Bioprinting High-Cell-Density Cardiac Tissue Constructs With Sustained Contractile Function

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Tissue Engineering

Background:

• Developing accurate in vitro models for cardiac physiology is crucial for drug efficacy and cardiotoxicity assessment.
• Current models often fail to replicate the complex structure and function of native cardiac tissue.
• Tissue engineering and biofabrication offer promising solutions for creating functional 3D tissue models.

Purpose of the Study:

• To develop and validate a novel 3D bioprinted cardiac in vitro model using reactive jet impingement (ReJI).
• To assess the functional and structural integrity of the bioprinted cardiac constructs over time.
• To evaluate the model's utility for drug-induced cardiotoxicity testing.

Main Methods:

• Fabrication of a 3D cardiac construct using reactive jet impingement (ReJI) biofabrication.
• Utilizing a hydrogel matrix composed of type I collagen, alginate, and fibrin for cell encapsulation.
• Employing the murine HL-1 cardiomyocyte cell line for construct development and assessment of contractility and biomarker expression.

Main Results:

• The ReJI bioprinted cardiac model demonstrated stable, functional 3D cardiac constructs with sustained spontaneous contractility for 21 days.
• Key cardiac contraction biomarkers, including desmin, myosin, and gap junction alpha-1 (GJA1), were expressed.
• Early-stage GJA1 expression indicated gap junction formation, and the model showed susceptibility to drug-induced dysrhythmia.

Conclusions:

• Reactive jet impingement (ReJI) biofabrication enables the creation of functional 3D cardiac in vitro models with sustained contractility.
• The developed 3D cardiac model accurately reflects key aspects of cardiac physiology and biomarker expression.
• This novel model holds significant potential for advancing cardiotoxicity testing and drug efficacy evaluation.