Preterm premature rupture of fetal membranes is a devastating complication of pregnancy with high risk of feto-maternal mortality and morbidity. Several attempts
have been made to seal spontaneous and iatrogenic fetal membrane ruptures but none has made it to clinics. Persistent leakage of amniotic fluid following invasive surgical and diagnostic procedures jeopardize the benefit of suchlife saving interventions and draw the limits for the developing field of intrauterine fetal surgery. Efforts are directed to take action before the commencement of leakage of amniotic fluid rather than after the leakage in iatrogenic maneuver: one avenue of research focuses on
prophylactic plugging of the fetoscopic lesion at the time of completion of the procedure, thus to increase the chance to prevent subsequent leakage of amniotic fluid. In order to design appropriate sealing strategies the knowledge of the mechanical and biological properties of intact and injured fetal membranes is indispensable.
The objective of this thesis is on the one hand to develop regimen that allow the repair of fetal membranes by plugging membrane lesions with fetoscopical interventions. On the other hand, we concentrate on the description of biophysical parameters of the fetal membrane by establishing biomechanical test regimen. Towards a fetoscopic repair mechanism I have developed a method to decellularize amniotic membranes in order to produce a non-immunogenic material. These
membranes proved to be stable enough for long term storage and for off-the-shelf use.
In our animal trials using rabbit does, the material exhibited good handling properties
as well as good sealing characteristics in absence of adverse biological effects.
Although the plugs were at best marginally remodeled and populated with cells in
these short term experiments in rabbits, the self locking features of the plugs and the
predictably long term stability of the material might be a critically important for
future clinical applications.
Towards the mechanical characterization of the fetal membranes I have together with
the group of Prof. Edoardo Mazza, Department for Mechanics, ETHZ worked on the
establishment of a novel device, which allows the measurement of mechanical
properties and the testing of membrane sealing regimen under near to physiological
conditions. I have compared measurements of mechanical properties using this new
generation device, which employs equibiaxial stretching with measurements
performed with uniaxial stretching. These initial results indicate that the materials
parameters can only be correctly estimated using biaxial stretching regimen and might
add to the understanding of elastic and plastic features of biological membranes.
Collectively a thorough understanding of mechanical and biological properties and
the design of materials platforms that can be adapted to the tissue requirements might
only approach the complexity of this problem. Although much more research is
needed, we think that our results on the membrane repair and the mechanical
properties presented in this thesis are promising starting points towards the
establishment of appropriate treatment regimen for PPROM of fetal membranes.