Open-source bioreactor delivers electrical and perfusion stimulation supporting 3D cardiac engineered tissue...

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Regenerative Medicine

Background:

• Cardiac tissue engineering requires precise control over physical stimuli to mature cardiomyocytes.
• The synergistic effects of direct perfusion and electrical stimulation in soft hydrogel environments are underexplored.
• Existing bioreactor systems often lack integration of multiple stimuli for optimal cardiac construct development.

Purpose of the Study:

• To develop and validate a cost-effective, integrated perfusion bioreactor system for electrical stimulation of cardiac constructs.
• To investigate the synergistic impact of combined perfusion and electrical stimulation on cardiomyocyte maturation and cardiac tissue functionality.
• To assess the system's efficacy in promoting cell retention, tissue remodeling, and functional performance of 3D cardiac tissues.

Main Methods:

• Development of a modified, commercially available perfusion bioreactor integrated with electrical stimulation capabilities.
• Validation of flow and electrical field uniformity using computational fluid dynamics and finite element analysis simulations.
• Culture of neonatal rat cardiac cell-based constructs under static and perfusion conditions, with and without electrical stimulation, followed by comprehensive cellular and functional analyses.

Main Results:

• Perfusion significantly improved cell retention and cardiomyocyte yield; electrical stimulation enhanced cardiomyocyte elongation and maturation.
• The combination of perfusion and electrical stimulation yielded the highest proportion of mature cardiomyocytes (51.4%), outperforming individual stimuli.
• Combined stimulation led to enhanced tissue remodeling, reduced fibroblast activation, and superior functional performance, including lower excitation thresholds and greater contraction displacement.

Conclusions:

• The integrated bioreactor system efficiently supports the culture of soft 3D cardiac tissues.
• Combining perfusion with electrical stimulation synergistically enhances cardiomyocyte maturation, construct remodeling, and functional performance.
• This scalable platform offers a powerful solution for cardiac tissue engineering, disease modeling, drug screening, and regenerative medicine applications.