Modular bioreactor for multi-well electrical stimulation of in vitro cardiac tissue engineering constructs

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Cell Biology

Background:

• Electrical stimulation systems are crucial for in vitro cell culture applications in tissue engineering.
• Existing systems can be costly and lack modularity for diverse experimental needs.

Purpose of the Study:

• To design and validate a novel, low-cost, modular bioreactor for electrical stimulation of in vitro cell cultures.
• To assess the effects of varying electrical stimulation amplitudes on neonatal rat cardiomyocytes (NRCMs).

Main Methods:

• Fabrication of a modular bioreactor using printed circuit board assembly and carbon paper electrodes, compatible with 12-well plates.
• Modeling and validation of stimulus delivery using SPICE and Finite Element Analysis (FEA).
• Application of 0 V, 0.1 V, 1 V, and 10 V electrical stimulation to NRCMs, with and without fibroblast co-culture.

Main Results:

• NRCMs maintained viability across most stimulation conditions, except for 10 V without fibroblast co-culture.
• 0.1 V electrical stimulation significantly enhanced cardiac electrophysiology markers (sarcomeric α-actinin, connexin 43) and upregulated key genes in NRCMs.
• The novel bioreactor demonstrated capability for simultaneous delivery of four different stimulus amplitudes.

Conclusions:

• The developed low-cost bioreactor is effective for electrical stimulation of cardiac cells.
• 0.1 V electrical stimulation promotes enhanced electrophysiological function in primary cardiac cells.
• This system holds promise for advancing tissue engineering and the maturation of induced pluripotent stem cell-derived cardiomyocytes.