ľ�ϸ���Ӱ��

Bone is a remarkable tissue with an exceptional capacity for regeneration. However, under some circumstances, the bone cannot repair the injury itself and surgical intervention is needed. During her PhD, Leanne De Silva explored the use of lab-engineered cartilage mimics as a clinical application for bone repair. She successfully defended her thesis on 10 December.  

‘The current “gold standard” treatment for bone defects that will not heal on their own is implantation of autologous bone. For this treatment, bone is harvested from one area of the patient’s body and transplanted to the injury site,’ Leanne explains. ‘This approach has its limitations, including limited donor bone availability, increased surgical time and patient morbidity. This is why we are developing an alternative.’  

A cartilage mimic as an off-the-shelf alternative

Prior to Leanne’s start as a PhD student, her team developed a cartilage construct made from donor cells. When this construct is implanted into a patient’s body, it gradually transforms into bone through the natural process that occurs during normal bone development. To make the constructs storable, they were made to be ‘non-living’: the cells were devitalized. The constructs had primarily been tested in a lab environment. Leanne’s main aim, therefore, was to explore the clinical translation of these constructs for the treatment of large-scale bone defects. 

The studies showed positive results: ‘We found that the non-living cartilage mimic shows comparable bone formation to the autologous bone in both small and large animals. Although living bone will always be the most effective treatment, our cartilage mimics paves the ways towards an off-the-shelf alternative.’ 

The challenge of providing blood flow to the new tissue

Vascularization is a common challenge across all fields of tissue engineering. Leanne and her team utilized an in vivo vascularization method to expand to bigger defects, going from millimeter to centimeter-scale: ‘In our experiments, we used an arteriovenous (AV) loop method. This approach provides a central line for blood flow using the patient’s own vessels. This innovative method enables the patient’s own body to supply blood vessels to a tissue-engineered construct. 

The need to adapt while moving from the laboratory to the clinic excited Leanne: ‘That is something I really enjoyed about my PhD: you can only optimize something in the lab so much, but when you implant it into a living being, it might not work as you expected.’ 

A whirlwind of a start

While her studies provided an important base for further research, Leanne’s PhD did not get off to a smooth start. ‘I had just started my PhD when the COVID pandemic hit. That put a hold on a lot of things, because I did not have any data yet,’ Leanne reminisces. ‘I also have a background in pharmacy, not regenerative medicine and bone, and I had to learn a new microsurgical technique for the AV loop that involved working with vessels of 0.6 millimetres. The first year of my PhD was a big challenge of getting into the topics; it was all very new to me.’ 

In overcoming these challenges, Leanne has found support with her colleagues and the other students from the RESCUE cohort, which she was a part of: ‘We all started at the same time, so we had a good community of people who shared the same experiences. I definitely miss that community, but more than anything I appreciate RMU for providing me with the knowledge and skills that I have now.’ 

A new chapter as a postdoc 

Now, Leanne is happy to start a new chapter as a postdoc in the Vasc-on-Demand project in Germany: ‘We are providing ready-to-go in vitro vascularization kits. I work in the biological development department, which is a new and exciting challenge. Throughout the 10 years of research I have done, I have worked a lot with animals, and now I get to work on an artificial blood vessel for drug testing. This can help to reduce the number of animals used for drug testing and other research in the future.’