Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling

The need for efficient and controlled expansion of cell populations is paramount in tissue engineering. Hollow fibre bioreactors (HFBs) have the potential to meet this need, but only with improved understanding of how operating conditions and cell seeding strategy affect cell proliferation in the bioreactor. This study is designed to assess the effects of two key operating parameters (the flow rate of culture medium into the fibre lumen and the fluid pressure imposed at the lumen outlet), together with the cell seeding distribution, on cell population growth in a single-fibre HFB. This is achieved using mathematical modelling and numerical methods to simulate the growth of cell aggregates along the outer surface of the fibre in response to the local oxygen concentration and fluid shear stress. The oxygen delivery to the cell aggregates and the fluid shear stress increase as the flow rate and pressure imposed at the lumen outlet are increased. Although the increased oxygen delivery promotes growth, the higher fluid shear stress can lead to cell death. For a given cell type and initial aggregate distribution, the operating parameters that give the most rapid overall growth can be identified from simulations. For example, when aggregates of rat cardiomyocytes that can tolerate shear stresses of up to 0:05 Pa are evenly distributed along the fibre, the inlet flow rate and outlet pressure that maximise the overall growth rate are predicted to be in the ranges 2.75 x 10(-5) m(2) s(-1) to 3 x 10(-5) m(2) s(-1) (equivalent to 2.07 ml min(-1) to 2.26 ml min(-1)) and 1.077 x 10(5) Pa to 1.083 x 10(5) Pa (or 15.6 psi to 15.7 psi) respectively. The combined effects of the seeding distribution and flow on the growth are also investigated and the optimal conditions for growth found to depend on the shear tolerance and oxygen demands of the cells.

Medienart:

E-Artikel

Erscheinungsjahr:

2014

Erschienen:

2014

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

PloS one - 9(2014), 8 vom: 24., Seite e105813

Sprache:

Englisch

Beteiligte Personen:

Chapman, Lloyd A C [VerfasserIn]
Shipley, Rebecca J [VerfasserIn]
Whiteley, Jonathan P [VerfasserIn]
Ellis, Marianne J [VerfasserIn]
Byrne, Helen M [VerfasserIn]
Waters, Sarah L [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Oxygen
Research Support, Non-U.S. Gov't
S88TT14065

Anmerkungen:

Date Completed 09.12.2015

Date Revised 21.10.2021

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1371/journal.pone.0105813

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM241304423