Mechanistic Image-Based Modelling: Concepts and Applications.

Advancements in imaging techniques have led to a rapid growth of available imaging data. Interpretation of the imaging data and extraction of biologically, physiologically and/or medically relevant information, however, remains challenging. In contrast, mechanistic computational modelling provides a means to formalise and dissect mechanisms governing the behaviour of complex systems.

Cell number in mesenchymal stem cell aggregates dictates cell stiffness and chondrogenesis.

Background: Although mesenchymal stem/stromal cell (MSC) chondrogenic differentiation has been thoroughly investigated, the rudiments for enhancing chondrogenesis have remained largely dependent on external cues. Focus to date has been on extrinsic variables such as soluble signals, culture conditions (bioreactors), and mechanical stimulation. However, the role of intrinsic mechanisms of MSC programming-based mechanobiology remains to be explored.

Generation of 3D Soluble Signal Gradients in Cell-Laden Hydrogels Using Passive Diffusion.

Soluble signal gradients play an important role in organ patterning, cell migration, and differentiation. Currently, signal gradients in 2D cell culture are realized using microfluidics and here cells are exposed to high and nonphysiological shear stress. Tissue morphogenesis (organogenesis) however occurs in 3D and therefore there is a need for simple and practical systems to impose gradients to cells dispersed in 3D matrix.

LBIBCell: a cell-based simulation environment for morphogenetic problems.

Motivation: The simulation of morphogenetic problems requires the simultaneous and coupled simulation of signalling and tissue dynamics. A cellular resolution of the tissue domain is important to adequately describe the impact of cell-based events, such as cell division, cell-cell interactions and spatially restricted signalling events. A tightly coupled cell-based mechano-regulatory simulation tool is therefore required.

Simulating tissue morphogenesis and signaling.

During embryonic development tissue morphogenesis and signaling are tightly coupled. It is therefore important to simulate both tissue morphogenesis and signaling simultaneously in in silico models of developmental processes. The resolution of the processes depends on the questions of interest.

Inter-dependent tissue growth and Turing patterning in a model for long bone development.

The development of long bones requires a sophisticated spatial organization of cellular signalling, proliferation, and differentiation programs. How such spatial organization emerges on the growing long bone domain is still unresolved. Based on the reported biochemical interactions we developed a regulatory model for the core signalling factors IHH, PTCH1, and PTHrP and included two cell types, proliferating/resting chondrocytes and (pre-)hypertrophic chondrocytes.