References of "Geris, Liesbet"
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See detailA semiquantitative framework for gene regulatory networks: increasing the time and quantitative resolution of Boolean networks
Kerkhofs, Johan ULg; Geris, Liesbet ULg

in PLoS ONE (2015), 10(6), 0130033

Boolean models have been instrumental in predicting general features of gene networks and more recently also as explorative tools in specific biological applications. In this study we introduce a basic ... [more ▼]

Boolean models have been instrumental in predicting general features of gene networks and more recently also as explorative tools in specific biological applications. In this study we introduce a basic quantitative and a limited time resolution to a discrete (Boolean) framework. Quantitative resolution is improved through the employ of normalized variables in unison with an additive approach. Increased time resolution stems from the introduction of two distinct priority classes. Through the implementation of a previously published chondrocyte network and T helper cell network, we show that this addition of quantitative and time resolution broadens the scope of biological behaviour that can be captured by the models. Specifically, the quantitative resolution readily allows models to discern qualitative differences in dosage response to growth factors. The limited time resolution, in turn, can influence the reachability of attractors, delineating the likely long term system behaviour. Importantly, the information required for implementation of these features, such as the nature of an interaction, is typically obtainable from the literature. Nonetheless, a trade-off is always present between additional computational cost of this approach and the likelihood of extending the model’s scope. Indeed, in some cases the inclusion of these features does not yield additional insight. This framework, incorporating increased and readily available time and semi-quantitative resolution, can help in substantiating the litmus test of dynamics for gene networks, firstly by excluding unlikely dynamics and secondly by refining falsifiable predictions on qualitative behaviour. [less ▲]

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See detailIn silico screening to predict chondrocyte hypertrophy using a semiquantitative gene network model
Kerkhofs, Johan ULg; Leijten, Jeroen; Luyten, Frank et al

Poster (2015, April 30)

PURPOSE: In development, chondrocyte hypertrophy is a crucial and well-studied step in endochondral ossification. Hypertrophy may also play a role in pathophysiological processes, including osteoarthritis ... [more ▼]

PURPOSE: In development, chondrocyte hypertrophy is a crucial and well-studied step in endochondral ossification. Hypertrophy may also play a role in pathophysiological processes, including osteoarthritis. We employ a computational approach to estimate the effect of individual factors in this complex process. METHODS: We have combined information gleaned from a high number of publications on chondrocyte differentiation into a gene regulatory network of 46 factors and over 150 interactions. This network can estimate the stability of proliferative chondrocytes/permanent cartilage (stable state with SOX9 activity) and hypertrophic chondrocytes (stable state with RUNX2 activity) by employing 2 measures. A first measure is a Monte Carlo analysis that assesses stability in the face of random initial conditions, the second modifies stable states to estimate the sensitivity to perturbation. RESULTS: For each factor, these qualitative measures are calculated in silico under knockout and overexpression conditions and compared to the wild type situation. This enables screening of the effects of all incorporated factors on cartilage homeostasis, differentiation and pathogenesis via the initiation of hypertrophy. Indeed, our gene network analysis indicated multiple candidate genes for the development of osteoarthritis. Factors that amplify the SOX9 attractor basin include TGFβ, PPR, IGF-I, and PKA. The presence of RAS, IHH, GLI2 and FGF is required for the Runx2 stable state. Using a literature study, we corroborated several of the proposed factors. CONCLUSIONS: In silico screening of overexpression and knockout presents a novel strategy to improve bone and cartilage tissue engineering approaches, and can be used to propose a list of putative therapeutic targets for e.g. osteoarthritis. [less ▲]

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See detailInvestigation of shear stress evolution during neotissue growth in a perfusion bioreactor using 3d multiphysics modeling
Guyot, Yann ULg; Papantoniou, Ioannis; Schrooten, Jan et al

Conference (2014, October)

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See detailA Multiphysics model of neotissue growth in a perfu sion bioreactor
Guyot, Yann ULg; Papantoniou, Ioannis; Schrooten, Jan et al

Conference (2014, September)

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See detail3D MODELING OF SHEAR STRESS DEVELOPMENT DURING NEOTISSUE GROWTH IN A PERFUSION BIOREACTOR
Guyot, Yann ULg; Papantoniou, Ioannis; Schrooten, Jan et al

Conference (2014, July)

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See detailA Multiphycics approach to calculate shear stresses during neotissue growth in perfusion bioreactor
Guyot, Yann ULg; Papantoniou, Ioannis; Schrooten, Jan et al

Conference (2014, July)

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See detailSpatial optimization in perfusion bioreactors improves bone tissue-engineered construct quality attributes
Papantoniou, Ioannis; Guyot, Yann ULg; Sonnaert, Maarten et al

in Biotechnology and Bioengineering (2014)

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 ... [more ▼]

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 [less ▲]

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See detailA computational model for cell/ECM growth on 3D surfaces using the level set method: a bone tissue engineering case study
Guyot, Yann ULg; papantoniou, Ioannis; Chai, Yoke Chin et al

in Biomechanics and Modeling in Mechanobiology (2014)

Three dimensional (3D) open porous scaffolds are commonly used in tissue engineering (TE) applications to provide an initial template for cell attachment and subsequent cell growth and construct ... [more ▼]

Three dimensional (3D) open porous scaffolds are commonly used in tissue engineering (TE) applications to provide an initial template for cell attachment and subsequent cell growth and construct development. The macroscopic geometry of the scaffold is key in determining the kinetics of cell growth and thus in vitro ‘tissue’ formation. In this study we developed a computational framework based on the level set methodology to predict curvature-dependent growth of the cell/extracellular matrix domain within TE constructs. Scaffolds with various geometries (hexagonal, square, triangular) and pore sizes (500 and 1000 µm) were produced in house by additive manufacturing, seeded with human periosteum-derived cells and cultured under static conditions for 14 days. Using the projected tissue area as an output measure, the comparison between the experimental and the numerical results demonstrated a good qualitative and quantitative behavior of the framework. The model in its current form is able to provide important spatio-temporal information on final shape and speed of pore-filling of tissue engineered constructs by cells and extracellular matrix during static culture. [less ▲]

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See detailBringing regenerating tissues to life: the importance of angiogenesis in tissue engineering
Carlier, Aurélie ULg; Van Gastel, Nick; Geris, Liesbet ULg et al

Poster (2014, March 11)

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See detailRegenerative orthopaedics: in vitro, in vivo ... in silico.
Geris, Liesbet ULg

in International orthopaedics (2014), 38(9), 1771-8

In silico, defined in analogy to in vitro and in vivo as those studies that are performed on a computer, is an essential step in problem-solving and product development in classical engineering fields ... [more ▼]

In silico, defined in analogy to in vitro and in vivo as those studies that are performed on a computer, is an essential step in problem-solving and product development in classical engineering fields. The use of in silico models is now slowly easing its way into medicine. In silico models are already used in orthopaedics for the planning of complicated surgeries, personalised implant design and the analysis of gait measurements. However, these in silico models often lack the simulation of the response of the biological system over time. In silico models focusing on the response of the biological systems are in full development. This review starts with an introduction into in silico models of orthopaedic processes. Special attention is paid to the classification of models according to their spatiotemporal scale (gene/protein to population) and the information they were built on (data vs hypotheses). Subsequently, the review focuses on the in silico models used in regenerative orthopaedics research. Contributions of in silico models to an enhanced understanding and optimisation of four key elements-cells, carriers, culture and clinics-are illustrated. Finally, a number of challenges are identified, related to the computational aspects but also to the integration of in silico tools into clinical practice. [less ▲]

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See detailIn silico biology of bone regeneration inside calcium phosphate scaffolds
Carlier, Aurélie ULg; Van Oosterwyck, Hans; Geris, Liesbet ULg

in Tissue Engineering: Computer Modeling, Biofabrication and Cell Behavior (2014)

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See detailOxygen: a critical component of critically sized defects
Carlier, Aurélie ULg; Van Gastel, Nick; Geris, Liesbet ULg et al

Poster (2013, December 19)

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See detailA mathematical model of the role of oxygen during normal and delayed fracture repair
Carlier, Aurélie ULg; Van Gastel, Nick; Carmeliet, Geert et al

Conference (2013, October 24)

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See detailAssessing local Ca2+ concentrations in calcium phosphate scaffolds by computational modelling
Manhas, Varun ULg; Guyot, Yann ULg; Chai, Yoke Chin et al

Poster (2013, October 24)

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See detailModeling cell/matrix growth in three dimensional scaffolds under dynamic culture conditions
Guyot, Yann ULg; Papantoniou, Ioannis; Chai, Yoke Chin et al

Conference (2013, October)

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See detailCongenital pseudarthrosis of the tibia: a mathematical approach
Van Schepdael, An; Carlier, Aurélie ULg; Ashbourn, Joanna et al

Conference (2013, September 13)

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See detailA MODEL FOR CELL/MATRIX GROWTH ON 3D SURFACES: A COUPLING OF LEVEL SET METHOD AND BRINKMAN EQUATION
Guyot, Yann ULg; Papantoniou, Ioannis; Chai, Yoke Chin et al

Conference (2013, September 11)

Detailed reference viewed: 64 (6 ULg)