InnovaTivE in situ 4D biopriNTing for regenerAtion of CoLorEctal mucosa and submucosa

Colorectal diseases are a cohort of pathologies that affect the mucosa and submucosa layers of the anus, rectum, and colon of more than 2 million individual in the EU.

Among them, familiar adenomatous polyposis (FAP) and ulcerative colitis (UC) seriously compromise the patients quality of life.

These pathologies could benefit from the removal of the intestinal mucosa and submucosa, however no strategies exist nowadays for their replacement.

Then, when their removal is necessary, the patients undergo a proctocolectomy (i.e., surgical removal of the rectum and all or part of the colon) with a subsequent ileal pouch.

Although preserving the patient's continence, the procedure is burdened by significant complications.In this scenario, TENTACLE pioneers a radically new strategy for the surgical treatment of UC and FAP, providing an innovative in situ 4D bioprinting strategy, for the regeneration of colorectal mucosa and submucosa.

The TENTACLE in situ 4D bioprinting suite include: i) a colonoscopic bioprinter, featuring an extrusion-based bioprinting unit, an valvejet printhead, a mesh delivery system and a photocrosslinking device; ii) in silico tools for personalizing the bioprinting procedure; iii) two novel bespoken bioink formulations containing patients cells, including suitable functionalization strategies.

The mucosal formulation will feature a 4D shape morphing behavior to recreate the colorectal mucosal crypts.

Within TENTACLE, the entire procedure will be validated ex vivo and in vivo, thus paving the way for translating the bioprinting suite toward the clinics, by: i) identifying a GMP-compliant cell expansion protocol, ii) scaling up of the manufacturing routes, iii) promoting involvement and acceptance of surgeons and patients, iv) aligning with the EU regulation.

Collectively, our project will introduce a minimally invasive alternative to proctocolectomy and is expected to have a high impact on the quality of life of patients affected by FAP and UC.