The best replacement for bone is bone itself’. This might have been a fun little sound bite delivered in one of the undergraduate lectures in my first year, but it is also the statement that I can safely credit as having sparked my interest in biomaterials.
Then, in my rather inexperienced mind, scientists pretty much knew how the world worked, and if they didn’t, then that would have been because they were solving age-old problems about the universe and how it began, or trying to achieve things beyond what was possible by nature alone. As the years went by, I had the privilege of learning about the theories and choices in design that underpin most modern materials, yet I could not shake the assertion about bone from my mind. What is it about the native healthy tissue in our body that makes it so special? How can we make further progress with finding better replacements?
This interest has been shared by many scientists who came before me. One strategy has been to aim for the regeneration of our ideal, healthy tissues. Of course, when disease or injury strikes this is easier said than done. Research efforts are currently focused on creating structures known as tissue-engineering scaffolds that behave as the original tissue would, while successfully guiding the repair process. So, I too set off five years ago to try to understand how we might be able to mimic tissues synthetically, when our body cannot quite do this itself.
The bulk of my doctoral work has focused on collagen, the main structural protein in our body. I realised very quickly that achieving the best scaffold for a given application was more than an issue of getting the right structure, mechanics or biochemistry to mimic the natural tissue environment. It was about getting them all right, all at once. This was a tricky pursuit, because some of the effects of one process can affect the structure or property of the scaffold at another level. As an example, we can employ a reaction called cross-linking to form chemical bridges that strengthen the whole device. However, this means that we must also be careful not to use up any chemical groups that cells recognise as the cues found in native healthy tissue.
This inherent hierarchical structure and fine-tuned balance of structure and properties is exactly what makes healthy tissues so special, and why the slightest misstep through injury or disease can lead to a breakdown of healthy function. Replicating this intricate structure in the lab is made even more complicated by the fact that we might not even fully understand what drives the underlying fabrication processes or have the best tools to analyse the data we get. So I thought that, as a materials scientist, I would pick apart as many of these structure-property-processing relationships as I could, from the effects on the smallest molecular receptors in collagen, all the way to the shape and size of the sub-millimetre pores created in the scaffolds through ice-templating. I am grateful to have had a chance to journey through collagen scaffolds at various scales of length. To do this, I have immersed myself in ice physics and polymer chemistry, and even dabbled in some cell biology and machine learning along the way.
While regeneration might be the biochemical gold standard, we are far from being able to grow back entire limbs, or restore the mobility and functionality provided by many permanent implants such as prosthetics or pacemakers.
At Emmanuel, my research now focuses on taking everything I have learned by deconstructing the fabrication of collagen-based constructs, just to put it all back together again, this time with the aim of creating something that surpasses what we can do with biological materials in the lab. Our bodies constantly change over time, and the physiological environment is likely to vary even more across different people. I use novel materials and fabrication methods to create implants that can respond dynamically to their environment, all while keeping in mind the fine balance that must be maintained for tissue regeneration. These devices are unlikely to replace permanent implants any time soon, but they can offer greater functionality than the current regenerative scaffolds and be produced using the same scalable technologies we currently use, whilst offering the promise of more personalised healthcare solutions for a wider range of ailments.
Research Fellowships are much sought-after positions as a next step after completing a PhD. We were delighted to welcome Malavika to Emmanuel in October 2020.