Engineering parameters in bioreactor's design: a critical aspect in tissue engineering

Abstract

Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

Figure 1

Comparison between unsteady state model and experimental results for the partial pressure of oxygen in the headspace of the ventilation flasks f1, f4, f7, f9 (sterile plug dimensions in f1 < f4 < f7 < f9) is obtained for the fermentation of C. glutamicum DM 1730 on 10 g/L glucose and 21 g/L MOPS (V _L = 10 mL, n = 400 rpm, T = 30°C, d _o = 5 cm, Y _x/s = 0.48, Y _x/o2 = 53 g/mol, RQ = 1 where d _o, V _L, Y _x/s, Y _x/o2, and RQ are shaking diameter, filling volume, yield of biomass with respect to substrate, yield of biomass with respect to oxygen, and respiration quotient, resp.).

Figure 2

Radial velocity distribution in a shaken 24-wells bioreactor that illustrates inhomogeneous map of radial velocity at the interface of liquid and air.

Figure 3

Volume fraction distribution in a shaken 24-wells bioreactor that allows accurate prediction of gas-liquid interface area within the shaking bioreactor.

Figure 4

Energy dissipation rate (a) and shear stress distribution (b) versus radial position on a scaffold with radius of 1 cm that obviously represents safe generated shear stress on the scaffold for mammalian cell cultures.

Figure 5

Schematics of cell morphology (a) before (b) after initiation of flow indicating flow assisted elongation of cells under continuous flow.

Figure 6

Demonstration of path lines to track the fluid particles within the bioreactor (a) and velocity magnitude to evaluate maximal shear stress in order to optimize shear stress distribution (b) in a perfusion bioreactor belonging to UTLSE.

Figure 7

Comparison of OTR resulting from model and from experiments for a specific aerobic microorganism. The plot provides evidence of the proximity of OTR values between experimental and simulation results and of the efficacy of the simulation efforts.