Intraamniotic sealing of fetoscopic membrane defects in ex vivo and in vivo sheep models using an integrated semi-rigid bioadhesive patch

Abstract

Background Preterm prelabor rupture of membranes is the most frequent complication of fetoscopic surgery. Strategies to seal the membrane defect created by fetoscopy have been attempted with little success. We previously developed an integrated semi-rigid bioadhesive patch to seal fetal membrane defects composed of silicone and hydroxypropyl methylcellulose (HPMC) that achieved ex vivo sealing of membrane defects. Objective To evaluate the feasibility of the insertion of our integrated semi-rigid bioadhesive patches using a fetoscopic technique and to test the adhesion in ex vivo human membranes and in vivo ovine model. Study design An experimental study involving two experiments 1) Ex vivo: human fetal membranes were mounted in a custom-designed model with saline solution simulating intraamniotic pressure. The insertion of two different bioadhesive patches made of silicone-HPMC (S-HPMC) and silicone-polyurethane-HPMC (SPU-HPMC) was performed through a 12-Fr cannula mimicking fetoscopic surgery technique. The experiment was repeated 10 times with membranes from different donors. Measures insertion time, successful insertion and adhesion at five minutes. 2) In vivo: 16 patches S-HPMC were inserted by fetoscopy in the amniotic cavity of pregnant sheep (4 bioadhesives per animal, in 4 ewes). Measures successful insertion, adhesion at 5 minutes and adhesion at the end of surgery. Results 1) Ex vivoinsertion study: there was no difference in the insertion time between S-HPMC and SPU-HPMC (p=0.49). Insertion was successful in all cases, but complete adhesion at 5 minutes was superior for S-HPMC (p=0.02). 2) In vivostudy: Insertion of S-HPMC by fetoscopy was feasible and successful in the totality of cases and no complications were reported. Adhesion persisted at 5 minutes and at the end of the surgery in 68.8 and 56.3% of the patches, respectively. Conclusion We describe the feasibility of deploying through a fetoscopic trocar a semi-rigid S-HPMC patch that seals fetal membranes after a fetal invasive procedure. The results warrant further research for improving long-term adhesion and develop a clinically applicable system.