Study of effects of surface bound, low-dose PDGF on cell motility – towards improved wound healing (360G-Wellcome-206953_Z_17_Z)

In vivo, GFs are secreted by cells and tether to the extracellular matrix (ECM), e.g. the heparin-binding domain of fibronectin. This ECM interaction allows cells to exploit low-dose GF signals in topical locations. In clinic, GFs are supplied in soluble format in supraphysiological dose to maintain concentration at the injury site, accepting that much of the GF will distribute around the body; this causes unwanted off-target side effects that can be serious (e.g. death). Materials are being designed to deliver GFs to specific targets and to control the release of the GFs, but still released at high dose and in unbound format allowing systemic distribution. The ideal is to use materials to mimic the human ECM. However, proteins such as FN bind to materials in globular conformation so that GFs do not efficiently bind/cannot be exploited by cells. We have discovered a polymer, polyethylacrylate (PEA) that causes spontaneous opening of FN in fibrilar conformation and this allows biomimetic GF tethering. In the project we will bind PDGF and study cell motility, key in wound healing, as cell recruitment will determine wound closure.