Injectable Drug-Releasing Microporous Annealed Particle Scaffolds for Treating Myocardial Infarction
Injectable Drug-Releasing Microporous Annealed Particle Scaffolds for Treating Myocardial Infarction
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DOI：
10.1002/adfm.202004307
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发表时间：
2020-09-06
影响因子：
19
通讯作者：
Li, Song
中科院分区：
文献类型：
--
作者：
Fang, Jun;Koh, Jaekyung;Li, Song
心肌内注射水凝胶为以微创方式治疗心肌梗死（MI）提供了巨大的潜力。然而，传统的本体水凝胶通常缺乏微孔结构以支持快速组织向内生长和生物化学信号以防止朝向心力衰竭的纤维化重塑。为了解决这些挑战，开发了一种新型的药物释放微孔退火颗粒（drugMAP）系统，通过微流体制造将疏水性载药纳米颗粒封装到微凝胶构建块中。通过调节纳米颗粒亲水性和预凝胶溶液粘度，产生具有纳米颗粒的一致和均匀包封的drugMAP结构单元。此外，证明了毛喉素（F）和Repsox（R）对体外心肌细胞、成纤维细胞和内皮细胞功能调节的互补作用。之后，将两种疏水性药物（F和R）加载到drugMAP中以产生用于大鼠模型中的MI治疗的FR/drugMAP。心肌内注射MAP凝胶改善了左心室功能，FR/drugMAP治疗进一步增强了左心室功能，增加了血管生成，减少了纤维化和炎症反应。该drugMAP平台代表了新一代用于MI治疗的微凝胶颗粒，并将在再生医学和疾病治疗中具有广泛的应用。
Intramyocardial injection of hydrogels offers great potential for treating myocardial infarction (MI) in a minimally invasive manner. However, traditional bulk hydrogels generally lack microporous structures to support rapid tissue ingrowth and biochemical signals to prevent fibrotic remodeling toward heart failure. To address such challenges, a novel drug-releasing microporous annealed particle (drugMAP) system is developed by encapsulating hydrophobic drug-loaded nanoparticles into microgel building blocks via microfluidic manufacturing. By modulating nanoparticle hydrophilicity and pregel solution viscosity, drugMAP building blocks are generated with consistent and homogeneous encapsulation of nanoparticles. In addition, the complementary effects of forskolin (F) and Repsox (R) on the functional modulations of cardiomyocytes, fibroblasts, and endothelial cells in vitro are demonstrated. After that, both hydrophobic drugs (F and R) are loaded into drugMAP to generate FR/drugMAP for MI therapy in a rat model. The intramyocardial injection of MAP gel improves left ventricular functions, which are further enhanced by FR/drugMAP treatment with increased angiogenesis and reduced fibrosis and inflammatory response. This drugMAP platform represents a new generation of microgel particles for MI therapy and will have broad applications in regenerative medicine and disease therapy.