Physically Active Bioreactors for Tissue Engineering Applications

Abstract

Tissue engineering (TE) is a dynamic and growing scientific field that merges the knowledge of different areas such as biology, physics, medicine, and engineering. [1] The TE discipline was first coined at a National Science Foundation sponsored meeting in 1987, thus originating a field that employs life sciences and engineering with the purpose of developing biologic or synthetic supports to restore, keep, or enhance tissue functions or damaged organs. [2] The classical TE approach has been mainly focusing on associating cells with a supporting matrix, also called biomaterials or scaffolds, that essentially acts as a passive template for tissue formation in vitro by allowing cells to adhere, migrate, differentiate, and produce tissue. Usually, the cells are seeded onto the scaffolds and, occasionally, growth factors are also added. The combination of cells, growth factors, and scaffold is often referred as the TE triad. [3] Nevertheless, novel approaches in TE that include the application of a biophysical stimuli to the scaffolds through the use of a bioreactor are emerging. [4] Tissue engineering (TE) is a strongly expanding research area. TE approaches require biocompatible scaffolds, cells, and different applied stimuli, which altogether mimic the natural tissue microenvironment. Also, the extracellular matrix serves as a structural base for cells and as a source of growth factors and biophysical cues. The 3D characteristics 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 of smart and multifunctional materials design, whose properties improve the cell behavior control 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, creating an appropriate biomimetic microenvironment, is developed to obtain active bioreactors. This review provides a comprehensive overview on the important microenvironments of different cells and tissues, the smart materials type used for providing such microenvironments and the specific bioreactor technologies that allow subjecting the cells/ tissues to the required biomimetic biochemical and biophysical cues. Further, it is shown that microfluidic bioreactors represent a growing and interesting field that hold great promise for achieving suitable TE strategies.

Exploring electroactive microenvironments in polymer-based nanocomposites to sensitize bacterial cells to low-dose embedded silver nanoparticles

“…Under static condition, one well plate was placed in the incubator for 12 h at the temperature of 37 ºC, without shaking or any other stimulus to bacteria. On the other side, under the dynamic conditions, the 24-well plate was placed on a lab-made bioreactor system [17,29] with mechanical stimulation for 12…”

Finite Element Modelling of a Cellular Electric Microenvironment

“…As the end goal of tissue engineering is to create bioreactors that not only mimic one or two aspects of in vivo environments, but replicate and control all cellular developmental cues 61 , electromagnetic and mechanical in silico models as well as models of heat transfer between bioreactor components will need to be combined. In a subsequent modelling phase, coupling phenomena between those interactions such as ohmic heating, electrolytic fluid flow, morphological scaffold deformations in response to electrical stimulation 60 and piezoelectricity 62 can also be added.…”

Oxygen Biosensors and Control in 3D Physiomimetic Experimental Models

“…In addition to controlling the standard parameters as in classical CO 2 incubators (such as temperature or relative humidity), bioreactors are designed to mainly control gas gradients [ 73 ], mechanical stresses (static [ 74 ] and dynamic [ 75 ]) and electrical currents [ 76 ]. The main idea is to control a high number of the physicochemical stimuli to which cells are subjected within the organs and tissues in vivo [ 77 ]. Historically, bioreactors have been developed with discrete components (sensors and actuators) by adapting the available CO 2 incubators.…”