A completely biological and human tissue-engineered sling produced from Cell-Assembled extracellular Matrix (CAM) in vitro for the treatment of Stress Urinary Incontinence (SUI)

Informazioni relative al progetto

SUITEX

ID dell’accordo di sovvenzione: 101189393

DOI

10.3030/101189393

Progetto chiuso

Data della firma CE 16 Ottobre 2024

Data di avvio 1 Gennaio 2025

Data di completamento 30 Giugno 2026

Finanziato da

• European Research Council (ERC)

Costo totale

Nessun dato

Contributo UE

€ 150 000,00

Coordinato da

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France

Periodic Reporting for period 1 - SUITEX (A completely biological and human tissue-engineered sling produced from Cell-Assembled extracellular Matrix (CAM) in vitro for the treatment of Stress Urinary Incontinence (SUI))

Periodo di rendicontazione: 2025-01-01 al 2026-06-30

Sintesi del contesto e degli obiettivi generali del progetto

Stress Urinary Incontinence (SUI) is a major medical issue affecting 1 in 5 women. Implantation of synthetic slings, made of knitted plastic monofilament, is the gold standard surgical treatment. They provide mechanical support to the urethra, avoiding involuntary loss of urine on effort. However, they are associated with serious complications, and some countries have already suspended their use. Hence, there is a strong medical and societal need for breakthrough innovations. The two fundamental problems of synthetic slings are the excessive hardness of the material and the foreign body reaction it creates. We propose a new paradigm by providing a non-living tissue-engineered sling that is soft, yet strong, as well as completely biological and human. Our strategy is based on a unique material: the Cell-Assembled extracellular Matrix (CAM) produced by fibroblasts in vitro, used to produce CAM-based slings.

The overall objectives of this project were to :
1) Prove that human CAM slings can have clinically relevant mechanical properties;
2) Demonstrate that equivalent ovine CAM slings can be successfully implanted in a clinically relevant, allogenic, large animal model;
3) Show a superior integration of ovine CAM slings compared to synthetic slings (absence of foreign body reaction and positive remodeling).

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

In this work, we provided a design and manufacturing protocol of human and ovine CAM slings suitable for in vivo implantation, i.e. with a relevant size and clinically relevant mechanical properties.

Then, we implanted ovine CAM slings in the urogenital area of an allogenic sheep model, evaluated the host response, and the CAM remodeling.

We confirmed, for the first time, the implantability of this drastically new generation of slings. Surgeons were able to manipulate and suture the graft as is done with synthetic grafts, using the same surgical technique used clinically in patients.

After explantation, the tissue was largely intact, which supports our hypothesis that this allogenic implant will be long-lived and provide mechanical support without creating a sustained inflammatory response or foreign body reaction. We performed immunostaining on these tissues to identify the various cell types present and more precisely characterize the immune response in terms of macrophage types one and two. This in vivo study has provided important technical knowledge about this animal model that we will learn from and that will allow us to adapt our next study.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

We successfully demonstrated that CAM slings are an excellent candidate to replace synthetic slings and treat millions of patients with SUI with no complications (the global market for SUI devices was estimated at 1 billion US$ in 2025).

Overall, this PoC increased the technology readiness level of our product from 1-2 to 3-4. The outcomes justify an expanded in vivo analysis and support a commercial endeavor targeting clinical application.

In the future, we will need to perform larger animal studies of the CAM slings and also focus on regulatory, manufacturing, and business aspects to ensure translation of the technology from the research to the patient.