Introduction: The benefits of endoscopic fetal surgery are deteriorated by the high risk of iatrogenic preterm prelabor rupture of fetal membranes (iPPROM). While previous studies have reported good sealing candidates to prevent membrane rupture, the delivery of these materials to the location of membrane puncture remains unsolved. Materials and Methods: We describe an approach to apply sealing materials onto the amnion through the fetoscopy port. We developed a device composed of an umbrella-shaped polyester coated nitinol mesh and an applicator. The spontaneously unfolding umbrella is pushed through the port, pulled against the amnion, and glued onto the amnion defect site. We tested the adhesion strength of multiple glues and tested the feasibility and reproducibility of this fetal membrane sealing approach in an ex vivo model. Results: The umbrella unfolded and was well positioned in all tests (n = 18). When applied via the fetoscopy port, umbrellas were successfully glued onto the fetal membrane, and all of them completely covered the defect (n = 5). The mean time needed for the whole procedure was 3 min. Discussion: This study is a proof of concept presenting a potential future solution for the precise local application of bioadhesives for the prevention of iPPROM.

Keywords:
iPPROM, Minimally invasive therapy, Fetoscopy, Fetal endoscopy, Bioadhesives, Application, Umbrella
1.
Beck V, Lewi P, Gucciardo L, Devlieger R: Preterm prelabor rupture of membranes and fetal survival after minimally invasive fetal surgery: a systematic review of the literature. Fetal Diagn Ther 2012; 31: 1–9.
2.
Gratacos E, Sanin-Blair J, Lewi L, Toran N, Verbist G, Cabero L, Deprest J: A histological study of fetoscopic membrane defects to document membrane healing. Placenta 2006; 27: 452–456.
3.
Devlieger R, Deprest JA, Gratacos E, Pijnenborg R, Leask R, Riley SC: Matrix metalloproteinases-2 and-9 and their endogenous tissue inhibitors in fetal membrane repair following fetoscopy in a rabbit model. Mol Hum Reprod 2000; 6: 479–485.
4.
Devlieger R, Riley SC, Verbist L, Leask R, Pijnenborg R, Deprest JA: Matrix metalloproteinases-2 and -9 and their endogenous tissue inhibitors in tissue remodeling after sealing of the fetal membranes in a sheep model of fetoscopic surgery. J Soc Gynecol Investig 2002; 9: 137–145.
5.
Sopher D: The response of rat fetal membranes to injury. Ann R Coll Surg Engl 1972; 51: 240–249.
6.
Quintero RA, Carreno CA, Yelian F, Evans MI: Repair kinetics of amnion cells after microsurgical injury. Fetal Diagn Ther 1996; 11: 348–356.
7.
Devlieger R, Gratacos E, Verbist L, Pijnenborg R, Deprest J: Gestational age-dependent repair kinetics of microsurgical defects in monolayers of human amniocytes. Gynecol Obstet Invest 2010; 69: 62–66.
8.
Bilic G, Ochsenbein-Kolble N, Hall H, Huch R, Zimmermann R: In vitro lesion repair by human amnion epithelial and mesenchymal cells. Am J Obstet Gynecol 2004; 190: 87–92.
9.
Ochsenbein-Kolble N, Jani J, Lewi L, Verbist G, Vercruysse L, Portmann-Lanz B, Marquardt K, Zimmermann R, Deprest J: Enhancing sealing of fetal membrane defects using tissue engineered native amniotic scaffolds in the rabbit model. Am J Obstet Gynecol 2007; 196: 263 e261–e267.
10.
Mallik AS, Fichter MA, Rieder S, Bilic G, Stergioula S, Henke J, Schneider KT, Kurmanavicius J, Biemer E, Zimmermann R, Zisch AH, Papadopulos NA: Fetoscopic closure of punctured fetal membranes with acellular human amnion plugs in a rabbit model. Obstet Gynecol 2007; 110: 1121–1129.
11.
Devlieger R, Ardon H, Verbist L, Gratacos E, Pijnenborg R, Deprest JA: Increased polymorphonuclear infiltration and iatrogenic amniotic band after closure of fetoscopic access sites with a bioactive membrane in the rabbit at midgestation. Am J Obstet Gynecol 2003; 188: 844–848.
12.
Gratacos E, Wu J, Yesildaglar N, Devlieger R, Pijnenborg R, Deprest JA: Successful sealing of fetoscopic access sites with collagen plugs in the rabbit model. Am J Obstet Gynecol 2000; 182: 142–146.
13.
Luks FI, Deprest JA, Peers KH, Steegers EA, van Der Wildt B: Gelatin sponge plug to seal fetoscopy port sites: technique in ovine and primate models. Am J Obstet Gynecol 1999; 181: 995–996.
14.
Engels AC, Van Calster B, Richter J, De-Koninck P, Lewi L, De Catte L, Devlieger R, Deprest JA: Collagen plug sealing of iatrogenic fetal membrane defects after fetoscopic surgery for congenital diaphragmatic hernia. Ultrasound Obstet Gynecol 2014; 43: 54–59.
15.
Harmanli OH, Wapner RJ, Lontz JF: Efficacy of fibrin glue for in vitro sealing of human chorioamniotic membranes. J Reprod Med 1998; 43: 986–990.
16.
Louis-Sylvestre C, Rand JH, Gordon RE, Salafia CM, Berkowitz RL: In vitro studies of the interactions between platelets and amniotic membranes: a potential treatment for preterm premature rupture of the membranes. Am J Obstet Gynecol 1998; 178: 287–293.
17.
Papadopulos NA, Van Ballaer PP, Ordonez JL, Laermans IJ, Vandenberghe K, Lerut TE, Deprest JA: Fetal membrane closure techniques after hysteroamniotomy in the mid-gestational rabbit model. Am J Obstet Gynecol 1998; 178: 938–942.
18.
Quintero RA, Morales WJ, Allen M, Bornick PW, Arroyo J, LeParc G: Treatment of iatrogenic previable premature rupture of membranes with intra-amniotic injection of platelets and cryoprecipitate (amniopatch): preliminary experience. Am J Obstet Gynecol 1999; 181: 744–749.
19.
Lewi L, Van Schoubroeck D, Van Ranst M, Bries G, Emonds MP, Arabin B, Welch R, Deprest J: Successful patching of iatrogenic rupture of the fetal membranes. Placenta 2004; 25: 352–356.
20.
Young BK, Roque H, Abdelhak YE, Poiolek D, Demopulos R, Lockwood CJ: Minimally invasive endoscopy in the treatment of preterm premature rupture of membranes by application of fibrin sealant. J Perinat Med 2000; 28: 326–330.
21.
Young BK, Roman AS, MacKenzie AP, Stephenson CD, Minior V, Rebarber A, Timor-Tritsch I: The closure of iatrogenic membrane defects after amniocentesis and endoscopic intrauterine procedures. Fetal Diagn Ther 2004; 19: 296–300.
22.
Sener T, Ozalp S, Hassa H, Yalcin OT, Polay S: Maternal blood clot patch therapy: a model for postamniocentesis amniorrhea. Am J Obstet Gynecol 1997; 177: 1535–1536.
23.
Kivelio A, Dekoninck P, Perrini M, Brubaker CE, Messersmith PB, Mazza E, Deprest J, Zimmermann R, Ehrbar M, Ochsenbein-Koelble N: Mussel mimetic tissue adhesive for fetal membrane repair: initial in vivo investigation in rabbits. Eur J Obstet Gynecol Reprod Biol 2013; 171: 240–245.
24.
Haller CM, Buerzle W, Brubaker CE, Messersmith PB, Mazza E, Ochsenbein-Koelble N, Zimmermann R, Ehrbar M: Mussel-mimetic tissue adhesive for fetal membrane repair: a standardized ex vivo evaluation using elastomeric membranes. Prenat Diagn 2011; 31: 654–660.
25.
Haller CM, Buerzle W, Kivelio A, Perrini M, Brubaker CE, Gubeli RJ, Mallik AS, Weber W, Messersmith PB, Mazza E, Ochsenbein-Koelble N, Zimmermann R, Ehrbar M: Mussel-mimetic tissue adhesive for fetal membrane repair: an ex vivo evaluation. Acta Biomater 2012; 8: 4365–4370.
26.
Bilic G, Brubaker C, Messersmith PB, Mallik AS, Quinn TM, Haller C, Done E, Gucciardo L, Zeisberger SM, Zimmermann R, Deprest J, Zisch AH: Injectable candidate sealants for fetal membrane repair: bonding and toxicity in vitro. Am J Obstet Gynecol 2010; 202: 85 e81–89.
27.
Melton KN, Mercier O: The mechanical-properties of NiTi-based shape memory alloys. Acta Metall Mater 1981; 29: 393–398.
28.
Riboldi SA, Sampaolesi M, Neuenschwander P, Cossu G, Mantero S: Electrospun degradable polyesterurethane membranes: potential scaffolds for skeletal muscle tissue engineering. Biomaterials 2005; 26: 4606–4615.
29.
Brubaker CE, Kissler H, Wang LJ, Kaufman DB, Messersmith PB: Biological performance of mussel-inspired adhesive in extrahepatic islet transplantation. Biomaterials 2010; 31: 420–427.
30.
Burke SA, Ritter-Jones M, Lee BP, Messersmith PB: Thermal gelation and tissue adhesion of biomimetic hydrogels. Biomed Mater 2007; 2: 203–210.
31.
Lee BP, Dalsin JL, Messersmith PB: Synthesis and gelation of DOPA-modified poly(ethylene glycol) hydrogels. Biomacromolecules 2002; 3: 1038–1047.
32.
Lee H, Lee BP, Messersmith PB: A reversible wet/dry adhesive inspired by mussels and geckos. Nature 2007; 448: 338–341.
33.
Lee H, Scherer NF, Messersmith PB: Single-molecule mechanics of mussel adhesion. Proc Natl Acad Sci USA 2006; 103: 12999–13003.
34.
Devlieger R, Gratacos E, Ardon H, Vanstraelen S, Deprest J: Factors influencing the flow rate through a surgical defect in human fetal membranes. Prenat Diagn 2002; 22: 201–205.
35.
Bilsel Y, Abci I: The search for ideal hernia repair; mesh materials and types. Int J Surg 2012; 10: 317–321.
36.
Van Steenbergen W: The first prospective endoscopic experience with the ePTFE-covered Viabil stent in patients with a distal malignant biliary stenosis. Acta Gastroenterol Belg 2010; 73: 18–24.
37.
Saygun O, Topaloglu S, Avsar FM, Ozel H, Hucumenoglu S, Sahin M, Hengirmen S: Reinforcement of the suture line with an ePTFE graft attached with histoacryl glue in duodenal trauma. Can J Surg 2006; 49: 107–112.
38.
Shorr N, Cohen MS, Lessner A: Histoacryl closure of eyelid skin grafts. Ophthal Plast Reconstr Surg 1991; 7: 190–193.
39.
Hellmund A, Berg C, Geipel A, Bludau M, Heydweiller A, Bachour H, Muller A, Muller A, Gembruch U: Prenatal diagnosis and evaluation of sonographic predictors for intervention and adverse outcome in congenital pulmonary airway malformation. PLoS One 2016; 11:e0150474.
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