title: Engineered cell instructive matrices for fetal membrane healing.
abstract: Iatrogenic preterm prelabour rupture of fetal membranes (iPPROM) occurs in 6-45% of the cases after fetoscopic procedures, posing a significant threat to fetal survival and well-being. The number of diagnostic and therapeutic prenatal interventions available is increasing, thus developing treatment options for iPPROM is becoming more important than ever before. Fetal membranes exhibit very restricted regeneration and little is known about factors which might modulate their healing potential, rendering various materials and strategies to seal or heal fetal membranes pursued over the past decades relatively fruitless. Additionally, biocompatible materials with tunable in vivo stability and mechanical and biological properties have not been available. Using poly(ethylene glycol)-based biomimetic matrices, we provide evidence that, upon presentation of appropriate biological cues in three dimensions, mesenchymal progenitor cells from the amnion can be mobilized, induced to proliferate and supported in maintaining their native extracellular matrix production, thus creating a suitable environment for healing to take place. These data suggest that engineering materials with defined mechanical and biochemical properties and the ability to present migration- and proliferation-inducing factors, such as platelet-derived growth factor, basic fibroblast growth factor or epidermal growth factor, could be key in resolving the clinical problem of iPPROM and allowing the field of fetal surgery to move forward.
authors.affiliation: Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland; Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Kivelio
authors.affiliation: Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Ochsenbein-Koelble
authors.affiliation: Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland; Zurich Centre for Integrative Human Physiology, Zurich, Switzerland. Electronic address: martin.ehrbar@usz.ch.
authors.forename: M
authors.initials: M
authors.lastname: Ehrbar
mesh_terms: D000650:Amnion / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011247:Pregnancy; D023822:Tissue Engineering / Q000379:methods*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D036341:Intercellular Signaling Peptides and Proteins
keywords: Fetal membrane; Growth factor; Healing; PEG; Synthetic matrix