Research Reports: Microtia

This research project aims to revolutionise how we offer ear reconstruction surgery for patients born with an absent or misshapen ear: microtia, through the design of a new ink for 3D printing cartilage tissue.

One of the initial findings of this research was to determine the number of patients affected by microtia in the UK, and using Welsh patient records over a 19 year period, we were able to determine that the condition was more common than expected, with 2.13 cases of microtia diagnosed for every 10,000 babies born in Wales (previously reported as 0.7 per 10,000 births in England).

We had previously identified a novel biological material derived from a renewable plant source, called nanocellulose which offered great preliminary promise as a material for forming the base component of our biological 3D printing ink. By combining this with varying amounts of hyaluronic acid: commonly used as an injectable filler in cosmetic practices, we were able to significantly strengthen the material allowing it to be easily printed into 3D shapes, even holding its shape as a human ear. Furthermore, in the laboratory setting we have been able to demonstrate that the combination of nanocellulose and hyaluronic acid supports the growth and development of new cartilage tissue. We are currently performing additional tests to ensure that the material is safe for use in humans, and that the cells it comes into contact with behave normally and expectedly. Preliminary data suggests that cells in contact with the material survive as expected and do behave normally. This is all contributing to building an extremely promising case for the future of 3D printing cartilage tissue with this novel material combination. Ultimately, this would mean that children may be one day offered the possibility of having customised ear implants with living cartilage tissue, providing a realistic replica of their missing ear, rather than needing lengthy surgery requiring the removal of rib tissue.

The last couple of years have been unpredictable and unusual for everyone but has had a particular impact on clinicians, researchers and specifically in my case, clinician researchers!

Although the pandemic meant a return to clinical duties I was fortunate in that along with peers in my research group, we were able to use some of the 3D printing technology we have been optimising for the PhD work to help with the global pandemic by turning our attention to 3D printing visors and venturi valves for use in the hospital.

In line with government restrictions access to university laboratories was suspended during the first wave. As such, I managed to initiate an epidemiology/big data project through a collaboration with the SAIL databank at Swansea University to look at the epidemiology of microtia in Wales, its impact on affective disorders and school performance and access to surgical intervention which offers greater insight into this patient demographic and further justification for pursuing 3D printed tissue options for microtia patients.

The pandemic notwithstanding, research has now resumed to normality as part of this research project on 3D printing facial cartilage.

Despite the setbacks of the pandemic, progress has not been significantly hindered since the resumption of lab activity with tissue samples now becoming available more frequently for this research project which has been broadly focussing on characterising the cartilage cells for tissue engineering, developing and optimising the novel biological ink, determining its ability to encourage cartilage formation and verifying its biocompatibility. The data generated so far is novel, promising and helping to build a foundation for clinical translation – I am in the process of finalising several publications from the data generated and have had the opportunity to present the research nationally, internationally and from my front room via zoom wherever the opportunities arise at conferences such as BAPRAS, TERMIS and the upcoming EURAPS conference.

The fellowship has helped to realise my ambitions of developing independent thought processes, designing my own clinical research questions and developing the skillset needed to approach and answer those questions. Through collaborations both within and outside the university, I have been able to develop experience in numerous techniques from molecular biology (PCR and protein analysis) to imaging (histology, confocal and atomic force microscopy) and engineering (mechanical compression testing). The collaborations and techniques will be instrumental in enabling me to engage in multidisciplinary basic science research for the rest of my career.

Personally I have found it extremely rewarding, challenging and intellectually stimulating and despite the hurdles, obstacles and difficulties lab research presents I remain as determined as ever to retain a career that integrates clinical work and academia, to ultimately yield superior treatment options for patients.

This research project has generated pilot data that has helped to secure a grant from the Scar Free Foundation to establish a Centre for 3D Bioprinting for Facial Reconstruction in Swansea University (>£1million). The research specifically demonstrates that the biological ink I have developed has suitable mechanical properties to be 3D printed and hold its shape as an ear, that it supports the growth of cartilage cells and tissue and that the material is non-toxic to the cells within it. The next stages of the research will be further in depth toxicology and immunology experiments and animal studies to help push this research along a trajectory to clinical translation.

As a clinical-academic trainee I will have 20% protected academic time for the remainder of my plastic surgery training and I hope to use this time to progress my skills as an independent clinician researcher, apply for intermediate research fellowships and drive this research towards clinical translation.

Through my clinical work I have exposure to children affected by craniofacial abnormalities such as cleft and microtia and the impact of these diagnoses for the patient, their self-perception, psychosocial integration and their families is profound. More recently having been involved with big data projects investigating the associations between ear anomalies and affective disorders has highlighted the effects of ear anomalies on school performance and mental wellbeing. Our current interventions: surgery and prosthetics – go a long way to helping restore form and function in these patients, but prostheses discolour, displace and degrade and surgery requires long and complex surgery with the use of tissue borrowed from other bodily sites. Better options could exist for these patients, and 3D bioprinting technology is one such approach that could transform how we restore form function and psychological wellbeing to these patients without the need for extensive surgery. However, a novel technology such as 3D printing, combines stem cell biology, material science and bioengineering expertise to render a suitable living tissue replacement. This in turn demands significant investment from scientists, clinicians, engineers and funders to ensure robust laboratory-based research is undertaken and a convincing evidence base is built for developing this novel technology into a meaningful, clinically-viable option for patients. Every funded research project in the field helps add to this evidence base and pushes us closer to this technology being a possibility for children affected by visible differences.