Cardiac Tissue Structure Research Articles

Comparison of the histology and stiffness of ventricles in Anura of different habitats

Vertebrate hearts have undergone marked morphological and structural changes to adapt to different environments and lifestyles as part of the evolutionary process. Amphibians were the first vertebrates to migrate to land. Transition from aquatic to terrestrial environments required the ability to circulate blood against the force of gravity. In this study, we investigated the passive mechanical properties and histology of the ventricles of three species of Anura (frogs and toads) from different habitats, Xenopus laevis (aquatic), Pelophylax nigromaculatus (semiaquatic), and Bufo japonicus formosus (terrestrial). Pressure-loading tests demonstrated stiffer ventricles of P. nigromaculatus and B. j. formosus compared X. laevis ventricles. Histological analysis revealed a remarkable difference in the structure of cardiac tissue: thickening of the compact myocardium layer of P. nigromaculatus and B. j. formosus and enrichment of the collagen fibers of B. j. formosus. The amount of collagen fibers differed among the species, as quantitatively confirmed by second-harmonic generation light microscopy. No significant difference was observed in cardiomyocytes isolated from each animal, and the sarcomere length was almost the same. The results indicate that the ventricles of Anura stiffen during adaptation to life on land.

Understanding the molecular role of syndecan-1 in the regulation of caspase-6 during the progression of cardiac arrhythmia.

The role of caspase-6 in heart disease is not well understood, particularly with respect to cardiac arrhythmia. Also, the function of syndecan-1 in the stimulation of inflammation or a regenerative response after cardiac injury is unclear. Leptin receptor-deficient (C57BL/KS-leprdb/leprdb) mice were used in the present study. In addition to developing type 2 diabetes, they also develop initial- and end-stage cardiac arrhythmia after 5 and 8 months, respectively. The initial and end-stage arrhythmias were confirmed through progressive variations in the PP intervals observable in electrocardiograms. Histopathological images of the cardiac tissue exhibited scattered and loosened cardiac cells at the initial stage of cardiac arrhythmia, whereas tissue hardness and extensive structural changes in cardiomyocytes were evident at the end stage. At the molecular level, the progressive upregulation of caspase-6 was observed as the cardiac arrhythmia progressed. In the initial stage of arrhythmia, immunohistochemistry revealed that caspase-6 was expressed at the surface of cardiac cells, suggesting that caspase-6 targeted the extracellular matrix, leading to a loosening of the cardiac tissue structure. In the end stage of cardiac arrhythmia, caspase-6 expression was abundant in the cytoplasm, as well as at the cell surface, suggesting that caspase-6 may have cleaved intermediate filaments, paving the way for cellular morphological changes and apoptosis. Notably, syndecan-1 was upregulated 5.8-fold in the initial stage of cardiac arrhythmia, but downregulated at the end stage. Syndecan-1 may restrict the expression of caspase-6 in the initial stage of cardiac arrhythmia, while its downregulation at the end stage may allow destructive changes via caspase-6 overexpression. Furthermore, the knockdown of syndecan-1 using small interfering RNA enhanced the expression of caspase-6 in the cardiac tissue by factors of 1.8 and 1.2 at the initial and end stages of cardiac arrhythmia, respectively, compared with that in non-silenced cardiac tissue. Therefore, it may be concluded that syndecan-1 plays a major role in the regulation of caspase-6 during the pathological stages of cardiac arrhythmia.

Mimicking cardiac tissue complexity through physical cues: A review on cardiac tissue engineering approaches

Cardiovascular diseases are the number one killer in the world.1,2 Currently, there are no clinical treatments to regenerate damaged cardiac tissue, leaving patients to develop further life-threatening cardiac complications. Cardiac tissue has multiple functional demands including vascularization, contraction, and conduction that require many synergic components to properly work. Most of these functions are a direct result of the cardiac tissue structure and composition, and, for this reason, tissue engineering strongly proposed to develop substitute engineered heart tissues (EHTs). EHTs usually have combined pluripotent stem cells and supporting scaffolds with the final aim to repair or replace the damaged native tissue. However, as simple as this idea is, indeed, it resulted, after many attempts in the field, to be very challenging. Without design complexity, EHTs remain unable to mature fully and integrate into surrounding heart tissue resulting in minimal in vivo effects.3 Lately, there has been a growing body of evidence that a complex, multifunctional approach through implementing scaffold designs, cellularization, and molecular release appears to be essential in the development of a functional cardiac EHTs.4–6 This review covers the advancements in EHTs developments focusing on how to integrate contraction, conduction, and vascularization mimics and how combinations have resulted in improved designs thus warranting further investigation to develop a clinically applicable treatment.

Repercussions of pathway inhibition response of Panaxginseng fractions ameliorate cardiac dysfunction in hypertensive model rats

This study examined the preventive and therapeutic benefits of various Panax ginseng fractions against NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension in rats. Rats injected with L-NAME plus vehicle exhibited persistently elevated SBP, serum concentrations of the cardiac injury biomarkers creatine kinase (CK), CK-MB, and troponin, total cholesterol, triglyceride (TG), low-density lipoprotein (LDL), and interleukin (IL)-6, but lower high-density lipoprotein (HDL) compared to the vehicle control group. Furthermore, L-NAME disrupted the normal histological structure and function of rat cardiac tissue. All ginseng fractions and losartan restored SBP to a normal level, reversed the changes in CK, CK-MB, troponin, total cholesterol, TG, HDL, and LDH, and preserved normal myocardial histology, with the WGF demonstrating the greatest cardioprotective and antihypertensive effects. Compounds within multiple ginseng fractions, but especially the aqueous fraction, possess potent and effective antihypertensive, antilipidemic, anti-inflammatory, and cardioprotective properties.

Proanthocyanidin alleviates doxorubicin-induced cardiac injury by inhibiting NF-kB pathway and modulating oxidative stress, cell cycle, and fibrogenesis.

This study investigated the potential mechanism(s) and the signaling pathway(s) underlying the prophylactic effect of proanthocyanidin extract (PE) against doxorubicin (DOX)-induced cardiotoxicity in rats. A total of 32 male albino rats were randomly allocated into four groups. Control rats were orally administrated normal saline. Rats in the second group were orally administrated PE (50 mg/kg bw/once daily) for 4 weeks. Rats in the third group were intraperitoneally injected with DOX (10 mg/kg on Days 3, 9, 15, and 21 of the experiment). Rats in the fourth group were injected with DOX and PE simultaneously for 4 weeks. DOX significantly augmented the levels of serum heart damage biomarkers. In addition, histopathology indicated that DOX-induced cardiac tissue injury upregulated the expression of fibrogenic factors, alpha smooth muscle actin (α-SMA), transforming growth factor β1 (TGF- β1), and p16INK4A . Downregulation of cell proliferation markers, cyclin-dependent kinase-4 (CDK4), and retinoblastoma (Rb) was also observed. Furthermore, DOX-induced oxidative and inflammatory stress resulted in increased cardiac malondialdehyde (MDA), protein carbonyl (PC), interleukin-2 (IL-2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Decreased cardiac glutathione (GSH) levels and enzyme activity of catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) were observed. Treatment of DOX-induced rat cardiotoxicity with PE normalized serum parameters for the aforementioned parameters and alleviated cardiac tissue structure. Furthermore, reduced cardiac tissue α-SMA and TGF-β1, and increased CDK4 and Rb protein expression, along with the amelioration of oxidative and inflammatory effects were observed. PE attenuates DOX-induced cardiomyocyte inflammation possibly by attenuating the nuclear factor kappa-B (NF- kB) signaling pathway. These results indicate that PE may be useful as a preventative agent against DOX-induced cardiac toxicity.

Evolving roles of cardiac fibroblasts in cardiogenesis and immunology, electrophysiology, and aging.

Cardiac fibroblasts (CFs), one of the major groups of cardiac cells, play a prominent role in the cardiac microenvironment through communicating with other cells such as cardiomyocytes, endothelial cells and immune cells. These communications are required not only during cardiac development but also during pathogenesis. CFs are also involved in developmental changes in the post-natal and pre-natal heart through depositing extra cellular matrix (ECM) and maintaining cardiac tissue structure. Furthermore, CFs show both detrimental and beneficial effects in maintenance of the electrophysiology of the heart. Senescent CFs in the cardiac microenvironment influence other cardiac cells through paracrine signaling, which would worsen or cure the diseases. Therefore, there is a need of exclusive study on CFs' role in the developmental stage of the heart, electrophysiology, and senescence. This review discusses the current research about CFs' function, especially the CFs' role in cardiac development, electrophysiology, and senescence, and proposes a certain gap filling future prospective.

X-ray diffraction and second harmonic imaging reveal new insights into structural alterations caused by pressure-overload in murine hearts

We demonstrate a label-free imaging approach to study cardiac remodeling of fibrotic and hypertrophic hearts, bridging scales from the whole organ down to the molecular level. To this end, we have used mice subjected to transverse aortic constriction and imaged adjacent cardiac tissue sections by microfocus X-ray diffraction and second harmonic generation (SHG) imaging. In this way, the acto-myosin structure was probed in a spatially resolved manner for entire heart sections. From the recorded diffraction data, spatial maps of diffraction intensity, anisotropy and orientation were obtained, and fully automated analysis depicted the acto-myosin filament spacing and direction. X-ray diffraction presented an overview of entire heart sections and revealed that in regions of severe cardiac remodeling the muscle mass is partly replaced by connective tissue and the acto-myosin lattice spacing is increased at these regions. SHG imaging revealed sub-cellular structure of cardiac tissue and complemented the findings from X-ray diffraction by revealing micro-level distortion of myofibrils, immune cell infiltration at regions of cardiac remodeling and the development of fibrosis down to the scale of a single collagen fibril. Overall, our results show that both X-ray diffraction and SHG imaging can be used for label-free and high-resolution visualization of cardiac remodeling and fibrosis progression at different stages in a cardiac pressure-overload mouse model that cannot be achieved by conventional histology.

Donor and Recipient Characteristics in Heart Transplantation Are Associated with Altered Myocardial Tissue Structure and Cardiac Function

To use structure-function cardiac MRI in the evaluation of relationships between donor and heart transplantation (HTx) recipient characteristics and changes in cardiac tissue structure and function. HTx candidates and donor hearts are evaluated for donor-recipient matches to improve survival, but the impact of donor and recipient characteristics on changes in myocardial tissue and function in the transplanted heart is not fully understood. Cardiac MRI at 1.5 T was performed from August 2014 to June 2017 in 58 HTx recipients (mean age, 51.1 years ± 12.6 [standard deviation], 26 female patients) and included T2 mapping (to evaluate edematous and/or inflammatory changes), precontrast and postcontrast T1 mapping (allowing the calculation of extracellular volume fraction [ECV] to estimate interstitial expansion), and tissue phase mapping (allowing the calculation of myocardial velocities and twist). Donor and recipient demographics (age, sex, height, weight, and body mass index [BMI]) and comorbidities (hypertension, diabetes, and smoking history) were evaluated for relationships with cardiac MRI measures. Sex-influenced cardiac MRI measures of myocardial tissue and function are as follows: Female HTx recipients demonstrated increased precontrast T1 (P = .002) and reduced systolic peak long-axis velocities (P = .015). Increased age of the donor heart was associated with elevated T2 (r = 0.32; P < .05) and ECV (r = 0.47; P < .01), indicating increased edema and interstitial expansion, as well as impaired diastolic peak long-axis velocities (r = 0.41; P < .01). Recipient-donor differences in age, weight, and BMI were significantly associated with elevated ECV (r = 0.36-0.48; P < .05). Hypertension in donors resulted in increased ECV (31.0% ± 4.2 vs 26.0% ± 3.3; P = .001). Donor and HTx recipient characteristics were significantly associated with cardiac MRI-derived measures of myocardial tissue structure and function.© RSNA, 2019.

Characterization of the human myocardium by optical coherence tomography.

Imaging of cardiac tissue structure plays a critical role in the treatment and understanding of cardiovascular disease. Optical coherence tomography (OCT) offers the potential to provide valuable, high-resolution imaging of cardiac tissue. However, there is a lack of comprehensive OCT imaging data of the human heart, which could improve identification of structural substrates underlying cardiac abnormalities. The objective of this study was to provide qualitative and quantitative analysis of OCT image features throughout the human heart. Fifty human hearts were acquired, and tissues from all chambers were imaged with OCT. Histology was obtained to verify tissue composition. Statistical differences between OCT image features corresponding to different tissue types and chambers were estimated using analysis of variance. OCT imaging provided features that were able to distinguish structures such as thickened collagen, as well as adipose tissue and fibrotic myocardium. Statistically significant differences were found between atria and ventricles in attenuation coefficient, and between adipose and all other tissue types. This study provides an overview of OCT image features throughout the human heart, which can be used for guiding future applications such as OCT-integrated catheter-based treatments or ex vivo investigation of structural substrates.

Toxicity Effects of Intraperitoneal Injection of Biochemical Nanosilver on Cardiac Tissue Structure Following Aerobic Training in Male Wistar Rats

Aims Silver nanoparticles are among the most valuable products of nanoscale technology, widely used in various sciences. The present study investigated the effects of biochemical silver nanoparticles on the structure of the heart tissue of non-observatory rats in the course of aerobic training. Methods &amp; Materials In this experimental study, 30 male Wistar rats aged 8 to 12 weeks and weighing 34.9±202 g were studied. The rats were randomly divided into 6 groups of control, aerobic training, aerobic training, and nanobiological injection, aerobic and-nanochemical injection, nanobiological injection, and nanochemical injection. Chemical and biological silver was injected intraperitoneally after a period of aerobic training. The specimens were discarded after 48 hours, and the heart tissue was removed. Findings The obtained results revealed the tissue changes, including irregularities and the convergence of chemical nanosilver group significantly increased, compared to the controls. Additionally, in the biological group, there was a slight dispersion of blood in some areas. Following the aerobic training and injection of toxic nanosilver, there was no irregularities, detachment, and hypertension. Only in some areas, sporadically, the accumulation of blood cells was observed in the aerobic training and nanochemical groups. Conclusion More tissue damage occurred in chemical silver nanoparticles, than the biological nanoparticle. Possibly, aerobic training can be highly predictive of these effects.

Reduced graphene oxide–reinforced gellan gum thermoresponsive hydrogels as a myocardial tissue engineering scaffold

Myocardial infarction is one of the most prevalent diseases around the world. Cardiac tissue engineering is a new approach to repair and revive the structure and functionality of cardiac damaged tissue. In this study, gellan gum/reduced graphene oxide composite hydrogels were fabricated, characterized, and evaluated. The hydrogels were prepared using the solvent casting method and characterized via scanning electron microscopy and Fourier-transform infrared spectroscopy. Compressive mechanical analysis, injectability as well as electrical conductivity test were run. Furthermore, water swelling and degradation analyses were conducted. MTT assay was performed using rat myoblasts (H9C2) to determine the cytotoxicity of our samples. Results showed that reduced graphene oxide fillers dispersed acceptably and enhanced the compressive modulus and electrical conductivity of gellan gum hydrogels. However, in this regard, compressive strength and ductility were not significantly boosted with reduced graphene oxide addition. The water-swelling ratio (%) rised in the presence of reduced graphene oxide, whereas the degradation rate was not significantly affected by them. Meanwhile, synthesized hydrogels showed suitable injectability. MTT assay results revealed that gellan gum hydrogels containing 1% and 2% reduced graphene oxide were not cytotoxic. According to the findings, gellan gum/2% reduced graphene oxide composite hydrogel can be a promising candidate for repairing and healing infarcted myocardial tissue.

Optical coherence tomography imaging of cardiac substrates.

Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Knowledge of a patient's heart structure will help to plan procedures, potentially identifying arrhythmia substrates, critical structures to avoid, detect transplant rejection, and reduce ambiguity when interpreting electrograms and functional measurements. Similarly, basic research of numerous cardiac diseases would greatly benefit from structural imaging at cellular scale. For both applications imaging on the scale of a myocyte is needed, which is approximately 100 µm × 10 µm. The use of optical coherence tomography (OCT) as a tool for characterizing cardiac tissue structure and function has been growing in the past two decades. We briefly review OCT principles and highlight important considerations when imaging cardiac muscle. In particular, image penetration, tissue birefringence, and light absorption by blood during in vivo imaging are important factors when imaging the heart with OCT. Within the article, we highlight applications of cardiac OCT imaging including imaging heart tissue structure in small animal models, quantification of myofiber organization, monitoring of radiofrequency ablation (RFA) lesion formation, structure-function analysis enabled by functional extensions of OCT and multimodal analysis and characterizing important substrates within the human heart. The review concludes with a summary and future outlook of OCT imaging the heart, which is promising with progress in optical catheter development, functional extensions of OCT, and real time image processing to enable dynamic imaging and real time tracking during therapeutic procedures.

CARDIOPROTECTIVE EFFECT OF DATE PALM AGAINST DOXORUBICIN-INDUCED CARDIOTOXICITY

Objective: Doxorubicin (Dox), an anthracycline antibiotic, has been widely used to treat cancer, principally hematological malignancies, and solid tumors. The administration of Dox is a topic of concern in the medical community, as it frequently related to dose-dependent cardiotoxicity. Therefore, the present study was designed to investigate the protective potential of date palm fruit extract on Dox-induced cardiotoxicity.Methods: A total of 40 female albino rats were used in this study and classified into four groups including control, date palm fruit extract, Dox, and treated date palm fruit extract groups.Results: Dox produced a significant increase in creatine kinase-MB and lactate dehydrogenase activities. It also decreased the activities of cardiac glutathione peroxidase and superoxide dismutase but increase levels of cardiac malondialdehyde and also of urinary 8-hydroxy-2-deoxyguanosine. Myocardial toxicity of Dox also appeared in the elevation of serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels, while level of high-density lipoprotein cholesterol decreased. Histopathological studies revealed alteration of cardiac tissue structure by Dox. Treatment with date palm fruit extract restored the aforementioned parameters.Conclusion: Date palm fruit exhibits a cardioprotective influence on the heart tissue against toxicity induced by Dox.

Quantitative descriptions of extended volume cardiac tissue architecture from multiple large hearts.

The arrangement of cardiac cells into strand and sheet-like structures within the heart wall, confers important electrical properties onto heart tissue. Unraveling cardiomyocyte architecture in both healthy and diseased hearts is fundamental to understanding the mechanisms generating normal rhythm and arrhythmia. We analyzed five extended volume serial image stacks of normal pig left ventricular tissue. Analysis included: (1) reconstruction of original tissue volume and shape with non-linear correction maps; (2) segmentation and higher-order descriptions, areas and orientations of laminar structures through the heart wall; (3)computation of fiber directions; (4) computation of tissue connectivity using a shell filter. These measures contributed to a deeper and more objective understanding of cardiac tissue structures and their spatial variation than previously possible.

Cytoskeleton structure and total methylation of mouse cardiac and lung tissue during space flight.

The purpose of this work was to evaluate the protein and mRNA expression levels of multiple cytoskeletal proteins in the cardiac and lung tissue of mice that were euthanized onboard the United States Orbital Segment of the International Space Station 37 days after the start of the SpaceX-4 mission (September 2014, USA). The results showed no changes in the cytoskeletal protein content in the cardiac and lung tissue of the mice, but there were significant changes in the mRNA expression levels of the associated genes, which may be due to an increase in total genome methylation. The mRNA expression levels of DNA methylases, the cytosine demethylases Tet1 and Tet3, histone acetylase and histone deacetylase did not change, and the mRNA expression level of cytosine demethylase Tet2 was significantly decreased.

Downregulation of P2Y12 in the superior cervical ganglia alleviates abnormal sympathetic activity after myocardial ischemia.

Superior cervical ganglia (SCG) innervate the myocardium and participate in sympathoexcitatory transmission. P2Y12 receptor is expressed in satellite glial cells (SGCs). This study seeks to clarify whether the P2Y12 receptor is involved in the sympathoexcitation reflex after myocardial ischemia (MI). MI model was induced by occlusion of the left coronary artery. P2Y12 were assayed by real time PCR and Western blotting. Our results showed that expression levels of P2Y12 mRNA and protein were significantly higher in the MI group than in the sham group. Administration of P2Y12 short hairpin RNA (shRNA) caused downregulation of the P2Y12 receptor in the SCG. In MI rats plus P2Y12 shRNA treatment group, the abnormal changes in diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR), electrocardiograms (ECGs), and cardiac tissue structures were alleviated. When the treatment of P2Y12 shRNA in MI rats, upregulated co-expression values of P2Y12 and glial fibrillary acidic protein (GFAP), the upregulation of tumor necrosis factor α (TNF-α) and phosphorylated P38 mitogen activated protein kinase (p-P38 MAPK) in the SCG were decreased. Downregulation of the P2Y12 receptor in the SCG after MI may improve cardiac function by alleviating the sympathoexcitatory reflex.

Virtual cardiac monolayers for electrical wave propagation

The complex structure of cardiac tissue is considered to be one of the main determinants of an arrhythmogenic substrate. This study is aimed at developing the first mathematical model to describe the formation of cardiac tissue, using a joint in silico–in vitro approach. First, we performed experiments under various conditions to carefully characterise the morphology of cardiac tissue in a culture of neonatal rat ventricular cells. We considered two cell types, namely, cardiomyocytes and fibroblasts. Next, we proposed a mathematical model, based on the Glazier-Graner-Hogeweg model, which is widely used in tissue growth studies. The resultant tissue morphology was coupled to the detailed electrophysiological Korhonen-Majumder model for neonatal rat ventricular cardiomyocytes, in order to study wave propagation. The simulated waves had the same anisotropy ratio and wavefront complexity as those in the experiment. Thus, we conclude that our approach allows us to reproduce the morphological and physiological properties of cardiac tissue.

Free-of-Acrylamide SDS-based Tissue Clearing (FASTClear) for three dimensional visualization of myocardial tissue

Several pathologic conditions of the heart lead to cardiac structural remodelling. Given the high density and the opaque nature of the myocardium, deep three dimensional (3D) imaging is difficult to achieve and structural analysis of pathological myocardial structure is often limited to two dimensional images and of thin myocardial sections. Efficient methods to obtain optical clearing of the tissue for 3D visualisation are therefore needed. Here we describe a rapid, simple and versatile Free-of-Acrylamide SDS-based Tissue Clearing (FASTClear) protocol specifically designed for cardiac tissue. With this method 3D information regarding collagen content, collagen localization and distribution could be easily obtained across a whole 300 µm-thick myocardial slice. FASTClear does not induce structural or microstructural distortion and it can be combined with immunostaining to identify the micro- and macrovascular networks. In summary, we have obtained decolorized myocardial tissue suitable for high resolution 3D imaging, with implications for the study of complex cardiac tissue structure and its changes during pathology.

Interwoven Aligned Conductive Nanofiber Yarn/Hydrogel Composite Scaffolds for Engineered 3D Cardiac Anisotropy.

Mimicking the anisotropic cardiac structure and guiding 3D cellular orientation play a critical role in designing scaffolds for cardiac tissue regeneration. Significant advances have been achieved to control cellular alignment and elongation, but it remains an ongoing challenge for engineering 3D cardiac anisotropy using these approaches. Here, we present a 3D hybrid scaffold based on aligned conductive nanofiber yarns network (NFYs-NET, composition: polycaprolactone, silk fibroin, and carbon nanotubes) within a hydrogel shell for mimicking the native cardiac tissue structure, and further demonstrate their great potential for engineering 3D cardiac anisotropy for cardiac tissue engineering. The NFYs-NET structures are shown to control cellular orientation and enhance cardiomyocytes (CMs) maturation. 3D hybrid scaffolds were then fabricated by encapsulating NFYs-NET layers within hydrogel shell, and these 3D scaffolds performed the ability to promote aligned and elongated CMs maturation on each layer and individually control cellular orientation on different layers in a 3D environment. Furthermore, endothelialized myocardium was constructed by using this hybrid strategy via the coculture of CMs on NFYs-NET layer and endothelial cells within hydrogel shell. Therefore, these 3D hybrid scaffolds, containing NFYs-NET layer inducing cellular orientation, maturation, and anisotropy and hydrogel shell providing a suitable 3D environment for endothelialization, has great potential in engineering 3D cardiac anisotropy.

Engineering Microphysiological Models of Human Cardiac and Skeletal Muscle Disease

Cardiovascular diseases are the leading cause of death in the United States. Furthermore, unforeseen cardiotoxicity is a prevalent reason for market withdrawal of pharmaceuticals. These two statistics highlight our limited mechanistic understanding of heart disease and our inadequate ability to predict the function of the human heart. One reason for these shortcomings is that researchers in academia and industry have been forced to rely on experimental models, such as rodents or basic cell culture systems, that lack relevance to native human heart tissue. In this talk, I will describe our efforts in engineering microphysiological models of human cardiac tissue as next‐generation platforms for cardiac disease modeling and drug screening. To build these platforms, our research group is focused on maturing and integrating three core technologies: (1) Enhancing the differentiation of human induced pluripotent stem cells (hiPSCs) into cardiac myocytes. Because mammalian cardiac myocytes are post‐mitotic, hiPSC‐derived cardiac myocytes are the only renewable source of human cardiac myocytes that are patient‐specific, which is especially important for modeling inherited cardiomyopathies. However, current cardiac differentiation protocols rely primarily on soluble factors and have limited efficiency and consistency. Thus, we are microfabricating cellular microenvironments designed to enhance the differentiation efficiency of cardiac myocytes from hiPSCs to expand the utility of these cells. (2) Engineering cellular microenvironments that mimic key features of native cardiac tissue. Native cardiac tissue is uniaxially aligned and surrounded by a compliant extracellular matrix. We are utilizing photolithography and tunable hydrogels to mimic key physical features of native cardiac tissue and determine their independent and synergistic effects on cardiac tissue structure and function. (3) Developing quantitative assays for characterizing essential functional outputs, such as contractility. The primary function of cardiac tissue is to contract to pump blood. Cardiac myocytes contract due to the release of calcium from the sarcoplasmic reticulum, which is triggered by depolarization of the plasma membrane. We have developed quantitative assays to measure both contractility and action potential propagation to determine how these parameters are affected by different pathological stimuli. In addition to cardiac tissue, I will also describe our recent efforts in extending our technologies to skeletal muscle tissue as new platforms for modeling human skeletal myopathies. Together, these microphysiological models of human striated muscle tissue have many applications in establishing human disease mechanisms and screening the functional effects of drugs with disease and patient specificity.Support or Funding InformationThis work is funded by the American Heart Association Scientist Development Grant 16SDG29950005, the Eli and Edythe Broad Foundation Innovation Award, the USC Viterbi School of Engineering, and the USC Women in Science and Engineering.