Final Report Summary - MASC (MASC: Materials that Impose Architecture within Stem Cell Populations) This ERC Advanced Grant has resulted in the invention and publication of a range of new materials that change the behavior of cells and tissues in the lab and in the body. We have demonstrated that the architecture and composition of new materials can unlock functions in cell populations. As a result we have described new methodologies that will be of use to scientists across interdisciplinary fields including physics, developmental biology and regenerative medicine. We have new patent applications that we aim to underpin job creation and new product launches within Europe. We have also made a major contribution to engaging the public in our science via public exhibition and television programmes.The original application envisaged the design of 3 new tools that would be used in 3 new demonstrator projects. We have succeeded in all 6 of these areas with publications in world leading journals and exemplification of our concepts in clinically and commercially important areas.Under Tool 1 (Spatial and Temporal Presentation of Molecules) we developed and patented a new delivery system for protein drugs that control the differentiation of induced pluripotent stem cells. The work was published in Proceedings of the National Academy of Sciences USA. We also demonstrated the use of 3D printing and additive manufacturing to create gradients of proteins within cell populations.Under Tool 2 (3D addressing of Cells and Polymers) we described the first use of holographic optical tweezers to pattern mouse embryonic stem cells and polymers into complex patterns. The work to be published in Scientific Reports is the highest resolution pattern ever achieved for living cells and showed the ability to slowly deliver drugs to these cells in precise locations.Under Tool 3 (Integration of Surface, Cells, Gradients and Biomechanics) we published a paper in 2014 in Proceedings of the National Academy of Sciences USA that used a new material in which cells could be loaded and their surface interactions and local biomechanical environment controlled. Uniquely we could switch this material from a state that promoted cell division to a state that promoted cell differentiation.The 3 Demonstrator projects were designed to show that the Tools were beneficial in key problems in biology and regenerative medicine. For all 3 we have successes in preclinical and in vitro experiments that provide a platform for future impact in research and industry. Under “Injectable Scaffolds” we have seen enhancements in tissue repair in animal models of hind limb ischeamia and critical sized bone defects. For “In Vitro Tissue with Tubular Structures” we created a contractile smooth muscle structure and an automated cell sheet roller for formation of tubular tissues. These tissues and the methodology are being used by collaborators for preclinical experiments. Finally, we aimed to show that our Tools could allow new types of experiments to be performed in developmental biology. Our Nature Communications paper in 2012 described the first observation of a polarization event in a mouse embryo made possible by a hydrogel material with controlled elasticity. More recently we have created a gradient system for the intracellular delivery of the transcription factor MYOD.Beyond high impact scientific publications we are actively involved in transfer of our Tools into industry. We have patent applications filed for 3 key inventions and commercial partners assessing the technology. An ERC Proof-of-Concept award will allow a business plan for our intracellular delivery system to be finalized in 2015.
