PCL membranes as a tool for a mini-invasive approach to prevent spina bifida malformation

摘要

Introduction: Spina bifida is a developmental congenital disorder caused by the incomplete closing of the embryonic neural tube with a worldwide incidence of about 1 in every 1000 births. The spinal cord is exposed to the intrauterine environment causing irreversible neurological damage. Spina bifida can be surgically closed after birth but this does not restore normal function to the affected part of the spinal cord. Therefore, therapeutic innovations aim to achieve earlier surgical correction, during prenatal life. Prenatal surgery by open laparotomy in mid-trimester has recently been shown to improve overall prognosis in a clinical trial carried out at the Children's Hospital of Philadelphia (CHOP) . A pediatric neurosurgeon performs a complete repair. Although these results are encouraging the maternal and obstetric morbidity remains a significant concern. As an alternative to fetal surgical repair, the use of "innovative implants" has the potential to provide a less invasive approach for tissue coverage applicable at an earlier stage of gestation. In this context, we develop a "biocompatible membrane" (Figure 1) to cover and protect the spinal con) from the intrauterine environment and this has been achieved by the utilization of fibrous and flexible membranes made of polycaprolactone (PCL). Figure 1: Membrane of PCL to cover the spinal cord Materials and Methods: Membrane fabrication: Membranes of polycaprolactone are obtained by electrospinnng technology. Grafting procedure: To graft the membrane of PCL with bioactive polymers, the surface was first ozonized. Then, the grafting was carried out for 3 h at 45°C in water solution. Finally, samples were washed in NaCl solution and then vacuum-dried. The grafted membranes have been characterized by different techniques: ATR-FTIR, energy dispersive X-ray spectroscopy (EDX) and colorimetric method (blue of toluidine). Results and Discussion: First, membranes are obtained by electrospinnng technology and are partially occlusive to their small pore size (5-10μm). To prevent infection and release of the implant in the intrauterine environment, bioactive polymers containing ionic groups will be grafted onto this surface. PCL samples were ozonized to produce peroxide on its surface. Then, ionic groups (sulfonate) were covalently attached to PCL implant by radical polymerization of sodium styrene sulfonate (NaSS) initiated by radicals issued from the decomposition of peroxide. The grafting degree of bioactive polymers on these membranes measured by colorimetric method was 2.10~(-7) mol.cm~(-2). Conclusion: We have developed a bioactive membrane implant to cover and to protect the spinal cord. To prevent infection and release of the implant in the intrauterine environment, bioactive polymers containing ionic groups (sulfonate) have been grafted onto this surface. This research will be conducted in an ovine surgical model of Spina Bifida in pregnant sheep.