title: 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.
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Onderwijs en Navorsing 1 (+8), Herestraat 49-PB813, B-3000, Leuven, Belgium; Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papantoniou
authors.forename: Yann
authors.initials: Y
authors.lastname: Guyot
authors.forename: Maarten
authors.initials: M
authors.lastname: Sonnaert
authors.forename: Greet
authors.initials: G
authors.lastname: Kerckhofs
authors.forename: Frank P
authors.initials: FP
authors.lastname: Luyten
authors.forename: Liesbet
authors.initials: L
authors.lastname: Geris
authors.forename: Jan
authors.initials: J
authors.lastname: Schrooten
mesh_terms: D019149:Bioreactors; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D006801:Humans; D010477:Perfusion; D010521:Periosteum / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed
chemical_list: D004247:DNA
keywords: contrast enhanced nanoCT; human periosteum derived stem cells; perfusion bioreactor; quality attributes; tissue engineered construct