Demonstration of doxorubicin's cardiotoxicity and screening using a 3D bioprinted spheroidal droplet-based system

Khoury, Raven El; Ramirez, Salma P.; Loyola, Carla D.; Joddar, Binata

doi:10.1039/d3ra00421j

Cited by 3 publications

(3 citation statements)

References 60 publications

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“…Cytotoxicity of the Au-NPs was measured using a Live–Dead Assay Kit (Thermo Fisher Scientific, USA) according to the protocol provided by the vendor. Calcein AM (green) stained live cells, while ethidium homodimer (red) was used to stain dead cells after being incubated in the samples for at least 1 h at room temperature (RT) (25 °C) . Live–dead assay images collected were analyzed by using ImageJ to determine cell viability.…”

Section: Methodsmentioning

confidence: 99%

“…Calcein AM (green) stained live cells, while ethidium homodimer (red) was used to stain dead cells after being incubated in the samples for at least 1 h at room temperature (RT) (25 °C). 11 Live−dead assay images collected were analyzed by using ImageJ to determine cell viability. Live and dead cells were counted utilizing the cell-counter tool on ImageJ.…”

Section: Preparation and Characterization Of Au-np Solutions For 3dbpmentioning

confidence: 99%

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Microcomputed Tomography for the Microstructure Evaluation of 3D Bioprinted Scaffolds

Ramirez,

Hernandez,

Balcorta

et al. 2023

ACS Appl. Bio Mater.

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This study implemented the application of microcomputed tomography (micro-CT) as a characterization technique for the study and investigation of the microstructure of 3D scaffold structures produced via three-dimensional bioprinting (3DBP). The study focused on the preparation, characterization, and cytotoxicity analysis of gold nanoparticles (Au-NPs) incorporated into 3DBP hydrogels for micro-CT evaluation. The Au-NPs were characterized by using various techniques, including UV−vis spectrometry, dynamic light scattering (DLS), zeta potential measurement, and transmission electron microscopy (TEM). The characterization results confirmed the successful coating of the Au-NPs with 2 kDa methoxy-PEG and revealed their spherical shape with a mean core diameter of 66 nm. Cytotoxicity analysis using live−dead fluorescent microscopy indicated that all tested Au-NP solutions were nontoxic to AC16 cardiomyocytes in both 2D and 3D culture conditions. Scanning electron microscopy (SEM) showed distinguishable differences in image contrast and intensity between samples with and without Au-NPs, with high concentrations of Au-NPs displaying nanoparticle aggregates. Micro-CT imaging demonstrated that scaffolds containing Au-NPs depicted enhanced imaging resolution and quality, allowing for visualization of the microstructure. The 3D reconstruction of scaffold structures from micro-CT imaging using Dragonfly software further supported the improved visualization. Mechanical analysis revealed that the addition of Au-NPs enhanced the mechanical properties of acellular scaffolds, including their elastic moduli and complex viscosity, but the presence of cells led to biodegradation and reduced mechanical strength. These findings highlight the successful preparation and characterization of Au-NPs, their nontoxic nature in both 2D and 3D culture conditions, their influence on imaging quality, and the impact on the mechanical properties of 3D-printed hydrogels. These results contribute to the development of functional and biocompatible materials for tissue engineering and regenerative medicine applications.

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Section: Methodsmentioning

confidence: 99%

Section: Preparation and Characterization Of Au-np Solutions For 3dbpmentioning

confidence: 99%

Microcomputed Tomography for the Microstructure Evaluation of 3D Bioprinted Scaffolds

Ramirez,

Hernandez,

Balcorta

et al. 2023

ACS Appl. Bio Mater.

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“…In a similar scenario of pathological oxygen tension and doxorubicin treatment in a cardiac spheroid model, Sharma et al focused on the mechanistic events following ischemia/reperfusion damage, and drug toxicity by deeply studying the molecular alterations in terms of the sarcomeric array, calcium handling, cell viability, and cardiac remodeling ( Sharma et al, 2022a ). In a 3D bioprinted cardiac spheroidal droplet-based system, El Khoury et al confirmed the side effects in cell viability and contractility at 1 µM and proved that the administration in tissue culture of the strong antioxidants N -acetylcysteine and Tiron could alleviate cardiotoxicity through the cardioprotection mediated by apoptotic caspase-3 inhibition ( El Khoury et al, 2023 ).…”

Section: The Shortening Gap Between Preclinical Research and Clinical...mentioning

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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A critical review on advances and challenges of bioprinted cardiac patches

Zhang,

Zhao,

et al. 2024

Acta Biomaterialia

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Demonstration of doxorubicin's cardiotoxicity and screening using a 3D bioprinted spheroidal droplet-based system

Abstract: A unique 3D bioprinted cardiac spheroidal droplet model used to test the cytotoxic effects of DOX.

Cited by 3 publications

References 60 publications

Microcomputed Tomography for the Microstructure Evaluation of 3D Bioprinted Scaffolds

Microcomputed Tomography for the Microstructure Evaluation of 3D Bioprinted Scaffolds

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

A critical review on advances and challenges of bioprinted cardiac patches

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