Exploiting nanoclay self-assembly for stem-cell driven tissue regeneration (Ext.)

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This is an extension of the Fellowship: "Harnessing clay nanoparticles for stem-cell driven tissue regeneration"Stem cells have great potential to cure a wide variety of conditions by regenerating diseased or damaged tissue. During the body's development from an embryo and during its repair after injury, stem cells are activated by a highly co-ordinated system of signals from the local micro-environment. Intricate patterns of spatially and temporally changing concentrations of biochemical molecules direct how tissues grow and the form that they take. Being able to deliver and control these environments in the body is vital if we are to harness the potential of stem cells for healthcare. The aim of my research is to develop a new type of hydrogel formed from nano-sized (1 millionth of a millimetre) clay particles that, when delivered into the body, provides an environment able to stimulate and direct stem cells to repair and regenerate diseased or damaged tissues such as bone, cartilage or skin. Hydrogels are gels with a very high water content. They are excellent candidates for delivering stem cells as they allow diffusion of nutrients and their basic physical properties mimic the cell's native environment. Their major drawback is that, because they are formed mainly of water, they do not tend to allow for the precise control of biochemical signalling molecules that is so important in directing how a stem cell functions. Certain nano-clay particles are also able to form hydrogels by forming physical interactions with each other to create a structure that locks in water. They also display the very unusual and potentially useful property of being extremely sticky for biological molecules. Over the past five years, EPSRC has funded my research exploring ways to use these properties for creating gel environments in the body that can activate stem cells to form bone. We have developed gels that can be injected into an injury site to deliver and bind bone growth factors and stimulate bone formation at much lower doses than previously reported. However, though promising, our approach of injecting large volumes of gel with protein mixed uniformly through is rather crude when compared with the precise concentration gradients that regulate bone formation in the body. Over the course of this exploration we have, however, discovered a new unexpected property of nanoclay gels that could potentially make them even more effective at stimulating regeneration. As well as being able to hold onto mixed-in growth factors, we have now found a simple way to precisely pattern the arrangement of these biomolecules within the gel itself. This is very exciting as it could allow us to begin to mimic the intricate patterning so important in natural stem cell behaviour. The current funding will allow us to explore this property and test ways to apply clay biomolecule patterning in regenerative medicine. It is exciting because we do not currently understand how and why these patterns form and so we are working with physicists specialising in nanoparticle gels to gain new insights into this surprising behaviour. It is also exciting because it allows a new approach to exploring the role of biomolecule patterning in stem cell repair and regeneration. We hope that this work will allow us to harness, more effectively and reliably, the great potential of stem cells to cure disease.