P Riva, MD1, G Alonci2, F Fiorini2, B Dallemagne, MD3, J Marescaux, MD, FACS, Hon, FRCS, Hon, FJSES, Hon, APSA3, L De Cola, Prof2, S Perretta, MD, PhD3. 1Institute of Image-Guided Surgery (IHU Strasbourg), c/o IRCAD, Strasbourg (France), 2Institut de Science et d’Ingénierie Supramoléculaires, Université de Strasbourg, Strasbourg (France), 3IRCAD, Institut de Recherche contre les Cancers de l’Appareil Digestif, Strasbourg (France)
Motivation: Acute and chronic gastrointestinal (GI) fistula remain a challenging problem for both surgeons and gastroenterologists. Despite recent progress in interventional endoscopy GI fistula healing rate is still insufficient especially for complex fistula or large anastomotic leaks resulting in high morbidity and mortality. To date endoscopic sealant, alone or in combination with mechanical closure such as clips and SEMS have been evaluated with inconsistent success.
This preliminary feasibility study aims to demonstrate the use of hydrogels (H) for fistula closure.
Background: Hydrogels are 3D water-swollen polymer networks that investigated for many biomedical applications, thanks to their similarities to native tissues. However, the successful medical use is still limited by the difficulties of injection. To overcome this problem, we optimized the synthesis of injectable polyamidoamines-based hydrogels, modified with catechol-containing moieties to improve their mucoadhesive properties. These hydrogels were selected for their proven biocompatibility and minimal response from the body’s immune system.
Methods: To investigate the injectability and in vivo spontaneous formation, we prepared a set of pre-H solutions, by mixing the precursors at room temperature (RT). Hydrogels networks were formed via Michael polyaddition of a nucleophile (amine) to an α,β-unsaturated carbonyl, such as N,N’-methylene bisacrylamide.
The pre-H solutions proved to have sufficiently low viscosity for extrusion through a 25G hypodermic needle, without blocking the needle.
To study the gelation kinetic of the synthetized hydrogels, the pre-H solutions were injected into fistula models (FM) made of porcine intestine, in ex vivo and in vivo tissue settings. Intraluminal and submucosal injection were tried. FM, when ex vivo specimen were used, were kept at 37°C.
Results: The injectability of these materials enabled an effective space filling of FM, through molding of hydrogels shapes in situ by the neighboring tissue. 10 minutes post-injection complete gelation and adhesion to the mucosa were observed in six of the eight different tested samples (i.e. as expected hydrogels with lower cross-link degree did not show a complete gelation in the study conditions).
Conclusions: Here we show a spontaneous hydrogels network formation in physiological conditions, most likely favored by temperature increase. Strong adhesion to tissue mucosa was also detected. Such preliminary results suggest that optimized pre-H solutions can easily be injected and undergo gelation within short time in physiological conditions.
Overall, the proposed hydrogel proved to have great potential for fistula treatment.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 80266
Program Number: P076
Presentation Session: Poster (Non CME)
Presentation Type: Poster
