Bioreactor Design for Dynamic Process Optimization in Tissue Engineering

Tissue engineering is an interdisciplinary field in which cell biology, biomaterials science, and surgery are combined and its main goal is to repair, replace and reproduce tissues and organs. Following this procedure, cells are seeded on proper scaffolds and induced in sequence to adhere, eventually differentiate, proliferate and finally to produce the wanted extracellular matrix (ECM). During cell culture, the usefulness of applying proper physiological-like stimuli, i.e., biochemical but also mechanical signals to drive and accelerate both cell differentiation and ECM production has been demonstrated. Tissue regeneration can be either conducted entirely in vivo or assisted by a previous in vitro phase. Considering the latter situation, a bioreactor can be defined as any apparatus that attempts to mimic physiological conditions in order to maintain and encourage tissue regeneration in dynamic conditions. Dynamic cell cultures using bioreactors can be considered a good intermediate step between the conventional in vitro static approach and in vivo studies. Therefore it is possible to promote the formation of the specific tissue by simulating physiological conditions via the application of specific mechanical and biochemical stimuli. The proposed work is focused on the design and development of bioreactors for bone and cartilage regeneration, in which optimal cell culture conditions are controlled (temperature, nutrients, carbon dioxide and oxygen levels), and mechanical stimuli are applied on the cell constructs. This study presents a wide investigation concerning these mechanical stimulations in order to understand the best cell culture parameters for the activations of cells, naturally accustomed to similar stresses inside the joint. In particular, direct compression, change in hydrodynamic pressure and perfusion modes are compared and analyzed.