Methods in Molecular Biology (2022) 2436: 127–134

DOI 10.1007/7651_2021_410

© Springer Science+Business Media, LLC 2021

Published online: 04 June 2021

Optimized Method to Improve Cell Activity in 3D Scaffolds

Under a Dual Real-Time Dynamic Bioreactor System

Flavia Pedrini, Moema A. Hausen, and Eliana A. R. Duek

Abstract

Bioreactor systems that allow the simulation of in vivo variables in a controlled in vitro environment, were a

great advance in the field of tissue engineering. Due to the dynamic-mechanical features that some tissues

present, 3D-engineered constructs often do not exhibit the biomechanical properties of these native tissues.

Thus, a successful approach must not only achieve tissue repair but also restore its function after injury.

Here, we describe a method to improve cell activity in 3D scaffolds in a dynamic bioreactor system through

the application of mechanical compression and fluid flow for tissue engineering approaches.

Key words 3D Scaffolds, Bioreactor, Cell culture, Fluid flow, Mechanical compression, Tissue

Engineering

1

Introduction

Tissue engineering emerged as an alternative approach that encom-

passes the architecture of bioartificial tissues in vitro through the

implantation of cells on 3D scaffolds [1]. A key factor in the

generation of these 3D constructs is the application of mechanical

stimuli during maturation to regulate the nascent tissue to a func-

tional activity similar to the quiescent one. In this context,

bioreactor-based systems have gained particular interest as they

produce clinically effective tissue-based constructs [2, 3]. An

important finding was that, when mechanical compression is

applied under static conditions, its effects are harmful to cell

growth,

while

dynamic

compression

promotes

cell

activity

[4]. Thus, a bioreactor should be able to meet the following

requirements: (a) intensify mass transfer through perfusion strate-

gies that generate a dynamic environment that promotes cell pro-

liferation and differentiation, and (b) subject the tissue to

physiologically relevant loads that can accelerate the production of

extracellular matrix in vitro [5]. Studies indicate that when fluid

dynamics are applied, cells experience stimuli to which they respond

more actively (Fig. 1) [6–9]. In addition to nutrient diffusion, fluid

flow is also a way to induce shear stress and give rise to 3D

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