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Development of an Artificial Placenta for use in Bridging Extremely Premature Infants to Viability

Samski, Katelin (2023) Development of an Artificial Placenta for use in Bridging Extremely Premature Infants to Viability. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Complications from preterm birth is the leading global cause of mortality in children under 5 years of age. Those infants at the lowest threshold of fetal viability, the extremely premature infant (EPI), are at the greatest risk for impairment or death. Current medical practice focuses on respiratory support, as the lungs of an EPI have not begun alveolar differentiation or surfactant production and are unable to achieve the gas exchange needed for survival. The neonate is provided with antenatal steroids to expedite lung development, surfactant to prevent acinus collapse, and mechanical ventilation (MV) to supplement native gas exchange. The pressures, volumes, and relatively high oxygen tensions involved in MV predispose the infant to chronic lung disease. As an alternative to MV, neonatologists have turned to utilizing extracorporeal life support as a way to mimic in utero conditions for continued fetal development. In this experimental therapy a fluidic environment is created for the fetal respiratory system, the artificial uterus, while an oxygenator, the artificial placenta (AP), is used to provide supportive gas exchange in place of the native placenta.

This dissertation details the design and development of a hollow fiber membrane (HFM) based AP. A mathematical model was improved to provide more accurate predictions of CO2 removal in HFM bundles. The improved model was used to determine AP bundle geometry which then underwent in vitro and in vivo testing. A protocol was developed to biopassivate the AP utilizing a commercially available zwitterionic material. The CO2 removal target of 12.2 mL (min)-1 and 100% O2 saturation at the outlet of the device was achieved at the target blood flow rate of 165 mL (min)-1 in benchtop experiments. Resistance measured in vitro was 33% less than the maximum acceptable value and no plasma free hemoglobin generation was generated by the device during 6-hour benchtop testing. The device functioned according to physiological principles during in vivo testing. The preliminary biopassivation protocol decreased platelet deposition on HFM swatches removed from coated devices compared to uncoated controls. Together these results indicate the feasibility of using this device design and biopassivation technique in future clinical testing.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Samski, Katelinkso14@pitt.edukso140000-0003-0689-567X
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorFederspiel, Williamfederspielwj@pitt.edu
Committee MemberBorovetz, Harveyborovetz@pitt.edu
Committee MemberWagner, Williamwagner@pitt.edu
Committee MemberMaul, Timothytimothy.maul@nemours.org
Date: 13 June 2023
Date Type: Publication
Defense Date: 22 March 2023
Approval Date: 13 June 2023
Submission Date: 27 February 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 147
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Artificial Placenta, Extracorporeal Life Support, Extracorporeal Membrane Oxygenation, Extracorporeal Co2 Removal, Haldane Effect, Mathematical Model
Date Deposited: 13 Jun 2024 05:00
Last Modified: 13 Jun 2024 05:00
URI: http://d-scholarship.pitt.edu/id/eprint/44321

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  • Development of an Artificial Placenta for use in Bridging Extremely Premature Infants to Viability. (deposited 13 Jun 2024 05:00) [Currently Displayed]

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