Development of bioactive therapeutics harnessing stem cell mechanobiology

Tissue engineering is an emerging field of medicine that aims to treat diseased or damaged tissue through regeneration, rather than replacement. In order to achieve this, implantable scaffolds, that act as templates for tissue formation, are designed so that they not only provide structural support but also provide signals to cells that encourage them to grow and develop into desired tissue types. The signals that are provided by the scaffolds can either be biological, such as growth factors, or physical, such as the stiffness of the scaffold that cells grow upon. Not only can cells sense the stiffness of their underlying material, but they can also sense other forms of physical stimulation, such as the flow of fluid (e.g. blood). Previously, we have shown that adult stem cells, known as mesenchymal stem cells (MSCs), respond to fluid flow by producing a biological molecule known as placental growth factor (PGF). This growth factor is capable of directing the MSCs to differentiate towards bone cells and could therefore be incorporated in scaffolds to enhance bone regeneration. The proposed study aims to study the therapeutic potential of PGF and other factors produced by cells in response to physical stimulation. It will also look at the influence of age on these factors as it is well established that children have a remarkable ability for natural wound healing. By identifying how age changes the ability of cells to respond to physical stimulation, bioactive agents capable of harnassing the immense regenerative capacity of children will be identified and incorporated into tissue engineered scaffolds. In doing so, these scaffolds will recapitulate the regenerative capacity of children in the application of therapeutics to promote bone regeneration in adults.

Award Date: 19 June 2014
Award Value: €285,163
Principal Investigator: Professor Fergal O'Brien
Host Institution: Royal College of Surgeons in Ireland
Scheme: Health Research Awards