Guiding cell and matrix organization by scaffold fiber curvature
In situ tissue-engineering of heart valves using cell-free biodegradable electrospun scaffolds is a promising technique for heart valve replacement. By tuning fiber architecture and dimensions, the technique allows to control specific neo-tissue formation inside the human body, while avoiding the potential risks of bioactives, such as growth factors and cells. For in situ heart valve tissue engineering, it is essential that the fibrous scaffold guides colonization by (circulating) cells as well as tissue formation and remodeling, thus maintaining mechanical functionality of the valve. It has been shown that cells can feel and respond to the (an)isotropy of the scaffold fibers(1).Moreover, it has been observed that different cell types orient differently on the curved surface of the fibers(2). However, to determine the extent of control over tissue homeostasis using scaffold fiber dimensions and organization, an in-depth understanding of cellular sensing and responding in terms of matrix synthesis and remodeling is required. In this project we will investigate how cells can sense the scaffold fiber curvature and orientation. Furthermore we will explore how we can guide specific cell and tissue organization by scaffold geometry under hemodynamic loading conditions. We will systematically investigate the influence of fiber curvature on cell orientation, cytoskeleton organization, adhesion points localization and collagen organization in real time using confocal time lapse microscopy. Ultimately, the gained knowledge will help in the design of 3D heart valve scaffolds that guide and promote specific cell behavior.
- Heo, S.-J. et al. Fiber stretch and reorientation modulates mesenchymal stem cell morphology and fibrous gene expression on oriented nanofibrous microenvironments. Ann. Biomed. Eng,39:2780–90 (2011).)
- Fioretta, E. S., Simonet, M., Smits, A. I. P. M., Baaijens, F. P. T. & Bouten, C. V. C. Differential Response of Endothelial and Endothelial Colony Forming Cells on Electrospun Scaffolds with Distinct Micro fiber Diameters, Biomacromolecules15:821–829 (2014).