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
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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
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Ziraldo, C | | | | Solovyev, A | | | | Allegretti, A | | | | Krishnan, S | | | | Henzel, MK | | | | Sowa, GA | gas26@pitt.edu | GAS26 | | Brienza, D | DBRIENZA@pitt.edu | DBRIENZA | | An, G | | | | Mi, Q | qim3@pitt.edu | QIM3 | | Vodovotz, Y | vodovotz@pitt.edu | VODOVOTZ | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
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Editor | Gabhann, Feilim Mac | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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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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