Nanofibrous Composite with Tailorable Electrical and Mechanical Properties for Cardiac Tissue Engineering

The generation of 3D tissue constructs with multiple cell types and matching mechanical properties remains a challenge in cardiac tissue engineering. Recently, 3D bioprinting has become a powerful tool to achieve these goals. Decellularized extracellular matrix (dECM) is a common scaffold material due to providing a native biochemical environment. Unfortunately, dECM’s low mechanical stability prevents usage for bioprinting applications alone. In this study, we developed bioinks composed of decellularized human heart ECM (dhECM) with either gelatin methacryloyl (GelMA) or GelMA-methacrylated hyaluronic acid (MeHA) hydrogels dual crosslinked with UV light and microbial transglutaminase (mTGase). We characterized the bioinks’ mechanical, rheological, swelling, printability, and biocompatibility properties. Composite GelMA–MeHA–dhECM (GME) hydrogels demonstrated improved mechanical properties by an order of magnitude compared to the GelMA–dhECM (GE) hydrogels. All hydrogels were extrudable and compatible with human induced pluripotent stem cell derived cardiomyocytes (iCMs) and human cardiac fibroblasts (hCFs). Tissue-like beating of the printed constructs with striated sarcomeric alpha-actinin and connexin 43 expression was observed. The order of magnitude difference between the elastic modulus of these hydrogel composites offers applications in in vitro modeling of the myocardial infarct boundary. Here, as a proof of concept, we created an infarct boundary region with control over the mechanical properties along with the cellular and macromolecular content through printing iCMs with GE bioink and hCFs with GME bioink.

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Tunable human myocardium derived decellularized extracellular matrix for 3D bioprinting and cardiac tissue engineering

10.1101/2021.03.30.437600 ◽

2021 ◽

Author(s):

Gozde Basara ◽

S. Gulberk Ozcebe ◽

Bradley W. Ellis ◽

Pinar Zorlutuna

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Extracellular Matrix ◽

Connexin 43 ◽

Cardiac Tissue ◽

Myocardial Infarct ◽

Cardiac Tissue Engineering ◽

3D Bioprinting ◽

Decellularized Extracellular Matrix ◽

Order Of Magnitude

AbstractThe generation of 3D tissue constructs with multiple cell types and matching mechanical properties remains a challenge in cardiac tissue engineering. Recently, 3D bioprinting has become a powerful tool to achieve these goals. Decellularized extracellular matrix (dECM) is a common scaffold material due to providing a native biochemical environment. Unfortunately, dECM’s low mechanical stability prevents usage for bioprinting applications alone. In this study, we developed bioinks composed of decellularized human heart ECM (dhECM) with either gelatin methacryloyl (GelMA) or GelMA- methacrylated hyaluronic acid (MeHA) hydrogels dual crosslinked with UV light and microbial Transglutaminase (mTGase). We characterized the bioinks’ mechanical, rheological, swelling, printability and biocompatibility properties. Composite GelMA-MeHA-dhECM (GME) hydrogels demonstrated improved mechanical properties by an order of magnitude, compared to GelMA-dhECM (GE) hydrogels. All hydrogels were extrudable and compatible with human induced pluripotent stem cells derived cardiomyocytes (iCMs) and human cardiac fibroblasts (hCFs). Tissue-like beating of the printed constructs with striated sarcomeric alpha-actinin and Connexin 43 expression was observed. The order of magnitude difference between the elastic modulus of these hydrogel composites offers applications in in vitro modelling of the myocardial infarct boundary. Here, as a proof of concept, we created an infarct boundary region with control over mechanical properties along with cellular and macromolecular content through printing iCMs with GE bioink and hCFs with GME bioink.

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Graphene-Based Scaffolds: Fundamentals and Applications for Cardiovascular Tissue Engineering

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.797340 ◽

2021 ◽

Vol 9 ◽

Author(s):

Alex Savchenko ◽

Rose T. Yin ◽

Dmitry Kireev ◽

Igor R. Efimov ◽

Elena Molokanova

Keyword(s):

Mechanical Properties ◽

Electrical Conductivity ◽

Tissue Engineering ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Cardiac Cells ◽

Great Promise ◽

Cardiovascular Tissue ◽

Cell Scaffolds

Cardiac tissue engineering requires materials that can faithfully recapitulate and support the native in vivo microenvironment while providing a seamless bioelectronic interface. Current limitations of cell scaffolds include the lack of electrical conductivity and suboptimal mechanical properties. Here we discuss how the incorporation of graphene into cellular scaffolds, either alone or in combination with other materials, can affect morphology, function, and maturation of cardiac cells. We conclude that graphene-based scaffolds hold great promise for cardiac tissue engineering.

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Elastic serum-albumin based hydrogels: mechanism of formation and application in cardiac tissue engineering

Journal of Materials Chemistry B ◽

10.1039/c8tb01014e ◽

2018 ◽

Vol 6 (35) ◽

pp. 5604-5612 ◽

Cited By ~ 8

Author(s):

Nadav Amdursky ◽

Manuel M. Mazo ◽

Michael R. Thomas ◽

Eleanor J. Humphrey ◽

Jennifer L. Puetzer ◽

...

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Serum Albumin ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Mechanism Of Formation ◽

Tunable Mechanical Properties

The simplicity of making hydrogels with tunable mechanical properties from commercially available proteins is demonstrated for cardiac tissue engineering.

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Micro and Nano-mediated 3D Cardiac Tissue Engineering

10.21236/ada604913 ◽

2010 ◽

Author(s):

Rashid Bashir

Keyword(s):

Tissue Engineering ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering

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Extrinsically Conductive Nanomaterials for Cardiac Tissue Engineering Applications

Micromachines ◽

10.3390/mi12080914 ◽

2021 ◽

Vol 12 (8) ◽

pp. 914

Author(s):

Arsalan Ul Haq ◽

Felicia Carotenuto ◽

Paolo Di Nardo ◽

Roberto Francini ◽

Paolo Prosposito ◽

...

Keyword(s):

Tissue Engineering ◽

Cardiac Tissue ◽

Scar Tissue ◽

Cardiac Tissue Engineering ◽

Assistive Device ◽

Long Run ◽

Fibrotic Scar ◽

Regeneration Capability ◽

Conductive Nanomaterials

Myocardial infarction (MI) is the consequence of coronary artery thrombosis resulting in ischemia and necrosis of the myocardium. As a result, billions of contractile cardiomyocytes are lost with poor innate regeneration capability. This degenerated tissue is replaced by collagen-rich fibrotic scar tissue as the usual body response to quickly repair the injury. The non-conductive nature of this tissue results in arrhythmias and asynchronous beating leading to total heart failure in the long run due to ventricular remodelling. Traditional pharmacological and assistive device approaches have failed to meet the utmost need for tissue regeneration to repair MI injuries. Engineered heart tissues (EHTs) seem promising alternatives, but their non-conductive nature could not resolve problems such as arrhythmias and asynchronous beating for long term in-vivo applications. The ability of nanotechnology to mimic the nano-bioarchitecture of the extracellular matrix and the potential of cardiac tissue engineering to engineer heart-like tissues makes it a unique combination to develop conductive constructs. Biomaterials blended with conductive nanomaterials could yield conductive constructs (referred to as extrinsically conductive). These cell-laden conductive constructs can alleviate cardiac functions when implanted in-vivo. A succinct review of the most promising applications of nanomaterials in cardiac tissue engineering to repair MI injuries is presented with a focus on extrinsically conductive nanomaterials.

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Designing of spider silk proteins for hiPSC-based cardiac tissue engineering

Materials Today Bio ◽

10.1016/j.mtbio.2021.100114 ◽

2021 ◽

pp. 100114

Author(s):

Tilman U. Esser ◽

Vanessa T. Trossmann ◽

Sarah Lentz ◽

Felix B. Engel ◽

Thomas Scheibel

Keyword(s):

Tissue Engineering ◽

Spider Silk ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Silk Proteins

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Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Biomedicines ◽

10.3390/biomedicines9050563 ◽

2021 ◽

Vol 9 (5) ◽

pp. 563

Author(s):

Magali Seguret ◽

Eva Vermersch ◽

Charlène Jouve ◽

Jean-Sébastien Hulot

Keyword(s):

Tissue Engineering ◽

Drug Testing ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Cardiac Cells ◽

Cardiac Functions ◽

Different Types ◽

Recent Developments ◽

Human Cardiac Tissue ◽

Key Aspects

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

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