Background: It has previously been shown that the mechanical and physical properties of the cellular environment have a distinct influence on cell functions like migration and stem cell differentiation. Additionally to the well accepted impact of the biological environment, material properties like substrate stiffness and geometry have moved into the focus of research. However, the mechanism by which mechanical substrate parameters influence cell behavior is still under debate [1-3]. In this context, most experiments have been carried out in 2D environments. Cell morphology seems to be of great importance in material-guided cell behavior, thus additional work in 3D environments is needed to understand the role of the mechanical microenvironment.

Scope of work: The goal of this project is to investigate the role of substrate stiffness on human mesenchymal stromal cell (MSC) migration and differentiation into the adipogenic or osteogenic lineage. This is of importance to understand the physiological processes of tissue regeneration and to be able to develop biomaterials with specific material properties to guide the regeneration process.

Assays for cell migration and differentiation in 3D macroporous scaffolds have been developed previously and will be employed. MSCs from multiple patients will be expanded in conventional cell culture and seeded into the scaffolds homogeneously (differentiation) or with a high density gradient (migration) and cultured under specific media. The sample evaluation is based on histological stainings and confocal imaging as well as protein and gene expression analysis.

Mechanical forces act everywhere in the body, especially in load bearing structures like bone or muscle. Thus, additional experiments will be carried out in a bioreactor to mimic better the physiological environment. Cyclic mechanical compression will be applied to the scaffolds and the impact on MSC migration and differentiation will be studied. Altogether the results will give a clearer picture about the relevance of the individual mechanical parameters for MSC behavior in tissue regeneration.

What do we expect?

•       fun in working in an interdisciplinary field covering cell biology and material science

•       high motivation, cell culture experience

methods:

Cell Biology, Molecular Biology, immunohisto-chemistry, Bioreactor

Start Date: 2 November 2012

Estimated Duration: 6-8 months

Subjects: Biology
Topic: Thesis: Influence of scaffold stiffness on the functional behavior of human mesenchymal stromal cells
Contact: Ms. Darya Könnig
Reply to: darja.koennig @ charite.de
Institution: Julius Wolff Institute - Charité Universitätsmedizin Berlin
Location: 13353 Berlin, August Platz 1