期刊
ACS APPLIED MATERIALS & INTERFACES
卷 8, 期 34, 页码 21923-21932出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.5b11671
关键词
nanotopography; cardiomyocytes; chimeric self-assembling peptide; biomimetic surface; human induced pluripotent stem cells
资金
- American Heart Association (AHA) [13SDG14560076]
- Washington State Life Sciences Discovery Fund grant
- International Collaborative RD Program Grant
- KIAT - MOTE [N0000894]
- NIH-NIAMS grant [AR062249-03]
- AHA [12POST11940060, 14POST20310023]
- NIH T32 postdoctoral fellowship [2T32HL007312-36A1]
- NIH [R01 HL084642, P01 HL094374, P01 GM81619, U01 HL100405, R01 HL111197, R01 HD048895]
Understanding the phenotypic development of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is a prerequisite to advancing regenerative cardiac therapy, disease modeling, and drug screening applications. Lack of consistent hiPSC-CM in vitro data can be largely attributed to the inability of conventional culture methods to mimic the structural, biochemical, and mechanical,aspects of the myocardial niche accurately. Here, we present a nanogrid culture array, comprised of nanogrooved topographies, with groove widths ranging, from 350 to 2000 nm, to,study the effect of different nanoscale structures on the,structural development of, hiPSC-CMs in vitro. Nanotopographies were designed to have a biomimetic interface, based on observations of the oriented myocardial extracellular:matrix (ECM) fibers found in vivo. Nanotopographic substrates, were integrated with a self-assembling chimeric peptide containing the Arg-Gly-Asp (RGD) cell adhesion motif: Using this platform, tell adhesion to peptide-coated substrates was found to be comparable to that of conventional fibronectin-coated surfaces. Cardiomyocyte organization and structural development were found to be dependent on the nanotopographical feature size in a biphasic manner, with improved development achieved on grooves In the 700-1000 nm, range. These findings highlight the capability of surface-functionalized, bioinspired substrates to influence cardiomyocyte development, and the capacity for such platforms to serve as a versatile assay for investigating the role of topographical guidance cues on cell behavior. Such substrates could potentially create more physiologically relevant in vitro cardiac tissue's for future drug screening and disease modeling studies.
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