FC3R 3Rs Prize 2024
Read the interview with the winner of the FC3R 'Culture of care' 3Rs Prize 2024.
Fabien Kawecki, could you please introduce yourself?
I'm a contract researcher at Inserm's Tissue Bioengineering Laboratory (BioTis), affiliated to the University of Bordeaux. I develop biological approaches for cardiovascular surgical repair, with a particular focus on pediatric applications. After obtaining my Ph.D. in bone tissue engineering and microvascularization at the University of Laval in Canada, I worked in 4D bioprinting at Poietis before joining the BioTis team of Dr. Nicolas L'Heureux in 2019. In 2020, thanks to funding from the Fédération Française de Cardiologie and the ANR, I launched my own research program.
We're working on Tetralogy of Fallot, a congenital heart defect that affects 7-10% of newborns and requires surgical correction to treat complex defects that affect heart function. The goal of our project is to improve the quality of life of patients by contributing to the development of new therapeutic approaches. In fact, the solutions used clinically are chemically treated synthetic or animal-derived materials that generate major complications, such as rejection by the patient's body, leading to a chronic inflammatory response, as well as calcification and thrombosis.
Furthermore, these materials are conducive to bacterial adhesion, putting them at high risk for infective endocarditis, which can be fatal for these young patients. Finally, they do not grow with the child, necessitating reoperation with significant risks of morbidity and mortality. The solution we have developed is a biological material made from human cells that does not trigger a rejection reaction and is able to integrate into the patient's body. It also has the potential to grow with the patient and thus have a significant positive impact on the health of these pediatric patients.
In summary, our project has the potential to generate significant spin-offs on several fronts, contributing to more ethical and effective research practices in pediatric cardiovascular surgery, while also having a positive impact on society.
How do you apply the 3Rs to your research?
We have established a multimodal in vitro/in silico platform that has helped to develop new therapeutic approaches while replacing, reducing and refining the use of animals for scientific purposes.
We developed a digital biorobotic heart model to study the use of an innovative biological material synthesized in vitro for surgical repair of tetralogy of Fallot. The biorobotic heart model we created, consisting of heart tissue and synthetic pneumatic muscles connected by a silicone elastomer matrix, is capable of mimicking in vitro the altered cardiac function found in this malformation. By preserving the native tissue architecture of the heart and controlling its beating, we have been able to study various surgical reconstructions and their effects in vitro.
After obtaining these mechanical and hemodynamic data, we also created a digital heart model with altered cardiac function. These models allowed us to optimize our surgical approach in vitro and in silico before validating it in a sheep model.
For example, the integration of biorobotic and digital heart models in our study allowed us to partially replace, and therefore significantly reduce, the number of animals required for the development and validation of a new therapeutic approach. In addition, these models allowed us to better understand the use of our new biomaterial for the repair of Tetralogy of Fallot, which in turn allowed us to refine our surgical approach during implantation in animals. Indeed, the optimization of our approach through in vitro and in silico studies before moving to animal studies has not only helped to reduce the use of animals, but also to improve animal welfare in line with the 3Rs. In fact, the model we have developed has reduced the need for invasive and repetitive testing, resulting in less stress and suffering for the animals.
Our project is part of a wider effort to reduce the number of animals used in research, as well as those used by industry to produce animal-derived materials (such as heart valves) currently used in the clinic. This is in response to growing public concern about animal ethics.
How do you share these advances?
On a scientific level, the use of a multimodal model combining a biorobotic and digital core provides controlled and standardized experimental conditions. This increases the reproducibility of results, which is a major concern in scientific research. Our work has been published in Science Translational Medicine, one of the most influential journals in our field. I am committed to sharing my knowledge and our discoveries with the broader scientific community and have presented the results of this work at numerous international conferences. Two patents have also been filed. The first relates to the development of the biorobotic heart model and the second to the use of our human-derived biological material for surgical repair of tetralogy of Fallot. This work has also led to the creation of a start-up company, Biovalve Therapeutics, which is currently negotiating the licensing of at least one of these patents. Transparent communications have been made with radio stations (Europe 1, AirZen Radio, France Info) and newspapers (Presse Inserm, Science et Avenir, Huffington Post, Le Quotidien du Médecin, Pourquoi Docteur ?, Journal International de Médecine, etc.) to share our research progress with the general public.
What does the 'Research' 3Rs Prize mean to you?
Since I've always worked in the field of translational research, I've always been confronted with the problems and ethical issues associated with animal experimentation. Although I'm convinced that it's impossible to do without animals in research today, it's a real concern of mine to contribute to reduction and replacement by actively participating in the process of developing new non-animal approaches. This "Research" 3Rs Prize is the validation of these efforts and the culmination of 4 years of very intensive research involving numerous partners in France and the United States: I'm happy and proud to start my research career on this note.