Towards Cardiovascular Tissue Engineering: Macro to Micro Bioreactors

It has long been recognized that the combination of several factors, such as the electrical and mechanical stimulation, coupled with biochemical conditioning, is the most promising approach for in vitro development of fully functional engineered tissue-like structures having concrete chances of success when implanted in vivo for the repair of the impaired myocardium. In this scenario, the design of advanced technological platforms, i.e., bioreactors, represents a key element to define standardized, automated and repeatable bioprocessing steps replicating in vitro the physicochemical and mechanical cues triggering maturation of engineered cardiac tissues. We describe our technological advances in developing macroand micro-scale bioreactors aimed at providing single or combined mechanical/electrical stimulation either to cultured cells or tissue constructs. Additional design requirements are: i) trading off the technical specifications with the needs of the final user’s environment, i.e. the biological lab; ii) the straightforward operability and the compliance with good laboratory practice; iii) a smart use of the concept of modularity, i.e. allowing simultaneous multiple cultures with independent stimulation patterns, which speeds up the experimental campaigns. The developed devices allow for a fine tuning of cellular electrical/mechanical stimulations, representing ideal tools for standardized and high-throughput analyses in cell biology and cardiac regenerative medicine. I. THE ROLE OF BIOREACTORS IN MYOCARDIAL TISSUE