Characterization of a reversible thermally-actuated polymer-valve: A potential dynamic treatment for congenital diaphragmatic hernia

Abstract

BackgroundCongenital diaphragmatic hernia (CDH) is a fetal defect comprising an incomplete diaphragm and the herniation of abdominal organs into the chest cavity that interfere with fetal pulmonary development. Though the most promising treatment for CDH is via interventional fetoscopic tracheal occlusion (TO) surgery in-utero, it has produced mixed results due to the static nature of the inserted occlusion. We hypothesize that a suitable noninvasively-actuatable, cyclic-release tracheal occlusion device can be developed to enable dynamic tracheal occlusion (dTO) implementation.ObjectiveTo conduct an in-vitro proof-of-concept investigation of the construction of thermo-responsive polymer valves designed for targeted activation within a physiologically realizable temperature range as a first step towards potential development of a noninvasively-actuatable implantable device to facilitate dynamic tracheal occlusion (dTO) therapy.MethodsSix thermo-responsive polymer valves, with a critical solution temperature slightly higher than normal physiological body temperature of 37°C, were fabricated using a copolymer of n-isopropylacrylamide (NIPAM) and dimethylacrylamide (DMAA). Three of the valves underwent ethylene oxide (EtO) sterilization while the other three served as controls for EtO-processing compatibility testing. Thermal response actuation of the valves and their steady-state flow performances were evaluated using water and caprine amniotic fluid.ResultsAll six valves consisting of 0.3-mole fraction of DMAA were tested for thermal actuation of caprine amniotic fluid flow at temperatures ranging from 30–44°C. They all exhibited initiation of valve actuation opening at ~40°C with full completion at ~44°C. The overall average coefficient of variation (CV) for the day-to-day flow performance of the valves tested was less than 12%. Based on a Student t-test, there was no significant difference in the operational characteristics for the EtO processed versus the non-EtO processed valves tested.ConclusionsWe successfully fabricated and demonstrated physiological realizable temperature range operation of thermo-responsive polymer valves in-vitro and their suitability for standard EtO sterilization processing, a prerequisite for future in-vivo surgical implantation testing.

Perinatal Outcomes after Fetal Endoscopic Tracheal Occlusion for Isolated Congenital Diaphragmatic Hernia: Rapid Review

“… 5 Ever since, various attempts to improve the technique have been made, and currently there is a better understanding of the pathophysiology of the disease before and after FETO. 20 21 22 23 24 25 26 27 28 29 30 31 32 33 …”

“…5 Ever since, various attempts to improve the technique have been made, and currently there is a better understanding of the pathophysiology of the disease before and after FETO. [20][21][22][23][24][25][26][27][28][29][30][31][32][33] Although CDH has been extensively studied, there are many gaps in the current knowledge, especially regarding perinatal outcomes. The clinical implications of these are challenges during patient counselling and suitable antenatal management, 34 which can only be resolved when large and well-conducted RCTs are available.…”