A mathematical model of calcium ion influence on the activity of osteogenic cells

Poster (2010, November 19)

A Boolean network model of the growth plate

Poster (2010, October 10)

Occurrence and Treatment of Bone Atrophic Non-Unions Investigated by an Integrative Approach

in PLoS Computational Biology (2010), 6(9), 1000915

Recently developed atrophic non-union models are a good representation of the clinical situation in which many nonunions develop. Based on previous experimental studies with these atrophic non-union ... [more ▼]

Recently developed atrophic non-union models are a good representation of the clinical situation in which many nonunions develop. Based on previous experimental studies with these atrophic non-union models, it was hypothesized that in order to obtain successful fracture healing, blood vessels, growth factors, and (proliferative) precursor cells all need to be present in the callus at the same time. This study uses a combined in vivo-in silico approach to investigate these different aspects (vasculature, growth factors, cell proliferation). The mathematical model, initially developed for the study of normal fracture healing, is able to capture essential aspects of the in vivo atrophic non-union model despite a number of deviations that are mainly due to simplifications in the in silico model. The mathematical model is subsequently used to test possible treatment strategies for atrophic non-unions (i.e. cell transplant at post-osteotomy, week 3). Preliminary in vivo experiments corroborate the numerical predictions. Finally, the mathematical model is applied to explain experimental observations and identify potentially crucial steps in the treatments and can thereby be used to optimize experimental and clinical studies in this area. This study demonstrates the potential of the combined in silico-in vivo approach and its clinical implications for the early treatment of patients with problematic fractures. [less ▲]

Cross-talk Modeling of Wnt, BMP and ERK Pathways during Osteochondrogenic Differentiation

in Proceedings of the TERMIS-EU meeting (2010, June)

Mechanical loading affects angiogenesis and osteogenesis in an in vivo bone chamber: a modeling study.

in Tissue Engineering. Part A (2010), 16(11), 3353-3361

Despite a myriad of studies confirming the interaction between biology and mechanics, the exact nature of the main mechanical stimuli and their influence on the bone regeneration processes are still ... [more ▼]

Despite a myriad of studies confirming the interaction between biology and mechanics, the exact nature of the main mechanical stimuli and their influence on the bone regeneration processes are still unclear. The hypothesis of this study was that the outcome of peri-implant healing under different implant loading regimens can be explained by the influence of fluid flow on the combination of angiogenesis and osteogenesis through its influence on cell proliferation and differentiation. To investigate this hypothesis a mathematical model of bone regeneration was applied to simulate the peri-implant healing in an in vivo repeated sampling bone chamber for different axial micromechanical implant loading regimes. When mechanical loading was modeled to influence both osteogenic and angiogenic processes, a good agreement was observed between simulations and experiments concerning the amount of bone in the bone chamber, its radial and longitudinal distribution, and the bone-implant contact for different implant displacement magnitudes. [less ▲]

In vivo, in vitro, in silico: computational tools for tissue engineering

in proceedings of the 2nd International Conference on Innovation for Sustainable Production i-SUP (2010)

Experimental and computational study of the correlation between oxygen tension, cell viability and proliferation in fibrin hydrogels

in Proceedings of the 17th conference of the European Society of Biomechanics (2010)

Crosstalk Modeling of Wnt, BMP and ERK Pathways during osteochondrogenic differentiation

in proceedings of the International Symposium on Biomechanics and Biology of Bone Regeneration “From Functional Assessment To Guided Tissue Formation (2009, November)

The in vitro engineering of tissues may be achieved by mimicking in vivo tissue development. Although multiple skeletal tissue engineering applications already exist, the underlying mechanisms at protein ... [more ▼]

The in vitro engineering of tissues may be achieved by mimicking in vivo tissue development. Although multiple skeletal tissue engineering applications already exist, the underlying mechanisms at protein level are often poorly understood. Growth factors and protein pathways precisely navigate mesenchymal stem cells trough the correct cascades. A detailed understanding of these cascades will enable us to develop efficient and robust production methods, which are required for large scale tissue engineering applications. Multiple studies hypothesize that the Wnt/β-catenin pathway acts as a switching mechanism to determine the differential fate of esenchymal cells in osteoblasts or chondrocytes during skeletogenesis. The concentration of β-catenin is a key factor in this mechanism. Wnt upregulates the productionof β-catenin which in turn upregulates Runx2 and downregulates Sox9. High concentrations of Runx2 relative to Sox9 lead to osteoblasts, while the opposite situation leads to chondrocytes. Crosstalks of the Wnt pathway with other pathways such as that of BMP and ERK expand the amount of factors that can influence β-catenin, turning the linear signaling cascade into a complex network with multiple starting conditions. A mathematical model was derived from literature describing the pathways of BMP, Wnt and ERK as well as various crosstalks between these pathways that were suggested in literature. CellDesigner™ was used to formulate, solve and visualize the Ordinary Differential Equations describing the temporal evolution of the various model constituents. Multiple starting conditions (various concentrations of BMP, Wnt and ERK) were examined to clarify the crosstalk effect. Modeling various crosstalks proposed in literature resulted in a mutual inhibitory effect between Wnt and BMP signaling, an effect independently described in literature. Experiments are ongoing to corroborate the model predictions. [less ▲]

Mathematical modeling of bone regeneration during fracture healing

in proceedings of the National Conference on Theoretical and Applied Mechanics (2009)

Modelling of in vitro mesenchymal stem cell cultivation, chondrogenesis and osteogenesis

in Journal of Biomechanics (2008, July), 41