References of "Geris, Liesbet"
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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 detailSize does matter: an integrative in vivo-in silico approach for the treatment of critical size bone defects.
Carlier, Aurelie; van Gastel, Nick; Geris, Liesbet ULg et al

in PLoS computational biology (2014), 10(11), 1003888

Although bone has a unique restorative capacity, i.e., it has the potential to heal scarlessly, the conditions for spontaneous bone healing are not always present, leading to a delayed union or a non ... [more ▼]

Although bone has a unique restorative capacity, i.e., it has the potential to heal scarlessly, the conditions for spontaneous bone healing are not always present, leading to a delayed union or a non-union. In this work, we use an integrative in vivo-in silico approach to investigate the occurrence of non-unions, as well as to design possible treatment strategies thereof. The gap size of the domain geometry of a previously published mathematical model was enlarged in order to study the complex interplay of blood vessel formation, oxygen supply, growth factors and cell proliferation on the final healing outcome in large bone defects. The multiscale oxygen model was not only able to capture the essential aspects of in vivo non-unions, it also assisted in understanding the underlying mechanisms of action, i.e., the delayed vascularization of the central callus region resulted in harsh hypoxic conditions, cell death and finally disrupted bone healing. Inspired by the importance of a timely vascularization, as well as by the limited biological potential of the fracture hematoma, the influence of the host environment on the bone healing process in critical size defects was explored further. Moreover, dependent on the host environment, several treatment strategies were designed and tested for effectiveness. A qualitative correspondence between the predicted outcomes of certain treatment strategies and experimental observations was obtained, clearly illustrating the model's potential. In conclusion, the results of this study demonstrate that due to the complex non-linear dynamics of blood vessel formation, oxygen supply, growth factor production and cell proliferation and the interactions thereof with the host environment, an integrative in silico-in vivo approach is a crucial tool to further unravel the occurrence and treatments of challenging critical sized bone defects. [less ▲]

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See detailStaphylococcal biofilm growth on smooth and porous titanium coatings for biomedical applications.
Braem, Annabel; Van Mellaert, Lieve; Mattheys, Tina et al

in Journal of biomedical materials research. Part A (2014), 102(1), 215-24

Implant-related infections are a serious complication in prosthetic surgery, substantially jeopardizing implant fixation. As porous coatings for improved osseointegration typically present an increased ... [more ▼]

Implant-related infections are a serious complication in prosthetic surgery, substantially jeopardizing implant fixation. As porous coatings for improved osseointegration typically present an increased surface roughness, their resulting large surface area (sometimes increasing with over 700% compared to an ideal plane) renders the implant extremely susceptible to bacterial colonization and subsequent biofilm formation. Therefore, there is particular interest in orthopaedic implantology to engineer surfaces that combine both the ability to improve osseointegration and at the same time reduce the infection risk. As part of this orthopaedic coating development, the interest of in vitro studies on the interaction between implant surfaces and bacteria/biofilms is growing. In this study, the in vitro staphylococcal adhesion and biofilm formation on newly developed porous pure Ti coatings with 50% porosity and pore sizes up to 50 mum is compared to various dense and porous Ti or Ti-6Al-4V reference surfaces. Multiple linear regression analysis indicates that surface roughness and hydrophobicity are the main determinants for bacterial adherence. Accordingly, the novel coatings display a significant reduction of up to five times less bacterial surface colonization when compared to a commercial state-of-the-art vacuum plasma sprayed coating. However, the results also show that a further expansion of the porosity with over 15% and/or the pore size up to 150 mum is correlated to a significant increase in the roughness parameters resulting in an ascent of bacterial attachment. Chemically modifying the Ti surface in order to improve its hydrophilicity, while preserving the average roughness, is found to strongly decrease bacteria quantities, indicating the importance of surface functionalization to reduce the infection risk of porous coatings. [less ▲]

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See detailIn vivo ectopic bone formation by devitalized mineralized stem cell carriers produced under mineralizing culture condition.
Chai, Yoke Chin; Geris, Liesbet ULg; Bolander, Johanna et al

in BioResearch open access (2014), 3(6), 265-77

Functionalization of tissue engineering scaffolds with in vitro-generated bone-like extracellular matrix (ECM) represents an effective biomimetic approach to promote osteogenic differentiation of stem ... [more ▼]

Functionalization of tissue engineering scaffolds with in vitro-generated bone-like extracellular matrix (ECM) represents an effective biomimetic approach to promote osteogenic differentiation of stem cells in vitro. However, the bone-forming capacity of these constructs (seeded with or without cells) is so far not apparent. In this study, we aimed at developing a mineralizing culture condition to biofunctionalize three-dimensional (3D) porous scaffolds with highly mineralized ECM in order to produce devitalized, osteoinductive mineralized carriers for human periosteal-derived progenitors (hPDCs). For this, three medium formulations [i.e., growth medium only (BM1), with ascorbic acid (BM2), and with ascorbic acid and dexamethasone (BM3)] supplemented with calcium (Ca(2+)) and phosphate (PO4 (3-)) ions simultaneously as mineralizing source were investigated. The results showed that, besides the significant impacts on enhancing cell proliferation (the highest in BM3 condition), the formulated mineralizing media differentially regulated the osteochondro-related gene markers in a medium-dependent manner (e.g., significant upregulation of BMP2, bone sialoprotein, osteocalcin, and Wnt5a in BM2 condition). This has resulted in distinguished cell populations that were identifiable by specific gene signatures as demonstrated by the principle component analysis. Through devitalization, mineralized carriers with apatite crystal structures unique to each medium condition (by X-ray diffraction and SEM analysis) were obtained. Quantitatively, BM3 condition produced carriers with the highest mineral and collagen contents as well as human-specific VEGF proteins, followed by BM2 and BM1 conditions. Encouragingly, all mineralized carriers (after reseeded with hPDCs) induced bone formation after 8 weeks of subcutaneous implantation in nude mice models, with BM2-carriers inducing the highest bone volume, and the lowest in the BM3 condition (as quantitated by nano-computed tomography [nano-CT]). Histological analysis revealed different bone formation patterns, either bone ossicles containing bone marrow surrounding the scaffold struts (in BM2) or bone apposition directly on the struts' surface (in BM1 and BM3). In conclusion, we have presented experimental data on the feasibility to produce devitalized osteoinductive mineralized carriers by functionalizing 3D porous scaffolds with an in vitro cell-made mineralized matrix under the mineralizing culture conditions. [less ▲]

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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)

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See detailA gene regulatory network model evaluating the impact of individual factors in the hypertrophic switch
Kerkhofs, Johan ULg; Van Oosterwyck, Hans; Geris, Liesbet ULg

Conference (2013, September 11)

Chondrocytes undergoing hypertrophy show a major switch in phenotype underlied by a change in expression from the chondrocyte master gene, Sox9, to the osteoblastic one, Runx2. Strategies to stimulate or ... [more ▼]

Chondrocytes undergoing hypertrophy show a major switch in phenotype underlied by a change in expression from the chondrocyte master gene, Sox9, to the osteoblastic one, Runx2. Strategies to stimulate or inhibit this switch are of use in bone and cartilage tissue engineering respectively, as well as in the prevention of ectopic hypertrophy in osteoarthritis. We have constructed a literature based network comprised of 46 nodes and 161 interactions shown to play a part in chondrocyte hypertrophy. Network dynamics are simulated in discrete time through random updating by the use of additive functions to determine each node’s value. Furthermore, each species is represented by a fast variable (activity level, as determined by post translation modifications) which is assumed to be in equilibrium with a slow variable (mRNA) at all times. Through a Monte Carlo approach the importance of each node in the stability of chondrocytic phenotypes (proliferating, hypertrophic) is assessed in random initial conditions. A perturbation analysis of the stable states is used to determine the transition likelihood between states and the influence of individual nodes in this transition as a second measure of stability. Our results show that the hypertrophic state, marked by Runx2 expression, has a larger attractor basin and is more stable to perturbation than the proliferative state characterized by Sox9. The added time resolution seems to favour the Runx2 phenotype. The results for single nodes in overexpression or knockout simulations show a certain asymmetry, indicating that factors that are necessary for maintaining a certain phenotype are not necessarily useful in inducing it. [less ▲]

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See detailTo heal or not to heal: modeling the influence of oxygen during fracture healing.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Conference (2013, September 11)

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See detailA Gene Regulatory Network Model to Assess the Stability of the Cartilage Phenotype
Kerkhofs, Johan ULg; Van Oosterwyck, Hans; Geris, Liesbet ULg

Poster (2013, August 29)

Introduction Chondrocyte hypertrophy entails the switching of a genetic program driven by Sox9 to one under control of the osteoblast master regulator Runx2. The switch is a prerequisite step in the bone ... [more ▼]

Introduction Chondrocyte hypertrophy entails the switching of a genetic program driven by Sox9 to one under control of the osteoblast master regulator Runx2. The switch is a prerequisite step in the bone forming process (endochondral ossification) during development and in postnatal fracture repair of larger bone defects. However, this switch can also be detrimental in tissue engineered cartilage constructs and in osteoarthritis development [Saito, 2010]. Therefore, a detailed model of the pathways that can facilitate, or inhibit, this phenotypic switch will lead to a more profound understanding of these processes and provide hints as to how to manipulate them. Methods The model formalism accommodates the qualitative information that is typically available in developmental studies. The literature based network comprises 46 nodes and 161 interactions, shown to be important in endochondral ossification. To simulate network dynamics in discrete time the normalized value of each gene is determined by additive functions where all interactions are assumed to be equally powerful. Furthermore, each species is represented by a fast variable (activity level, as determined by post translation modifications) which is assumed to be in equilibrium with a slow variable (mRNA) at all times. Through a Monte Carlo approach the importance of each node in the stability of chondrocytic phenotypes (proliferating, hypertrophic) is assessed in random initial conditions. A perturbation analysis of the stable states is used to determine the transition likelihood between them as a second measure of stability. Results Both measures of stability indicate that the hypertrophic (Runx2 driven) state is more stable than the proliferating one driven by Sox9. The results for the second measure are given in Fig.1. This higher stability seems to be partly conferred by faster reactions that favour the hypertrophic phenotype. In addition, the results point out that some transcription factors are necessary for the induction of a certain phenotype, whereas other transcription factors are required to maintain the phenotype, but are not necessary capable of inducing it. Discussion These results may relate to the difficulty experienced by researchers in maintaining a stable cartilage phenotype in culture and the occurrence of ectopic hypertrophy in osteoarthritis. By analysing the effect of changes to individual nodes, strategies to stabilise the proliferating phenotype can be developed. Overall, the model allows the importance of several important factors in the fate decision of mesenchymal cells to be quantitatively assessed based mainly on topological information. [less ▲]

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See detailMULTIPHYSICS MODELING OF CELL/MATRIX GROWTH ON 3D STRUCTURES.
Guyot, Yann ULg; Papantoniou, Ioannis; Chai, Yoke Chin et al

Conference (2013, August 26)

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See detailModeling the influence of oxygen in delayed bone fracture healing.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Conference (2013, August 25)

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See detailContrast-enhanced nanofocus X-ray computed tomography allows virtual 3D histopathology and morphometric analysis of osteoarthritis in small animal models
Kerckhofs, Greet ULg; Sainz, J.; Maréchal, M. et al

in Cartilage (2013)

Objective: One of the early hallmarks of osteoarthritis (OA) is a progressive degeneration of the articular cartilage. Early diagnosis of OA-associated cartilage alterations would be beneficial for ... [more ▼]

Objective: One of the early hallmarks of osteoarthritis (OA) is a progressive degeneration of the articular cartilage. Early diagnosis of OA-associated cartilage alterations would be beneficial for disease prevention and control, and for the development of disease-modifying treatments. However, early diagnosis is still hampered by a lack of quantifiable readouts in preclinical models. Design: In this study, we have shown the potency of contrast-enhanced nanofocus x-ray computed tomography (CE-nanoCT) to be used for virtual 3-dimensional (3D) histopathology in established mouse models for OA, and we compared with standard histopathology. Results: We showed the equivalence of CE-nanoCT images to histopathology for the modified Mankin scoring of the cartilage structure and quality. Additionally, a limited set of 3D cartilage characteristics measured by CE-nanoCT image analysis in a user-independent and semiautomatic manner, that is, average and maximum of the noncalcified cartilage thickness distribution and loss in glycosaminoglycans, was shown to be predictive for the cartilage quality and structure as can be evaluated by histopathological scoring through the use of an empirical model. Conclusions: We have shown that CE-nanoCT is a tool that allows virtual histopathology and 3D morphological quantification of multitissue systems, such as the chondro-osseous junction. It provides faster and more quantitative data on cartilage structure and quality compared with standard histopathology while eliminating user bias. CE-nanoCT thus should allow capturing subtle differences in cartilage characteristics, carefully mapping OA progression and, ultimately, asses the beneficial changes when testing a candidate disease-modifying treatment. [less ▲]

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