From idea to demonstration of a materials macroscope: our seven-year journey
I am Morgan Alexander, a materials scientist (plastics, not fabrics), and I have the pleasure of being the Director of the Engineering and Physical Sciences Research Council (EPSRC) Programme grant in Next Generation Biomaterials Discovery, a project involving researchers and investigators across the Faculties of Science, Engineering and Medicine at the University of Nottingham. This is the story of one part of our research, its impact and potential applications, and of the team who helped bring it to life.
It’s also the story of just one of the 20 research papers our project generated in the last year, published by Biomaterials, which describes a method to screen a large range of materials and surface textures, with potential use in medicine to modify the response of cells. In regenerative medicine that would mean guiding cell behaviour to improve bone repair, with potential applications in requiring fixing large defects or achieving better integration of implanted medical devices.
The idea at the heart of this research paper came out of discussions at a conference in Long Beach, California, in October 2013 between myself and Jan de Boer, the inventor of Topochip, a Dutch scientist with research interests cell control with topography (surface texture). I’d invited Jan to speak at the conference after seeing one of his research papers. After our discussions I was keen to see if we could create a chip to investigate the influence on cells of both topography and material chemistries simultaneously, and this is how the idea of the ChemoTopoChip came about. This looks at a large number of different materials, so let’s call it a metaphorical materials macroscope, in contrast to a microscope that focuses on a small bit of a single material.
The first major hurdle was to obtain funding. We were unusually fortunate that we succeeded on our first attempt in getting government funding in the form of an EPSRC Programme Grant, reflecting the potential that materials control of cells has in medical therapies. Programme Grants are longer and larger than normal research grants in order to tackle substantial challenges and aim to give greater directional freedom to the researchers.
Developing new research methods takes a long time, although initially, we didn’t realise this one would take so long. A significant part of this is the human side that contributed to creating the content of this paper; which I’ll focus on to highlight the myriad challenges were navigated, additional to those in the laboratory.
"No one person could have done the work since it required deep expertise in stem cells, immune cells, materials fabrication and characterisation, artificial intelligence, statistics and chemistry. "
Once we had the money, the challenge posed by the interdisciplinary nature of the work was to recruit researchers with the selection of skills to realise the plans, including chemistry, tissue engineering, immunology, computational science, topographical engineering, stem cell biology and surface characterisation. To date 27 Post docs and 11 PhD students have worked on the grant, with representatives from all five continents of the world. Facilitating the discussion of complex science across the different scientific languages of these disciplines has been a major part of my job in guiding this research.
The final author list of this paper includes 15 people, who have all invested much experimental and thinking time. No one person could have done the work since it required deep expertise in stem cells, immune cells, materials fabrication and characterisation, artificial intelligence, statistics and chemistry. From the point the work was funded in 2014 up until today, five of these researchers left for careers outside academia, one moved on to a personal academic fellowship in another university, one academic took early retirement but continued to contribute from new institutes, one moved university, twice; two were promoted to Professor, and we recruited a new Nottingham collaborator en route.
These events are not linked to this paper, or the grant, but they are life, which rolls on whilst we are trying to achieve our scientific goals; people’s partners move countries (two), new opportunities appear for individuals and their priorities change. With so many people involved, it is inevitable that life doesn’t cut a nice path to serve the scientific goal, no matter how hard we plan. I think recognising that as early as possible in a career for those managing research and embracing it to recruit fresh viewpoints can reduce stress levels in such lengthy efforts.
That is of course easy for me to say in this instance; if this grant had not been five years in length, or the collaborators weren’t able to offer the necessary support, the story of this particular paper may well have had a far less happy ending, with incomplete experiments, results and possibly no paper. There have been many unfinished research stories where our best plans collide with life that I’ve put to the back of my mind, I think most academics (natural optimists?) do that to avoid being weighed down by the failures that accompany the successes.
On my birthday this year, I pleasingly received notification that our paper had been accepted by Biomaterials, the leading journal specialising in my research area, after a seven-year journey to realise our idea and being declined by a number of multidisciplinary journals. Not all ideas and papers take this long, but sometimes they do. A benefit of the long time that this took to complete is that the new ideas that emerged in the data did have time to be developed. Could it have been completed faster? Probably. Would we have learnt as much? Probably not.
Finally, looking back at how this paper came about and the work it entailed is not a luxury I normally make time for, it is normally straight onto the next task, but this has reminded me how many of the authors, unknown to each other before this work, are now friends. In addition to developing this materials macroscope to enable development of new medical materials, we have learned a lot from each other and have many great shared memories through this scientific journey, as varied as walks down the river Trent, mountain bike rides in Zeist, and skiing the French Alps.
Other papers from this grant can be found here.