MicroRNA-based therapies that target cardiomyocyte proliferation have great potential for the treatment of myocardial infarction (MI). In previous work, we showed that the miR-302/367 cluster regulates cardiomyocyte proliferation in the prenatal and postnatal heart. Here, we describe the development and application of an injectable hyaluronic acid (HA) hydrogel for the local and sustained delivery of miR-302 mimics to the heart. We show that the miR-302 mimics released in vitro promoted cardiomyocyte proliferation over one week, and that a single injection of the hydrogel in the mouse heart led to local and sustained cardiomyocyte proliferation for two weeks. After MI, gel/miR-302 injection caused local clonal proliferation and increased cardiomyocyte numbers in the border zone of a Confetti mouse model. Gel/miR-302 further decreased cardiac end-diastolic (39%) and end-systolic (50%) volumes, and improved ejection fraction (32%) and fractional shortening (64%) four weeks after MI and injection, compared to controls. Our findings suggest that biomaterial-based miRNA delivery systems can lead to improved outcomes in cardiac regeneration.

中文翻译：

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从可注射水凝胶局部和持续传递miRNA可以促进缺血性损伤后心肌细胞的增殖和功能的再生。

靶向心肌细胞增殖的基于MicroRNA的疗法在治疗心肌梗塞（MI）方面具有巨大潜力。在以前的工作中，我们显示了miR-302 / 367簇可调节产前和产后心脏中的心肌细胞增殖。在这里，我们描述了可注射的透明质酸（HA）水凝胶的开发和应用，用于将miR-302模拟物局部和持续递送至心脏。我们显示，miR-302模拟物在体外释放可促进心肌细胞增殖超过一周，并且在小鼠心脏中单次注射水凝胶可导致局部和持续两周的心肌细胞增殖。MI后，在Confetti小鼠模型的边界区域中，gel / miR-302注射引起局部克隆增殖和心肌细胞数量增加。与对照组相比，Gel / miR-302在MI和注射后4周进一步降低了心脏舒张末期（39％）和收缩末期（50％）的体积，并改善了射血分数（32％）和缩短分数（64％）。 。我们的发现表明，基于生物材料的miRNA递送系统可以改善心脏再生的结果。