J. R. Bardill1, D. Park1, S. Williams3, A. Marwan1,2,3 3University Of Colorado Denver,Pediatric Surgery,Aurora, CO, USA 1University Of Colorado Denver,Bioengineering,Aurora, CO, USA 2Children’s Hospital Colorado,Aurora, CO, USA
Introduction: Neural tube defects (NTDs) result in lifelong neurological and functional deficits. Currently, an in-utero surgical repair of NTDs covers/patches the defect, resulting in a significant 50% reduction in post-natal ventriculoperitoneal shunting. However, this surgery is complicated by risks of morbidity to the mother and infant. Studies have found that early in gestation, failed neural tube closure results in progressive tissue damage secondary to exposure to amniotic fluid. Therefore, the goal of current NTD repair is to cover the defect at an earlier gestational age to prevent the irreversible damage to neural tissue from taking effect. The development of a novel, biomimetic, Reverse Thermal Gel (RTG) has posed a unique solution to deliver an early, minimally invasive method to patch a NTD. Here, we demonstrate two in-vitro properties of the RTG for NTD applicability: 1.) Fast in-situ gelling properties in amniotic fluids, 2.) Gel stability after 1 month of exposure to amniotic fluid.
Methods: RTG gelling stability and lower critical solution temperature (LCST) testing in amniotic fluids: In glass vials, RTGs were dissolved in phosphate buffered saline (PBS), sheep amniotic fluid (SAF), and human amniotic fluid (HAF) and gelled in a warm water bath. Stable gels were assessed using the vial tilt test and the LCST was determined using temperature sensitive UV-VIS spectroscopy. B.) RTG 1 month degradation: RTGs were exposed to PBS, SAF, and HAF for 1 month and the LCST was tested to determine if RTG properties had changed.
Results: The RTG shows stability when gelled in amniotic fluids and an LCST below physiologic temperature, which is necessary for in-situ gelling properties for this NTD application. After 1 month of exposure to amniotic fluids, the LCST remained below physiologic temperatures, indicating the RTG will remain stable for 1 month in the amniotic environment.
Conclusion: The RTG has fast in-situ gelling properties in amniotic fluid that remain stable over time, making it an ideal candidate for an early, minimally invasive method to patch NTDs.
