Supplementary Material for: In vivo Sealing of Fetoscopy-Induced Fetal Membrane Defects by Mussel Glue

Introduction: The benefits of fetal surgery are impaired by the high incidence of iatrogenic preterm prelabor rupture of the fetal membranes (iPPROM), for which chorioamniotic separation has been suggested as a potential initiator. Despite the urgent need to prevent iPPROM by sealing the fetoscopic puncture site after intervention, no approach has been clinically translated. Methods: A mussel-inspired biomimetic glue was tested in an ovine fetal membrane (FM) defect model. The gelation time of mussel glue (MG) was first optimized to make it technically compatible with fetal surgery. Then, the biomaterial was loaded in polytetrafluoroethylene-coated nitinol umbrella-shaped receptors and applied on ovine FM defects (N = 10) created with a 10 French trocar. Its sealing performance and tissue response were analyzed 10 days after implantation by amniotic fluid (AF) leakage and histological methods. Results: All ewes and fetuses recovered well after the surgery, and 100% ewe survival and 91% fetal survival were observed at explantation. All implants were tight at explantation, and no AF leakage was observed in any of them. Histological analysis revealed a mild tissue response to the implanted glue. Conclusion: MG showed promising properties for the sealing of FM defects and thereby the prevention of preterm birth. Studies to analyze the long-term tissue response to the sealant should be performed.

引言：胎儿手术的临床获益因医源性早产胎膜早破（iatrogenic preterm prelabor rupture of the fetal membranes, iPPROM）的高发生率而大幅受损，有研究提示绒毛膜羊膜分离可能是该并发症的潜在诱因。尽管临床亟需通过封堵术后胎儿镜穿刺位点来预防iPPROM，但目前尚无任何相关方案实现临床转化。
方法：本研究在羊胎膜（fetal membrane, FM）缺损模型中测试了一款贻贝仿生胶。首先优化贻贝胶（mussel glue, MG）的胶凝时间，使其在技术层面适配胎儿手术操作；随后将该生物材料装载于聚四氟乙烯包覆的镍钛合金伞形载体，并应用于10例由10号法式套管针构建的羊胎膜缺损模型（N=10）。于植入后10天，通过羊水（amniotic fluid, AF）渗漏检测及组织学方法分析其封堵性能与组织反应性。
结果：所有母羊与胎儿术后均恢复良好，取出植入物时母羊存活率达100%，胎儿存活率为91%。所有植入物在取出时均贴合紧密，未观察到任何一例出现羊水渗漏。组织学分析显示，植入胶仅引发轻度组织反应。
结论：贻贝胶（MG）在羊胎膜缺损封堵方面展现出良好的应用潜力，有望用于预防早产。未来需开展相关研究以分析该密封剂的长期组织反应。