Periodic Reporting for period 1 - POPTex (A completely biological and human tissue-engineered mesh produced from Cell-Assembled extracellular Matrix (CAM) in vitro for the treatment of Pelvic Organ Prolapse (POP))
Periodo di rendicontazione: 2023-02-01 al 2024-07-31
Pelvic Organ Prolapse (POP) is a major medical issue for women. It is estimated that 1 in 10 women will undergo a surgery to treat POP during her lifetime. To provide mechanical support to the organ, strong and stiff synthetic meshes have been used. Transvaginal meshes are now withdrawn from the market in many countries due to high complication rates. Hence, there is a strong medical and societal need for breakthrough innovations.
We propose a new paradigm targeting the fundamental problem of synthetic meshes, i.e. the foreign body reaction, by providing a completely biological, tissue-engineered mesh to treat POP. Our strategy is based on a unique, biological material: the Cell-Assembled extracellular Matrix (CAM) produced by cells in vitro. Strong CAM sheets are cut to produce threads subsequently knitted into a mesh.
In 12 months, this proof of concept (PoC) aims to deliver unambiguous experimental evidence that a CAM-based tissue-engineered mesh has the potential to become a relevant alternative surgical solution to treat POP. This project is divided in 2 main tasks:
1) Production and mechanical characterization of a human CAM mesh, and of an equivalent ovine mesh, with mechanical properties justifying a preclinical test.
2) In vivo validation of an allogenic CAM mesh (i.e. ovine in ovine) in a female sheep model at 2 and 6 months.
This PoC will provide:
1) Proof that a human CAM-based knitted mesh can have clinically relevant mechanical properties;
2) Demonstration that an ovine CAM mesh can be successfully implanted to treat POP in a clinically relevant, allogenic, large animal model;
3) Direct comparison between the biointegration of an ovine CAM mesh setting and the inflammatory response to a synthetic mesh.
Overall, this PoC will increase the Technology Readiness Level (TRL) of our product from 1-2 to 3-4 by validating the functionality and safety of CAM meshes in a relevant in vivo environment. These outcomes will lead us closer to clinical trials and support a commercial endeavor.
We propose a new paradigm targeting the fundamental problem of synthetic meshes, i.e. the foreign body reaction, by providing a completely biological, tissue-engineered mesh to treat POP. Our strategy is based on a unique, biological material: the Cell-Assembled extracellular Matrix (CAM) produced by cells in vitro. Strong CAM sheets are cut to produce threads subsequently knitted into a mesh.
In 12 months, this proof of concept (PoC) aims to deliver unambiguous experimental evidence that a CAM-based tissue-engineered mesh has the potential to become a relevant alternative surgical solution to treat POP. This project is divided in 2 main tasks:
1) Production and mechanical characterization of a human CAM mesh, and of an equivalent ovine mesh, with mechanical properties justifying a preclinical test.
2) In vivo validation of an allogenic CAM mesh (i.e. ovine in ovine) in a female sheep model at 2 and 6 months.
This PoC will provide:
1) Proof that a human CAM-based knitted mesh can have clinically relevant mechanical properties;
2) Demonstration that an ovine CAM mesh can be successfully implanted to treat POP in a clinically relevant, allogenic, large animal model;
3) Direct comparison between the biointegration of an ovine CAM mesh setting and the inflammatory response to a synthetic mesh.
Overall, this PoC will increase the Technology Readiness Level (TRL) of our product from 1-2 to 3-4 by validating the functionality and safety of CAM meshes in a relevant in vivo environment. These outcomes will lead us closer to clinical trials and support a commercial endeavor.
Work package 1 focused on the production of human and ovine CAM meshes and their mechanical characterization.
The first Work Package (WP) provided a design and manufacturing protocol of human and ovine CAM meshes suitable for in vivo implantation (planned in WP2), i.e. with a relevant size and clinically relevant mechanical properties (Milestones 1.1-1.3 achieved).
Work package 2 focused on the in vivo implantation of ovine CAM meshes in the urogenital area of an allogenic sheep model, including the evaluation of the host response and their remodeling.
We confirmed, for the first time, the implantability of this drastically new generation of meshes (Milestone 2.1.1 achieved). Surgeons were able to manipulate and suture the graft as it is done with synthetic grafts using the same surgical technique used clinically in patients.
The implanted 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 are in the process of performing immuno-staining of these tissues to identify the various cell types present and more precisely characterized the immune response in terms of macrophages type one and two (Milestone 2.1.2 partially achieved). This work has been slow going but will be completed through institutional funding and permanent human resources. 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.
The first Work Package (WP) provided a design and manufacturing protocol of human and ovine CAM meshes suitable for in vivo implantation (planned in WP2), i.e. with a relevant size and clinically relevant mechanical properties (Milestones 1.1-1.3 achieved).
Work package 2 focused on the in vivo implantation of ovine CAM meshes in the urogenital area of an allogenic sheep model, including the evaluation of the host response and their remodeling.
We confirmed, for the first time, the implantability of this drastically new generation of meshes (Milestone 2.1.1 achieved). Surgeons were able to manipulate and suture the graft as it is done with synthetic grafts using the same surgical technique used clinically in patients.
The implanted 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 are in the process of performing immuno-staining of these tissues to identify the various cell types present and more precisely characterized the immune response in terms of macrophages type one and two (Milestone 2.1.2 partially achieved). This work has been slow going but will be completed through institutional funding and permanent human resources. 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.
This project aims at developing a new generation of human and completely biological tissue-engineered grafts for the treatment of POP. It is a major medical issue for women since over 1 in 10 will undergo a POP surgery during her lifetime. However, transvaginal meshes for POP repair have been removed from the market since 2019 in France, USA, United Kingdom, and other countries due to overwhelming evidence of frequent complications. Consequently, a successful device for POP repair will provide a solution for an important unmet medical and societal need in addition to represent a remarkable business opportunity. Indeed, the global market for POP repair, shared mainly between north America and Europe (≈ 75%) was estimated at 400 M US$ in 2022.