Agonistic and antagonistic roles of fibroblasts and cardiomyocytes on viscoelastic stiffening of engineered human myocardium

Schlick, Susanne F.; Spreckelsen, Florian; Tiburcy, Malte; Iyer, Lavanya M; Meyer, Tim; Zelarayán, Laura C.; Parlitz, Ulrich; Zimmermann, Wolfram‐Hubertus; Rehfeldt, Florian

doi:10.1016/j.pbiomolbio.2018.11.011

Cited by 17 publications

(5 citation statements)

References 36 publications

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“…Our data show that the here‐generated hydrogels are shear thinning with a G′ value being in the ranges less than 200 Pa. While being significantly softer than ≈10 kPa reported for the shear storage modulus of human myocardium (end diastolic), [ 30 ] these values are greater than the storage moduli reported in the literature for collagen hydrogels in engineered cardiac tissues that are between 20–30 Pa. [ 31 ] However, very large forces are generated during cardiac cycle that should be tolerated by the material to ensure no drug or cell leakage due to compression cycles. Generating hydrogel‐based engineered cardiac tissues that could bear the mechanical stress of large animals is challenging.…”

Section: Resultsmentioning

confidence: 69%

Collagen Hydrogel Containing Polyethylenimine‐Gold Nanoparticles for Drug Release and Enhanced Beating Properties of Engineered Cardiac Tissues

Roshanbinfar

Koleśnik-Gray

Angeloni

et al. 2023

Adv Healthcare Materials

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Cardiac tissue engineering is a promising strategy to prevent heart failure. However, several issues remain unsolved, including efficient electrical coupling and incorporating factors to enhance tissue maturation and vascularization. Herein, a biohybrid hydrogel that enhances beating properties of engineered cardiac tissues and allows drug release concurrently is developed. Gold nanoparticles (AuNPs) with different sizes (18–241 nm) and surface charges (33.9–55.4 mV) are synthesized by reducing gold (III) chloride trihydrate using branched polyethyleneimine (bPEI). These nanoparticles increase gel stiffness from ≈91 to ≈146 kPa, enhance electrical conductivity of collagen hydrogels from ≈40 to 49–68 mS cm−1, and allow slow and steady release of loaded drugs. Engineered cardiac tissues based on bPEI‐AuNP‐collagen hydrogels and either primary or human induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes show enhanced beating properties. hiPSC‐derived cardiomyocytes exhibit more aligned and wider sarcomeres in bPEI‐AuNP‐collagen hydrogels compared to collagen hydrogels. Furthermore, the presence of bPEI‐AuNPs result in advanced electrical coupling evidenced by synchronous and homogenous calcium flux throughout the tissue. RNA‐seq analyses are in agreement with these observations. Collectively, this data demonstrate the potential of bPEI‐AuNP‐collagen hydrogels to improve tissue engineering approaches to prevent heart failure and possibly treat diseases of other electrically sensitive tissues.

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Section: Resultsmentioning

confidence: 69%

Collagen Hydrogel Containing Polyethylenimine‐Gold Nanoparticles for Drug Release and Enhanced Beating Properties of Engineered Cardiac Tissues

Roshanbinfar

Koleśnik-Gray

Angeloni

et al. 2023

Adv Healthcare Materials

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“…Given minimal effects on maturation through prolonged culture of PSC-CMs, we may need to reconsider our current strategies to achieve better CM maturation in vitro 47 . Indeed, several efforts were put into promoting CM maturation by mimicking in vivo circumstances, such as 3D culture, physical conditioning, and engineered cardiac tissues using non-cardiac fibroblasts 26,27,[48][49][50] , underscoring the importance of delineating the cellular microenvironment surrounding CMs. To this end, our study unbiasedly scrutinized postnatal heart maturation at single-cell resolution.…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation

et al. 2020

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Cardiac maturation lays the foundation for postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation. By integrating single-cell RNA-sequencing data of mouse hearts at multiple postnatal stages, we construct cellular interactomes and regulatory signaling networks. Here we report switching of fibroblast subtypes from a neonatal to adult state and this drives cardiomyocyte maturation. Molecular and functional maturation of neonatal mouse cardiomyocytes and human embryonic stem cell-derived cardiomyocytes are considerably enhanced upon coculture with corresponding adult cardiac fibroblasts. Further, single-cell analysis of in vivo and in vitro cardiomyocyte maturation trajectories identify highly conserved signaling pathways, pharmacological targeting of which substantially delays cardiomyocyte maturation in postnatal hearts, and markedly enhances cardiomyocyte proliferation and improves cardiac function in infarcted hearts. Together, we identify cardiac fibroblasts as a key constituent in the microenvironment promoting cardiomyocyte maturation, providing insights into how the manipulation of cardiomyocyte maturity may impact on disease development and regeneration.

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“…This is particularly problematic for CMs. Hydrogel formulations were adopted to improve cell-to-cell connectivity ( Latifi et al, 2018 ; Joshi et al, 2019 ; Schlick et al, 2019 ; Lu et al, 2021 ). Their engineering with magnetic nanoparticles or carbon nanotubes further contributed to improving cell alignment and electrical crosstalk ( Sun et al, 2017 ; Yu et al, 2017 ; Zwi-Dantsis et al, 2020 ).…”

Section: Biomimetic Design: From Extracellular Matrix To Scaffoldmentioning

confidence: 99%

Advances in the design, generation, and application of tissue-engineered myocardial equivalents

Bernava,

Iop

2023

Front. Bioeng. Biotechnol.

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Due to the limited regenerative ability of cardiomyocytes, the disabling irreversible condition of myocardial failure can only be treated with conservative and temporary therapeutic approaches, not able to repair the damage directly, or with organ transplantation. Among the regenerative strategies, intramyocardial cell injection or intravascular cell infusion should attenuate damage to the myocardium and reduce the risk of heart failure. However, these cell delivery-based therapies suffer from significant drawbacks and have a low success rate. Indeed, cardiac tissue engineering efforts are directed to repair, replace, and regenerate native myocardial tissue function. In a regenerative strategy, biomaterials and biomimetic stimuli play a key role in promoting cell adhesion, proliferation, differentiation, and neo-tissue formation. Thus, appropriate biochemical and biophysical cues should be combined with scaffolds emulating extracellular matrix in order to support cell growth and prompt favorable cardiac microenvironment and tissue regeneration. In this review, we provide an overview of recent developments that occurred in the biomimetic design and fabrication of cardiac scaffolds and patches. Furthermore, we sift in vitro and in situ strategies in several preclinical and clinical applications. Finally, we evaluate the possible use of bioengineered cardiac tissue equivalents as in vitro models for disease studies and drug tests.

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Agonistic and antagonistic roles of fibroblasts and cardiomyocytes on viscoelastic stiffening of engineered human myocardium

Cited by 17 publications

References 36 publications

Collagen Hydrogel Containing Polyethylenimine‐Gold Nanoparticles for Drug Release and Enhanced Beating Properties of Engineered Cardiac Tissues

Collagen Hydrogel Containing Polyethylenimine‐Gold Nanoparticles for Drug Release and Enhanced Beating Properties of Engineered Cardiac Tissues

Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation

Advances in the design, generation, and application of tissue-engineered myocardial equivalents

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