Shrink‐Film Configurable Multiscale Wrinkles for Functional Alignment of Human Embryonic Stem Cells and their Cardiac Derivatives

Chen, Aaron; Lieu, Deborah K.; Freschauf, Lauren R.; Lew, Valerie; Sharma, Himanshu; Wang, Jiaxian; Nguyen, Duc‐Trung; Karakikes, Ioannis; Hajjar, Roger J.; Gopinathan, Ajay; Botvinick, Elliot; Fowlkes, Charless C.; Tse, Gary; Khine, Michelle

doi:10.1002/adma.201103463

Cited by 116 publications

(103 citation statements)

References 33 publications

(45 reference statements)

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“…The surfaces created by these conventional fabrication processes are not representative of the underlying extra cellular matrix (ECM) fibrils in the native heart. We have previously demonstrated that a wrinkled substrate derived from plasma treated pre-stressed thermoplastic shrink film can potentially serve as an efficacious biomimetic surface to functionally align hPSC-CMs and prevent re-entry of ventricular arrhythmia [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Integrated platform for functional monitoring of biomimetic heart sheets derived from human pluripotent stem cells

Chen

Lee

et al. 2014

Biomaterials

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a b s t r a c tWe present an integrated platform comprised of a biomimetic substrate and physiologically aligned human pluripotent stem cell-derived cardiomyocytes (CMs) with optical detection and algorithms to monitor subtle changes in cardiac properties under various conditions. In the native heart, anisotropic tissue structures facilitate important concerted mechanical contraction and electrical propagation. To recapitulate the architecture necessary for a physiologically accurate heart response, we have developed a simple way to create large areas of aligned CMs with improved functional properties using shrink-wrap film. Combined with simple bright field imaging, obviating the need for fluorescent labels or beads, we quantify and analyze key cardiac contractile parameters. To evaluate the performance capabilities of this platform, the effects of two drugs, E-4031 and isoprenaline, were examined. Cardiac cells supplemented with E-4031 exhibited an increase in contractile duration exclusively due to prolonged relaxation peak. Notably, cells aligned on the biomimetic platform responded detectably down to a dosage of 3 nM E-4031, which is lower than the IC 50 in the hERG channel assay. Cells supplemented with isoprenaline exhibited increased contractile frequency and acceleration. Interestingly, cells grown on the biomimetic substrate were more responsive to isoprenaline than those grown on the two control surfaces, suggesting topography may help induce more mature ion channel development. This simple and low-cost platform could thus be a powerful tool for longitudinal assays as well as an effective tool for drug screening and basic cardiac research.

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Section: Introductionmentioning

confidence: 99%

“…Electrophysiological properties are often measured through the use of patch clamps [21] or fluorescent voltage sensitive dyes [19,20] which typically serve as end-point assays. With the prohibitive Fig.…”

Section: Introductionmentioning

confidence: 99%

Integrated platform for functional monitoring of biomimetic heart sheets derived from human pluripotent stem cells

Chen

Lee

et al. 2014

Biomaterials

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“…It has been found that hESCs aligned parallel to the wrinkled topography within hours of seeding when they were seeded onto polyethylene shrink films that included aligned wrinkles with depths that ranged from 150 to 300 nm. 70 Their nucleus became deformed and showed a decreased surface area. The cardiomyocytes differentiated from hESCs had contractions that were more synchronized than unaligned controls and the conduction velocity of the aligned cell action potentials was higher as well.…”

Section: The Effect Of Nanotopography Of a Substrate On Hpsc Lineage-mentioning

confidence: 99%

Mechanobiology of Human Pluripotent Stem Cells

Earls

Jin

2013

Tissue Engineering Part B: Reviews

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Human pluripotent stem cells (hPSCs) are self-renewing and have the potential to differentiate into any cell type in the body, making them attractive cell sources for applications in tissue engineering and regenerative medicine. However, in order for hPSCs to find use in the clinic, the mechanisms underlying their self-renewal and lineage commitment must be better understood. Many technologies that have been developed for the maintenance and directed differentiation of hPSCs involve the use of soluble growth factors, but recent studies suggest that other elements of the hPSC microenvironment also influence the growth and differentiation of hPSCs. This includes the influences of cell-cell interactions, substrate mechanics, cellular interactions with extracellular matrix, as well as the nanotopography of the substrate and physical forces such as shear stress, cyclic mechanical strain, and compression. In this review, we highlight the recent progress of this area of research and discuss ways in which the mechanical cues may be incorporated into hPSC culture regimes to improve methods for expanding and differentiating hPSCs.

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“…4 These approaches include techniques such as razor-blade cutting (xurography), 6,7 adhesive film masking, 8 and structuring through shape-memory polymers (SMPs), 9,10 among many others. Using these techniques, it has been possible to prototype microfluidic channels, [11][12][13] pattern thin films and surfaces, 8,14 and produce micro and nanostructured metallic surfaces [15][16][17] that have been applied mostly to Surface Enhanced Raman Scattering (SERS) applications. [18][19][20] The simplicity and cost-effectiveness of bench-top fabrication methods make them ideal for prototyping, optimizing, and producing low-cost disposable LoC devices.…”

Section: Introductionmentioning

confidence: 99%

Enhanced single-cell printing by acoustophoretic cell focusing

et al. 2015

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Recent years have witnessed a strong trend towards analysis of single-cells. To access and handle single-cells, many new tools are needed and have partly been developed. Here, we present an improved version of a single-cell printer which is able to deliver individual single cells and beads encapsulated in free-flying picoliter droplets at a single-bead efficiency of 96% and with a throughput of more than 10 beads per minute. By integration of acoustophoretic focusing, the cells could be focused in x and y direction. This way, the cells were lined-up in front of a 40 μm nozzle, where they were analyzed individually by an optical system prior to printing. In agreement with acoustic simulations, the focusing of 10 μm beads and Raji cells has been achieved with an efficiency of 99% (beads) and 86% (Raji cells) to a 40 μm wide center region in the 1 mm wide microfluidic channel. This enabled improved optical analysis and reduced bead losses. The loss of beads that ended up in the waste (because printing them as single beads arrangements could not be ensured) was reduced from 52% ± 6% to 28% ± 1%. The piezoelectric transducer employed for cell focusing could be positioned on an outer part of the device, which proves the acoustophoretic focusing to be versatile and adaptable.

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Shrink‐Film Configurable Multiscale Wrinkles for Functional Alignment of Human Embryonic Stem Cells and their Cardiac Derivatives

Abstract: A biomimetic substrate for cell‐culture is fabricated by plasma treatment of a prestressed thermoplastic shrink film to create tunable multiscaled alignment “wrinkles”. Using this substrate, the functional alignment of human embryonic stem cell derived cardiomyocytes is demonstrated.

Cited by 116 publications

References 33 publications

Integrated platform for functional monitoring of biomimetic heart sheets derived from human pluripotent stem cells

Integrated platform for functional monitoring of biomimetic heart sheets derived from human pluripotent stem cells

Mechanobiology of Human Pluripotent Stem Cells

Enhanced single-cell printing by acoustophoretic cell focusing

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