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

Abstract

Here, congenital 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. To 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.Methods: Six 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. As a result, all six valves consisting of 0.3-mole fraction ofmore » 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. In conclusion, we 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.« less

Authors:
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [2];  [3];  [3];  [2];  [4]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Vanderbilt Univ., Nashville, TN (United States)
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  3. Baylor College of Medicine, Houston, TX (United States); Univ. of Texas, Houston, TX (United States)
  4. Max-Planck-Institut fur Kolloid und Grenzflachenforschung (Germany)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1488991
Alternate Identifier(s):
OSTI ID: 1489581
Grant/Contract Number:  
AC05-00OR22725; 32102300
Resource Type:
Published Article
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 13; Journal Issue: 12; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Baba, Justin S., McKnight, Timothy E., Ericson, M. Nance, Johnson, Anthony, Moise, Jr., Kenneth J., Evans, III, Boyd M., and Schmidt, Bernhard. Characterization of a reversible thermally-actuated polymer-valve: A potential dynamic treatment for congenital diaphragmatic hernia. United States: N. p., 2018. Web. doi:10.1371/journal.pone.0209855.
Baba, Justin S., McKnight, Timothy E., Ericson, M. Nance, Johnson, Anthony, Moise, Jr., Kenneth J., Evans, III, Boyd M., & Schmidt, Bernhard. Characterization of a reversible thermally-actuated polymer-valve: A potential dynamic treatment for congenital diaphragmatic hernia. United States. doi:10.1371/journal.pone.0209855.
Baba, Justin S., McKnight, Timothy E., Ericson, M. Nance, Johnson, Anthony, Moise, Jr., Kenneth J., Evans, III, Boyd M., and Schmidt, Bernhard. Thu . "Characterization of a reversible thermally-actuated polymer-valve: A potential dynamic treatment for congenital diaphragmatic hernia". United States. doi:10.1371/journal.pone.0209855.
@article{osti_1488991,
title = {Characterization of a reversible thermally-actuated polymer-valve: A potential dynamic treatment for congenital diaphragmatic hernia},
author = {Baba, Justin S. and McKnight, Timothy E. and Ericson, M. Nance and Johnson, Anthony and Moise, Jr., Kenneth J. and Evans, III, Boyd M. and Schmidt, Bernhard},
abstractNote = {Here, congenital 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. To 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.Methods: Six 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. As a result, all 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. In conclusion, we 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.},
doi = {10.1371/journal.pone.0209855},
journal = {PLoS ONE},
number = 12,
volume = 13,
place = {United States},
year = {2018},
month = {12}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1371/journal.pone.0209855

Figures / Tables:

Fig 1 Fig 1: Schematic representation of the dynamic tracheal occlusion valve. It comprises a saline filled detachable balloon that obstructs the fetal trachea and provides an internal flow path via an RF actuatable thermo-responsive polymer-valve.

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    Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.