Repair of iatrogenic fetal membrane defects with an adhesive tissue scaffold

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DESCRIPTION (provided by applicant): Healthy and intact fetal membranes (amnion and chorion) are required for optimal pregnancy outcomes. Damage to the fetal membranes, incident to the insertion of a needle or fetoscope, can lead to iatrogenic preterm rupture of the membranes accompanied by a significantly increased risk of preterm labor and subsequent delivery. The goal of this project is to develop a unique adhesive patch system to seal amniotic cavity access ports following fetoscopic surgeries. The system consists of a tissue membrane patch, tethered with a suture that will be inserted into the amniotic cavity, and then drawn back through the access port like an inverted umbrella. A non-degradable adhesive, based on complex coacervates, will be applied around the circumference to seal the tissue patch to the uterine wall and fetal membranes. Complex coacervates are dense, aqueous fluids of phase-separated, oppositely charged polyelectrolytes. As such, they have several ideal properties as the foundation of adhesives that can be applied to wet, even completely submerged substrates, such as tissues in the fluid-filled amniotic cavity. The biomimetic adhesive complex coacervates were inspired by the undersea glue of sandcastle worms, which is composed of oppositely charged polyelectrolytic adhesive proteins. The research strategy entails progressive refinement of the material and mechanical properties of the adhesive tissue patch through i) quantitative modeling of fetal membranes and the adhesive patch, ii) in vitro mechanical testing to establish constitutive relationships between adhesive chemistry and the material properties of the adhesive patch system, and iii) preclinical evaluation of the adhesive patch in a pregnant animal model. The adhesive patch system could significantly reduce the risk of preterm fetal membrane rupture, preterm delivery, and associated fetal morbidity after in utero fetal interventions. Further, the adhesive patch, by reducing the risk of preterm fetal membrane rupture, could open the way for development of in utero treatments for other fetal congenital anomalies that are currently untreatable.