Repair of iatrogenic fetal membrane defects with an adhesive tissue scaffold

描述（由申请人提供）：健康和完整的胎膜（羊膜和绒毛膜）是最佳妊娠结局的必要条件。对胎膜的损伤，意外插入针头或胎儿镜，可导致医源性胎膜早破，并伴有早产和随后分娩的风险显著增加。本项目的目标是开发一种独特的粘接贴片系统，用于在胎儿镜手术后密封羊膜腔通道。该系统由一个组织膜贴片组成，用缝合线系在一起，缝合线将插入羊膜腔，然后像一把倒置的伞一样通过入口向后拉。一种基于复杂凝聚体的不可降解粘合剂将被应用于子宫周围，将组织贴片密封在子宫壁和胎膜上。复杂凝聚体是一种致密的、相分离的、带相反电荷的聚电解质的水溶液。因此，它们具有一些理想的特性，可以作为粘合剂的基础，应用于湿的，甚至完全浸没的基底，例如充满液体的羊膜腔中的组织。这种仿生粘接复合体的灵感来自沙堡蠕虫的海底胶，它是由带相反电荷的聚电解质粘接蛋白组成的。研究策略包括：1)对胎膜和黏附贴片进行定量建模，2)通过体外力学测试建立黏附化学与黏附贴片系统材料性能之间的本构关系，3)在怀孕动物模型中对黏附贴片进行临床前评估，逐步完善黏附组织贴片的材料和力学性能。贴片系统可以显著降低子宫内胎儿干预后的胎膜破裂、早产和相关胎儿发病率的风险。此外，通过降低早产胎膜破裂的风险，这种黏附贴片可以为目前无法治疗的其他胎儿先天性异常的子宫内治疗开辟道路。

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.