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)

Introduction

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.

Problem Statement

The two fundamental problems of synthetic slings are:

• The excessive hardness of the material
• The foreign body reaction it creates

Proposed Solution

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. We can produce robust CAM sheets from human or ovine cells with similar properties. They are cut to produce threads subsequently woven into CAM slings.

Project Tasks

The potential of CAM slings to treat SUI will be demonstrated through two main tasks:

1. Development of human and ovine CAM slings with mechanical properties justifying a preclinical study.
2. In vivo validation of allogenic CAM slings in a female sheep model at 2 and 6 months.

Proof of Concept (PoC) Outcomes

This PoC will:

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 (reduced immune response and positive remodeling).

Conclusion

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