Developing a heart-on-a-chip platform to study cellular responses to mechanical forces
Sofia Gomez defended her PhD thesis at the Department of Mechanical Engineering on July 18th.
The platform that developed, applies dynamic, cyclic mechanical stimulation to 2D and 3D cultured cells without damaging the cells or disrupting the experimental setup. This requires advanced systems, especially for 3D cell cultures. These cultures more closely mimic real tissues compared to traditional 2D models. The heart-on-a-chip platform uses pneumatic actuation to deliver repeated stretching motions similar to those experienced by tissues in the body, such as rhythmic contractions of the heart. Next to that, the system is compact, modular, and easy to integrate into existing laboratory workflows, making it both user-friendly and adaptable for various research needs.
Replicating physiological conditions
To ensure that the platform could accurately replicate physiological conditions, it was calibrated using a combination of experimental measurements and computer simulations. The system was also tested for biocompatibility and mechanical reliability, showing that it could maintain cell health, preserve the structural integrity of hydrogels (used to mimic tissue environments), and perform consistently over extended periods.
Demonstrations of applications
The capabilities of the platform were demonstrated through two key applications. First, 3D cultures of C2C12 muscle precursor cells were embedded in collagen and exposed to different mechanical loading patterns. The results showed that specific types and rhythms of mechanical strain significantly influenced how well the cells developed into mature muscle fibers. Second, human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) were grown in 2D layers and subjected to customized stretching protocols. Analysis revealed that optimized mechanical conditions improved markers of heart cell maturation, demonstrating the effectiveness of the system in guiding functional development.
A powerful tool
Overall, this research offers a powerful and accessible tool for studying how mechanical forces influence cellular behavior. By bridging the gap between engineering and biology, the platform supports more accurate modeling of tissue-specific environments and provides new opportunities to explore the role of biomechanics in health and disease. It lays the foundation for future work focused on automating the system, increasing its experimental throughput, and expanding its use to other cell types and tissue models. Ultimately, this work contributes to the advancement of in vitro modeling technologies that can accelerate biomedical research and improve therapeutic development.
Title of PhD thesis: . Supervisors: Dr. and Prof. Jaap den Toonder.