A data-driven computational model for engineered cardiac microtissues

Jilberto, Javiera; DePalma, Samuel J.; Lo, Jason; Kobeissi, Hiba; Quach, Lani; Lejeune, Emma; Baker, Brendon M.; Nordsletten, David

doi:10.1016/j.actbio.2023.10.025

Cited by 3 publications

(1 citation statement)

References 42 publications

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“…In addition, we perform additional validation against a single computationally generated synthetic example of “Type 2” data based on a more sophisticated tissue-specific FE model described in detail in Jilberto et al [ 89 ] and S1 Appendix . For more information on implementing the Finite Element model, image warping, and the addition of Perlin noise [ 90 ], we refer the reader to S1 Appendix .…”

Section: Methodsmentioning

confidence: 99%

MicroBundleCompute: Automated segmentation, tracking, and analysis of subdomain deformation in cardiac microbundles

Kobeissi,

Jilberto,

Karakan

et al. 2024

PLoS ONE

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Advancing human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) technology will lead to significant progress ranging from disease modeling, to drug discovery, to regenerative tissue engineering. Yet, alongside these potential opportunities comes a critical challenge: attaining mature hiPSC-CM tissues. At present, there are multiple techniques to promote maturity of hiPSC-CMs including physical platforms and cell culture protocols. However, when it comes to making quantitative comparisons of functional behavior, there are limited options for reliably and reproducibly computing functional metrics that are suitable for direct cross-system comparison. In addition, the current standard functional metrics obtained from time-lapse images of cardiac microbundle contraction reported in the field (i.e., post forces, average tissue stress) do not take full advantage of the available information present in these data (i.e., full-field tissue displacements and strains). Thus, we present “MicroBundleCompute,” a computational framework for automatic quantification of morphology-based mechanical metrics from movies of cardiac microbundles. Briefly, this computational framework offers tools for automatic tissue segmentation, tracking, and analysis of brightfield and phase contrast movies of beating cardiac microbundles. It is straightforward to implement, runs without user intervention, requires minimal input parameter setting selection, and is computationally inexpensive. In this paper, we describe the methods underlying this computational framework, show the results of our extensive validation studies, and demonstrate the utility of exploring heterogeneous tissue deformations and strains as functional metrics. With this manuscript, we disseminate “MicroBundleCompute” as an open-source computational tool with the aim of making automated quantitative analysis of beating cardiac microbundles more accessible to the community.

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Section: Methodsmentioning

confidence: 99%

MicroBundleCompute: Automated segmentation, tracking, and analysis of subdomain deformation in cardiac microbundles

Kobeissi,

Jilberto,

Karakan

et al. 2024

PLoS ONE

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Generating in-silico Models of Engineered Heart Tissues: The Importance of Using Length-Dependent Activation

Jilberto,

DePalma,

et al. 2024

Lecture Notes in Computational Vision and Biomechanics

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Matrix architecture and mechanics regulate myofibril organization, costamere assembly, and contractility of engineered myocardial microtissues

DePalma,

Jillberto,

Stis

et al. 2023

Preprint

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The mechanical function of the myocardium is defined by cardiomyocyte contractility and the biomechanics of the extracellular matrix (ECM). Understanding this relationship remains an important unmet challenge due to limitations in existing approaches for engineering myocardial tissue. Here, we established arrays of cardiac microtissues with tunable mechanics and architecture by integrating ECM-mimetic synthetic, fiber matrices and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), enabling real-time contractility readouts, in-depth structural assessment, and tissue-specific computational modeling. We find that the stiffness and alignment of matrix fibers distinctly affect the structural development and contractile function of pure iPSC-CM tissues. Further examination into the impact of fibrous matrix stiffness enabled by computational models and quantitative immunofluorescence implicates cell-ECM interactions in myofibril assembly and notably costamere assembly, which correlates with improved contractile function of tissues. These results highlight how iPSC-CM tissue models with controllable architecture and mechanics can inform the design of translatable regenerative cardiac therapies.

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A data-driven computational model for engineered cardiac microtissues

Cited by 3 publications

References 42 publications

MicroBundleCompute: Automated segmentation, tracking, and analysis of subdomain deformation in cardiac microbundles

MicroBundleCompute: Automated segmentation, tracking, and analysis of subdomain deformation in cardiac microbundles

Generating in-silico Models of Engineered Heart Tissues: The Importance of Using Length-Dependent Activation

Matrix architecture and mechanics regulate myofibril organization, costamere assembly, and contractility of engineered myocardial microtissues

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