ROS-responsive polyurethane fibrous patches loaded with methylprednisolone (MP) for restoring structures and functions of infarcted myocardium in vivo
ROS-responsive polyurethane fibrous patches loaded with methylprednisolone (MP) for restoring structures and functions of infarcted myocardium in vivo
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负载甲基泼尼松龙 (MP) 的 ROS 响应性聚氨酯布状贴片，用于恢复体内梗塞心肌的结构和功能
DOI：
10.1016/j.biomaterials.2019.119726
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发表时间：
2019
期刊：
影响因子：
14
通讯作者：
Changyou Gao
中科院分区：
文献类型：
--
作者：
Yuejun Yao;Jie Ding;Zhaoyi Wang;Haolan Zhang;Jieqi Xie;Yingchao Wang;Liangjie Hong;Zhengwei Mao;Jianqing Gao;Changyou Gao
活性氧（Reactive oxygen species，ROS）在动脉粥样硬化、糖尿病、炎症和心肌梗死等多种疾病的发病机制中起重要作用。以聚己内酯二醇（PCL-diol）、1，6-二异氰酸酯（HDI）和ROS可裂解扩链剂为原料，合成了一种具有ROS响应性的可生物降解的含硫缩酮（PUTK）键的聚氨酯弹性体。将PUTK电纺成纤维贴片，并选择负载糖皮质激素甲基强的松龙（MP），然后用于治疗大鼠体内MI。纤维贴片表现出合适的机械性能和高弹性。在1 mM H2 O2溶液中孵育2周后，由于聚合物主链上的硫代缩酮键降解，PUTK的分子量显著降低。PUTK和PUTK/MP纤维补片在体外氧化降解中均表现出良好的抗氧化性能。在大鼠MI模型中植入ROS反应聚氨酯补片较非ROS反应聚氨酯补片能更好地保护心肌细胞免于早期死亡（24 h）。PUTK/MP纤维补片植入28 d可有效改善心脏功能重建，包括射血分数增加，梗死面积缩小，梗死心肌血运重建增强。
Reactive oxygen species (ROS) play an important role in the pathogenesis of numerous diseases including atherosclerosis, diabetes, inflammation and myocardial infarction (MI). In this study, a ROS-responsive biodegradable elastomeric polyurethane containing thioketal (PUTK) linkages was synthesized from polycaprolactone diol (PCL-diol ), 1,6-hexamethylene diisocyanate (HDI), and ROS-cleavable chain extender. The PUTK was electrospun into fibrous patches with the option to load glucocorticoid methylprednisolone (MP), which were then used to treat MI of ratsin vivo. The fibrous patches exhibited suitable mechanical properties and high elasticity. The molecular weight of PUTK was decreased significantly after incubation in 1 mM H2O2solution for 2 weeks due to the degradation of thioketal bonds on the polymer backbone. Both the PUTK and PUTK/MP fibrous patches showed good antioxidant property in an oxidative environmentin vitro. Implantation of the ROS-responsive polyurethane patches in MI of ratsin vivocould better protect cardiomyocytes from death in the earlier stage (24 h) than the non ROS-responsive ones. Implantation of the PUTK/MP fibrous patches for 28 days could effectively improve the reconstruction of cardiac functions including increased ejection fraction, decreased infarction size, and enhanced revascularization of the infarct myocardium.