Humanoid robot upregulates cellular stress pathways in tendon tissue engineering

Mechanical stimulation is essential in tissue engineering and regenerative medicine for proper tissue maturation. However, conventional dynamic stimulation is typically achieved with uniaxial platforms, which limit functionality due to the oversimplified mechanics compared to the complex mechanical inputs of the human body. In this study, we explore human cell responses to stimulation using a humanoid robot shoulder and a uniaxial platform at equivalent strains. A flexible, biocompatible sensor monitoring in situ strains shows that external maximum forces of 25 N and 50 N during robot abduction-adduction motions lead to strains of approximately 3.5% and 9.5%, respectively. Additionally, we demonstrate in situ cell imaging by utilizing the transparency of the bioreactor membrane. The robot motions significantly enhance cell orientation and induce notable changes in gene and protein expression, particularly within the PI3K-Akt signaling pathway, compared to both static and uniaxial stimulation controls. These findings underscore the need to better match human biomechanics in bioreactor platforms to improve tissue engineering outcomes. Comparative gene expression profiling analysis of RNA-seq data for Green fluorescent protein (GFP)-modified human MSCshTERT) of cell responses to the different stimulation platforms and different loading regime.