For over ten years, facial reconstruction has been a central area of interest for UCL researchers. Their objective is to develop innovative techniques to adapt as closely as possible to the patient. We find out more.
In 2005, Professor Benoît Lengelé of UCL performed the world’s first face graft. It was a significant première, but the feat has only been repeated some thirty times since then: ‘Face grafting is not a minor procedure. It requires a combination of two disciplines: plastic surgery and organ transplantation. This means that the patient has to receive immunosuppressive treatment for life in order to prevent the graft from being rejected,’ explains Dr Jérôme Duisit, assistant physician in plastic surgery and PhD candidate at the laboratories of experimental morphology (Prof. B. Lengelé) and experimental surgery and transplantation (Prof. P. Gianello). ‘What’s more, for obvious reasons, you need a donor with physical similarities to the recipient. These different factors mean that this kind of transplant is only possible for a very specific type of patient: young patients in good health who suffer from a major disfigurement with a functional impact, such as the loss of both lips.’
Aware of the limitations of this restorative surgery, Jérôme Duisit decided to approach the problem from another angle, that of tissue engineering. His plan was to make grafts that would adapt to the recipient and not the other way around. ‘When you think about building tissue, or in more general terms, organs, 3D printing immediately springs to mind. However, this technique is confined to very small structures, so it is of no use to us at present,’ he explains. Instead, his idea was to focus on existing tissue, which could be treated in order to make it compatible. ‘More precisely, the idea is to take a donor graft and empty it of its own cells, while preserving its biological architecture as well as its nerves and blood vessels. This leaves us with a kind of matrix which has no cells and is therefore not subject to rejection. It’s an ambitious undertaking, because the face is composed of a large number of different tissues: skin, cartilage, muscle, blood vessels and so on.’
Step 1: neutralise the graft
To begin with, the researcher focused on a ‘non-motor graft’ – a part of the face which, unlike the ear or the nose, is not functional.‘We developed a technique capable of neutralising the graft by removing all its cells. Specifically, this involves pumping a so-called decellularisation liquid from a reservoir using a peristaltic pump. This liquid gradually diffuses into the graft and causes the walls of the donor cells to be broken down. The graft is then washed and degreased. For an ear, this process takes an average of ten days.’
Sterilised ear and finger matrices (J. Duisit/UCL)
Step 2: prepare the graft for transplantation
Once the graft has been cleared of all cells from the donor, it must be prepared for regeneration by repopulating it with new cells – ultimately, those of the recipient. Jérôme Duisit does this with a bioreactor that he developed himself in collaboration with the Louvain School of Engineering and Louvain Bionics. ‘The purpose of this bioreactor is to recreate a regenerative environment: to circulate a nourishing culture medium as though it were blood and to promote the seeding of the graft using cells taken from the donor.’ In this way, the graft is gradually colonised by the recipient’s cells, and will therefore be perfectly compatible without the need for immunosuppressive treatment. ‘The bioreactor we have developed, which is adapted for the regenerative treatment of body parts, is the first of its kind in the world. It’s also the subject of a UCL patent,’ he adds.
Preparation for graft culturing in the bioreactor with culture medium (red) (J. Duisit/UCL)
Introduction in a sterile incubator for maturation (J. Duisit/UCL)
One bioreactor per organ
Following these conclusive tests on the ear, the researcher is now interested in the lip. This introduces an added complication: the lip must be capable of moving when the muscle is used. ‘We therefore need to develop a bioreactor that’s capable of mimicking the contraction movements of the lip muscles so that the graft quickly becomes functional after transplanting. Ideally, one bioreactor per organ needs to be invented, so that the organ concerned is subjected to the same conditions as when it is in the body.’
Injection of stem cells into a lip matrix (J. Duisit/UCL)
Final challenge: bone!
When his work on the lip is finished, Jérôme Duisit will tackle the final challenge: bone. Specifically, the grafting of a finger. ‘If we manage to apply this technique to the finger, it will be possible to graft any other structure consisting of bones, tendons and joints. This project is really innovative and opens up promising prospects for surgical reconstruction for people currently unable to benefit from a limb allograft. It would also get round the major obstacle encountered with allografts: the lack of availability of compatible donors.’
Despite the exciting nature of this project, some realism is called for. Although revolutionary therapeutic prospects will be opened up for patients, doctors will still face two major problems: an urgent need for donors and the need to take the individual’s specific characteristics into account. It is essential for a face graft to be true to the recipient’s morphological identity. ‘In order to address this, it is conceivable that an entirely synthetic three-dimensional matrix could be created, in the recipient’s likeness, which would then be colonised by his or her cells. The ultimate aim would be a custom graft! But numerous obstacles still need to be overcome in order to reach that point,’ Duisit cautiously concludes.
A glance at Jérôme Duisit's bio
2004 : Doctor of Dental Surgery (Université Claude Bernard Lyon)
2010 : Doctor of Medicine (UCL)
2010 : Assistant physician and trainee specialist in Plastic and Reconstructive Surgery (UCL)
2013-2017 : Doctorate in Science (UCL) supported by the Foundation Saint-Luc, the Special Research Fund (UCL) and the Fonds Dr Gaëtan Lagneaux.