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Combining in silico and in vitro models to inform cell seeding strategies in tissue engineering

Coy, R; Al-Badri, G; Kayal, C; O'Rourke, C; Kingham, PJ; Phillips, JB; Shipley, RJ; (2020) Combining in silico and in vitro models to inform cell seeding strategies in tissue engineering. Journal of the Royal Society Interface , 17 (164) , Article 20190801. 10.1098/rsif.2019.0801. Green open access

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Abstract

The seeding density of therapeutic cells in engineered tissue impacts both cell survival and vascularization. Excessively high seeded cell densities can result in increased death and thus waste of valuable cells, whereas lower seeded cell densities may not provide sufficient support for the tissue in vivo, reducing efficacy. Additionally, the production of growth factors by therapeutic cells in low oxygen environments offers a way of generating growth factor gradients, which are important for vascularization, but hypoxia can also induce unwanted levels of cell death. This is a complex problem that lends itself to a combination of computational modelling and experimentation. Here, we present a spatio-temporal mathematical model parametrized using in vitro data capable of simulating the interactions between a therapeutic cell population, oxygen concentrations and vascular endothelial growth factor (VEGF) concentrations in engineered tissues. Simulations of collagen nerve repair constructs suggest that specific seeded cell densities and non-uniform spatial distributions of seeded cells could enhance cell survival and the generation of VEGF gradients. These predictions can now be tested using targeted experiments.

Type: Article
Title: Combining in silico and in vitro models to inform cell seeding strategies in tissue engineering
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1098/rsif.2019.0801
Publisher version: https://doi.org/10.1098/rsif.2019.0801
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Mathematical modelling; tissue engineering; interdisciplinary; nerve; oxygen
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10095105
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