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Contact

Dr. Nicolas L'Heureux

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Contact

Linkedin biotis-bordeaux

Secretary Email

33 (0)5 57 57 14 88

Bioingénierie Tissulaire (BioTis)       

Physical Address:

Batiment BBS (Bordeaux Biologie Santé), 5e étage

2, rue du Dr Hoffmann Martinot,

33000, Bordeaux, France

Mailing Address:

Université de Bordeaux, Campus Carreire

146, rue Léo Saignat, Case 84,

33076, Bordeaux Cedex, France

Abstract

References

Project Leader

The problem:

INewborns with congenital heart defects represent a major and complex clinical challenge  [1,2]. Many of these infants present with dysfunctional heart valves, resulting in reduced arterial oxygen saturation and the clinical manifestation commonly referred to as “blue baby” syndrome. Not only will these children be born in difficult conditions, but they will also face a series of major cardiac surgeries. Indeed, current cardiac implants, namely heart valves, are made of synthetic materials or chemically modified animal tissues that will not grow with the child. As a result, they will need to be replaced with larger versions through surgeries that have very significant mortality rates [3].

▷[1] C. Apitz, G. D. Webb, A. N. Redington, Lancet 2009, 374, 1462.

▷[2] C. A. Warnes, A. L. Waldo, ACC Cardiosource Rev. J. 2008, 17, 19.

▷[3] Giamberti, A., Chessa, M., Abella, R., Butera, G., Carlucci, C., Nuri, H., Frigiola, A., and Ranucci, M. Morbidity and Mortality Risk Factors in Adults With Congenital Heart Disease Undergoing Cardiac Reoperations. The Annals of Thoracic Surgery, (88), 1284-1289, doi: 10.1016/j.athoracsur.2009.05.060 (2009).

▷[4] Zakko, J., Blum, K.M., Drews, J.D., Wu, Y.L., Hatoum, H., Russell, M., Gooden, S., Heitkemper, M., Conroy, O., Kelly, J., Carey, S., Sacks, M., Texter, K., Ragsdale, E., Strainic, J., Bocks, M., Wang, Y., Dasi, L.P., Armstrong, A.K., and Breuer, C. Development of Tissue Engineered Heart Valves for Percutaneous Transcatheter Delivery in a Fetal Ovine Model. JACC Basic Transl Sci, (5), 815-828, doi: 10.1016/j.jacbts.2020.06.009 (2020).

▷[5] Torres, Y., Gluais, M., Da Silva, N., Rey, S., Grémare, A., Magnan, L., Kawecki, F., and L'Heureux, N. Cell-assembled extracellular matrix (CAM) sheet production: Translation from using human to large animal cells. J Tissue Eng, (12), 2041731420978327, doi: 10.1177/2041731420978327 (2021).



One very ambitious approach is to to intervene in utero by implanting a heart valve capable of remodeling and growing with the fetus. We propose to use a CAM-based heart valve mounted on a biodegradable stent , designed for prenatal deployment. This  strategy leverages the fetus’s unique regenerative  and remodeling capacities, potentially  enabling functional integration of the valve before birth. Assuming a successful remodeling and the growth potential of the valve, such an approach could not only  improve  the hemodynamic  condition at  birth but  also  eliminate  the  need for multiple high-risk  surgeries later in life, significantly improving long-term outcomes and  quality of  life.

Dr. Christopher K. Breuer

Stented heart valve for in utero repair

The solution:

The research group led by Dr. Christopher Breuer at Nationwide Children’s Hospital has developed the only relevant animal model to evaluate this strategy [4]. Notably, this model uses sheep, which is particularly advantageous given our ability to produce ovine CAM, which closely resembles its human counterpart [5]. This project also includes a collaboration with the laboratory of Dr. Lakshmi Prasad Dasi at Georgia Institute of Technology.