Biomimetic Microstructure Morphology in Electrospun Fiber Mats is Critical for Maintaining Healthy Cardiomyocyte Phenotype

Rath, Rutwik; Lee, Jung Bok; Tran, Truc‐Linh; Lenihan, Sean; Galindo, Cristi L.; Su, Yan; Absi, Tarek; Bellan, Leon M.; Sawyer, Douglas B.; Sung, Hak‐Joon

doi:10.1007/s12195-015-0412-9

Cited by 6 publications

(3 citation statements)

References 44 publications

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“…Studies have developed micropatterned grooves that enhanced cellular alignment and resulting CM maturity of 2D culture systems (Salick et al, 2014 ; Carson et al, 2016 ). Engineered nanofibrous scaffolds have been produced that mimic the natural fibrous cardiac ECM (Khan et al, 2015 ; Rath et al, 2016 ). 3D constructs have been created to promote CM alignment, such as the biowire technology (Nunes et al, 2013a ), and aligned and contiguous EHTs around flexible posts (Zhang et al, 2013 ; Hirt et al, 2014 ).…”

Section: Natural Engineering In Vitro Approaches Tmentioning

confidence: 99%

Naturally Engineered Maturation of Cardiomyocytes

Scuderi

Butcher

2017

Front. Cell Dev. Biol.

166

202

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Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte maturation. This information can then be utilized to develop natural engineering approaches that can emulate this fetal microenvironment and thus make prominent progress in pluripotent stem cell-derived maturity toward a more clinically relevant model for cardiac regeneration.

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Section: Natural Engineering In Vitro Approaches Tmentioning

confidence: 99%

Naturally Engineered Maturation of Cardiomyocytes

Scuderi

Butcher

2017

Front. Cell Dev. Biol.

166

202

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“…Heparin mimetics have also been used to include VEGF binding ability reflective of the functionality of heparan sulfate in the basement membrane [46, 47]. An electrospun poly(Ɛ-caprolactone) material with fiber diameters and arrangement designed to mimic the organization of healthy cECM was found to promote arrangement of cardiomyocytes and formation of organized actin/myosin bands compared to fibers arranged to mimic the ECM of a failing heart [48]. A Col I mimic which forms fibril-like structures and ultimately a hydrogel have also been created; however, to this point, the mimetic lacks cell-binding motifs and therefore is unlikely to be of much therapeutic benefit beyond a structural Band-Aid [49].…”

Section: In Vitro Control Systems To Evaluate Cell-cecm Interplay At mentioning

confidence: 99%

Cardiac Extracellular Matrix Modification as a Therapeutic Approach

Hall

Ogle

2018

Advances in Experimental Medicine and Biology

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The cardiac extracellular matrix (cECM) is comprised of proteins and polysaccharides secreted by cardiac cell types, which provide structural and biochemical support to cardiovascular tissue. The roles of cECM proteins and the associated family of cell surface receptor, integrins, have been explored in vivo via the generation of knockout experimental animal models. However, the complexity of tissues makes it difficult to isolate the effects of individual cECM proteins on a particular cell process or disease state. The desire to further dissect the role of cECM has led to the development of a variety of in vitro model systems, which are now being used not only for basic studies but also for testing drug efficacy and toxicity and for generating therapeutic scaffolds. These systems began with 2D coatings of cECM derived from tissue and have developed to include recombinant ECM proteins, ECM fragments, and ECM mimics. Most recently 3D model systems have emerged, made possible by several developing technologies including, and most notably, 3D bioprinting. This chapter will attempt to track the evolution of our understanding of the relationship between cECM and cell behavior from in vivo model to in vitro control systems. We end the chapter with a summary of how basic studies such as these have informed the use of cECM as a direct therapy.

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“…In addition to FBs, there exist structural extracellular proteins (e.g. collagens), which form the extracellular matrix (ECM) and affect the CM phenotype 2 . The latter is essential for proper mechanical functioning of the heart 3 and for uninterrupted electrical signal propagation 4 .…”

Section: Introductionmentioning

confidence: 99%

Virtual cardiac monolayers for electrical wave propagation

Kudryashova

Tsvelaya

Agladze

et al. 2017

Sci Rep

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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.

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Biomimetic Microstructure Morphology in Electrospun Fiber Mats is Critical for Maintaining Healthy Cardiomyocyte Phenotype

Cited by 6 publications

References 44 publications

Naturally Engineered Maturation of Cardiomyocytes

Naturally Engineered Maturation of Cardiomyocytes

Cardiac Extracellular Matrix Modification as a Therapeutic Approach

Virtual cardiac monolayers for electrical wave propagation

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