Fang Jun, Koh Jaekyung, Fang Qizhi, Qiu Huiliang, Archang Maani M, Hasani-Sadrabadi Mohammad Mahdi, Miwa Hiromi, Zhong Xintong, Sievers Richard, Gao Dong-Wei, Lee Randall, Carlo Dino Di, Li Song
Department of Bioengineering, University of California, Los Angeles, CA 90095, USA.
Department of Medicine, Cardiovascular Research Institute and Institute for Regeneration Medicine University of California, San Francisco, CA 94143, USA.
Adv Funct Mater. 2020 Oct 22;30(43). doi: 10.1002/adfm.202004307. Epub 2020 Sep 6.
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.
心肌内注射水凝胶以微创方式治疗心肌梗死（MI）具有巨大潜力。然而，传统的块状水凝胶通常缺乏微孔结构来支持组织快速向内生长，也缺乏生化信号来防止向心力衰竭的纤维化重塑。为应对这些挑战，通过微流控制造将负载疏水药物的纳米颗粒封装入微凝胶构建块中，开发了一种新型药物释放微孔退火颗粒（drugMAP）系统。通过调节纳米颗粒的亲水性和预凝胶溶液的粘度，生成了对纳米颗粒具有一致且均匀封装的drugMAP构建块。此外，还证明了福斯可林（F）和Repsox（R）在体外对心肌细胞、成纤维细胞和内皮细胞功能调节的互补作用。之后，将两种疏水药物（F和R）加载到drugMAP中，以生成用于大鼠模型MI治疗的FR/drugMAP。心肌内注射MAP凝胶可改善左心室功能，而FR/drugMAP治疗通过增加血管生成、减少纤维化和炎症反应进一步增强了这些功能。这种drugMAP平台代表了用于MI治疗的新一代微凝胶颗粒，将在再生医学和疾病治疗中具有广泛应用。
