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A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury

Ziraldo, C and Solovyev, A and Allegretti, A and Krishnan, S and Henzel, MK and Sowa, GA and Brienza, D and An, G and Mi, Q and Vodovotz, Y (2015) A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury. PLoS Computational Biology, 11 (6). ISSN 1553-734X

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Abstract

People with spinal cord injury (SCI) are predisposed to pressure ulcers (PU). PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM) of ischemia/reperfusion-induced inflammation and PU (the PUABM) was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments in silico. Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI. These morphological features, along with simulated cell counts and mediator concentrations, suggested that the influence of inflammatory dynamics caused simulations to be committed to “better” vs. “worse” outcomes by 4 days of simulated time and prior to ulcer formation. Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence. Using the PUABM, in silico trials of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs) suggested that, at best, early application at a sufficiently high dose could attenuate local inflammation and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ziraldo, C
Solovyev, A
Allegretti, A
Krishnan, S
Henzel, MK
Sowa, GAgas26@pitt.eduGAS26
Brienza, DDBRIENZA@pitt.eduDBRIENZA
An, G
Mi, Qqim3@pitt.eduQIM3
Vodovotz, Yvodovotz@pitt.eduVODOVOTZ
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorGabhann, Feilim MacUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Date: 25 June 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS Computational Biology
Volume: 11
Number: 6
DOI or Unique Handle: 10.1371/journal.pcbi.1004309
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Computational Biology
Dietrich School of Arts and Sciences > Mathematics
School of Health and Rehabilitation Sciences > Rehabilitation Science and Technology
School of Medicine > Computational and Systems Biology
School of Medicine > Physical Medicine and Rehabilitation
School of Medicine > Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 1553-734X
Date Deposited: 23 Aug 2016 13:43
Last Modified: 29 Apr 2022 11:55
URI: http://d-scholarship.pitt.edu/id/eprint/28513

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