Advances in 3D bioprinting technology for cardiac tissue engineering and regeneration

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.

Download Full-text

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.

Download Full-text

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

Download Full-text

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.

Download Full-text

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

Download Full-text

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.

Download Full-text

Cardiac tissue engineering, biomaterial scaffolds, and their fabrication techniques

Polymers for Advanced Technologies ◽

10.1002/pat.5273 ◽

2021 ◽

Author(s):

Marjan Roshandel ◽

Farid Dorkoosh

Keyword(s):

Tissue Engineering ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Biomaterial Scaffolds

Download Full-text

Recapitulating Cardiac Structure and Function In Vitro from Simple to Complex Engineering

Micromachines ◽

10.3390/mi12040386 ◽

2021 ◽

Vol 12 (4) ◽

pp. 386

Author(s):

Ana Santos ◽

Yongjun Jang ◽

Inwoo Son ◽

Jongseong Kim ◽

Yongdoo Park

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Computational Modeling ◽

Cardiac Tissue ◽

Cardiac Development ◽

Heart Tissue ◽

Cardiac Tissue Engineering ◽

Cardiac Cells

Cardiac tissue engineering aims to generate in vivo-like functional tissue for the study of cardiac development, homeostasis, and regeneration. Since the heart is composed of various types of cells and extracellular matrix with a specific microenvironment, the fabrication of cardiac tissue in vitro requires integrating technologies of cardiac cells, biomaterials, fabrication, and computational modeling to model the complexity of heart tissue. Here, we review the recent progress of engineering techniques from simple to complex for fabricating matured cardiac tissue in vitro. Advancements in cardiomyocytes, extracellular matrix, geometry, and computational modeling will be discussed based on a technology perspective and their use for preparation of functional cardiac tissue. Since the heart is a very complex system at multiscale levels, an understanding of each technique and their interactions would be highly beneficial to the development of a fully functional heart in cardiac tissue engineering.

Download Full-text