References of "Carlier, Aurélie"
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See detailMultiscale modelling of angiogenesis during normal and impaired bone regeneration
Carlier, Aurélie ULg

Doctoral thesis (2014)

Bone regeneration is, like many other healing events, a complex, well-orchestrated process involving a myriad of different cell types and regulated by countless biochemical, physical and mechanical ... [more ▼]

Bone regeneration is, like many other healing events, a complex, well-orchestrated process involving a myriad of different cell types and regulated by countless biochemical, physical and mechanical factors. But unlike other adult biological tissues, the majority of bone fractures can heal without the production of scar tissue, eventually recovering the original bone shape, size and strength. Despite bone’s remarkable healing capacity and the continuing research efforts, the impaired healing of complex orthopaedic cases is still not fully understood. This PhD work hypothesises that computational modelling can make a substantial contribution to the bone regeneration field by proposing and testing the underlying mechanisms of action as well as by designing and optimising experimental strategies in silico. In the first part of this work, an existing bioregulatory model of fracture healing is extended with an intracellular module of Dll4-Notch1 signalling in order to capture the ingrowth of new blood vessels through sprouting angiogenesis. The predictions of the new MOSAIC model are compared to experimental results and an extensive sensitivity analysis is performed on the newly introduced parameters. The potential of the MOSAIC model to investigate the influence of the molecular mechanisms on angiogenesis and consequently the bone formation process is illustrated. In the second part of this work, the MOSAIC model is further improved with a rigorous implementation of the influence of oxygen on the behaviour of skeletal cells. A comprehensive literature study is performed in order to ensure the correspondence of the oxygen ranges of the cell-specific oxygen-dependent processes with the state-of-the-art experimental knowledge. The oxygen model is corroborated with previously published experimental results. The robustness of the oxygen model with respect to the newly introduced oxygen thresholds is demonstrated by a sensitivity analysis. Some limitations and shortcomings of the oxygen model are identified together with suggestions for future work. In the last part of this work, the added value of the oxygen model is shown by applying it to three cases of impaired bone healing: the occurrence of nonunions in critical size defects, bone graft healing in a compromised environment and the impaired healing of bone fractures in NF1 patients. Not only is the oxygen model used to determine the underlying mechanisms of action, potential treatment strategies for the respective challenging orthopaedic conditions are also designed and optimised in silico. In conclusion, this PhD thesis demonstrates the potential of an integrative in vivo-in silico approach to advance our current understanding of bone regeneration as well as to design effective treatments of complex bone fractures. [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 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 detailCharacterization of tumor heterogeneity using bioimage informatics and 3D computational modeling
Stamatelos, Spyros; Carlier, Aurélie ULg; Kim, Eugene et al

Conference (2013, September 25)

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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 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 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 detailA multiscale model of the influence of oxygen during bone fracture healing.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Poster (2013, April 03)

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

Poster (2012, October 24)

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See detailA multiscale model of sprouting angiogenesis during fracture healing.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Conference (2012, September 18)

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See detailMultiscale modeling of in the influence of oxygen during bone fracture healing.
Carlier, Aurélie ULg; Van Gastel, Nick; Carmeliet, Geert et al

Poster (2012, September 17)

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See detailMultiscale modeling of sprouting angiogenesis: tip cells are selected for the top.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Poster (2012, September 05)

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See detailMultiscale modelling of the influence of VEGF on sprouting angiogenesis.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Poster (2012, July 06)

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See detailTip cells at the top: a multiscale model of sprouting angiogenesis.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Conference (2012, July 01)

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See detailTip cells at the top: multiscale modeling of angiogenesis during fracture healing
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

in Computer Methods in Biomechanics and Biomedical Engineering (CMBBE) - Proceedings (2012, April)

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See detailMOSAIC: a multiscale model of osteogenesis and sprouting angiogenesis with lateral inhibition of endothelial cells.
Carlier, Aurélie ULg; Geris, Liesbet ULg; Bentley, Katie et al

in PLoS Computational Biology (2012), 8(10), 1002724

The healing of a fracture depends largely on the development of a new blood vessel network (angiogenesis) in the callus. During angiogenesis tip cells lead the developing sprout in response to ... [more ▼]

The healing of a fracture depends largely on the development of a new blood vessel network (angiogenesis) in the callus. During angiogenesis tip cells lead the developing sprout in response to extracellular signals, amongst which vascular endothelial growth factor (VEGF) is critical. In order to ensure a correct development of the vasculature, the balance between stalk and tip cell phenotypes must be tightly controlled, which is primarily achieved by the Dll4-Notch1 signaling pathway. This study presents a novel multiscale model of osteogenesis and sprouting angiogenesis, incorporating lateral inhibition of endothelial cells (further denoted MOSAIC model) through Dll4-Notch1 signaling, and applies it to fracture healing. The MOSAIC model correctly predicted the bone regeneration process and recapitulated many experimentally observed aspects of tip cell selection: the salt and pepper pattern seen for cell fates, an increased tip cell density due to the loss of Dll4 and an excessive number of tip cells in high VEGF environments. When VEGF concentration was even further increased, the MOSAIC model predicted the absence of a vascular network and fracture healing, thereby leading to a non-union, which is a direct consequence of the mutual inhibition of neighboring cells through Dll4-Notch1 signaling. This result was not retrieved for a more phenomenological model that only considers extracellular signals for tip cell migration, which illustrates the importance of implementing the actual signaling pathway rather than phenomenological rules. Finally, the MOSAIC model demonstrated the importance of a proper criterion for tip cell selection and the need for experimental data to further explore this. In conclusion, this study demonstrates that the MOSAIC model creates enhanced capabilities for investigating the influence of molecular mechanisms on angiogenesis and its relation to bone formation in a more mechanistic way and across different time and spatial scales. [less ▲]

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See detailCurrent views on calcium phosphate osteogenicity and the translation into effective bone regeneration strategies.
Chai, Y. C.; Carlier, Aurélie ULg; Bolander, J. et al

in Acta Biomaterialia (2012), 8(11), 3876-87

Calcium phosphate (CaP) has traditionally been used for the repair of bone defects because of its strong resemblance to the inorganic phase of bone matrix. Nowadays, a variety of natural or synthetic CaP ... [more ▼]

Calcium phosphate (CaP) has traditionally been used for the repair of bone defects because of its strong resemblance to the inorganic phase of bone matrix. Nowadays, a variety of natural or synthetic CaP-based biomaterials are produced and have been extensively used for dental and orthopaedic applications. This is justified by their biocompatibility, osteoconductivity and osteoinductivity (i.e. the intrinsic material property that initiates de novo bone formation), which are attributed to the chemical composition, surface topography, macro/microporosity and the dissolution kinetics. However, the exact molecular mechanism of action is unknown. This review paper first summarizes the most important aspects of bone biology in relation to CaP and the mechanisms of bone matrix mineralization. This is followed by the research findings on the effects of calcium (Ca(2)(+)) and phosphate (PO(4)(3)(-)) ions on the migration, proliferation and differentiation of osteoblasts during in vivo bone formation and in vitro culture conditions. Further, the rationale of using CaP for bone regeneration is explained, focusing thereby specifically on the material's osteoinductive properties. Examples of different material forms and production techniques are given, with the emphasis on the state-of-the art in fine-tuning the physicochemical properties of CaP-based biomaterials for improved bone induction and the use of CaP as a delivery system for bone morphogenetic proteins. The use of computational models to simulate the CaP-driven osteogenesis is introduced as part of a bone tissue engineering strategy in order to facilitate the understanding of cell-material interactions and to gain further insight into the design and optimization of CaP-based bone reparative units. Finally, limitations and possible solutions related to current experimental and computational techniques are discussed. [less ▲]

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See detailMultiscale modeling of sprouting angiogenesis
Carlier, Aurélie ULg; Geris, Liesbet ULg; Van Oosterwyck, Hans

Poster (2011, December 02)

Detailed reference viewed: 24 (9 ULg)