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Injectable candidate sealants for fetal membrane repair: bonding and toxicity in vitro

      Objective

      This study was undertaken to test injectable surgical sealants that are biocompatible with fetal membranes and that are to be used eventually for the closure of iatrogenic membrane defects.

      Study Design

      Dermabond (Ethicon Inc, Norderstedt, Germany), Histoacryl (B. Braun GmbH, Tuttlingen, Germany), and Tissucol (Baxter AG, Volketwil, Switzerland) fibrin glue, and 3 types of in situ forming poly(ethylene glycol)-based polymer hydrogels were tested for acute toxicity on direct contact with fetal membranes for 24 hours. For the determination of elution toxicity, extracts of sealants were incubated on amnion cell cultures for 72 hours. Bonding and toxicity was assessed through morphologic and/or biochemical analysis.

      Results

      Extracts of all adhesives were nontoxic for cultured cells. However, only Tissucol and 1 type of poly(ethylene glycol)-based hydrogel, which is a mussel-mimetic tissue adhesive, showed efficient, nondisruptive, nontoxic bonding to fetal membranes. Mussel-mimetic tissue adhesive that was applied over membrane defects that were created with a 3.5-mm trocar accomplished leak-proof closure that withstood membrane stretch in an in vitro model.

      Conclusion

      A synthetic hydrogel-type tissue adhesive that merits further evaluation in vivo emerged as a potential sealing modality for iatrogenic membrane defects.

      Key words

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      References

        • Deprest J.
        • Lewi L.
        • Devlieger R.
        • et al.
        Enrichment of collagen plugs with platelets and amniotic fluid cells increases cell proliferation in sealed iatrogenic membrane defects in the fetal rabbit model.
        Prenat Diagn. 2008; 28: 878-880
        • Harrison M.R.
        • Keller R.L.
        • Hawgood S.B.
        • et al.
        A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia.
        N Engl J Med. 2003; 349: 1916-1924
        • Devlieger R.
        • Millar L.K.
        • Bryant-Greenwood G.
        • Lewi L.
        • Deprest J.A.
        Fetal membrane healing after spontaneous and iatrogenic membrane rupture: a review of current evidence.
        Am J Obstet Gynecol. 2006; 195: 1512-1520
        • Zisch A.
        • Zimmermann R.
        Bioengineering of foetal membrane repair.
        Swiss Med Wkly. 2008; 138: 596-601
        • Quintero R.A.
        Treatment of previable premature ruptured membranes.
        Clin Perinatol. 2003; 30: 573-589
        • Quintero R.A.
        New horizons in the treatment of preterm premature rupture of membranes.
        Clin Perinatol. 2001; 28: 861-875
        • Chang J.
        • Tracy Jr, T.F.
        • Carr S.R.
        • Sorrells Jr, D.L.
        • Luks F.I.
        Port insertion and removal techniques to minimize premature rupture of the membranes in endoscopic fetal surgery.
        J Pediatr Surg. 2006; 41: 905-909
        • Young B.K.
        • Roman A.S.
        • MacKenzie A.P.
        • et al.
        The closure of iatrogenic membrane defects after amniocentesis and endoscopic intrauterine procedures.
        Fetal Diagn Ther. 2004; 19: 296-300
        • Mallik A.S.
        • Fichter M.A.
        • Rieder S.
        • et al.
        Fetoscopic closure of punctured fetal membranes with acellular human amnion plugs in a rabbit model.
        Obstet Gynecol. 2007; 110: 1121-1129
        • Ochsenbein-Kolble N.
        • Jani J.
        • Lewi L.
        • et al.
        Enhancing sealing of fetal membrane defects using tissue engineered native amniotic scaffolds in the rabbit model.
        Am J Obstet Gynecol. 2007; 196: 263.e1-263.e7
        • Petratos P.B.
        • Baergen R.N.
        • Bleustein C.B.
        • Felsen D.
        • Poppas D.P.
        Ex vivo evaluation of human fetal membrane closure.
        Lasers Surg Med. 2002; 30: 48-53
        • Cortes R.A.
        • Wagner A.J.
        • Lee H.
        • et al.
        Pre-emptive placement of a presealant for amniotic access.
        Am J Obstet Gynecol. 2005; 193: 1197-1203
        • Reddy U.M.
        • Shah S.S.
        • Nemiroff R.L.
        • et al.
        In vitro sealing of punctured fetal membranes: potential treatment for midtrimester premature rupture of membranes.
        Am J Obstet Gynecol. 2001; 185: 1090-1093
        • Louis-Sylvestre C.
        • Rand J.H.
        • Gordon R.E.
        • Salafia C.M.
        • Berkowitz R.L.
        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
        • Gratacos E.
        • Sanin-Blair J.
        • Lewi L.
        • et al.
        A histological study of fetoscopic membrane defects to document membrane healing.
        Placenta. 2006; 27: 452-456
        • Liekens D.
        • Lewi L.
        • Jani J.
        • et al.
        Enrichment of collagen plugs with platelets and amniotic fluid cells increases cell proliferation in sealed iatrogenic membrane defects in the foetal rabbit model.
        Prenat Diagn. 2008; 28: 503-507
        • Papadopulos N.A.
        • Klotz S.
        • Raith A.
        • et al.
        Amnion cells engineering: a new perspective in fetal membrane healing after intrauterine surgery?.
        Fetal Diagn Ther. 2006; 21: 494-500
        • Leggat P.A.
        • Smith D.R.
        • Kedjarune U.
        Surgical applications of cyanoacrylate adhesives: a review of toxicity.
        Aust N Z J Surg. 2007; 77: 209-213
        • Burke S.A.
        • Ritter-Jones M.
        • Lee B.P.
        • Messersmith P.B.
        Thermal gelation and tissue adhesion of biomimetic hydrogels.
        Biomed Mater. 2007; 2: 203-210
        • West J.L.
        • Hubbell J.A.
        Separation of the arterial wall from blood contact using hydrogel barriers reduces intimal thickening after balloon injury in the rat: the roles of medial and luminal factors in arterial healing.
        Proc Natl Acad Sci U S A. 1996; 93: 13188-13193
        • Johns D.A.
        • Ferland R.
        • Dunn R.
        Initial feasibility study of a sprayable hydrogel adhesion barrier system in patients undergoing laparoscopic ovarian surgery.
        J Am Assoc Gynecol Laparosc. 2003; 10: 334-338
        • Mettler L.
        • Audebert A.
        • Lehmann-Willenbrock E.
        • Schive-Peterhansl K.
        • Jacobs V.R.
        A randomized, prospective, controlled, multicenter clinical trial of a sprayable, site-specific adhesion barrier system in patients undergoing myomectomy.
        Fertil Steril. 2004; 82: 398-404
        • Gillinov A.M.
        • Lytle B.W.
        A novel synthetic sealant to treat air leaks at cardiac reoperation.
        J Card Surg. 2001; 16: 255-257
        • McLaren J.
        • Malak T.M.
        • Bell S.C.
        Structural characteristics of term human fetal membranes prior to labour: identification of an area of altered morphology overlying the cervix.
        Hum Reprod. 1999; 14: 237-241
        • Ferland R.
        • Mulani D.
        • Campbell P.K.
        Evaluation of a sprayable polyethylene glycol adhesion barrier in a porcine efficacy model.
        Hum Reprod. 2001; 16: 2718-2723
        • Lee B.P.
        • Dalsin J.L.
        • Messersmith P.B.
        Synthesis and gelation of DOPA-modified poly(ethylene glycol) hydrogels.
        Biomacromolecules. 2002; 3: 1038-1047
        • Lee H.
        • Lee B.P.
        • Messersmith P.B.
        A reversible wet/dry adhesive inspired by mussels and geckos.
        Nature. 2007; 448: 338-341
        • Lee H.
        • Scherer N.F.
        • Messersmith P.B.
        Single-molecule mechanics of mussel adhesion.
        Proc Natl Acad Sci U S A. 2006; 103: 12999-13003
        • Lee M.G.
        • Jones D.
        Applications of fibrin sealant in surgery.
        Surg Innov. 2005; 12: 203-213
        • Oyen M.L.
        • Calvin S.E.
        • Landers D.V.
        Premature rupture of the fetal membranes: is the amnion the major determinant?.
        Am J Obstet Gynecol. 2006; 195: 510-515
        • Hill-West J.L.
        • Chowdhury S.M.
        • Slepian M.J.
        • Hubbell J.A.
        Inhibition of thrombosis and intimal thickening by in situ photopolymerization of thin hydrogel barriers.
        Proc Natl Acad Sci U S A. 1994; 91: 5967-5971
        • Lee H.
        • Dellatore S.M.
        • Miller W.M.
        • Messersmith P.B.
        Mussel-inspired surface chemistry for multifunctional coatings.
        Science. 2007; 318: 426-430
        • Waite J.H.
        Reverse engineering of bioadhesion in marine mussels.
        Ann N Y Acad Sci. 1999; 875: 301-309
        • Yamada K.
        • Chen T.
        • Kumar G.
        • et al.
        Chitosan based water-resistant adhesive.
        Biomacromolecules. 2000; 1: 252-258
        • Deming T.J.
        Mussel byssus and biomolecular materials.
        Curr Opin Chem Biol. 1999; 3: 100-105
        • Devlieger R.
        • Gratacos E.
        • Wu J.
        • et al.
        An organ-culture for in vitro evaluation of fetal membrane healing capacity.
        Eur J Obstet Gynecol Reprod Biol. 2000; 92: 145-150