Bone tissue engineering; Fibrin; Hydrogel; In vitro test; Modelling
Abstract :
[en] The in vitro culture of hydrogel-based constructs above a critical size is accompanied by problems of unequal cell distribution when diffusion is the primary mode of oxygen transfer. In this study, an
experimentally informed mathematical model was developed to relate cell proliferation and death
inside fibrin hydrogels to the local oxygen tension in a quantitative manner. The predictive capacity
of the resulting model was tested by comparing its outcomes to the density, distribution and viability
of human periosteum derived cells (hPDCs) that were cultured inside fibrin hydrogels in vitro. The
model was able to reproduce important experimental findings, such as the formation of a multilayered cell sheet at the hydrogel periphery and the occurrence of a cell density gradient
throughout the hydrogel. In addition, the model demonstrated that cell culture in fibrin hydrogels can
lead to complete anoxia in the centre of the hydrogel for realistic values of oxygen diffusion and
consumption. A sensitivity analysis also identified these two parameters, together with the
proliferation parameters of the encapsulated cells, as the governing parameters for the occurrence of anoxia. In conclusion, this study indicates that mathematical models can help to better understand oxygen transport limitations and its influence on cell behaviour during the in vitro culture of cellseeded hydrogels.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Demol, Jan; Division of Biomechanics and Engineering Design, K.U.Leuven, Celestijnenlaan 300C, 3001 Leuven, Belgium,
Lambrechts, Dennis; Division of Biomechanics and Engineering Design, K.U.Leuven, Celestijnenlaan 300C, 3001 Leuven, Belgium,
Geris, Liesbet ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique
Schrooten, Jan; Department of Metallurgy and Materials Engineering, K.U.Leuven, Kasteelpark Arenberg 44, 3001 Leuven, Belgium,
Van Oosterwyck, Hans; Division of Biomechanics and Engineering Design, K.U.Leuven, Celestijnenlaan 300C, 3001 Leuven, Belgium
Language :
English
Title :
Towards a quantitative understanding of oxygen tension and cell density evolution in fibrin hydrogels
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