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)是最佳妊娠结局所必需的。插入针头或胎儿内窥镜对胎膜造成损害，可能会导致医源性胎膜早破，并显著增加早产和随后分娩的风险。该项目的目标是开发一种独特的粘贴式补片系统，用于密封胎儿镜术后的羊膜腔入口。该系统由组织膜贴片组成，用缝合线捆绑，将缝线插入羊膜腔，然后像倒伞一样通过进入口拉回。一种不可降解的粘合剂，基于复杂的凝聚体，将在周长周围应用，将组织贴片密封到子宫壁和胎膜上。复合凝聚体是相分离的、带相反电荷的聚电解质的稠密的水溶液。因此，作为粘合剂的基础，它们具有几种理想的性能，可以应用于潮湿的、甚至完全淹没的衬底上，例如充满液体的羊膜腔中的组织。仿生黏附复合凝聚体的灵感来自沙堡蠕虫的海底胶水，这种胶水是由相反电荷的聚电解质黏附蛋白组成的。该研究策略包括通过i)对胎膜和粘连贴片进行定量建模，ii)体外力学测试以建立粘连化学与粘连贴片系统的材料特性之间的本构关系，以及iii)在怀孕动物模型中对粘连贴片进行临床前评估，逐步改进粘合组织贴片的材料和机械性能。该贴片系统可显著降低宫内胎儿干预后早产胎膜破裂、早产及相关胎儿发病率的风险。此外，这种粘合贴片通过降低早产胎膜破裂的风险，可能为开发目前无法治疗的其他胎儿先天性畸形的宫内治疗开辟道路。

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.