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：胎儿外科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）的高发生率而受到显著限制，有研究提示绒毛膜羊膜分离可能是该并发症的潜在诱因。尽管临床上亟需通过封堵胎儿镜术后穿刺位点来预防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）缺损模型中对一款贻贝仿生胶开展了测试。研究首先优化了贻贝胶（mussel glue, MG）的胶凝时间，使其在技术上适配胎儿外科手术操作要求；随后将该生物材料负载于聚四氟乙烯覆膜镍钛合金伞形承载装置上，并应用于由10号法式套管针制备的10个羊胎膜缺损位点（N=10）。于植入后10天，通过检测羊水（amniotic fluid, AF）渗漏情况及组织学方法，分析其密封性能与组织应答反应。
结果：所有母羊及胎儿术后均顺利恢复，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，未观察到任何一例羊水渗漏。组织学分析显示，该植入胶仅引发轻度组织应答反应。
结论：贻贝胶在封堵胎膜缺损、进而预防早产方面展现出良好的应用前景。未来仍需开展相关研究，以评估该密封剂的长期组织应答效应。