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)

Projektinformationen

SUITEX

ID Finanzhilfevereinbarung: 101189393

DOI

10.3030/101189393

Projekt abgeschlossen

EK-Unterschriftsdatum 16 Oktober 2024

Startdatum 1 Januar 2025

Enddatum 30 Juni 2026

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 150 000,00

Koordiniert durch

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))

Berichtszeitraum: 2025-01-01 bis 2026-06-30

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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).

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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.