Spatial optimization in perfusion bioreactors improves bone tissue‐engineered construct quality attributes

Abstract

Perfusion bioreactors have shown great promise for tissue engineering applications providing a homogeneous and consistent distribution of nutrients and flow-induced shear stresses throughout tissue-engineered constructs. However, non-uniform fluid-flow profiles found in the perfusion chamber entrance region have been shown to affect tissue-engineered construct quality characteristics during culture. In this study a whole perfusion and construct, three dimensional (3D) computational fluid dynamics approach was used in order to optimize a critical design parameter such as the location of the regular pore scaffolds within the perfusion bioreactor chamber. Computational studies were coupled to bioreactor experiments for a case-study flow rate. Two cases were compared in the first instance seeded scaffolds were positioned immediately after the perfusion chamber inlet while a second group was positioned at the computationally determined optimum distance were a steady state flow profile had been reached. Experimental data showed that scaffold location affected significantly cell content and neo-tissue distribution, as determined and quantified by contrast enhanced nanoCT, within the constructs both at 14 and 21 days of culture. However, gene expression level of osteopontin and osteocalcin was not affected by the scaffold location. This study demonstrates that the bioreactor chamber environment, incorporating a scaffold and its location within it, affects the flow patterns within the pores throughout the scaffold requiring therefore dedicated optimization that can lead to bone tissue engineered constructs with improved quality attributes.

An Integrated Bioprocess for the Expansion and Chondrogenic Priming of Human Periosteum‐Derived Progenitor Cells in Suspension Bioreactors

“…In addition, they have shown to possess superior bone forming properties to bone marrow derived and other MSCs when implanted on specific calcium phosphate (CaP) carriers . When cultured in perfusion bioreactors they have been shown to be able to differentiate into the osteogenic lineage producing mineralized extra cellular matrix (ECM) and to heal calvarial defects in mice . Previously, our group carried out expansion of these cells in large scale bioreactor systems, but till now, to the best of our knowledge, there has been no attempt to expand and prime these cells toward chondrogenic lineage in the same culture setup.…”

Regenerative orthopaedics: in vitro, in vivo … in silico

“…As reported on several occasions, bioreactor culture can be an important step in the TE product development cycle, allowing a reduction of the product variability [56][57][58]. A plethora of bioreactor setups are available on the market, from complete industrially developed closed systems to modular research variants.…”

“…Guyot and co-authors used a description of curvaturebased cell growth in combination with a detailed model of a perfusion bioreactor system. The combined multiphysics modelling platform has been used to optimize the location of the TE construct inside the bioreactor increasing product homogeneity and quality [56] and to screen various scaffold designs for optimal neotissue growth [39]. Once validated, these multi-physics models can become an inherent part of the bioreactor control loop providing an insight view in the TE product in culture by allowing to liaise the bioreactor sensor read-outs (e.g.…”

2D µ-Particle Image Velocimetry and Computational Fluid Dynamics Study Within a 3D Porous Scaffold

“…Zermatten et al36 compared the flow field inside a scaffold with regular microstructure and another with an irregular pore network showing that in irregular scaffold networks the streamlines follow preferable channels so no regular distribution of cells or nutrients can be reached. Furthermore, scaffold location inside the bioreactor and flow rate are also key parameters in perfusion systems as demonstrated by Papantoniou et al24 The geometry of the chamber can also modify the flow profile inside the scaffold as shown by Hidalgo-Bastida et al9 where a circular and a rectangular bioreactor-system were compared.…”