Fusing spheroids to aligned μ-tissues in a heart-on-chip featuring oxygen sensing and electrical pacing capabilities

Area of Science:

• Biotechnology
• Tissue Engineering
• Cardiovascular Research

Background:

• Organ-on-Chip (OoC) technology offers advanced in vitro models for physiological studies.
• Current cardiac tissue engineering faces challenges in large-scale, standardized production due to manual processes.

Purpose of the Study:

• To develop a novel, automated system for generating cardiac tissues using cell spheroids.
• To integrate electrical stimulation and in situ metabolic monitoring into microfluidic cardiac tissue models.
• To provide a blueprint for scalable and robust microtissue generation in an industrial setting.

Main Methods:

• Utilized induced pluripotent stem cell-derived cardiomyocytes to form uniform spheroids.
• Employed hydrostatic flow for spheroid transport and accumulation in custom-designed chambers.
• Integrated fluidic media connectors as electrodes for electrical stimulation.
• Incorporated optical O2 sensor spots for in situ oxygen partial pressure monitoring.

Main Results:

• Successfully generated aligned, contracting cardiac muscle fibers from fused spheroids.
• Demonstrated electrical stimulation and real-time metabolic activity monitoring in cardiac tissues.
• Developed a low-cost, open-source pulse generator for electrical stimulation.

Conclusions:

• The developed system facilitates facile and robust generation of high-density microtissues.
• This approach enables advanced OoCs with integrated biophysical stimulation and probing capabilities.
• The system serves as a blueprint for scaling up and automating microtissue production.