Tissue engineering (TE) has the potential to treat many medical conditions, but is hampered by a limited understanding of how the physical characteristics of a cell’s 3D niche direct its differentiation. The aim of this project is to engineer a platform system of novel, well-defined modular hydrogels to determine the key physical parameters that drive stem cell fate in 3D. We will design, synthesise and characterise well-defined 3D gels with systematically varied structural and mechanical characteristics. We will then encapsulate human mesenchymal stem cells within the gels and monitor their differentiation using a combination of histological and molecular biology techniques.
Walters, N. J. & Gentleman, E. Evolving insights in cell–matrix interactions: Elucidating how non-soluble properties of the extracellular niche direct stem cell fate. Acta Biomater. 11:3-16 doi:10.1016/j.actbio.2014.09.038 (2015).
Gentleman, E. et al. Comparative materials differences revealed in engineered bone as a function of cell-specific differentiation. Nat. Mater. 8:763-70 doi:10.1038/nmat2505 (2009).
Bozec, L. & Horton, M. Topography and mechanical properties of single molecules of type I collagen using atomic force microscopy. Biophys. J. 88(6):4223-31 (2005).
Ghasdian, N., Ward, M. A. & Georgiou, T. K. Well-defined “clickable” copolymers prepared via one-pot synthesis. Chem. Comm. 50:7114-16 doi: 10.1039/C4CC02660H (2014).
da Silva, R. M. P. et al. Super-resolution microscopy reveals structural diversity in molecular exchange among peptide amphiphile nanofibres. Nat. Commun. 7:11561 doi: 10.1038/ncomms11561 (2016).