Computational Analysis of Contractility in Engineered Heart Tissue

Mathews, Grant; Søndergaard, Claus S.; Jeffreys, Angela; Childs, W. J.; Le, Bao Linh; Sahota, Amrit; Najibi, S.; Nolta, Jan A.; Si, Magalini

doi:10.1109/tbme.2012.2187899

Cited by 3 publications

(1 citation statement)

References 17 publications

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“…The development of new approaches to measure biological tissues' contractile properties is therefore of high interest, and noninvasive techniques are always more attractive [ 23 , 24 ]. A contactless automated approach to measure this distinguished feature could therefore allow avoiding time consuming, incomplete and subjective measurements [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

A DIC Based Technique to Measure the Contraction of a Skeletal Muscle Engineered Tissue

Rizzuto

Carosio

Faraldi³

et al. 2016

Applied Bionics and Biomechanics

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Tissue engineering is a multidisciplinary science based on the application of engineering approaches to biologic tissue formation. Engineered tissue internal organization represents a key aspect to increase biofunctionality before transplant and, as regarding skeletal muscles, the potential of generating contractile forces is dependent on the internal fiber organization and is reflected by some macroscopic parameters, such as the spontaneous contraction. Here we propose the application of digital image correlation (DIC) as an independent tool for an accurate and noninvasive measurement of engineered muscle tissue spontaneous contraction. To validate the proposed technique we referred to the X-MET, a promising 3-dimensional model of skeletal muscle. The images acquired through a high speed camera were correlated with a custom-made algorithm and the longitudinal strain predictions were employed for measuring the spontaneous contraction. The spontaneous contraction reference values were obtained by studying the force response. The relative error between the spontaneous contraction frequencies computed in both ways was always lower than 0.15%. In conclusion, the use of a DIC based system allows for an accurate and noninvasive measurement of biological tissues' spontaneous contraction, in addition to the measurement of tissue strain field on any desired region of interest during electrical stimulation.

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Section: Introductionmentioning

confidence: 99%

A DIC Based Technique to Measure the Contraction of a Skeletal Muscle Engineered Tissue

Rizzuto

Carosio

Faraldi³

et al. 2016

Applied Bionics and Biomechanics

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Prevascularization of self-organizing engineered heart tissue by human umbilical vein endothelial cells abrogates contractile performance

et al. 2012

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Establishing vascularization is a critical obstacle to the generation of engineered heart tissue (EHT) of substantial thickness. Addition of endothelial cells to the formative stages of EHT has been demonstrated to result in prevascularization, or the formation of capillary-like structures. The detailed study of the effects of prevascularization on EHT contractile function is lacking. Here, we evaluated the functional impact of prevascularization by human umbilical vein endothelial cells (HUVECs) in self-organizing EHT. EHT fibers were generated by the self-organization of neonatal rat cardiac cells on a fibrin hydrogel scaffold with or without HUVECs. Contractile function was measured and force-length relationship and rate of force production were assessed. Immunofluorescent studies were used to evaluate arrangement and distribution of HUVECs within the EHT fibers. RT-PCR was used to assess the transcript levels of hypoxia inducible factor-1a (Hif-1α). EHT with HUVECs manifested tubule-like structures at the periphery during fiber formation. After fiber formation, HUVECs were heterogeneously located throughout the EHT fiber and human CD31+ tubule-like structures were identified. The expression level of Hif-1α did not change with the addition of HUVECs. However, maximal force and rate of force generation were not improved in HUVECs containing EHT as compared to control EHT fibers. The addition of HUVECs may result in sparse microvascularization of EHT. However, this perceived benefit is overshadowed by a significant decrease in contractile function and highlights the need for perfused vascularization strategies in order to generate EHT that approaches clinically relevant dimensions.

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Engineering Challenges for Instrumenting and Controlling Integrated Organ-on-Chip Systems

Wikswo

Block

Cliffel

et al. 2013

IEEE Trans. Biomed. Eng.

160

165

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The sophistication and success of recently reported microfabricated organs-on-chips and human organ constructs have made it possible to design scaled and interconnected organ systems that may significantly augment the current drug development pipeline and lead to advances in systems biology. Physiologically realistic live microHuman (µHu) and milliHuman (mHu) systems operating for weeks to months present exciting and important engineering challenges such as determining the appropriate size for each organ to ensure appropriate relative organ functional activity, achieving appropriate cell density, providing the requisite universal perfusion media, sensing the breadth of physiological responses, and maintaining stable control of the entire system, while maintaining fluid scaling that consists of ~5 mL for the mHu and ~5 µL for the µHu. We believe that successful mHu and µHu systems for drug development and systems biology will require low-volume microdevices that support chemical signaling, micro-fabricated pumps, valves and microformulators, automated optical microscopy, electrochemical sensors for rapid metabolic assessment, ion mobility-mass spectrometry for real-time molecular analysis, advanced bioinformatics, and machine learning algorithms for automated model inference and integrated electronic control. Toward this goal, we are building functional prototype components and are working toward top-down system integration.

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Computational Analysis of Contractility in Engineered Heart Tissue

Cited by 3 publications

References 17 publications

A DIC Based Technique to Measure the Contraction of a Skeletal Muscle Engineered Tissue

A DIC Based Technique to Measure the Contraction of a Skeletal Muscle Engineered Tissue

Prevascularization of self-organizing engineered heart tissue by human umbilical vein endothelial cells abrogates contractile performance

Engineering Challenges for Instrumenting and Controlling Integrated Organ-on-Chip Systems

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