Speaker
Description
Introduction: Ulcers are a breach in the membrane of the stomach or intestine caused by inflamed necrotic tissue. When they develop in the ileum and jejunum, ulcers represent a burden clinical challenge, since they are not accessible through colon- or gastroscopy[1]. To solve this clinical need, in the context of the PRIN2022 project Prometheus, we studied the fabrication of a multi-layered structure, designed for oral administration, physically programmed to reach a bleeding ulcer, self-deploy, wirelessly communicate, and promote tissue regeneration, thanks to bio-enabled materials processed via 4D printing.
Structure Design: To achieved all the envisioned functionalities, the structure comprises (from outer to inner, FigureA): i)a gastrointestinal protective layer, allowing the device to overcome the stomach without degrading; ii)a self-deploying scaffold able to attach to a bleeding ulcers, self-unfolds and promote tissue regeneration, iii)a cylindrical mandril for printing support and on which a biocompatible antenna for external communication could be inserted.
Gastro-intestinal protective layer: Alginate (5% w/v in dH20) and Acyl-EZE (20% w/v in dH2O) were identified as potential gastro-resistant materials.100 µm thin films of the sole solutions and their mixture in a ratio 1:1 were prepared by solvent casting and tested according to the European Pharmacopeia (3 hours in 0.1M HCl, 1 hours in KH2PO4 Buffer Solution). The wettability and the permeability of the films were also tested in 0.1M HCl. Tests revealed that the mixture solution is compliant with the standards and easily printable via extrusion-based bioprinting.
Self-deploying scaffold: The core part of the device is a bilayer C-shaped scaffold based on gelatin and silk[2], programmed to self-deploying when hydrated(FigureB), thus allowing to cover the entire ulcerated area. The shape-morphing over time was achieved through the differential swelling properties of the two layer of the structure that creates a deformation gradient. To allow the structure to anchor to a bleeding ulcer the silk solution was functionalized with a peptide able to bond the P-selectin, marker of activated platelets in the bleeding ulcers. The C-shaped structure was 4D printed on a rotating spindle made of a polyvinyl alcohol, able to degrade at different pHs upon 150 minutes.
Biocompatible antenna design and fabrication: PEDOT:PSS was chosen ad biocompatible conductive materials for the fabrication of the antenna. To enhance its conductibility, the addition of glycerol (1, 2.5, 5 and 10% w/v in dH20) and the implementation of thermal treatment to the structure were investigated (2h at 120°C). Tests revealed the PEDOT/Glycerol2.5% solution after the thermal treatment has the highest conductivity. To optimize the design of the antenna, computational models were performed to study the response of structures with different shapes(FigureC) hit by a plane electromagnetic wave.
Discussion and Conclusion
We are currently focusing on the fabrication of the entire structure in a single fabrication process, exploiting a customize multi-technology bioprinter[3] and an ad hoc slicing software[4], and its subsequential tests on an intestine phantom.
Acknowledgment: This work was funded by European Union–Next Generation EU–Mission 4–Component 1. CUP-I53D23002200006, under the project Prin2022 Prometheus, grant:2022BZLTTK
[1]doi:10.1016/j.giec.2011.07.012
[2]doi:10.1002/admt.202402200
[3]doi:10.1016/j.bprint.2024.e00372
[4]doi:10.36922/IJB025070053
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