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Characterization of a Novel Sorbent Polymer for The Treatment Of Sepsis

Valenti, Isabella Elfriede (2010) Characterization of a Novel Sorbent Polymer for The Treatment Of Sepsis. Master's Thesis, University of Pittsburgh.

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    Abstract

    Severe sepsis is defined as a systemic inflammation leading to organ failure and is characterized by the release of pro- and anti-inflammatory markers called cytokines. Current clinical techniques used to treat sepsis such as early goal-directed therapy, specific target drug therapies, and hemofiltration have had limited success and inconsistent outcomes. A newly investigated therapy, hemoadsorption, has proven to be nonselective and therefore broad-spectrum (i.e. restores homeostasis to the system as a whole); more efficient and cost-effective than affinity based removal; and is auto-regulating in that solutes at higher concentrations are removed more rapidly than those at lower, safer concentrations. The goal of this thesis was to characterize and compare adsorption profiles of several cytokines in our cytokine adsorption device (CAD) for use in the treatment of sepsis. To do this, we first characterized capture of our three main cytokines of interest in the original lot of CytoSorb resin for buffer and serum. This polymer is a highly porous polymer manufactured by Cytosorbents, Inc. (Monmouth Junction, NJ) and consists of a polystyrene divinylbenzene (PSDVB) copolymer covered in a biocompatible polyvinylpyrrolidone coating. We then detailed changes in adsorption profiles over a manufacturer's lot change and re-established our baseline capture rates with the main cytokines of interest as well as a secondary group of cytokines in both buffer and serum. Further investigation into a lot of smaller diameter polymer followed and a re-design of our CAD ensued. Finally, we tested the polymer in three distinct red blood cell suspensions in order to methodically increase the degree of complexity of the capture suspension. With the information included in this thesis, further optimization and development to our CAD and the polymer will be done. Additionally, the characterization of the resin is crucial for our in-house mathematical model as well as the development and calibration of a systems model of sepsis. This model will be used to simulate the development and progression of sepsis in humans and the integration of a therapeutic CAD intervention protocol into the timecourse of sepsis to improve patient outcomes.


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    Item Type: University of Pittsburgh ETD
    Creators/Authors:
    CreatorsEmailORCID
    Valenti, Isabella Elfriedeiwv5001@gmail.com
    ETD Committee:
    ETD Committee TypeCommittee MemberEmailORCID
    Committee ChairFederspiel, Williamfederspielwj@upmc.edu
    Committee MemberKellum, Johnkellumja@ccm.upmc.edu
    Committee MemberWagner, Williamwagnerwr@upmc.edu
    Title: Characterization of a Novel Sorbent Polymer for The Treatment Of Sepsis
    Status: Unpublished
    Abstract: Severe sepsis is defined as a systemic inflammation leading to organ failure and is characterized by the release of pro- and anti-inflammatory markers called cytokines. Current clinical techniques used to treat sepsis such as early goal-directed therapy, specific target drug therapies, and hemofiltration have had limited success and inconsistent outcomes. A newly investigated therapy, hemoadsorption, has proven to be nonselective and therefore broad-spectrum (i.e. restores homeostasis to the system as a whole); more efficient and cost-effective than affinity based removal; and is auto-regulating in that solutes at higher concentrations are removed more rapidly than those at lower, safer concentrations. The goal of this thesis was to characterize and compare adsorption profiles of several cytokines in our cytokine adsorption device (CAD) for use in the treatment of sepsis. To do this, we first characterized capture of our three main cytokines of interest in the original lot of CytoSorb resin for buffer and serum. This polymer is a highly porous polymer manufactured by Cytosorbents, Inc. (Monmouth Junction, NJ) and consists of a polystyrene divinylbenzene (PSDVB) copolymer covered in a biocompatible polyvinylpyrrolidone coating. We then detailed changes in adsorption profiles over a manufacturer's lot change and re-established our baseline capture rates with the main cytokines of interest as well as a secondary group of cytokines in both buffer and serum. Further investigation into a lot of smaller diameter polymer followed and a re-design of our CAD ensued. Finally, we tested the polymer in three distinct red blood cell suspensions in order to methodically increase the degree of complexity of the capture suspension. With the information included in this thesis, further optimization and development to our CAD and the polymer will be done. Additionally, the characterization of the resin is crucial for our in-house mathematical model as well as the development and calibration of a systems model of sepsis. This model will be used to simulate the development and progression of sepsis in humans and the integration of a therapeutic CAD intervention protocol into the timecourse of sepsis to improve patient outcomes.
    Date: 30 September 2010
    Date Type: Completion
    Defense Date: 29 June 2010
    Approval Date: 30 September 2010
    Submission Date: 22 July 2010
    Access Restriction: No restriction; The work is available for access worldwide immediately.
    Patent pending: No
    Institution: University of Pittsburgh
    Thesis Type: Master's Thesis
    Refereed: Yes
    Degree: MSBeng - Master of Science in Bioengineering
    URN: etd-07222010-191334
    Uncontrolled Keywords: Cytokine; Hemoadsorption; Sepsis
    Schools and Programs: Swanson School of Engineering > Bioengineering
    Date Deposited: 10 Nov 2011 14:53
    Last Modified: 20 Apr 2012 14:56
    Other ID: http://etd.library.pitt.edu/ETD/available/etd-07222010-191334/, etd-07222010-191334

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