References of "Geris, Liesbet"
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See detailA mechano-regulatory model for bone healing predictions under the influence of ultrasound.
Vavva, Maria G.; Grivas, Konstantinos N.; Carlier, Aurelie et al

in Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference (2015), 2015

The bone healing process involves a sequence of cellular action and interaction, regulated by biochemical and mechanical signals. Experimental studies have shown that ultrasound accelerates bone ... [more ▼]

The bone healing process involves a sequence of cellular action and interaction, regulated by biochemical and mechanical signals. Experimental studies have shown that ultrasound accelerates bone solidification and enhances the underlying healing mechanisms. An integrated computational model is presented for deriving predictions of bone healing under the presence of ultrasound. [less ▲]

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See detailA Three-Dimensional Computational Fluid Dynamics Model Of Shear Stress Distribution During Neotissue Growth In A Perfusion Bioreactor.
Guyot, Yann ULg; Luyten, F. P.; Schrooten, J. et al

in Biotechnology and bioengineering (2015)

Bone tissue engineering strategies use flow through perfusion bioreactors to apply mechanical stimuli to cells seeded on porous scaffolds. Cells grow on the scaffold surface but also by bridging the ... [more ▼]

Bone tissue engineering strategies use flow through perfusion bioreactors to apply mechanical stimuli to cells seeded on porous scaffolds. Cells grow on the scaffold surface but also by bridging the scaffold pores leading a fully filled scaffold following the scaffold's geometric characteristics. Current computational fluid dynamic approaches for tissue engineering bioreactor systems have been mostly carried out for empty scaffolds. The effect of 3D cell growth and extracellular matrix formation (termed in this study as neotissue growth), on its surrounding fluid flow field is a challenge yet to be tackled. In this work a combined approach was followed linking curvature driven cell growth to fluid dynamics modeling. The level-set method (LSM) was employed to capture neotissue growth driven by curvature, while the Stokes and Darcy equations, combined in the Brinkman equation, provided information regarding the distribution of the shear stress profile at the neotissue/medium interface and within the neotissue itself during growth. The neotissue was assumed to be micro-porous allowing flow through its structure while at the same time allowing the simulation of complete scaffold filling without numerical convergence issues. The results show a significant difference in the amplitude of shear stress for cells located within the micro-porous neo-tissue or at the neotissue/medium interface, demonstrating the importance of taking along the neotissue in the calculation of the mechanical stimulation of cells during culture.The presented computational framework is used on different scaffold pore geometries demonstrating its potential to be used a design as tool for scaffold architecture taking into account the growing neotissue. This article is protected by copyright. All rights reserved. [less ▲]

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See detailCell based advanced therapeutic medicinal products for bone repair: Keep it simple?
Leijten, J.; Chai, Y. C.; Papantoniou, I. et al

in Advanced drug delivery reviews (2015), 84

The development of cell based advanced therapeutic medicinal products (ATMPs) for bone repair has been expected to revolutionize the health care system for the clinical treatment of bone defects. Despite ... [more ▼]

The development of cell based advanced therapeutic medicinal products (ATMPs) for bone repair has been expected to revolutionize the health care system for the clinical treatment of bone defects. Despite this great promise, the clinical outcomes of the few cell based ATMPs that have been translated into clinical treatments have been far from impressive. In part, the clinical outcomes have been hampered because of the simplicity of the first wave of products. In response the field has set-out and amassed a plethora of complexities to alleviate the simplicity induced limitations. Many of these potential second wave products have remained "stuck" in the development pipeline. This is due to a number of reasons including the lack of a regulatory framework that has been evolving in the last years and the shortage of enabling technologies for industrial manufacturing to deal with these novel complexities. In this review, we reflect on the current ATMPs and give special attention to novel approaches that are able to provide complexity to ATMPs in a straightforward manner. Moreover, we discuss the potential tools able to produce or predict 'goldilocks' ATMPs, which are neither too simple nor too complex. [less ▲]

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See detailComputational modeling under uncertainty: challenges and opportunities
Gomez-Cabrero, David; Geris, Liesbet ULg

in Modeling under uncertainty: a computational modeling approach (2015)

Computational Biology has increasingly become an important tool for biomedical and translational research. In particular, when generating novel hypothesis despite fundamental uncertainties in data and ... [more ▼]

Computational Biology has increasingly become an important tool for biomedical and translational research. In particular, when generating novel hypothesis despite fundamental uncertainties in data and mechanistic understanding of biological processes underpinning diseases. While in the present book, we have reviewed the necessary background and existing novel methodologies that set the basis for dealing with uncertainty, there are still many “grey”, or less well-defined, areas of investigations offering both challenges and opportunities. This final chapter in the book provides some reflections on those areas, namely: (1) the need for novel robust mathematical and statistical methodologies to generate hypothesis under uncertainty; (2) the challenge of aligning those methodologies in a context that requires larger computational resources; (3) the accessibility of modeling tools for less mathematical literate researchers; and (4) the integration of models with –omics data and its application in clinical environments. [less ▲]

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See detailAn introduction to uncertainty in the development of computational models of biological processes
Geris, Liesbet ULg; Gomez-Cabrero, David

in Modeling under uncertainty: a computational modeling approach (2015)

This chapter aims to provide an introduction to the different ways in which uncertainty can be dealt with computational modelling of biological processes. The first step is model establishment under ... [more ▼]

This chapter aims to provide an introduction to the different ways in which uncertainty can be dealt with computational modelling of biological processes. The first step is model establishment under uncertainty. Once models have been established, data can further be used to select which of the proposed models best meets the predefined criteria. Subsequently, parameter values can be optimized for a specific model configuration. Sensitivity analyses allow to assess the influence of the previous choices on the model output. Additionally, model adaptation permits to focus on specific aspects of the model without losing its global predictive capacity. Finally, predictions with the established models should also consider the effect of uncertainty in the model development process. [less ▲]

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See detailOxygen as a critical determinant of bone fracture healing-a multiscale model.
Carlier, Aurelie; Geris, Liesbet ULg; Gastel, Nick Van et al

in Journal of theoretical biology (2015), 365

A timely restoration of the ruptured blood vessel network in order to deliver oxygen and nutrients to the fracture zone is crucial for successful bone healing. Indeed, oxygen plays a key role in the ... [more ▼]

A timely restoration of the ruptured blood vessel network in order to deliver oxygen and nutrients to the fracture zone is crucial for successful bone healing. Indeed, oxygen plays a key role in the aerobic metabolism of cells, in the activity of a myriad of enzymes as well as in the regulation of several (angiogenic) genes. In this paper, a previously developed model of bone fracture healing is further improved with a detailed description of the influence of oxygen on various cellular processes that occur during bone fracture healing. Oxygen ranges of the cell-specific oxygen-dependent processes were established based on the state-of-the art experimental knowledge through a rigorous literature study. The newly developed oxygen model is compared with previously published experimental and in silico results. An extensive sensitivity analysis was also performed on the newly introduced oxygen thresholds, indicating the robustness of the oxygen model. Finally, the oxygen model was applied to the challenging clinical case of a critical sized defect (3mm) where it predicted the formation of a fracture non-union. Further model analyses showed that the harsh hypoxic conditions in the central region of the callus resulted in cell death and disrupted bone healing thereby indicating the importance of a timely vascularization for the successful healing of a large bone defect. In conclusion, this work demonstrates that the oxygen model is a powerful tool to further unravel the complex spatiotemporal interplay of oxygen delivery, diffusion and consumption with the several healing steps, each occurring at distinct, optimal oxygen tensions during the bone repair process. [less ▲]

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See detailBringing computational models of bone regeneration to the clinic.
Carlier, Aurelie; Geris, Liesbet ULg; Lammens, Johan et al

in Wiley interdisciplinary reviews. Systems biology and medicine (2015), 7(4), 183-94

Although the field of bone regeneration has experienced great advancements in the last decades, integrating all the relevant, patient-specific information into a personalized diagnosis and optimal ... [more ▼]

Although the field of bone regeneration has experienced great advancements in the last decades, integrating all the relevant, patient-specific information into a personalized diagnosis and optimal treatment remains a challenging task due to the large number of variables that affect bone regeneration. Computational models have the potential to cope with this complexity and to improve the fundamental understanding of the bone regeneration processes as well as to predict and optimize the patient-specific treatment strategies. However, the current use of computational models in daily orthopedic practice is very limited or inexistent. We have identified three key hurdles that limit the translation of computational models of bone regeneration from bench to bed side. First, there exists a clear mismatch between the scope of the existing and the clinically required models. Second, most computational models are confronted with limited quantitative information of insufficient quality thereby hampering the determination of patient-specific parameter values. Third, current computational models are only corroborated with animal models, whereas a thorough (retrospective and prospective) assessment of the computational model will be crucial to convince the health care providers of the capabilities thereof. These challenges must be addressed so that computational models of bone regeneration can reach their true potential, resulting in the advancement of individualized care and reduction of the associated health care costs. WIREs Syst Biol Med 2015, 7:183-194. doi: 10.1002/wsbm.1299 For further resources related to this article, please visit the WIREs website. CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. [less ▲]

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See detailMultifactorial Optimization of Contrast-Enhanced Nanofocus Computed Tomography for Quantitative Analysis of Neo-Tissue Formation in Tissue Engineering Constructs.
Sonnaert, Maarten; Kerckhofs, Greet; Papantoniou, Ioannis et al

in PloS one (2015), 10(6), 0130227

To progress the fields of tissue engineering (TE) and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells ... [more ▼]

To progress the fields of tissue engineering (TE) and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells/tissue combined with scaffolds) becomes essential. In this study, we have defined the most optimal staining conditions for contrast-enhanced nanofocus computed tomography for three dimensional visualization and quantitative analysis of in vitro engineered neo-tissue (i.e. extracellular matrix containing cells) in perfusion bioreactor-developed Ti6Al4V constructs. A fractional factorial 'design of experiments' approach was used to elucidate the influence of the staining time and concentration of two contrast agents (Hexabrix and phosphotungstic acid) and the neo-tissue volume on the image contrast and dataset quality. Additionally, the neo-tissue shrinkage that was induced by phosphotungstic acid staining was quantified to determine the operating window within which this contrast agent can be accurately applied. For Hexabrix the staining concentration was the main parameter influencing image contrast and dataset quality. Using phosphotungstic acid the staining concentration had a significant influence on the image contrast while both staining concentration and neo-tissue volume had an influence on the dataset quality. The use of high concentrations of phosphotungstic acid did however introduce significant shrinkage of the neo-tissue indicating that, despite sub-optimal image contrast, low concentrations of this staining agent should be used to enable quantitative analysis. To conclude, design of experiments allowed us to define the most optimal staining conditions for contrast-enhanced nanofocus computed tomography to be used as a routine screening tool of neo-tissue formation in Ti6Al4V constructs, transforming it into a robust three dimensional quality control methodology. [less ▲]

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See detailInvestigating cell-carrier combinations for bone formation using a mathematical model
Manhas, Varun ULg; Guyot, Yann ULg; Chai, Yoke C et al

Poster (2014, November 28)

This study describes the development and implementation of a bio-regulatory model that focuses on the Ca2+ release from CaP scaffolds and aims to determine the local Ca2+ concentration of different ... [more ▼]

This study describes the development and implementation of a bio-regulatory model that focuses on the Ca2+ release from CaP scaffolds and aims to determine the local Ca2+ concentration of different clinical grade CaP scaffold types during bone formation. [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 detailModel-guided bone tissue engineering: from bench to bedside via in silico modeling
Geris, Liesbet ULg

Conference (2014, September)

The creation of man-made living implants is the holy grail of tissue engineering (TE). As basic science advances, one of the major challenges in TE is the translation of the increasing biological ... [more ▼]

The creation of man-made living implants is the holy grail of tissue engineering (TE). As basic science advances, one of the major challenges in TE is the translation of the increasing biological knowledge on complex cell and tissue behavior into a predictive and robust engineering process. Mastering this complexity is an essential step towards clinical applications of TE. Computational modeling allows to study the biological complexity in a more integrative and quantitative way. Specifically, computational tools can help in quantifying and optimizing the TE product and process but also in assessing the influence of the in vivo environment on the behavior of the TE product after implantation. In this talk, I will use the example of bone tissue engineering to demonstrate how computational modeling can contribute in all aspects of the TE product development cycle: cells, carriers, culture conditions and clinics (figure 1 and 2). Depending on the specific question that needs to be answered the optimal model systems can vary from single scale to multiscale. Furthermore, depending on the available information, model systems can be purely data-driven or more hypothesis-driven in nature. The talk makes the case for in silico models receiving proper recognition, besides the in vitro and in vivo work in the TE field. Figure 1: overview of the 4 important components in bone tissue engineering: cells, carriers, culture and clinics. Figure 2: overview of in silico contributions to the 4 important components in bone tissue engineering: cells [1], carriers, culture [3] and clinics [4]. Acknowledgements This work presented in this talk is part of Prometheus, the KU Leuven R&D division for skeletal tissue engineering. http://www.kuleuven.be/prometheus. The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreements 279100; from the Research Programme of the Research Foundation - Flanders (FWO, grant n. G.0982.11), from the Belgian National Fund for Scientific Research (FNRS) and from the special research fund of the KU Leuven (GOA/13/016) References 1. Kerkhofs J, Roberts SJ, Luyten FP, Van Oosterwyck H, Geris L. Relating the chondrocyte gene network to growth plate morphology: from genes to phenotype. PLoS One. 2012;7(4):e34729. doi: 10.1371/journal.pone.0034729 2. Guyot Y, Papantoniou I, Chai YC, Van Bael S, Schrooten J, Geris L. A computational model for cell/ECM growth on 3D surfaces using the level set method: a bone tissue engineering case study.Biomech Model Mechanobiol. 2014 3. Carlier A, Geris L, Bentley K, Carmeliet G, Carmeliet P, Van Oosterwyck H. MOSAIC: a multiscale model of osteogenesis and sprouting angiogenesis with lateral inhibition of endothelial cells. PLoS Comput Biol. 2012;8(10):e1002724. [less ▲]

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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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