In vivo Sealing of Fetoscopy-Induced Fetal Membrane Defects by Mussel Glue

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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 (<i>N</i> = 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

Is Spontaneous Preterm Prelabor of Membrane Rupture Irreversible? A Review of Potentially Curative Approaches

“…The elastic mussel glue tested by Avilla-Royo was elastic and resistant to spontaneous or proteolytic degradation, determining mild immune cell inflammation after 10 days. This glue firmly adhered to both the myometrium and the fetal membranes, and no cellular infiltration was observed [56].…”

“…One previous systematic review on this topic was excluded [46] because the authors described the same cases as this review and included one article with iatrogenic PPROM and one article that raised concerns. Finally, 14 studies met the eligibility criteria and were included and analyzed in this systematic review [47][48][49][50][51][52][53][54][55][56][57][58][59][60]. Four studies [47][48][49][50] on the spontaneous premature rupture of membranes analyzed the outcomes for 141 pregnancies and sealing and healing methods: 82 cases using an amniopatch with autologous or donor platelet concentrates and cryoprecipitate inserted by the ultrasound-guided amnioinfusion technique and 59 cases using an immunologic sealant or a mechanical cervical adapter for sealing (Table 1).…”