As a promising candidate, biodegradable Poly-L-lactic Acid (PLLA) has been extensively used in coronary artery stents. In our previous reports, PLLA stents implanted in porcine coronary arteries showed safety without stent thrombosis. However, inflammatory responses were observed, which needed further study. In this study, human aortic endothelial cells (HAEC) were treated with different volume percentages of extract of pre-degraded PLLA (extract of PLLA) in vitro, and the cell growth curve and morphological changes were examined. The expression of inflammatory cytokines such as NF-κB, VEGF and VCAM-1 were also observed by ELISA. In addition, PLLA stent was implanted in porcine coronary artery to examine morphological changes, functional marker eNOS and inflammatory responses. The extract of PLLA caused significant growth inhibition and release of NF-κB, VEGF and VCAM-1 in HAEC with volume percentage-dependence. Although re-endothelialization and expression of eNOS was observed, expression of NF-κB and lymphocytes surrounding PLLA were also found after PLLA stents were implanted in the artery. This study demonstrated the effects of inflammation on endothelial cells induced by PLLA degradation in vitro and showed the inflammation in vivo, suggesting that anti-inflammatory strategy is necessary for PLLA stent implantation in the artery.
Poly‐l‐lactic acid (PLLA) is widely used in clinic, for example, as biodegradable coronary artery stents. However, inflammatory responses in endothelial cells associated with PLLA degradation are relatively undefined. We previously reported inflammation in human aortic endothelial cells (HAEC) in vitro and in vivo. Here, we further assessed inflammatory injury, including cell migration, cell function, and inflammatory cytokines expressed in HAEC treated with PLLA and curcumin by CCK‐8, wound healing assay, ELISA, and Western blot. Significant inhibition of cell migration, remarkable dysfunction, and inflammatory responses were found in HAEC treated with PLLA degradation extract, and these effects were alleviated by Cur treatment. These findings indicated that cautious evaluation of biodegradable polymers should be performed, and Cur represents a promising anti‐inflammatory agent for alleviating endothelial dysfunction and inflammation caused by PLLA degradation. In addition, Cur should be further studied experimentally in in vivo experiments on animal models as a potential therapeutic to reduce thrombosis of biodegradable polymer stents.
Poly-L-lactic acid (PLLA) is considered to be a promising candidate material for biodegradable vascular scaffolds (BVS) in percutaneous coronary intervention (PCI). But, PLLA-BVS also faces the challenge of thrombosis (ST) and in-stent restenosis (ISR) caused by in-stent neo-atherosclerosis (ISNA) associated with inflammatory reactions in macrophage-derived foam cells. Our previous studies have confirmed that curcumin alleviates PLLA-induced injury and inflammation in vascular endothelial cells, but it remains unclear whether curcumin can alleviate the effect of inflammatory reactions in macrophage-derived foam cells while treated with degraded product of PLLA. In this study, PLLA-BVS was implanted in the porcine coronary artery to examine increased macrophages and inflammatory cytokines such as NF-κb and TNF-α by histology and immunohistochemistry. In vitro, macrophage-derived foam cells were induced by Ox-LDL and observed by Oil Red Staining. Foam cells were treated with pre-degraded PLLA powder, curcumin and PPARγ inhibitor GW9662, and the expression of IL-6, IL-10, TNF-α, NF-κb, PLA2 and PPARγ were investigated by ELISA or RT-qPCR. This study demonstrated that the macrophages and inflammatory factors increased after PLLA-BVS implantation in vivo, and foam cells derived from macrophages promoted inflammation by products of PLLA degradation in vitro. This present study was found that the inflammation of foam cells at the microenvironment of PLLA degraded products were significantly increased, and curcumin can attenuate the inflammation caused by the PLLA degradation via PPARγ signal pathway. In addition, curcumin should be further studied experimentally in vivo experiments on animal models as a potential therapeutic to reduce ISNA of PLLA-BVS.
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