自愈水凝胶
组织工程
材料科学
机械转化
细胞生物学
纳米技术
再生(生物学)
生物医学工程
化学
生物
医学
高分子化学
作者
Junmin Lee,Vijayan Manoharan,Louis Cheung,Seungkyu Lee,Byung‐Hyun Cha,Peter Newman,Razieh Farzad,Shreya Mehrotra,Kaizhen Zhang,Fazal Khan,Masoumeh Ghaderi,Yi-Dong Lin,Saira Aftab,Pooria Mostafalu,Mario Miscuglio,Joan Li,Biman B. Mandal,Mohammad Asif Hussain,Kai‐Tak Wan,Xiaowu Shirley Tang,Ali Khademhosseini,Su Ryon Shin
出处
期刊:ACS Nano
[American Chemical Society]
日期:2019-10-17
卷期号:13 (11): 12525-12539
被引量:100
标识
DOI:10.1021/acsnano.9b03050
摘要
Myocardial microenvironment plays a decisive role in guiding the function and fate of cardiomyocytes, and engineering this extracellular niche holds great promise for cardiac tissue regeneration. Platforms utilizing hybrid hydrogels containing various types of conductive nanoparticles have been a critical tool for constructing engineered cardiac tissues with outstanding mechanical integrity and improved electrophysiological properties. However, there has been no attempt to directly compare the efficacy of these hybrid hydrogels and decipher the mechanisms behind how these platforms differentially regulate cardiomyocyte behavior. Here, we employed gelatin methacryloyl (GelMA) hydrogels containing three different types of carbon-based nanoparticles: carbon nanotubes (CNTs), graphene oxide (GO), and reduced GO (rGO), to investigate the influence of these hybrid scaffolds on the structural organization and functionality of cardiomyocytes. Using immunofluorescent staining for assessing cellular organization and proliferation, we showed that electrically conductive scaffolds (CNT- and rGO-GelMA compared to relatively nonconductive GO-GelMA) played a significant role in promoting desirable morphology of cardiomyocytes and elevated the expression of functional cardiac markers, while maintaining their viability. Electrophysiological analysis revealed that these engineered cardiac tissues showed distinct cardiomyocyte phenotypes and different levels of maturity based on the substrate (CNT-GelMA: ventricular-like, GO-GelMA: atrial-like, and rGO-GelMA: ventricular/atrial mixed phenotypes). Through analysis of gene-expression patterns, we uncovered that the engineered cardiac tissues matured on CNT-GelMA and native cardiac tissues showed comparable expression levels of maturation markers. Furthermore, we demonstrated that engineered cardiac tissues matured on CNT-GelMA have increased functionality through integrin-mediated mechanotransduction (via YAP/TAZ) in contrast to cardiomyocytes cultured on rGO-GelMA.
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