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

Eva Avilla-Royo; Frauke Seehusen; Yannick R Devaud; Josep M Monné Rodriguez; Nele Strübing; Miriam Weisskopf; Phillip B Messersmith; Ladina Vonzun; Ueli Moehrlen; Martin Ehrbar; Nicole Ochsenbein-Kölble

doi:10.1159/000528473

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

Fetal Diagn Ther. 2022;49(11-12):518-527. doi: 10.1159/000528473. Epub 2023 Jan 12.

Authors

Eva Avilla-Royo^{1

2}, Frauke Seehusen³, Yannick R Devaud^{1

4}, Josep M Monné Rodriguez³, Nele Strübing¹, Miriam Weisskopf⁵, Phillip B Messersmith⁶, Ladina Vonzun^{1

7}, Ueli Moehrlen^{7

8

9}, Martin Ehrbar¹, Nicole Ochsenbein-Kölble^{1

7}

Affiliations

¹ Department of Obstetrics, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
² Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
³ Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, University of Zurich, Zurich, Switzerland.
⁴ KOVE medical AG, Zurich, Switzerland.
⁵ Center of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁶ Departments of Bioengineering and Materials Science and Engineering, University of California, Berkeley, California, USA.
⁷ The Zurich Center for Fetal Diagnosis and Therapy, Zurich, Switzerland.
⁸ Department of Pediatric Surgery, University Children's Hospital Zurich, Zurich, Switzerland.
⁹ Children's Research Center, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland.

Abstract

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.

Keywords: Fetal membranes; Fetoscopy; Iatrogenic preterm prelabor rupture of the fetal membranes; In vivo sealing; Mussel glue.

MeSH terms

Animals
Extraembryonic Membranes / pathology
Female
Fetal Membranes, Premature Rupture* / etiology
Fetoscopy / adverse effects
Fetus / pathology
Humans
Infant, Newborn
Pregnancy
Premature Birth*
Sheep

Grants and funding

This research was supported by Swiss National Science Foundation grant 31003A_141051/2, the Innosuisse grant 55482.1 IP-LS, and the National Institutes of Health (USA) grant R01 EB022031.