The physical properties of the extracellular matrix (ECM) and the use of growth factors are powerful tools to control cell behaviour, including fundamental processes such as cell migration and (stem) cell differentiation. Integrins are mechanotransductors that feel and respond to the viscoelastic properties of the ECM. We have shown that cells respond to pure viscous interfaces and that results are explained by the classical clutch model for cell adhesion.1 At the same time, growth factors are important molecules that trigger signalling cascades that control e.g osteogenesis and vascularisation. We have developed material systems that allow simultaneous stimulation of integrins and growth factors receptors.2 We have engineered polymers that unfold and assemble fibronectin to allow exposure of the integrin (FNIII9-10) and growth factor (FNIII12-14) binding regions. Decorating assembled fibronectin on surfaces with low doses of growth factors allows receptor crosstalk, leading to highly efficiency presentation of growth factors, to maximise effects with minimal doses. We show the use of BMP-2 in synergy with a5b1 integrins to promote osteogenesis and regeneration of critical-sized defects and VEGF to promote vascularisation.3,4 Importantly, we show translation of the technology to treat veterinary patients.
In parallel, we have also engineered dynamic systems that allow control over temporal release of adhesion molecules and growth factors. Unconventionally, we have used non-pathogenic bacteria that have been engineered to control release of a fribronectin fragment and BMP-2 in a dynamic way. We present bacteria-based materials in which symbiotic bacteria/mammalian cell interactions occur and their use for stem cell engineering. We have first genetically modified L. lactis to produce a fibronectin fragment (FNIII7-10) that allows integrin binding and cell adhesion to the bacteria biofilm and then stimulation of ostegenesis by inducing the expression of BMP-2 in a dose controlled manner.5
Prof Manuel Salmeron-Sanchez FRSE is Head of Biomedical Engineering at the University of Glasgow. He did a PhD in Valencia and postdoctoral research at the Institute for Macromolecular Chemistry in Prague and the Katholieke Universiteit Leuven. In 2005 he was appointed Assistant Professor at Universitat Politècnica de València, promoted to Associate Professor in 2008 and Full Professor in 2010. He did a sabbatical year at the Georgia Institute of Technology and the moved his group to the University of Glasgow in 2013. Manuel is an ERC (European Research Council) investigator developing advanced cell microenvironments that recapitulate properties of the natural ECM. This work has attracted significant additional funding from the ERC (PoC, 2 awards) and Research Councils UK and has set up the basis for a programme of research to help victims by landmines, funded by the Sir Bobby Charlton Foundation. Overall, his work spans fundamental mechanisms at the cell/material interface as well as translational research that has saved from amputation the leg of a first veterinary patient, a dog called Eva (https://goo.gl/1Z3r8t ). He has authored more than 160 papers in major journals including PNAS, Science Advances, Nature Biomedical Engineering and Advanced Materials. He has had his research featured in newspapers, websites and TV channels around the world.