Suarez Sophia L, Muñoz Adam, Mitchell Aaron, Braden Rebecca L, Luo Colin, Cochran Jennifer R, Almutairi Adah, Christman Karen L
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
ACS Biomater Sci Eng. 2016 Feb 8;2(2):197-204. doi: 10.1021/acsbiomaterials.5b00335. Epub 2015 Dec 14.
Injectable biomaterials are promising as new therapies to treat myocardial infarction (MI). One useful property of biomaterials is the ability to protect and sustain release of therapeutic payloads. In order to create a platform for optimizing the release rate of cardioprotective molecules we utilized the tunable degradation of acetalated dextran (AcDex). We created microparticles with three distinct degradation profiles and showed that the consequent protein release profiles could be modulated within the infarcted heart. This enabled us to determine how delivery rate impacted the efficacy of a model therapeutic, an engineered hepatocyte growth factor fragment (HGF-f). Our results showed that the cardioprotective efficacy of HGF-f was optimal when delivered over three days post-intramyocardial injection, yielding the largest arterioles, fewest apoptotic cardiomyocytes bordering the infarct and the smallest infarcts compared to empty particle treatment four weeks after injection. This work demonstrates the potential of using AcDex particles as a delivery platform to optimize the time frame for delivering therapeutic proteins to the heart.
可注射生物材料作为治疗心肌梗死（MI）的新疗法具有广阔前景。生物材料的一个有用特性是能够保护和持续释放治疗性载荷。为了创建一个优化心脏保护分子释放速率的平台，我们利用了乙酰化葡聚糖（AcDex）的可调降解特性。我们制备了具有三种不同降解曲线的微粒，并表明在梗死心脏中可以调节随之而来的蛋白质释放曲线。这使我们能够确定递送速率如何影响一种模型治疗药物——工程化肝细胞生长因子片段（HGF-f）的疗效。我们的结果表明，与注射四周后空颗粒治疗相比，心肌内注射后三天内递送HGF-f时心脏保护效果最佳，产生的小动脉最大，梗死灶周围凋亡心肌细胞最少，梗死灶最小。这项工作证明了使用AcDex颗粒作为递送平台来优化向心脏递送治疗性蛋白质的时间框架的潜力。
