Engineered Microtissues for Real-Time Characterization of Cardiomyocyte Function

Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tissue Engineering; Cerebral Aneurysms; Computational Biofluid Dynamics; Device Design, Human Dynamics, and Rehabilitation; Drug Delivery and Disease Treatment; Engineered Cellular Environments ◽

10.1115/sbc2013-14248 ◽

2013 ◽

Author(s):

Ariane C. C. van Spreeuwel ◽

Noortje A. M. Bax ◽

Jasper Foolen ◽

M. A. Borochin ◽

Daisy W. J. van der Schaft ◽

...

Keyword(s):

Real Time ◽

Cardiac Tissue ◽

Mechanical Performance ◽

Diagnostic Tools ◽

Cardiac Physiology ◽

Surrounding Matrix ◽

Speed Up ◽

Tissue Models

Engineered cardiac tissue models become increasingly important for understanding normal and disease cardiac physiology [1]. Where clinical diagnostic tools usually measure overall function of the heart, cardiac tissue models make it possible to focus on single CMs and their microenvironment. The use of in-vitro cardiac disease models can give more insight in the functionality changes of CMs during disease and thereby speed up the development of new therapies. Therefore, we aim to develop a model for healthy and diseased myocardium to study the effect of diseased microenvironments on the mechanical performance of CMs. The platform consists of 3D engineered microtissues with matrix, CMs and fibroblasts (FBs) on an array of polydimethylsiloxane (PDMS) microposts and allows for real-time characterization of CMs and their surrounding matrix. The design was adapted from Legant et. al. [2] and enables us to measure inhomogeneous tissue forces which may occur if not all cells contract equally. Here we focus on optimization and validation of the platform to measure contraction forces and gain insight in CM mechanical functioning.

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Biophysical stimulation for in vitro engineering of functional cardiac tissues

Clinical Science ◽

10.1042/cs20170055 ◽

2017 ◽

Vol 131 (13) ◽

pp. 1393-1404 ◽

Cited By ~ 14

Author(s):

Anastasia Korolj ◽

Erika Yan Wang ◽

Robert A. Civitarese ◽

Milica Radisic

Keyword(s):

Cardiac Tissue ◽

Culture Media ◽

Culture Conditions ◽

Lineage Specification ◽

Cardiac Tissues ◽

Cardiac Lineage ◽

And Function ◽

Tissue Models

Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the in vivo cardiac microenvironment and our ability to replicate those parameters in vitro are resulting in the development of increasingly sophisticated models of engineered cardiac tissues (ECT). This review examines some of the most relevant parameters that may be applied in culture leading to higher fidelity cardiac tissue models. These include the biochemical composition of culture media and cardiac lineage specification, co-culture conditions, electrical and mechanical stimulation, and the application of hydrogels, various biomaterials, and scaffolds. The review will also summarize some of the recent functional human tissue models that have been developed for in vivo and in vitro applications. Ultimately, the creation of sophisticated ECT that replicate native structure and function will be instrumental in advancing cell-based therapeutics and in providing advanced models for drug discovery and testing.

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In vitro cardiac tissue models: Current status and future prospects

Advanced Drug Delivery Reviews ◽

10.1016/j.addr.2015.09.011 ◽

2016 ◽

Vol 96 ◽

pp. 203-213 ◽

Cited By ~ 78

Author(s):

Anurag Mathur ◽

Zhen Ma ◽

Peter Loskill ◽

Shaheen Jeeawoody ◽

Kevin E. Healy

Keyword(s):

Cardiac Tissue ◽

Current Status ◽

Future Prospects ◽

Tissue Models

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Stent Geometry Reconstruction Using Imaging Techniques

ASME 2013 Conference on Frontiers in Medical Devices: Applications of Computer Modeling and Simulation ◽

10.1115/fmd2013-16152 ◽

2013 ◽

Author(s):

Daria Cosentino ◽

Iwona Zwierzak ◽

Vanessa Diaz-Zuccarini ◽

John W. Fenner ◽

Silvia Schievano ◽

...

Keyword(s):

Mechanical Performance ◽

Imaging Techniques ◽

Diagnostic Tools ◽

Clinical Images ◽

Stent Geometry ◽

Geometrical Data ◽

Transcatheter Valve ◽

Valve Implantation

Stents are most commonly used in the relief of coronary artery stenosis, but in the last decade have found increasing applications in the treatment of other cardiovascular disease and in particular in heart valve replacement [1]. In transcatheter valve implantation, acquisition of high temporal and spatial resolution images during stenting procedure and patients’ follow-up is required to help the correct positioning of the device and to assess the mechanical performance over time. The imaging techniques routinely used for this purpose are 2D X-ray fluoroscopy and 3D computed tomography (CT), and recent studies have demonstrated their value as diagnostic tools [1–3]. However, these image modalities carry errors and the resulting information might not be accurate enough to be employed in engineering analyses of stent deformations, mechanics, dynamics and fracture. In this study, we aim to evaluate the errors of conventionally used clinical images (fluoroscopy and CT) and post-processing by comparison with ultra-high resolution micro-CT (μCT) as gold standard. Additionally, an optical image acquisition method and a high-radiation CT scan were evaluated as potential techniques to acquire geometrical data that could be used for computational and in-vitro engineering experiments.

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Real-time model-based control of afterload for in vitro cardiac tissue experimentation

2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) ◽

10.1109/embc.2017.8037067 ◽

2017 ◽

Cited By ~ 1

Author(s):

Amy S. Garrett ◽

Toan Pham ◽

Denis S. Loiselle ◽

June-Chiew Han ◽

Andrew J. Taberner

Keyword(s):

Real Time ◽

Cardiac Tissue ◽

Time Model ◽

Model Based Control ◽

Model Based

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Composition and Clinical Significance of Exosomes in Tuberculosis: A Systematic Literature Review

Journal of Clinical Medicine ◽

10.3390/jcm10010145 ◽

2021 ◽

Vol 10 (1) ◽

pp. 145

Author(s):

Fantahun Biadglegne ◽

Brigitte König ◽

Arne C. Rodloff ◽

Anca Dorhoi ◽

Ulrich Sack

Keyword(s):

Vaccine Development ◽

Biological Fluids ◽

Diagnostic Tools ◽

Major Health ◽

Fast Detection ◽

Isolation And Characterization ◽

Culture Supernatants

Tuberculosis (TB) remains a major health issue worldwide. In order to contain TB infections, improved vaccines as well as accurate and reliable diagnostic tools are desirable. Exosomes are employed for the diagnosis of various diseases. At present, research on exosomes in TB is still at the preliminary stage. Recent studies have described isolation and characterization of Mycobacterium tuberculosis (Mtb) derived exosomes in vivo and in vitro. Mtb-derived exosomes (Mtbexo) may be critical for TB pathogenesis by delivering mycobacterial-derived components to the recipient cells. Proteomic and transcriptomic analysis of Mtbexo have revealed a variety of proteins and miRNA, which are utilized by the TB bacteria for pathogenesis. Exosomes have been isolated in body fluids, are amenable for fast detection, and could contribute as diagnostic or prognostic biomarker to disease control. Extraction of exosomes from biological fluids is essential for the exosome research and requires careful standardization for TB. In this review, we summarized the different studies on Mtbexo molecules, including protein and miRNA and the methods used to detect exosomes in biological fluids and cell culture supernatants. Thus, the detection of Mtbexo molecules in biological fluids may have a potential to expedite the diagnosis of TB infection. Moreover, the analysis of Mtbexo may generate new aspects in vaccine development.

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Nanostructured TiN-Coated Electrodes for High-Sensitivity Noninvasive Characterization of in Vitro Tissue Models

ACS Applied Nano Materials ◽

10.1021/acsanm.8b00345 ◽

2018 ◽

Vol 1 (5) ◽

pp. 2284-2293 ◽

Cited By ~ 4

Author(s):

Tobias Schmitz ◽

Matthias Schweinlin ◽

Robin T. Kollhoff ◽

Lisa Engelhardt ◽

Christian Lotz ◽

...

Keyword(s):

High Sensitivity ◽

Noninvasive Characterization ◽

Tissue Models ◽

Coated Electrodes

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Isolation, Culture, and Characterization of Primary Bovine Endometrial, Epithelial, and Stromal Cells for 3D In Vitro Tissue Models

Methods in Molecular Biology - Next Generation Culture Platforms for Reliable In Vitro Models ◽

10.1007/978-1-0716-1246-0_6 ◽

2021 ◽

pp. 103-110

Author(s):

Antonio Murillo ◽

Marta Muñoz

Keyword(s):

Stromal Cells ◽

Tissue Models

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Abstract 4113: In-Vitro Characterization of Ablation Lesions Using Oct

Circulation ◽

10.1161/circ.118.suppl_18.s_831-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Christine P Fleming ◽

Lee M Barwick ◽

Kara J Quan ◽

Andrew M Rollins

Keyword(s):

Real Time ◽

Cardiac Tissue ◽

Direct Method ◽

Lesion Size ◽

Three Dimensions ◽

Necrotic Tissue ◽

Triphenyltetrazolium Chloride ◽

Tissue Samples ◽

Oct Imaging

Radiofrequency ablation (RFA) is a clinical procedure that destroys tissue to cure cardiac arrhythmias. Presently, there is no direct method to monitor RFA lesion formation in real-time. Real time direct monitoring of the tissue could guide ablation and prevent complications such as tissue disruption that leads to perforation. Optical coherence tomography (OCT) provides real-time subsurface imaging with high spatial resolution in three dimensions. We hypothesized that OCT can distinguish necrotic ablated tissue from viable cardiac tissue. Freshly excised right ventricular wedges from swine were placed in a bath with phosphate buffered saline (PBS) maintained at 37°C with super-perfusion flow. RFA lesions were created with a temperature controlled (70°C) protocol, maximum delivered power of 50W for 10, 20, 30, and 60 seconds. Endocardial lesions were created using a 7Fr, 4mm tip RFA catheter. OCT imaging was conducted on a system with a 1310 nm light source and 10μm axial and 18 μm lateral resolution. Staining with 0.1% triphenyltetrazolium chloride in PBS for 15 minutes was used to confirm necrosis and quantify lesion size. The single scattering model of OCT images was used to extract three parameters (attenuation, backscattering, and correlation) to give an indication of tissue scattering, reflectivity, and heterogeneity respectively. OCT images of control (n=26) and ablated tissue (n=87) were analyzed with OCT. Viable tissue had a banding appearance due to the bifriengence property of highly organized myocardial tissue, absent in necrotic tissue caused by ablation. RFA lesions were characterized by increased imaging depth, increased scattering, and a heterogeneous appearance in OCT images. The real-time changes in tissue were detected after onset of ablation. 29 tissue samples had early detection of crater formation and tissue disruption before any adverse effect could occur. The correlation and attenuation coefficients of necrotic tissue were significantly smaller than viable tissue (p<0.01). Using OCT imaging, healthy endocardium and myocardium can be readily distinguished from necrotic tissue produced by RFA. This real-time monitoring may guide ablation by allowing the operator to see ablated tissue before an adverse event can occur.

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