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  1. Article ; Online: Next-generation engineered microsystems for cell biology: a systems-level roadmap.

    Sundaram, Subramanian / Chen, Christopher S

    Trends in cell biology

    2022  Volume 32, Issue 6, Page(s) 490–500

    Abstract: Engineered microsystems for in vitro studies of cultured cells are evolving from simple 2D platforms to 3D architectures and organoid cultures. Despite advances in reproducing ever more sophisticated biology in these systems, there remain foundational ... ...

    Abstract Engineered microsystems for in vitro studies of cultured cells are evolving from simple 2D platforms to 3D architectures and organoid cultures. Despite advances in reproducing ever more sophisticated biology in these systems, there remain foundational challenges in re-creating key aspects of tissue composition, architecture, and mechanics that are critical to recapitulating in vivo processes. Against the backdrop of current progress in 3D fabrication methods, we evaluate the key requirements for the next generation of cellular platforms. We postulate that these future platforms - apart from building tissue-like structures - will need to have the ability to readily sense and autonomously modulate tissue responses over time, as occurs in natural microenvironments. Such interactive robotic platforms that report and guide cellular events will enable us to probe a previously inaccessible class of questions in cell biology.
    MeSH term(s) Cells, Cultured ; Humans ; Organoids ; Tissue Engineering
    Language English
    Publishing date 2022-01-31
    Publishing country England
    Document type Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 30122-x
    ISSN 1879-3088 ; 0962-8924
    ISSN (online) 1879-3088
    ISSN 0962-8924
    DOI 10.1016/j.tcb.2022.01.003
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  2. Article ; Online: Forces as regulators of cell adhesions.

    Chen, Christopher S

    Nature reviews. Molecular cell biology

    2017  Volume 18, Issue 12, Page(s) 715

    Language English
    Publishing date 2017-11-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/nrm.2017.112
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  3. Article ; Online: 3D Biomimetic Cultures: The Next Platform for Cell Biology.

    Chen, Christopher S

    Trends in cell biology

    2016  Volume 26, Issue 11, Page(s) 798–800

    Abstract: Advances in engineering of cells and culture formats have led to the development of a new generation of 3D cultures that can recapitulate a variety of multicell-type, morphogenetic behaviors that were previously largely observable only in in vivo ... ...

    Abstract Advances in engineering of cells and culture formats have led to the development of a new generation of 3D cultures that can recapitulate a variety of multicell-type, morphogenetic behaviors that were previously largely observable only in in vivo settings. Ultimately, these systems are likely to be assimilated into and forever change the landscape of biomedical research.
    Language English
    Publishing date 2016-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 30122-x
    ISSN 1879-3088 ; 0962-8924
    ISSN (online) 1879-3088
    ISSN 0962-8924
    DOI 10.1016/j.tcb.2016.08.008
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  4. Article ; Online: Geometry and length control of 3D engineered heart tissues using direct laser writing.

    Karakan, M Çağatay / Ewoldt, Jourdan K / Segarra, Addianette J / Sundaram, Subramanian / Wang, Miranda C / White, Alice E / Chen, Christopher S / Ekinci, Kamil L

    Lab on a chip

    2024  Volume 24, Issue 6, Page(s) 1685–1701

    Abstract: Geometry and mechanical characteristics of the environment surrounding the Engineered Heart Tissues (EHT) affect their structure and function. Here, we employed a 3D tissue culture platform fabricated using two-photon direct laser writing with a high ... ...

    Abstract Geometry and mechanical characteristics of the environment surrounding the Engineered Heart Tissues (EHT) affect their structure and function. Here, we employed a 3D tissue culture platform fabricated using two-photon direct laser writing with a high degree of accuracy to control parameters that are relevant to EHT maturation. Using this platform, we first explore the effects of geometry based on two distinct shapes: a rectangular seeding well with two attachment sites, and a stadium-like seeding well with six attachment sites that are placed symmetrically along hemicylindrical membranes. The former geometry promotes uniaxial contraction of the tissues; the latter additionally induces diagonal fiber alignment. We systematically increase the length of the seeding wells for both configurations and observe a positive correlation between fiber alignment at the center of the EHTs and tissue length. With increasing length, an undesirable thinning and "necking" also emerge, leading to the failure of longer tissues over time. In the second step, we optimize the stiffness of the seeding wells and modify some of the attachment sites of the platform and the seeding parameters to achieve tissue stability for each length and geometry. Furthermore, we use the platform for electrical pacing and calcium imaging to evaluate the functional dynamics of EHTs as a function of frequency.
    MeSH term(s) Myocytes, Cardiac ; Tissue Engineering/methods ; Lasers ; Myocardial Contraction
    Language English
    Publishing date 2024-03-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2056646-3
    ISSN 1473-0189 ; 1473-0197
    ISSN (online) 1473-0189
    ISSN 1473-0197
    DOI 10.1039/d3lc00752a
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  5. Article ; Online: Nonclinical evaluation of chronic cardiac contractility modulation on 3D human engineered cardiac tissues.

    Feaster, Tromondae K / Ewoldt, Jourdan K / Avila, Anna / Casciola, Maura / Narkar, Akshay / Chen, Christopher S / Blinova, Ksenia

    Journal of cardiovascular electrophysiology

    2024  Volume 35, Issue 5, Page(s) 895–905

    Abstract: Introduction: Cardiac contractility modulation (CCM) is a medical device-based therapy delivering non-excitatory electrical stimulations to the heart to enhance cardiac function in heart failure (HF) patients. The lack of human in vitro tools to assess ... ...

    Abstract Introduction: Cardiac contractility modulation (CCM) is a medical device-based therapy delivering non-excitatory electrical stimulations to the heart to enhance cardiac function in heart failure (HF) patients. The lack of human in vitro tools to assess CCM hinders our understanding of CCM mechanisms of action. Here, we introduce a novel chronic (i.e., 2-day) in vitro CCM assay to evaluate the effects of CCM in a human 3D microphysiological system consisting of engineered cardiac tissues (ECTs).
    Methods: Cryopreserved human induced pluripotent stem cell-derived cardiomyocytes were used to generate 3D ECTs. The ECTs were cultured, incorporating human primary ventricular cardiac fibroblasts and a fibrin-based gel. Electrical stimulation was applied using two separate pulse generators for the CCM group and control group. Contractile properties and intracellular calcium were measured, and a cardiac gene quantitative PCR screen was conducted.
    Results: Chronic CCM increased contraction amplitude and duration, enhanced intracellular calcium transient amplitude, and altered gene expression related to HF (i.e., natriuretic peptide B, NPPB) and excitation-contraction coupling (i.e., sodium-calcium exchanger, SLC8).
    Conclusion: These data represent the first study of chronic CCM in a 3D ECT model, providing a nonclinical tool to assess the effects of cardiac electrophysiology medical device signals complementing in vivo animal studies. The methodology established a standardized 3D ECT-based in vitro testbed for chronic CCM, allowing evaluation of physiological and molecular effects on human cardiac tissues.
    MeSH term(s) Humans ; Myocardial Contraction ; Myocytes, Cardiac/metabolism ; Tissue Engineering ; Cells, Cultured ; Induced Pluripotent Stem Cells/metabolism ; Calcium Signaling ; Time Factors ; Excitation Contraction Coupling ; Fibroblasts/metabolism ; Gene Expression Regulation ; Electric Stimulation Therapy/instrumentation ; Heart Failure/physiopathology ; Heart Failure/therapy ; Heart Failure/metabolism
    Language English
    Publishing date 2024-03-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1025989-2
    ISSN 1540-8167 ; 1045-3873
    ISSN (online) 1540-8167
    ISSN 1045-3873
    DOI 10.1111/jce.16222
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  6. Article: High throughput screening system for engineered cardiac tissues.

    Ma, Marshall S / Sundaram, Subramanian / Lou, Lihua / Agarwal, Arvind / Chen, Christopher S / Bifano, Thomas G

    Frontiers in bioengineering and biotechnology

    2023  Volume 11, Page(s) 1177688

    Abstract: Introduction: ...

    Abstract Introduction:
    Language English
    Publishing date 2023-05-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2023.1177688
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  7. Article ; Online: Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure.

    Tefft, Juliann B / Chen, Christopher S / Eyckmans, Jeroen

    APL bioengineering

    2021  Volume 5, Issue 1, Page(s) 16102

    Abstract: The formation of healthy vascularized granulation tissue is essential for rapid wound closure and the prevention of chronic wounds in humans, yet how endothelial cells and fibroblasts coordinate during this process has been difficult to study. Here, we ... ...

    Abstract The formation of healthy vascularized granulation tissue is essential for rapid wound closure and the prevention of chronic wounds in humans, yet how endothelial cells and fibroblasts coordinate during this process has been difficult to study. Here, we have developed an
    Language English
    Publishing date 2021-01-19
    Publishing country United States
    Document type Journal Article
    ISSN 2473-2877
    ISSN (online) 2473-2877
    DOI 10.1063/5.0028651
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  8. Article ; Online: Microcontact printing: A tool to pattern.

    Alom Ruiz, Sami / Chen, Christopher S

    Soft matter

    2020  Volume 3, Issue 2, Page(s) 168–177

    Abstract: Microcontact printing has proven to be a useful technique in the patterned functionalization of certain chemicals onto surfaces. It has been particularly valuable in the patterning of biological materials. In this review, we describe the basic principles ...

    Abstract Microcontact printing has proven to be a useful technique in the patterned functionalization of certain chemicals onto surfaces. It has been particularly valuable in the patterning of biological materials. In this review, we describe the basic principles of the technology as well as its use in several applications, with an emphasis on biological ones. We also discuss the limitations and future directions of this method.
    Keywords covid19
    Language English
    Publishing date 2020-07-15
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2191476-X
    ISSN 1744-6848 ; 1744-683X
    ISSN (online) 1744-6848
    ISSN 1744-683X
    DOI 10.1039/b613349e
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  9. Article ; Online: Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes.

    Zhao, Bill / Zhang, Kehan / Chen, Christopher S / Lejeune, Emma

    PLoS computational biology

    2021  Volume 17, Issue 10, Page(s) e1009443

    Abstract: A better fundamental understanding of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has the potential to advance applications ranging from drug discovery to cardiac repair. Automated quantitative analysis of beating hiPSC-CMs is ... ...

    Abstract A better fundamental understanding of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has the potential to advance applications ranging from drug discovery to cardiac repair. Automated quantitative analysis of beating hiPSC-CMs is an important and fast developing component of the hiPSC-CM research pipeline. Here we introduce "Sarc-Graph," a computational framework to segment, track, and analyze sarcomeres in fluorescently tagged hiPSC-CMs. Our framework includes functions to segment z-discs and sarcomeres, track z-discs and sarcomeres in beating cells, and perform automated spatiotemporal analysis and data visualization. In addition to reporting good performance for sarcomere segmentation and tracking with little to no parameter tuning and a short runtime, we introduce two novel analysis approaches. First, we construct spatial graphs where z-discs correspond to nodes and sarcomeres correspond to edges. This makes measuring the network distance between each sarcomere (i.e., the number of connecting sarcomeres separating each sarcomere pair) straightforward. Second, we treat tracked and segmented components as fiducial markers and use them to compute the approximate deformation gradient of the entire tracked population. This represents a new quantitative descriptor of hiPSC-CM function. We showcase and validate our approach with both synthetic and experimental movies of beating hiPSC-CMs. By publishing Sarc-Graph, we aim to make automated quantitative analysis of hiPSC-CM behavior more accessible to the broader research community.
    MeSH term(s) Cells, Cultured ; Computational Biology ; Cytological Techniques ; Humans ; Image Processing, Computer-Assisted/methods ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/physiology ; Models, Cardiovascular ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/physiology ; Sarcomeres/physiology
    Language English
    Publishing date 2021-10-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1009443
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  10. Article ; Online: Harnessing Mechanobiology for Tissue Engineering.

    Kim, Sudong / Uroz, Marina / Bays, Jennifer L / Chen, Christopher S

    Developmental cell

    2021  Volume 56, Issue 2, Page(s) 180–191

    Abstract: A primary challenge in tissue engineering is to recapitulate both the structural and functional features of whole tissues and organs. In vivo, patterning of the body plan and constituent tissues emerges from the carefully orchestrated interactions ... ...

    Abstract A primary challenge in tissue engineering is to recapitulate both the structural and functional features of whole tissues and organs. In vivo, patterning of the body plan and constituent tissues emerges from the carefully orchestrated interactions between the transcriptional programs that give rise to cell types and the mechanical forces that drive the bending, twisting, and extensions critical to morphogenesis. Substantial recent progress in mechanobiology-understanding how mechanics regulate cell behaviors and what cellular machineries are responsible-raises the possibility that one can begin to use these insights to help guide the strategy and design of functional engineered tissues. In this perspective, we review and propose the development of different approaches, from providing appropriate extracellular mechanical cues to interfering with cellular mechanosensing machinery, to aid in controlling cell and tissue structure and function.
    MeSH term(s) Animals ; Biomechanical Phenomena ; Biophysics ; Cell Differentiation ; Humans ; Mechanotransduction, Cellular ; Morphogenesis ; Tissue Engineering/methods
    Language English
    Publishing date 2021-01-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2020.12.017
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