References of "Geris, Liesbet"
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See detailMathematical modeling of fracture healing: coupling between mechanics, angiogenesis and osteogenesis
Geris, Liesbet ULg; Vander Sloten, Jos; VanOosterwyck, Hans

in IFMBE Proceedings 22 (2008)

Both mechanical and biological factors play an important role in normal as well as impaired fracture healing. This study aims to provide a mathematical framework in which both regulatory mechanisms are ... [more ▼]

Both mechanical and biological factors play an important role in normal as well as impaired fracture healing. This study aims to provide a mathematical framework in which both regulatory mechanisms are included and angiogenesis is explicitly incorporated. To illustrate the added value of such a framework, a coupled mechanobioregulatory model was proposed. This model was based on a previously developed bioregulatory model [1], using a simple coupling between mechanics and biology whereby certain parameters of the bioregulatory model were made dependent on local mechanical stimuli. As a first example, in this study, the proliferation of osteoblasts and endothelial cells were made dependent on the local fluid flow [2]. Various loading situations, ranging from non-loading to overloading, were simulated. Simulations of adverse mechanical circumstances predicted the formation of avascular nonunions, a result that was corroborated by various experimental observations. This model allows testing various hypotheses concerning the nature of the mechanical stimulus influencing the healing process, as well as the most important cellular processes influenced by mechanical loading. It is one of the first models that provides an explicit coupling between mechanical and angiogenic factors. As both factors have been identified to play a key role in the occurrence of delayed and nonunions, the model allows to further explore their etiology and treatment. [less ▲]

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See detailModelling of peri-implant osteogenesis by means of a fracture healing mode
Amor, Nadia; Geris, Liesbet ULg; Vander Sloten, Jos et al

in Journal of Biomechanics (2008), 41(S1), 289

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See detailComputational modelling of peri-implant healing
Amor, Nadia; Geris, Liesbet ULg; Vander Sloten, Jos et al

in Middleton, J.; Jones, M. L.; Shrive, N. (Eds.) Proceedings of the 8th interantional symposium on Computer Methods in Biomechanics and Biomedical Engineering (2008)

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See detailApplication of mechanoregulatory models to simulate peri-implant tissue formation in an in vivo bone chamber
Geris, Liesbet ULg; Vandamme, Katleen; Naert, Ignace et al

in Journal of Biomechanics (2008), 41(1), 145-154

Several mechanoregulatory tissue differentiation models have been proposed over the last decade. Corroboration of these models by comparison with experimental data is necessary to determine their ... [more ▼]

Several mechanoregulatory tissue differentiation models have been proposed over the last decade. Corroboration of these models by comparison with experimental data is necessary to determine their predictive power. So far, models have been applied with various success rates to different experimental set-ups investigating mainly secondary fracture heating. In this study, the mechanoregulatory models are applied to simulate the implant osseointegration process in a repeated sampling in vivo bone chamber, placed in a rabbit tibia. This bone chamber provides a mechanically isolated environment to study tissue differentiation around titanium implants loaded in a controlled manner. For the purpose of this study, bone formation around loaded cylindrical and screw-shaped implants was investigated. Histologically, no differences were found between the two implant geometries for the global amount of bone formation in the entire chamber. However, a significantly larger amount of bone-to-implant contact was observed for the screw-shaped implant compared to the cylindrical implant. In the simulations, a larger amount of bone was also predicted to be in contact with the screw-shaped implant. However, other experimental observations could not be predicted. The simulation results showed a distribution of cartilage, fibrous tissue and (im)mature bone, depending on the mechanoregulatory model that was applied. In reality, no cartilage was observed. Adaptations to the differentiation models did not lead to a better correlation between experimentally observed and numerically predicted tissue distribution patterns. The hypothesis that the existing mechanoregulatory models were able to predict the patterns of tissue formation in the in vivo bone chamber could not be fully sustained. (c) 2007 Elsevier Ltd. All rights reserved. [less ▲]

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See detailAngiogenesis in bone fracture healing: a bioregulatory model.
Geris, Liesbet ULg; Gerisch, Alf; Sloten, Jos Vander et al

in Journal of Theoretical Biology (2008), 251(1), 137-58

The process of fracture healing involves the action and interaction of many cells, regulated by biochemical and mechanical signals. Vital to a successful healing process is the restoration of a good ... [more ▼]

The process of fracture healing involves the action and interaction of many cells, regulated by biochemical and mechanical signals. Vital to a successful healing process is the restoration of a good vascular network. In this paper, a continuous mathematical model is presented that describes the different fracture healing stages and their response to biochemical stimuli only (a bioregulatory model); mechanoregulatory effects are excluded here. The model consists of a system of nonlinear partial differential equations describing the spatiotemporal evolution of concentrations and densities of the cell types, extracellular matrix types and growth factors indispensable to the healing process. The model starts after the inflammation phase, when the fracture callus has already been formed. Cell migration is described using not only haptokinetic, but also chemotactic and haptotactic influences. Cell differentiation is controlled by the presence of growth factors and sufficient vascularisation. Matrix synthesis and growth factor production are controlled by the local cell and matrix densities and by the local growth factor concentrations. Numerical simulations of the system, using parameter values based on experimental data obtained from literature, are presented. The simulation results are corroborated by comparison with experimental data from a standardised rodent fracture model. The results of sensitivity analyses on the parameter values as well as on the boundary and initial conditions are discussed. Numerical simulations of compromised healing situations showed that the establishment of a vascular network in response to angiogenic growth factors is a key factor in the healing process. Furthermore, a correct description of cell migration is also shown to be essential to the prediction of realistic spatiotemporal tissue distribution patterns in the fracture callus. The mathematical framework presented in this paper can be an important tool in furthering the understanding of the mechanisms causing compromised healing and can be applied in the design of future fracture healing experiments. [less ▲]

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See detailA coupled mechanobioregulatory model for the simulation of peri-implant bone formation in an in vivo bone chamber
Geris, Liesbet ULg; Vandamme, K.; Duyck, J. et al

in Proceedings of the second thematic workshop of the European Society of Biomechanics on Finite Element modelling in Biomechanis and Mechanobiology (2007, August)

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See detailMathematical modeling of bone regeneration during fracture healing and implant osseointegration
Geris, Liesbet ULg

Doctoral thesis (2007)

Despite the extensive body of literature on bone regeneration, many questions remain on e.g. the regulatory mechanisms and potential treatment strategies of pathological regeneration cases. The hypothesis ... [more ▼]

Despite the extensive body of literature on bone regeneration, many questions remain on e.g. the regulatory mechanisms and potential treatment strategies of pathological regeneration cases. The hypothesis underlying this work states that mathematical models of bone regeneration can make a substantial contribution to this domain by proposing pathological regeneration mechanisms and designing therapies, which can subsequently be tested experimentally. In the first part of this work, existing mechanoregulatory and bioregulatory models of bone regeneration are implemented and applied to both implant osseointegration and fracture healing set-ups. A quantitative comparison with experimental results is performed. Thorough sensitivity analyses are carried out to assess the influence of various modelling aspects on the simulation outcome. Shortcomings of these models are identified and suggestions for improvements are made. In the second part of this work, a novel bioregulatory model of bone regeneration is developed in which several of the previously defined shortcomings are addressed. This model includes key aspects of the regeneration process such as intramembranous and endochondral ossification, angiogenesis and directed cell motion. The results obtained with this novel model are corroborated both qualitatively and quantitatively by comparison with experimental data for normal fracture healing. Cases of pathological fracture healing are simulated and experimentally testable therapeutic strategies are implemented. The last part of this work describes the establishment of a mathematical framework, based on the previously developed bioregulatory model, in which the regulatory influence of both biological and mechanical factors is combined. This is the first model of bone regeneration in which the coupling between mechanical loading and angiogenesis is made in an explicit and mechanistic manner. Several examples are given to illustrate the added value of this approach in simulating normal and pathological bone regeneration. In summary, this work demonstrates the potential of mathematical models in advancing the knowledge on bone regeneration and designing treatment strategies for pathological healing cases. [less ▲]

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See detailInfluence of immediate loading and implant design on bone formation
Vandamme, K.; Naert, Ignace; Geris, Liesbet ULg et al

in Proceedings of the 85th General Session & Exhibition of the IADR (2007)

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See detailThe effect of mechanical loading on peri-implant osteogenesis
Vandamme, K.; Naert, Ignace; Geris, Liesbet ULg et al

in proceedings of the 17th annual meeting of the Dutch society for calcium and bone metabolism (2007)

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See detailThe effect of micro-motion on the tissue response around immediately loaded roughened titanium implants in the rabbit.
Vandamme, Katleen; Naert, Ignace; Geris, Liesbet ULg et al

in European Journal of Oral Sciences (2007), 115(1), 21-9

Initial osteogenesis at the implant interface is, to a great extent, determined by the implant surface characteristics and the interfacial loading conditions. The present study investigated the effect of ... [more ▼]

Initial osteogenesis at the implant interface is, to a great extent, determined by the implant surface characteristics and the interfacial loading conditions. The present study investigated the effect of various degrees of relative movement on the tissue differentiation around a roughened screw-shaped immediately loaded implant. Repeated-sampling bone chambers were installed in the tibia of 10 rabbits. In each of the chambers, three experiments were performed by inducing 0 (control), 30, and 90 microm implant displacement for 9 wk. A linear mixed model and a logistic mixed model with alpha = 5% determined statistical significance. Tissue filling of the bone chamber was similar for the three test conditions. The bone area fraction was significantly higher for 90 microm implant displacement compared with no displacement. A significantly higher fraction of bone trabeculae was found for 30 and 90 microm implant displacement compared with the unloaded situation. The incidence of osteoid-to-implant and bone-to-implant contact was significantly higher for 90 microm implant displacement compared with 30 and 0 microm implant displacement. Significantly more osteoid in contact with the implant was found for the loaded conditions compared with no loading. Well-controlled micro-motion positively influenced bone formation at the interface of a roughened implant. An improved bone reaction was detected with increasing micro-motion. [less ▲]

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See detailInfluence of controlled immediate loading and implant design on peri-implant bone formation.
Vandamme, Katleen; Naert, Ignace; Geris, Liesbet ULg et al

in Journal of Clinical Periodontology (2007), 34(2), 172-81

AIM: Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in ... [more ▼]

AIM: Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs. MATERIAL AND METHODS: A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F-statistic model with alpha=5% determined statistical significance. RESULTS: A significantly higher bone area fraction was observed for SL compared with SU (p<0.0001). The mineralized bone fraction was the highest for SL and significantly different from SU (p<0.0001). The chance that osteoid- and bone-to-implant contact occurred was the highest for SL and significantly different from SU (p<0.0001), but not from CL. When bone-to-implant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition. CONCLUSIONS: Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant. [less ▲]

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See detailHistodynamics of bone tissue formation around immediately loaded cylindrical implants in the rabbit.
Vandamme, Katleen; Naert, Ignace; Geris, Liesbet ULg et al

in Clinical Oral Implants Research (2007), 18(4), 471-80

OBJECTIVES: The local mechanical environment influences early peri-implant tissue formation. It is still unclear whether immediate loading limits or promotes peri-implant osteogenesis and which mechanical ... [more ▼]

OBJECTIVES: The local mechanical environment influences early peri-implant tissue formation. It is still unclear whether immediate loading limits or promotes peri-implant osteogenesis and which mechanical parameters are important herein. The present study evaluated the influence of well-controlled mechanical stimuli on the tissue response around immediately loaded cylindrical turned titanium implants at two different observation periods. MATERIAL AND METHODS: A repeated sampling bone chamber, consisting of dual-structure perforated hollow cylinders with a cylindrical implant, was installed in the tibia of 14 rabbits and used to conduct three displacement-controlled immediate loading experiments: (i) 30 microm - 400 cycles/day - 1 Hz frequency - 2 x/week - 6 weeks; (ii) 30 microm - 400 cycles/day - 1 Hz - 2 x/week - 6 weeks, followed by another 6 weeks with a 50 microm - 800 cycles/day - 1 Hz - 2 x/week loading protocol; and (iii) 0 microm implant displacement for 12 weeks. A linear mixed model and logistic mixed model with alpha=5% were conducted on the data set. RESULTS: The tissue area fraction was significantly the highest after 12 weeks of loading. The bone area fraction was significantly different between all three loading conditions, with the highest values for the 12-week loading experiment. Twelve-week stimulation resulted in a significantly higher mineralized bone fraction than 6 weeks. Loading did have a significantly positive effect on the mineralized bone fraction. The incidence of osteoid-to-implant and bone-to-implant contact increased significantly when loading the implant for 12 weeks. CONCLUSION: Immediate loading had a positive effect on the tissue differentiation and bone formation around cylindrical turned titanium implants. Controlled implant micro-motion up to 50 microm had a positive effect on the bone formation at its interface. [less ▲]

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See detailImpact of implant geometry and loading on early bone formation, Clinical Oral Implants Research
Vandamme, Katleen; Naert, Ignace; Geris, Liesbet ULg et al

in Clinical Oral Implants Research (2007), 18(5), 71-72

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See detailA Finite Volume Spatial Discretisation for taxis-diffusion-reaction systems with axi-symmetry: application to fracture healing
Gerisch, Alf; Geris, Liesbet ULg

in Deutsch, A.; Brusch, L.; Byrne, H. (Eds.) et al Advances in Mathematical Modeling of Biological Systems (2007)

We consider the numerical simulation of a time-dependent taxis-diffusion-reaction model of fracture healing in mice using the method of lines. The partial differential equation problem has an axi ... [more ▼]

We consider the numerical simulation of a time-dependent taxis-diffusion-reaction model of fracture healing in mice using the method of lines. The partial differential equation problem has an axi-symmetric structure and this is employed to properly reduce the model to an equivalent problem in two-dimensional (2D) space leading subsequently to an efficient spatial discretisation. Special care is given to respect conservation of mass and the non-negativity of the solution. The numerical simulation results are contrasted to those obtained from a simplistic reduction of the axi-symmetric model to 2D space (at the same computational cost).We observe quantitative and qualitative differences. [less ▲]

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See detailMathematical modelling of growth factor induced bone regeneration: importance of angiogenesis
Van Oosterwyck, Hans; Vander Sloten, Jos; Geris, Liesbet ULg

in Tissue Engineering (2007)

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See detailMicro-macro mechanical modeling of bone-implant interface by means of the homogenization theory
Amor, Nadia; Van Cleynenbreugel, Tim; Geris, Liesbet ULg et al

Poster (2006, December)

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See detailBone Formation around Immediately Loaded Implants: a Bone Chamber Model
Vandamme, K.; Naert, Ignace; Geris, Liesbet ULg et al

in Proceedings of the 84th General Session & Exhibition of the IADR (2006)

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See detailThe influence of micro-motion on the tissue differentiation around immediately loaded cylindrical turned titanium implants.
Duyck, Joke; Vandamme, K.; Geris, Liesbet ULg et al

in Archives of Oral Biology (2006), 51(1), 1-9

OBJECTIVE: The aim of this study was to evaluate the effect of various degrees of implant displacement on the tissue differentiation around immediately loaded cylindrical turned titanium implants. DESIGN ... [more ▼]

OBJECTIVE: The aim of this study was to evaluate the effect of various degrees of implant displacement on the tissue differentiation around immediately loaded cylindrical turned titanium implants. DESIGN: The experiments were conducted in repeated sampling bone chambers placed in the tibia of 10 rabbits. Tissues could grow into the bone chambers via perforations. Due to its double structure, tissues inside the chamber could be harvested leaving the chamber intact. This allowed several experiments within the same animal. The chambers contained a cylindrical turned titanium implant that was loaded in a well-controlled manner. In each of the 10 chambers, four experiments were conducted with the following test conditions: immediate implant loading by inducing 0 (control), 30, 60 and 90 microm implant displacement, 800 cycles per day at a frequency of 1 Hz, twice a week during a period of 6 weeks. Histological and histomorphometrical analyses were performed on methylmethacrylate histological sections. An ANOVA was conducted on the dataset. RESULTS: The total tissue volume was significantly lowest in the unloaded control condition. The bone volume fraction on the other hand, was significantly larger in the unloaded and 90 microm implant displacement, compared to the 30 microm implant displacement. Bone density increased with increasing micro-motion with significantly higher values for the 60 microm- and 90 microm-test conditions compared to the unloaded situation. The chance to have bone-to-implant contact decreased in case of micro-motion at the tissues-implant interface. CONCLUSION: The magnitude of implant displacement had a statistically significant effect on the tissue differentiation around immediately loaded cylindrical turned titanium implants. Implant micro-motion had a detrimental effect on the bone-to-implant contact in an immediate loading regimen. [less ▲]

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See detailMathematical modeling of fracture healing in mice: comparison between experimental data and numerical simulation results.
Geris, Liesbet ULg; Gerisch, Alf; Maes, Christa et al

in Medical & Biological Engineering & Computing (2006), 44(4), 280-9

The combined use of experimental and mathematical models can lead to a better understanding of fracture healing. In this study, a mathematical model, which was originally established by Bailon-Plaza and ... [more ▼]

The combined use of experimental and mathematical models can lead to a better understanding of fracture healing. In this study, a mathematical model, which was originally established by Bailon-Plaza and van der Meulen (J Theor Biol 212:191-209, 2001), was applied to an experimental model of a semi-stabilized murine tibial fracture. The mathematical model was implemented in a custom finite volumes code, specialized in dealing with the model's requirements of mass conservation and non-negativity of the variables. A qualitative agreement between the experimentally measured and numerically simulated evolution in the cartilage and bone content was observed. Additionally, an extensive parametric study was conducted to assess the influence of the model parameters on the simulation outcome. Finally, a case of pathological fracture healing and its treatment by administration of growth factors was modeled to demonstrate the potential therapeutic value of this mathematical model. [less ▲]

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See detailMathematical modeling of bone regeneration including the angiogenic process
Geris, Liesbet ULg; Vander Sloten, Jos; Van Oosterwyck, Hans

in Journal of Biomechanics (2006), 39(S1), 411-412

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