Electric field stimulation integrated into perfusion bioreactor for cardiac tissue engineering

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Cardiovascular Research

Background:

• Developing functional cardiac tissue requires precise control over cellular microenvironments.
• Electrical stimulation is crucial for cardiomyocyte development and function.
• Perfusion bioreactors offer advanced control over nutrient delivery and waste removal.

Purpose of the Study:

• To develop and validate a novel perfusion bioreactor system for enhanced cardiac cell cultivation.
• To integrate electrical stimulation with medium perfusion for producing functional cardiac patches.
• To model and confirm optimal electrical field conditions for cardiomyocyte excitation.

Main Methods:

• A custom electrical stimulator was integrated into a perfusion bioreactor with carbon rod electrodes.
• Neonatal rat cardiac cell constructs were cultured under homogenous fluid flow and electrical stimulation.
• Electric field models (Comsol Multiphysics) were used to determine and match stimulation thresholds.
• Cell constructs were analyzed for elongation, striation, and Connexin-43 expression.

Main Results:

• The bioreactor system provided homogenous fluid flow and optimized electrical stimulation.
• Electric field models accurately predicted local electric conditions for cardiomyocyte excitation.
• 4 days of cultivation enhanced cell elongation, striation, and Connexin-43 expression.
• The system demonstrated validity for predicting optimal electrical stimulation in complex cultivation setups.

Conclusions:

• The novel perfusion bioreactor with integrated electrical stimulation effectively promotes cardiac cell development.
• Validated electric field modeling is essential for optimizing stimulation parameters in bioreactors.
• This system shows significant potential for generating functional cardiac patches for regenerative medicine.