Capsaicin reduces PLGA-induced fibrosis by promoting M2 macrophages and suppressing overall inflammatory Response.

Capsaicin reduced poly(lactic-co-glycolic) acid (PLGA)-induced fibrosis by promoting IL-10 secretion and suppressing alpha-smooth muscle actin (α-SMA) expression. The lifetime and efficacy of tissue engineering scaffolds are determined by the foreign body response. In this study, we investigated the in vitro and in vivo effects of capsaicin to reduce biomaterial-induced fibrosis. RAW 264.7 cells cultured on PLGA films with capsaicin responded with significant (p < 0.05) upregulation in M2 markers arginase-1 and IL-10 and downregulation of M1 markers iNOS and IL-12, demonstrating the potential of capsaicin to reduce PLGA-induced inflammation. Subsequent animal studies were conducted where PLGA and capsaicin-embedded PLGA discs were implanted in C57BL/6 mice for 2 and 14 days. Explanted capsaicin-embedded PLGA implants had 40% less collagen than PLGA-only implants. Capsaicin caused a 35% increase in IL-10 which played a key role in suppressing fibrosis. Macrophage phenotype markers in peritoneal cells and adherent cells were unaffected by capsaicin; however, capsaicin suppressed the myofibroblast marker α-SMA in adherent cells by day 14. Overall, our results revealed that capsaicin reduced biomaterial-induced fibrosis and demonstrates that capsaicin has the potential to extend the lifetime of a tissue engineering scaffold when used in long-term drug release applications from hydrophobic biomaterials. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2424-2432, 2018.