Microenvironment Oriented Bioreactors

Tissue engineering (TE), a field aiming to restore, maintain and/or improve damaged tissues and organs, is a strongly increasing research area. TE approaches require different factors that are relevant for proper tissue regeneration. These factors include biocompatible scaffolds, cells, and different applied stimuli, which altogether mimic the natural environment of the tissue. The increased knowledge in cell and tissue response and the way cells interplay has led to the notion of cell microenvironment, which is considered a determining factor for triggering proper cell behavior and function. Within this cell microenvironment, the extracellular matrix (ECM) serves as a structural base for cells and as a source of growth factors and biophysical cues. Also, the three-dimensional character of the microenvironment is one of the most recognized key factors for obtaining specific cell responses in vivo, being the physical cues increasingly investigated. Supporting those advances is the progress in the design of smart and multifunctional materials, whose properties improve the control of cell behavior through the possibility of providing specific chemical and physical stimuli to the cellular environment. In this sense, a varying set of bioreactors that properly stimulate those materials and cells in vitro and thus create an appropriate biomimetic microenvironment have been developed. This review provides a comprehensive overview on the important microenvironments of different cells and tissues, the type of smart materials used for providing such microenvironments and the specific bioreactor technologies that allow subjecting the cells and tissues to the required biomimetic biochemical and biophysical cues. Further, it is shown that microfluidic bioreactors represent an increasingly growing and interesting field that hold great promise for achieving suitable TE strategies.