Electroconductive Nanopatterned Substrates for Enhanced Myogenic Differentiation and Maturation

Yang, Hee Seok; Lee, Bora; Tsui, Jonathan H.; Macadangdang, Jesse; Jang, Seok Young; Im, Sung Gap; Kim, Deok Ho

doi:10.1002/adhm.201500003

Cited by 74 publications

(53 citation statements)

References 62 publications

(59 reference statements)

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“…Fluorescent images of F-actin fibers of cardiomyocytes on unpatterned and patterned substrates were analyzed for alignment using a custom MATLAB script as described previously 42 . A 2D convolution was performed on each image and a Sobel edge-emphasizing filter was applied to extract the horizontal and vertical edges within the image.…”

Section: Methodsmentioning

confidence: 99%

Nanopatterned Human iPSC-Based Model of a Dystrophin-Null Cardiomyopathic Phenotype

et al. 2015

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Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer unprecedented opportunities to study inherited heart conditions in vitro, but are phenotypically immature, limiting their ability to effectively model adult-onset diseases. Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy (DMD), but the pathogenesis of this disease phenotype is not fully understood. Therefore, we aimed to test whether biomimetic nanotopography could further stratify the disease phenotype of DMD hiPSC-CMs to create more translationally relevant cardiomyocytes for disease modeling applications. We found that anisotropic nanotopography was necessary to distinguish structural differences between normal and DMD hiPSC-CMs, as these differences were masked on conventional flat substrates. DMD hiPSC-CMs exhibited a diminished structural and functional response to the underlying nanotopography compared to normal cardiomyocytes at both the macroscopic and subcellular levels. This blunted response may be due to a lower level of actin cytoskeleton turnover as measured by fluorescence recovery after photobleaching. Taken together these data suggest that DMD hiPSC-CMs are less adaptable to changes in their extracellular environment, and highlight the utility of nanotopographic substrates for effectively stratifying normal and structural cardiac disease phenotypes in vitro.

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Section: Methodsmentioning

confidence: 99%

Nanopatterned Human iPSC-Based Model of a Dystrophin-Null Cardiomyopathic Phenotype

et al. 2015

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“…Topographical cues have been shown to enhance myogenic differentiation and maturation of myoblasts [18] and to induce myogenic commitment of human mesenchymal stem cells in vitro [19]. Surface topography alone [20] or in combination with substrate rigidity [21] have been shown to control mesenchymal stem cell lineage commitment.…”

Section: Introductionmentioning

confidence: 99%

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

et al. 2015

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractControlling the cell-substrate interactions at the bio-interface is becoming an inherent element in the design of implantable devices. Modulation of cellular adhesion in vitro, through topographical cues, is a well-documented process that offers control over subsequent cellular functions. However, it is still unclear whether surface topography can be translated into a clinically functional response in vivo at the tissue / device interface. Herein, we demonstrated that anisotropic substrates with a groove depth of ~317 nm and ~1,988 nm promoted human tenocyte alignment parallel to the underlying topography in vitro. However, the rigid poly(lactic-co-glycolic acid) substrates used in this study upregulated the expression of chondrogenic and osteogenic genes, indicating possible tenocyte trans-differentiation. Of significant importance is that none of the topographies assessed (~37 nm, ~317 nm and ~1,988 nm groove depth) induced extracellular matrix orientation parallel to the substrate orientation in a rat patellar tendon model. These data indicate that two-dimensional imprinting technologies are useful tools for in vitro cell phenotype maintenance, rather than for organised neotissue formation in vivo, should multifactorial approaches that consider both surface topography and substrate rigidity be established.

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“…In addition, nanopatterned substrates have been widely used to encourage maturation of chemically defined CMs 73–76 . However, new methods proposed thus far have not yielded highly mature, patient-specific CMs on a scale sufficient to meet clinical needs 77 .…”

Section: Cell Therapy For Salvage and Regeneration Of Heart Tissuementioning

confidence: 99%

Multiscale technologies for treatment of ischemic cardiomyopathy

et al. 2017

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The adult mammalian heart possesses only limited capacity for innate regeneration and the response to severe injury is dominated by the formation of scar tissue. Current therapy to replace damaged cardiac tissue is limited to cardiac transplantation and thus many patients suffer progressive decay in the heart’s pumping capacity to the point of heart failure. Nanostructured systems have the potential to revolutionize both preventive and therapeutic approaches for treating cardiovascular disease. Here, we outline recent advancements in nanotechnology that could be exploited to overcome the major obstacles in the prevention of and therapy for heart disease. We also discuss emerging trends in nanotechnology affecting the cardiovascular field that may offer new hope for patients suffering massive heart attacks.

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Electroconductive Nanopatterned Substrates for Enhanced Myogenic Differentiation and Maturation

Cited by 74 publications

References 62 publications

Nanopatterned Human iPSC-Based Model of a Dystrophin-Null Cardiomyopathic Phenotype

Nanopatterned Human iPSC-Based Model of a Dystrophin-Null Cardiomyopathic Phenotype

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

Multiscale technologies for treatment of ischemic cardiomyopathy

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