Minimally Invasive Precise Application of Bioadhesives to Prevent IPPROM on a Pregnant Sheep Model

Abstract

<b><i>Introduction:</i></b> Iatrogenic preterm premature rupture of the membrane remains the Achille’s heel of fetoscopy. The aim of this study was to show in vivo feasibility of fetal membrane (FM) defect sealing by the application of tissue glues with umbrella-shaped receptors. <b><i>Methods:</i></b> First, we adapted our previously described ex vivo strategy and evaluated the adhesion strength of different tissue glues, Histoacryl® and Glubran2®, by bonding polytetrafluoroethylene or silicone encapsulated nitinol glue receptor to human FM. Then, we exposed pregnant sheep uterus through a laparotomy and placed a 10-French trocar into the amniotic cavity through which the umbrella-shaped glue receptor (<i>n</i> = 9) was inserted and fixated onto the FM with the tissue glues (<i>n</i> = 8). The tightness of the sealed defects was assessed 4 h post-surgery. <b><i>Results:</i></b> Both tissue glues tested resulted in adhesion of the glue receptors to the FM ex vivo. In vivo, all glue receptors opened in the amniotic cavity (<i>n</i> = 9) and all successfully placed glue receptors sealed the FM defect (<i>n</i> = 8). Four hours post-surgery, 2 treatment sites showed minimal leakage whereas the negative control without glue (<i>n</i> = 1) showed substantial leakage. <b><i>Discussion:</i></b> This in vivo study confirms that fetoscopically induced FM defects can be sealed by the application of tissue adhesives.

Biomaterial-based treatments for the prevention of preterm birth after iatrogenic rupture of the fetal membranes

“…77 Unfortunately, the use of this glue caused compression, contraction and crush artifact of the chorion. Other glues such as the cyanoacrylates Dermabond and Histoacryl have been shown to greatly glue to the FMs, 81 but they increased apoptosis and caused epithelial cell disruption when tested ex vivo. 78 Furthermore, cyanoacrylates have been reported to show non-elastic adhesion to tissues, 82 which increases the risk of tissue damage due to traction.…”

“…9B), but FM integrity was not examined. Recently, several cyanoacrylates with the support of a PTFE-coated nitinol receptor 81,111 (Fig. 9C) and integrated semirigid bioadhesive patches 90 (Fig.…”

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

“…Next, to evaluate the in vivo biocompatibility, stability, and FM sealing capacity of the elastic MG, we adapted our earlier described sheep model for the closure of FM defects with sealing patches [26].…”

Tissue Glue-Based Sealing Patch for the in vivo Prevention of Iatrogenic Prelabor Preterm Rupture of Fetal Membranes

“…In the last years, approaches have been developed to apply commercially available glues (cyanoacrylates) [[21], [22]] or methylcellulose-based patches [[23]] to seal the FM defect. Those studies reported a 100% fetal survival, but the use of cyanoacrylates seemed to prevent AF leakage to a higher extent [[22]].…”

“…In the last years, approaches have been developed to apply commercially available glues (cyanoacrylates) [[21], [22]] or methylcellulose-based patches [[23]] to seal the FM defect. Those studies reported a 100% fetal survival, but the use of cyanoacrylates seemed to prevent AF leakage to a higher extent [[22]]. This particular sealing approach is based on an umbrella-shaped receptor made of the shape-memory alloy nitinol coated with polytetrafluoroethylene.…”