Speaker
Description
Colorectal diseases refer to a range of conditions that affect the mucosal and submucosal layers of the anus, rectum, and colon, impacting over 2 million individuals across the European Union [1]. Among these, familial adenomatous polyposis (FAP) and ulcerative colitis (UC) significantly reduce the quality of life of affected patients. While these conditions might benefit from removing the affected intestinal layers, no current solutions exist to replace them. As a result, when removal is necessary, patients typically undergo a proctocolectomy, which involves the surgical removal of the rectum and part or all of the colon, followed by the formation of an ileal pouch.
In this context, the EU-funded project “DAEDALUS” aims at pioneering a novel approach, which combines advanced biomaterials featuring four-dimensional (4D) functionalities (i.e., triggered shape morphing and controlled molecule/drug release) with an innovative delivery system, to in situ reconstruct colorectal mucosa and submucosa. Two injectable biomaterial formulations able to respectively mimic the colorectal mucosa and submucosa will be developed. Both biomaterials will be based on the same photo-crosslinkable biocompatible matrix: star polyethylene glycol - polylactic acid polymers or poly(2-oxazoline)s, mixed with cell-laden photo-crosslinkable gelatine-based solutions. The biomaterials will contain patient-derived cells and will be enriched with magnetic and engineered particles to allow the shape morphing of the structure and a controlled release of drugs/molecules, such as oxygen, growth factors, glucose and anti-fibrotic drugs.
To translate the DAEDALUS concept into a minimally invasive procedure, a multifunctional toolhead compatible with commercial endoscopes will be designed and engineered for in situ biomaterial injection, actuation and crosslinking. The validated advanced materials and methods are intended to be used for clinical applications requiring mucosa and submucosa regeneration; their development will follow the Safe-by-Design (SSbD) approach with the support of in silico models. Additionally, engagement with patients, researchers, professionals, and stakeholders will be promoted to improve the level of understanding of the DAEDALUS solution.
DAEDALUS biomaterials and bioprinting process will be validated both ex vivo and in vivo, setting the stage for translating 4D biomaterials with advanced functionalities into clinical applications.
In summary, DAEDALUS will offer a minimally invasive alternative to proctocolectomy and is anticipated to significantly improve the quality of life for patients suffering from FAP and UC.
Acknowledgment: This project has received funding by the European Union under the call HORIZON-CL4-2024-RESILIENCE-01-36 (acronym: DAEDALUS, number: 101178568).
[1] Arnold, Melina, et al. "Global patterns and trends in colorectal cancer incidence and mortality." Gut 66.4 (2017): 683-691.
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