We explore the interaction between cells, their surrounding matrix, and biomaterials for the development of new muskuloskeletal treatment strategies. We design micro-environments that provide specific mechanical, geometrical, and biochemical signals to support and control endogenous healing cascades.
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Role of Mechanical and Geometrical Signals in Regeneration
Mechanical loading enhances growth factor signaling
Biochemical signaling via proteins is fundamental for the development of muskuloskeletal tissues but also for their regeneration. Bone Morphogenetic Proteins (BMPs) have proven to be potent inducers of bone formation but potential side effects e.g. ectopic bone formation, currently limit their clinical applications. To reduce risks associated with growth factor therapy, the underlying signaling mechanisms have to be better understood. Interestingly, beside biochemical factors also mechanical signals arising from tissue deformation or fluid flow were found to influence growth factor signaling. In fact, we have shown in collaboration with the Knaus Lab that BMP2 and mechanical loading synergistically promote events in the BMP2 signaling pathway. Based on this finding we currently investigate the underlying molecular mechanism how mechanical forces are integrated into signaling events. Such an understanding would help to develop and improve treatment strategies in which both, mechanical and biochemical, stimuli act cooperatively.
Geometrical cues control cell behavior
The local curvature that cells perceive inside porous biomaterials is controlled by the inherent architecture of the material. To understand how surface curvature on the meso-scale, e.g. found in pores with diameters between 100µm and 1mm, influences the behavior of mesenchymal stromal cells, we developed elastomer-based topographic cell culture substrates featuring simplified geometries like spheres and cylinders (convex and concave). We use these so-called GeoChips (Fig.1a) in combination with 3D time-laps microscopy and immune-histology to systematically study cell attachment morphology (Fig.1b), migration and differentiation of mesenchymal stromal cells (MSCs) (Fig.1c) as well as mechanisms behind curvature-controlled cell behavior.
(Reference: Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation. Werner M, Blanquer SBG., Haimi SP, Korus G, Dunlop JWC, Duda GN, Grijpma DW, Petersen A. Advanced Science 2017; 4(2). [go to PubMed])