BIOREACTOR-BASED MODEL PLATFORM FOR CARDIAC TISSUE

Aim: A bioreactor-based model platform was developed for culturing cardiac constructs in a native-like environment and for investigating cardiac tissue developmental aspects and factors that influence the generation of functional cardiac tissues. Methods: The platform is composed of: (1) a stand-alone sensorized bioreactor, which provides cyclic stretch and on-line monitoring of culture parameters; and (2) 3D fibrin engineered heart tissue (fEHT) rings, acting as cardiac pseudo-tissues. The culture chamber is equipped with sensors (temperature, pH, and CO sub(2)/O sub(2)) and a heating strip, and can house up to three fEHT rings. The mechanical stimulation unit supplies controlled cyclic stretch (1-200% deformation, 1-6 Hz frequency). The monitoring/control unit allows real-time monitoring and control of the stimulation unit and chamber temperature. The operating conditions are set and monitored by a purposely-built software. As for the fEHT rings, neonatal rat cardiomyocytes were mixed with fibrin and medium, cast into circular moulds, incubated for 48 hours, and finally dynamically cultured. Results: In-house tests confirmed the effectiveness of chamber isolation, mechanical stimulation unit, and monitoring/control unit. fEHT rings were obtained and characterized by histological analyses before and after physiological/pathological stimulation. Preliminary tests demonstrated the system suitability to culture cardiac constructs. Conclusions: By allowing control and monitoring of individual parameters to be separated from in vivo systemic effects, this closed automated platform provides a reliable model system, with high reproducibility and low contamination risk, to study the effects of chemical-physical stimuli on cardiac tissue maturation and function.