Speaker
Description
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 individuals in the European Union [1]. 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 [2].
Thus, in this context of the EU funded projects “TENTACLE”, we envision a radically new strategy for the surgical treatment of UC and FAP, by developing an innovative in situ 4D bioprinting suite to fabricate a shape-morphing layered bioconstructs directly inside the patient rectum/colon, able to replicate the human colorectal mucosa and submucosa (Figure 1). This bioconstructs will promote the regeneration of colorectal mucosa and submucosa thanks to its composition, and the delivery of specific active pharmaceutical ingredients, such as antibiotic and antifibrotic. Moreover, the mucosa layer will possess a shape morphing capability, triggered by humidity, that will induce the creation of crypts on its surface, mimicking the colorectal ones.
TENTACLE in situ 4D bioprinting suite will comprise a first-of-its-kind colonoscopic bioprinter that will be inserted on commercial colonoscopes and will feature an extrusion-based bioprinting unit, a valvejet printhead, and a photocrosslinking apparatus. Multiple artificial intelligent empowered in silico tools will be developed to improve the performance the bioprinting suite. More in detail, an algorithm able to build the bioconstruct’s geometry on the patient defect starting from patient medical image will be developed. Then, a second algorithm for the path planning, namely the ideal distribution of ink, will be developed. Final, an algorithm to real-time monitor the in situ bioprinting process via image analysis will be implemented.
Regarding the inks, two novel bioink formulations containing patients’ cells will be developed, based on photocrosslinkable gelatin and thiolated polysaccharides. Those bioinks will be enriched with engineered micro- and nano-carriers incorporating antibiotic and anti-fibrotic agents.
The entire in situ 4D bioprinting procedure will be validated ex vivo and in vivo, thus paving the way for translating the bioprinting suite toward the clinics.
Collectively, TENTACLE 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.
Acknowledgment: This project has received funding by the European Union under the call HORIZON-HLTH-2024-TOOL-11-02 (TENTACLE, number: 101191747).
[1] Arnold, Melina, et al. "Global patterns and trends in colorectal cancer incidence and mortality." Gut 66.4 (2017): 683-691.
[2] Killeen, S., et al. "Complete mesocolic resection and extended lymphadenectomy for colon cancer: a systematic review." Colorectal Disease 16.8 (2014): 577-594.
53381516387
