene expression of inflammatory cytokines when compared to non-seeded fibroblasts, but these genes were significantly downregulated when seeded on AS-PLGA. Furthermore, culture of macrophage on AS-PLGA led to upregulated M2 marker gene expression and downregulated M1 marker gene expression. Collectively, these results indicate that, AS might be an ideal drug for loading into electrospun polymer nanofibers and thus favoring for tissue regeneration via mediating macrophage polarization.