scholarly journals Modular assembly of thick multifunctional cardiac patches

2017 ◽  
Vol 114 (8) ◽  
pp. 1898-1903 ◽  
Author(s):  
Sharon Fleischer ◽  
Assaf Shapira ◽  
Ron Feiner ◽  
Tal Dvir
Keyword(s):  
Cardiac Tissue ◽  
Electrospun Fiber ◽  
Signal Propagation ◽  
Electrical Signal ◽  
Modular Assembly ◽  
Cardiac Tissues ◽  
Structure Morphology ◽  
Biomaterial Scaffolds ◽  
Fiber Scaffolds ◽  
And Function

In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac tissues exhibiting anisotropic electrical signal propagation. Microchannels were patterned within the scaffolds and seeded with endothelial cells to form closed lumens. Moreover, cage-like structures were patterned within the scaffolds and accommodated poly(lactic-co-glycolic acid) (PLGA) microparticulate systems that controlled the release of VEGF, which promotes vascularization, or dexamethasone, an anti-inflammatory agent. The structure, morphology, and function of each layer were characterized, and the tissue layers were grown separately in their optimal conditions. Before transplantation the tissue and microparticulate layers were integrated by an ECM-based biological glue to form thick 3D cardiac patches. Finally, the patches were transplanted in rats, and their vascularization was assessed. Because of the simple modularity of this approach, we believe that it could be used in the future to assemble other multicellular, thick, 3D, functional tissues.

Biophysical stimulation for in vitro engineering of functional cardiac tissues

2017 ◽  
Vol 131 (13) ◽  
pp. 1393-1404 ◽  
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.

3D bioprinted and integrated platforms for cardiac tissue modeling and drug testing

2021 ◽  
Author(s):  
Uijung Yong ◽  
Byeongmin Kang ◽  
Jinah Jang
Keyword(s):  
Electrical Properties ◽  
Real Time ◽  
Drug Testing ◽  
Cardiac Tissue ◽  
The Body ◽  
Cardiac Tissues ◽  
Tissue Modeling ◽  
Recent Trends ◽  
Cardiac Models ◽  
And Function

Abstract Recent advances in biofabrication techniques, including 3D bioprinting, have allowed for the fabrication of cardiac models that are similar to the human heart in terms of their structure (e.g., volumetric scale and anatomy) and function (e.g., contractile and electrical properties). The importance of developing techniques for assessing the characteristics of 3D cardiac substitutes in real time without damaging their structures has also been emphasized. In particular, the heart has two primary mechanisms for transporting blood through the body: contractility and an electrical system based on intra and extracellular calcium ion exchange. This review introduces recent trends in 3D bioprinted cardiac tissues and the measurement of their structural, contractile, and electrical properties in real time. Cardiac models have also been regarded as alternatives to animal models as drug-testing platforms. Thus, perspectives on the convergence of 3D bioprinted cardiac tissues and their assessment for use in drug development are also presented.

Coiled fiber scaffolds embedded with gold nanoparticles improve the performance of engineered cardiac tissues

Nanoscale ◽  
2014 ◽  
Vol 6 (16) ◽  
pp. 9410-9414 ◽  
Author(s):  
Sharon Fleischer ◽  
Michal Shevach ◽  
Ron Feiner ◽  
Tal Dvir
Keyword(s):  
Gold Nanoparticles ◽  
Cardiac Tissue ◽  
Cardiac Tissues ◽  
Fiber Scaffolds ◽  
Coiled Fiber

We report here on the fabrication of coiled fiber scaffolds incorporated with gold nanoparticles for improved cardiac tissue performance.

scholarly journals Endurance Training Regulates Expression of Some Angiogenesis-Related Genes in Cardiac Tissue of Experimentally Induced Diabetic Rats

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 498
Author(s):  
Mojdeh Khajehlandi ◽  
Lotfali Bolboli ◽  
Marefat Siahkuhian ◽  
Mohammad Rami ◽  
Mohammadreza Tabandeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endurance Training ◽  
Molecular Mechanisms ◽  
Cardiac Tissue ◽  
Critical Role ◽  
Diabetic Rats ◽  
Moderate Intensity ◽  
Pcr Analysis ◽  
Cardiac Tissues ◽  
The Impact

Exercise can ameliorate cardiovascular dysfunctions in the diabetes condition, but its precise molecular mechanisms have not been entirely understood. The aim of the present study was to determine the impact of endurance training on expression of angiogenesis-related genes in cardiac tissue of diabetic rats. Thirty adults male Wistar rats were randomly divided into three groups (N = 10) including diabetic training (DT), sedentary diabetes (SD), and sedentary healthy (SH), in which diabetes was induced by a single dose of streptozotocin (50 mg/kg). Endurance training (ET) with moderate-intensity was performed on a motorized treadmill for six weeks. Training duration and treadmill speed were increased during five weeks, but they were kept constant at the final week, and slope was zero at all stages. Real-time polymerase chain reaction (RT-PCR) analysis was used to measure the expression of myocyte enhancer factor-2C (MEF2C), histone deacetylase-4 (HDAC4) and Calmodulin-dependent protein kinase II (CaMKII) in cardiac tissues of the rats. Our results demonstrated that six weeks of ET increased gene expression of MEF2C significantly (p < 0.05), and caused a significant reduction in HDAC4 and CaMKII gene expression in the DT rats compared to the SD rats (p < 0.05). We concluded that moderate-intensity ET could play a critical role in ameliorating cardiovascular dysfunction in a diabetes condition by regulating the expression of some angiogenesis-related genes in cardiac tissues.

scholarly journals Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration

2020 ◽  
Vol 8 (1) ◽  
pp. 4
Author(s):  
Devan L. Puhl ◽  
Jessica L. Funnell ◽  
Derek W. Nelson ◽  
Manoj K. Gottipati ◽  
Ryan J. Gilbert
Keyword(s):  
Nervous System ◽  
Glial Cell ◽  
Cell Response ◽  
Electrospun Fiber ◽  
Neural Regeneration ◽  
Cell Phenotype ◽  
Comprehensive Overview ◽  
Fiber Alignment ◽  
Wide Range ◽  
Fiber Scaffolds

Electrospinning is a fabrication technique used to produce nano- or micro- diameter fibers to generate biocompatible, biodegradable scaffolds for tissue engineering applications. Electrospun fiber scaffolds are advantageous for neural regeneration because they mimic the structure of the nervous system extracellular matrix and provide contact guidance for regenerating axons. Glia are non-neuronal regulatory cells that maintain homeostasis in the healthy nervous system and regulate regeneration in the injured nervous system. Electrospun fiber scaffolds offer a wide range of characteristics, such as fiber alignment, diameter, surface nanotopography, and surface chemistry that can be engineered to achieve a desired glial cell response to injury. Further, electrospun fibers can be loaded with drugs, nucleic acids, or proteins to provide the local, sustained release of such therapeutics to alter glial cell phenotype to better support regeneration. This review provides the first comprehensive overview of how electrospun fiber alignment, diameter, surface nanotopography, surface functionalization, and therapeutic delivery affect Schwann cells in the peripheral nervous system and astrocytes, oligodendrocytes, and microglia in the central nervous system both in vitro and in vivo. The information presented can be used to design and optimize electrospun fiber scaffolds to target glial cell response to mitigate nervous system injury and improve regeneration.

Abstract MP216: Identification Of Novel Phosphoprotein Signaling Pathways In Human Dilated Cardiomyopathy By Integrative Proteomic And Phosphoproteomic Analysis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Cristine J Reitz ◽  
Marjan Tavassoli ◽  
Da Hye Kim ◽  
Sina Hadipour-Lakmehsari ◽  
Saumya Shah ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Cardiac Tissue ◽  
Regulatory Element ◽  
Critical Role ◽  
Left Ventricular ◽  
Confocal Imaging ◽  
Intercalated Disc ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
And Function

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure, yet the majority of the underlying signaling mechanisms remain poorly characterized. Protein phosphorylation is a key regulatory element with profound effects on the activity and function of signaling networks; however, there is a lack of comprehensive phosphoproteomic studies in human DCM patients. We assessed the hypothesis that an integrative phosphoproteomics analysis of human DCM would reveal novel phosphoprotein candidates involved in disease pathophysiology. Combined proteomic and phosphoproteomic analysis of explanted left ventricular tissue samples from DCM patients ( n =4) and non-failing controls ( n =4) identified 5,570 unique proteins with 13,624 corresponding phosphorylation sites. From these analyses, we identified αT-catenin as a unique candidate protein with a cluster of 4 significantly hyperphosphorylated sites in DCM hearts ( P <0.0001), with no change in total αT-catenin expression at the protein level. Bioinformatics analyses of human datasets and confocal imaging of human and mouse cardiac tissue show highly cardiac-enriched expression of αT-catenin, localized to the cardiomyocyte intercalated disc. High resolution 3-dimensional reconstruction shows elongated intercalated disc morphology in DCM hearts (10.07±0.76 μm in controls vs. 17.20±1.87 μm in DCM, P <0.05, n =3/group), with significantly increased colocalization of αT-catenin with the intercalated disc membrane protein N-cadherin (Pearson’s coefficient 0.55±0.04 in controls vs. 0.71±0.02 in DCM, P <0.05, n =3/group). To investigate the functional role of cardiac αT-catenin phosphorylation, we overexpressed WT protein vs. non-phosphorylatable forms based on the loci identified in DCM hearts, in adult mouse cardiomyocytes using lentiviral transduction. Confocal imaging revealed significant internalization of the phospho-null form, as compared to the prominent intercalated disc staining of the WT protein (17.78±0.79% of WT vs. 9.25±0.49% of 4A mutant, P <0.0001, n =50 cells/group). Together, these findings suggest a critical role for αT-catenin phosphorylation in maintaining cardiac intercalated disc organization in human DCM.

Abstract 126: Peroxisomal Proliferator Activated Receptor Alpha Overexpression in Hypertrophied Cardiomyocytes Restores Mitochondrial Integrity and Function

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sagartirtha Sarkar ◽  
Santanu Rana
Keyword(s):  
Energy Demand ◽  
Cardiac Tissue ◽  
Structural Integrity ◽  
Heart Function ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atp Production ◽  
Receptor Alpha ◽  
And Function

Cardiac tissue engineering is an interdisciplinary field that engineers modulation of viable molecular milieu to restore, maintain or improve heart function. Myocardial workload (energy demand) and energy substrate availability (supply) are in continual flux to maintain specialized cellular processes, yet the heart has a limited capacity for substrate storage and utilization during pathophysiological conditions. Damage to heart muscle, acute or chronic, leads to dysregulation of cardiac metabolic processes associated with gradual but progressive decline in mitochondrial respiratory pathways resulting in diminished ATP production. The Peroxisome Proliferator Activated Receptor Alpha ( PPARα ) is known to regulate fatty acid to glucose metabolic balance as well as mitochondrial structural integrity. In this study, a non-canonical pathway of PPARα was analyzed by cardiomyocyte targeted PPARα overexpression during cardiac hypertrophy that showed significant downregulation in p53 acetylation as well as GSK3β activation levels. Targeted PPARα overexpression during hypertrophy resulted in restoration of mitochondrial structure and function along with significantly improved mitochondrial ROS generation and membrane potential. This is the first report of myocyte targeted PPARα overexpression in hypertrophied myocardium that results in an engineered heart with significantly improved function with increased muscle mitochondrial endurance and reduced mitochondrial apoptotic load, thus conferring a greater resistance to pathological stimuli within cardiac microenvironment.

Abstract 14201: The Application of Hipsc-derived Cardiomyocytes Paced by Re-entrant Waves for Drug Assessment

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Junjun Li ◽  
Itsunari Minami ◽  
Shigeru Miyagawa ◽  
Xiang Qu ◽  
YING HUA ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Troponin T ◽  
Field Potential ◽  
Electrical Signal ◽  
Assessment System ◽  
K Channel ◽  
Control Group ◽  
Culture Dish ◽  
Robust Response

Introduction: How to precisely evaluate response in newly developed medications in vitro may be a great concern in drug screening. We modified normal low-attachment culture dish and created closed-loop tissue ring from single hiPSC-CMs. We hypothesized that the re-entrant wave (ReW) could originate and pace the cardiac tissue ring, and the CMs under pacing could be matured and used for drug assessment. Methods: PDMS wells and pillars were mounted in low-attachment petri dishes (Figure 1A). 4 х 10 5 hiPSC-CMs were plated into the wells to form tissue ring where the ReW could spontaneously originate. After cultivation for 14 days, the hiPSC-CMs were evaluated by immunostaining and gene expression. Micro electrode array (MEA) were used to evaluating the CM response to different drugs. Results: The electrical signal recorded by MEA indicated that the ReWs could make the CMs beat at a much higher rate than the Control group (Figure 1B, 123.26 ± 10.36 bpm vs. 14.08 ± 4.53 bpm, p<0.0001). After 14 day culture, the ReW group demonstrated significantly higher expression of Troponin T (TnT2), myosin heavy chain 7 (β-MHC), and α-actinin. Interestingly, the α-actinin staining indicated alignment of CMs within the ReW group (Figure 1C). The CMs under ReW pacing showed robust response to several cardiac compounds including E4031, (hERG K+ channel blocker, Figure 1D and E), isoproterenol (β adrenoceptor agonist) and propranolol (beta-blocker). Both the field potential as well as the Ca 2+ transients showed correlated dose-dependent change and the recovering after washout of the drugs. Conclusions: The ReWs could spontaneously originate in the cultured cardiac tissue ring with enhancement of the maturation in the hiPSC-CMs and robust response to various drugs, indicating the system as a robust drug assessment system with multiple read-out methods.

Abstract 37: Nrip Deficiency Leads to Dilated Cardiomyopathy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Show-Li Chen
Keyword(s):  
Calcium Transient ◽  
Receptor Interaction ◽  
Cell Width ◽  
Interacting Protein ◽  
Cardiac Tissues ◽  
Calmodulin Binding ◽  
Calcineurin Phosphatase ◽  
And Function

Previously, we demonstrate a gene, nuclear receptor interaction protein (NRIP, also named DCAF6 or IQWD1) as a Ca2+- dependent calmodulin binding protein that can activate calcineurin phosphatase activity. Here, we found that α-actinin-2 (ACTN2), is one of NRIP-interacting proteins from the yeast two-hybrid system using NRIP as a prey. We further confirmed the direct bound between NRIP and ACTN2 using in vitro protein-protein interaction and in vivo co-immunoprecipitation assays. To further map the binding domain of each protein, the results showed the IQ domain of NRIP responsible for ACTN2 binding, and EF hand motif of ACTN2 responsible for NRIP bound. Due to ACTN2 is a biomarker of muscular Z-disc complex; we found the co-localization of NRIP and ACTN2 in cardiac tissues by immunofluorescence assays. Taken together, NRIP is a novel ACTN2-interacting protein. To investigate insights into in vivo function of NRIP, we generated conventional NRIP-null mice. The H&E staining results are shown in the hearts of NRIP KO mice are enlarged and dilated and the cell width of NRIP KO cardiomyocyte is increased. The EM of NRIP KO heart muscles reveal the reduction of I-band width and extension length of Z-disc in sarcomere structure; and the echocardiography shows the diminished fractional shortening in heart functions. Additionally, the calcium transient and sarcomere contraction length in cardiomyocytes of NRIP KO is weaker and shorter than wt; respectively. In conclusion, NRIP is a novel Z-disc protein and has function for maintenance of sarcomere integrity structure and function for calcium transient and muscle contraction.

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