Development of a multifunctional uniaxial bioreactor with real-time monitoring of culture conditions and tissue health

Bioreactors are used to dynamically condition engineered tissues to achieve the required degree of maturation before in vivo implantation. Integrating sensors and imaging capabilities into bioreactors can help us understand how the culture environment influences tissue maturation and growth. Additionally, this enables the monitoring of tissue constructs and provides critical information for quality control. This study aimed to develop a standardized, self-contained, uniaxial bioreactor module for the clinical manufacturing of tissue constructs; this system would benefit from unidirectional mechanical or electrical stimulation, or both. We achieved this goal by integrating stimulation and sensing components that provide an optimal culture environment and monitoring capabilities to improve tissue manufacturing. The uniaxial bioreactor module included integrated, user-friendly mechanical and electrical stimulations with force measurement to enhance the preconditioning of the engineered tissues. Also, a sensor loop and media exchange system were integrated to monitor the culture environment and cellular metabolites over time, and the camera system above the tissue construct enabled the macroscopic visualization of tissue maturation. Furthermore, the onboard media exchange system was programmed into the module to maintain aseptic culture conditions in the long term. Subsequently, using native skeletal muscle tissue and tissue-engineered skeletal muscle constructs, the performance of the uniaxial bioreactor module was validated for its application in preconditioning and enhancing tissue maturation.