AuNP–Collagen Matrix with Localized Stiffness for Cardiac‐Tissue Engineering: Enhancing the Assembly of Intercalated Discs by β1‐Integrin‐Mediated Signaling

Li, Yang; Shi, Xiaoli; Tian, Lei; Sun, Haiyan; Wu, Yujing; Li, Xia; Li, Jianjun; Wei, Yujie; Han, Xinxiao; Zhang, Jiao; Jia, Xiaowei; Bai, Rui; Jing, Limin; Ding, Peng; Liu, Huiliang; Han, Dong

doi:10.1002/adma.201603027

Cited by 78 publications

(69 citation statements)

References 31 publications

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“…The mechanistic study indicated that the integrin signaling pathway was involved in the modulation of CFs to the function of NRCMs. It has been demonstrated in literatures that the integrins not only act as a mechanosensors connecting the cytoskeleton to the extracellular matrix, but also play a central role in the regulation of cardiac electrical and mechanical junction proteins induced by mechanical stretch, and the β1‐integrin signaling pathway plays a role in conductive material–mediating cell–matrix interactions . It should be noted that PVA is a synthetic material and lacks sequences that are present in some biological macromolecules like gelatin and fibronectin.…”

Section: Discussionmentioning

confidence: 99%

High Modulus Conductive Hydrogels Enhance In Vitro Maturation and Contractile Function of Primary Cardiomyocytes for Uses in Drug Screening

Gao

Liu

et al. 2018

Adv Healthcare Materials

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Effective and quick screening and cardiotoxicity assessment are very crucial for drug development. Here, a novel composite hydrogel composed of carbon fibers (CFs) with high conductivity and modulus with polyvinyl alcohol (PVA) is reported. The conductivity of the composite hydrogel PVA/CFs is similar to that of natural heart tissue, and the elastic modulus is close to that of natural heart tissue during systole, due to the incorporation of CFs. PVA/CFs remarkably enhance the maturation of neonatal rat cardiomyocytes (NRCM) in vitro by upregulating the expression of α‐actinin, troponin T, and connexin‐43, activating the signaling pathway of α5 and β1 integrin‐dependent ILK/p‐AKT, and increasing the level of RhoA and hypoxia‐inducible factor‐1α. As a result, the engineered cell sheet–like constructs NRCM@PVA/CFs display much more synchronous, stable, and robust beating behavior than NRCM@PVA. When exposed to doxorubicin or isoprenaline, NRCM@PVA/CFs can retain effective beating for much longer time or change the contractile rate much faster than NRCM@PVA, respectively, therefore representing a promising heart‐like platform for in vitro drug screening and cardiotoxicity assessment.

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Section: Discussionmentioning

confidence: 99%

High Modulus Conductive Hydrogels Enhance In Vitro Maturation and Contractile Function of Primary Cardiomyocytes for Uses in Drug Screening

Gao

Liu

et al. 2018

Adv Healthcare Materials

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“…Similar to the MHC isoforms, PSC-CMs contain both isoforms of MLC (Zhang et al, 2013). PSC-CMs likewise exhibit low levels of expression of troponin isoforms, the protein involved in regulating myosin binding to actin, and alpha-actin isoforms, which contributes to the actin myofilaments, compared to adult CMs (Khan et al, 2015; Veerman et al, 2015; Li et al, 2016). Fetal CMs express mostly cTnT1 and cTnT2 which then switch to higher amounts of cTnT3 and cTnT4 during the neonatal stage and is abundant in adult CMs (Siedner et al, 2003).…”

Section: Maturation Differences Between Four Cardiomyocyte Developmenmentioning

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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“…Substrates with multiscale topography are designed to resolve this issue; the topography leads to variation in localized mechanical properties and associated micromechanical changes result in the manipulation of focal adhesion formation for the regulation of cell behaviors and functions ( Figure a) . For instance, Han's group developed a scaffold by mixing gold nanoparticles with collagen and the formative localized stiffness could efficiently regulate the assembly of intercalated discs through the β1 integrin‐mediated ILK/p‐AKT/GATA4 pathway . However, this method is relatively simple and has narrow application range.…”

Section: Hierarchical Hydrogel With Robust Micro/nanoscale Interfacesmentioning

confidence: 99%

Hierarchical Hydrogel Composite Interfaces with Robust Mechanical Properties for Biomedical Applications

et al. 2019

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Since mechanotransduction and interactions at the interface between materials and cells play crucial roles in the regulation of cell behaviors and the genotype-to-phenotype relation ship, mechanical properties are important parameters in the Cells sense and respond to a wide range of external signals, including chemical signals, topography, and interface mechanics, via interactions with the extracellular matrix (ECM), triggering the regulation of behavior and function. The ECM can be considered a hierarchical multiphase porous matrix with various components. Highly porous hydrogel-based biomaterials can mimic the critical ECM properties, to provide mechanical support for tissues and to regulate cellular behaviors, such as adhesion, proliferation, and differentiation. Herein, based on micro/nanoscale-topography-coupled mechanical action, recent advances in the fabrication and application of hydrogel composites with tunable mechanical properties and topography in biomedicine are summarized. In particular, recent findings showing that hydrogels with specifically designed structures not only influence a range of cellular processes and fit the needs of engineered tissues but also have pharmacological effects are emphasized. Hydrogels

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AuNP–Collagen Matrix with Localized Stiffness for Cardiac‐Tissue Engineering: Enhancing the Assembly of Intercalated Discs by β1‐Integrin‐Mediated Signaling

Cited by 78 publications

References 31 publications

High Modulus Conductive Hydrogels Enhance In Vitro Maturation and Contractile Function of Primary Cardiomyocytes for Uses in Drug Screening

High Modulus Conductive Hydrogels Enhance In Vitro Maturation and Contractile Function of Primary Cardiomyocytes for Uses in Drug Screening

Naturally Engineered Maturation of Cardiomyocytes

Hierarchical Hydrogel Composite Interfaces with Robust Mechanical Properties for Biomedical Applications

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