Nicolas LHeureux

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Is a globally recognized expert in tissue engineering and regenerative medicine. Dr. L’Heureux was an early believer in the possibility of developing completely biological tissue engineering approaches to produce constructs with physiologically relevant biomechanical properties. At a time when synthetic scaffolds were seen as a defining part of any tissue-engineered construct, he demonstrated that sheets of Cell-Assembled extracellular Matrix (CAM), produced by normal human cells in vitro, can be rolled into completely biological, living, autologous, and human blood vessels that display remarkable mechanical strength without the need for any exogenous scaffolding (FASEB J. 1998). This was the first example of a so-called “scaffold-free tissue engineering” approach yielding tissue-level mechanical properties. During his years at Cytograft Tissue Engineering (a start-up he co-founded in 2000, in California), Dr. L’Heureux has sought to accelerate the translation of this technology to the clinic. This effort has led to the first clinical use of tissue-engineered blood vessels under arterial pressure and the demonstration of long-term durability (NEJM. 2007, Lancet. 2009, JVA. 2024) . Clinical data have also shown the possibility of using devitalized allogeneic CAM (JVS. 2014).

Profile / Expertise

Patents:

1- McAllister, T., and L'Heureux, N. Tissue engineered cellular sheets, and methods of making same. USPTO Patent No. 8,076,137 (December 13, 2011).

2- McAllister, T., and L'Heureux, N. Bioreactor for the manufacture of tissue engineered blood vessels. USPTO Patent No. 7,744,526 (June 29, 2010).

3- McAllister, T., and L'Heureux, N. Tissue engineered cellular sheets, methods of making and use thereof. USPTO Patent No. 7,504,258 (March 17, 2009).

4- McAllister, T., and L'Heureux, N. Method of culturing cells to produce a tissue sheet. USPTO Patent No. 7,166,464 (January 23, 2007).

5- McAllister, T., and L'Heureux, N. Tissue engineered blood vessels and apparatus for their manufacture. USPTO Patent No. 7,112,218 (September 26, 2006).

6- McAllister, T., and L'Heureux, N. Tissue engineered blood vessels and methods and apparatus for their manufacture. USPTO Patent No. 6,503,273 (January 7, 2003).

7- L'Heureux, N., Auger, F.A., and Germain, L. Production of a contractile smooth muscle. USPTO Patent No. 5,618,718 (April 8, 1997).

✔ Fibroblasts

✔ Endothelium

✔ Smooth muscle cells

✔ Bioreactors

✔ Vascular graft

✔ Extracellular matrix

✔ Tissue-engineering

✔ Bioengineering

✔ Regenerative Medicine

✔ Cardiovascular biology

✔ Cell-based therapies

✔ Human cell culture

✔ Collagen

✔ Histology

✔ Immunofluorescence

✔ Electron microscopy

✔ Mechanical properties

✔ Mechanical stimulation

Links

Contact

Profiles

+(33) 05.57.57.17.23

Nicolas.lheureux@inserm.fr

ReaserchGate

BIOMAT

ISACB

Dr. Nicolas L'Heureux

Director of BioTis (UMR 1026)

Director of Research (DR2 - Inserm)

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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

Projects

CAM-based implant to repair Stress Urinary Incontinence (SUI)

CAM-based implant to repair Pelvic Organ Prolapsus (POP)

Tissue-Engineered Vascular Grafts using Cell-Assembled extracellular matrix (CAM) and a textile approach

Stented heart valve for in utero repair

Injectable CAM formulation to rebuild tissues

📚 Publications:

CAM-based vascular graft produced

by rolling sheets

A spool of dry CAM thread

A vascular graft produced

by weaving CAM trheads

Returning to academia has allowed Dr. L’Heureux to formally demonstrate the incredible ability of the CAM to integrate and persist in vivo. Thanks to the fact that the matrix is not chemically modified or denatured, its native-like tridimensional architecture and complex protein composition are preserved (Acta B. 2018, Biomat. Sci. 2022). As a result, the CAM does not trigger a degradative immune response, as shown in two studies where human CAM was implanted in nude rats, where it was positively remodelled and could be retrieved after up to 10 months (Biomat. 2021, Acta B. 2023). To fully evaluate the performance of CAM-based implants in an immunocompetent animal model, which is needed to support clinical evaluation, his team developed a method to produce ovine CAM that is very similar to its human counterpart (JTE. 2021). In a first study, allogenic ovine CAM was implanted subcutaneously and retrieved after 1 month. Results confirmed that the ovine CAM was rapidly colonized by the host cells with little inflammatory reaction, while the human (xenogeneic) CAM triggered an intense immune response (Acta B. 2025). A soon-to-be-published study has observed the remodeling of CAM in this model for up to 6 months and confirmed the integration and persistence of the allogeneic CAM, as well as documented the chronic inflammatory response to the xenogeneic CAM (even when decellularized). Based on these results, woven vascular grafts have been designed for arterial bypass as well as for arteriovenous shunt bypass. Both graft types have been implanted in this allogeneic large-animal model, which will allow us to evaluate their remodeling and performance in an immunological and mechanical environment that mimics the clinical situation.

In addition to blood vessel development (supported in part by an ERC Advanced Grant), Dr. L’Heureux has also developed a program on CAM-based heart valve engineering at BioTis with Dr. Fabien Kawecki and in collaboration with MIT (Cambridge, Massachusetts, USA). This effort has led to the appointment of Dr. Kawecki as a tenured assistant research professor (CRN INSERM) at BioTis (SCT. 2024). He is now driving the development of pediatric applications focused on cardiac congenital defect repairs (including heart valves). Meanwhile, Dr. L’Heureux is also collaborating with Dr. Christopher Breuer at Nationwide Children’s Hospital in Columbus, Ohio (USA) on the development of a heart valve mounted on a biodegradable stent for in utero repairs. Adult stented heart valves are also being developed for aortic valve replacement through a start-up (BioValve Therapeutics) co-founded by Dr. L’Heureux.

Dr. L’Heureux recently received two ERC Proof-of-Concept grants as well as an ANR grant to develop a new generation of CAM-based grafts to treat urogenital conditions. Currently, Pelvic Organ Prolapse (POP) and Stress Urinary Incontinence (SUI) are often treated by implanting a plastic mesh to mechanically support lax tissues. However, these plastics are foreign materials that the body tries to eliminate through a chronic inflammatory response called the foreign body reaction. Also, because these plastics are much harder than natural tissues, these implants can erode surrounding tissues and be exposed through the vaginal wall, the urethra, the bladder, or even the colon. Complications include bleeding, infection, granuloma, and chronic pain. As a result, implants for the transvaginal repair of POP have been pulled from the market in major countries, and companies have facing multiple lawsuits around the world. CAM can allow us to produce implants that are both strong and compliant, and have the biological qualities to be truly integrated in the patient’s body and avoid the complications caused by chronic inflammation. A startup (CAMATISS) is in preparation and is accompanied by the incubator Chrysa-link of the SATT Aquitaine Science Transfert and the GDR Réparer l’Humain.

Dr. L’Heureux most recently received an ERC Proof-of-Concept grant to explore the use of CAM sheets as an injectable material, which could be used for various minimally invasive procedures to treat SUI, skin aging, vocal cord dysfunction, or to deliver cells.

Today, the CAM is a technology platform that can use sheets, threads, or particles of CAM to create an array of human (or ovine) tissues. This technology is one of the pillars of BioTis’ research, and many other projects are ongoing or in preparation, both internally and through collaborations, including dental pulp regeneration, biological suture development, esophageal repair, tracheal replacement, artificial heart improvement, intervertebral disc repair, and the use of the CAM as a bioprinting substrate (biopaper).

Cell-Assembled extracellular

Matrix (CAM)

Since at BioTis (2015), his efforts have focused on the development of textile-based approaches to assemble CAM threads into blood vessels and other constructs for therapeutic applications (Acta B. 2020). These “human textiles” have a remarkable potential for clinical applications because of the versatility of the approach. Indeed, textile assembly allows fine control over tissue geometry, density, permeability, as well as directional and local mechanical properties. As an example, by changing thread size and thread count (density), we have shown that the properties of a CAM-based woven vascular graft can be tuned to achieve the desired values (Biofab. 2023). In addition, a textile assembly is more rapid than a sheet-based approach since it does not require a long maturation phase or a complex bioreactor to achieve fusion of the sheet layers. A key advantage of this approach is the immense know-how available for textile automation, which will be critical to facilitate commercialisation. Through sewing, weaving, braiding, and knitting, the possibilities of tissue design are almost endless and can address a wide range of applications.