Microenvironmental control of adult stem cell differentiation: Influence of biochemical ECM composition, ECM stiffness and electric fields

点击翻译按钮获取中文摘要

Cellular development is strongly dependent on numerous biochemical and physical signals provided by the cellular microenvironment. Traditionally, in vitro experimental studies concentrate on the influence of one signaling type and do not faithfully recapitulate the complex and dynamic signaling that predominates in vivo. However, it is increasingly clear that various signals - both of biochemical and physical in nature - interact strongly with each other and especially the combination of these stimuli is essential for terminal differentiation. Thus, the aim of this project is to study the interaction of multiple biochemical (matrix composition) and biophysical (matrix stiffness, electric fields) signals in their combined effects on differentiation behavior of human MSCs. In particular, a hybrid-sandwich gel incorporating various ECM molecules, based on collagen in combination with selected GAG-derivatives, will be designed and evaluated for its efficacy in eliciting differential response in MSCs. Moreover, the stiffness of the gel will be tailored over a wide range, to match the compliance of native tissues such as adipose (~ 2 kPa), cartilage (~ 20 kPa) and pre-calcified bone (~ 40 kPa). Further, by the additional application of electric field this project intent to determine the parameters sets best suited for osteogenic differentiation and to gain a first understanding of how signaling pathways are influenced by such combined stimulations. Overall, this project will provide new insights into the cellular differentiation process. Understanding such complex cell-material-interactions will create new opportunities for designing and developing novel tissue engineering constructs.