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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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